Review

Cite This: ACS Catal. 2020, 10, 2260−2297 pubs.acs.org/acscatalysis

Machine Learning for Catalysis Informatics: Recent Applications and

Prospects
Takashi Toyao,†,‡ Zen Maeno,† Satoru Takakusagi,† Takashi Kamachi,‡,§ Ichigaku Takigawa,*,∥,⊥
and Ken-ichi Shimizu*,†,‡
†
Institute for Catalysis, Hokkaido University, N-21, W-10, Sapporo 001-0021, Japan
‡
Elements Strategy Initiative for Catalysts and Batteries, Kyoto University, Katsura, Kyoto 615-8520, Japan
§
Department of Life, Environment and Materials Science, Fukuoka Institute of Technology, 3-30-1Wajiro-Higashi, Higashi-ku,
Fukuoka 811-0295, Japan
See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

∥
RIKEN Center for Advanced Intelligence Project, 1-4-1 Nihonbashi, Chuo-ku, Tokyo 103-0027, Japan
⊥
Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Kita 21 Nishi 10, Kita-ku, Sapporo,
Hokkaido 001-0021, Japan
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ABSTRACT: The discovery and development of catalysts and catalytic

processes are essential components to maintaining an ecological balance in the
future. Recent revolutions made in data science could have a great impact on
traditional catalysis research in both industry and academia and could
accelerate the development of catalysts. Machine learning (ML), a subfield of
data science, can play a central role in this paradigm shift away from the use of
traditional approaches. In this review, we present a user’s guide for ML that we
believe will be helpful for scientists performing research in the field of catalysis
and summarize recent progress that has been made in utilizing ML to create
homogeneous and heterogeneous catalysts. The focus of the review is on the
design, synthesis, and characterization of catalytic materials/compounds as
well as their applications to catalyzed processes. The ML technique not only
enhances ways to discover catalysts but also serves as a powerful tool to
establish a deeper understanding of relationships between the properties of materials/compounds and their catalytic activities,
selectivities, and stabilities. This knowledge facilitates the establishment of principles employed to design catalysts and to
enhance their efficiencies. Despite such advantages of ML, it is noteworthly that the current ML-assisted development of real
catalysts remains in its infancy, mainly because of the complexity of catalysis associated with the fact that catalysis is a time-
dependent dynamic event. In this review, we discuss how seamless integration of experiment, theory, and data science can be
used to accelerate catalyst development and to guide future studies aimed at applications that will impact society’s need to
produce energy, materials, and chemicals. Moreover, the limitations and difficulties of ML in catalysis research originating from
the complex nature of catalysis are discussed in order to make the catalysis community aware of challenges that need to be
addressed for effective and practical use of ML in the field.
KEYWORDS: machine learning, catalysis informatics, high-throughput experiments/computations, data mining,
structure−activity relationships

1. INTRODUCTION under a variety of conditions.8,9 Also, fundamental kinetic,

Catalysis is a complex, multidimensional, dynamic, and
multiscale method for promoting chemical reactions.1 In
particular, heterogeneous catalysis is still a largely empirical
science because of the complexity of the surface chemistry
involved.1−3 As depicted in Figure 1, wide length and time
scale ranges need to be considered in order to fully understand
the dynamic nature of catalytic reactions. Recent experimental
and theoretical studies have yielded atomic-level insight into
these processes.4−7 Nevertheless, the discovery of truly novel
catalysts and catalytic reactions is still a formidable task, and as
a result, many of the advances in this area have arisen from
trial-and-error investigations. This empirical approach has
uncovered numerous multicomponent catalysts that operate
characterization, and theoretical studies have been carried out
to develop preparation−structure relationships or structure−
performance relationships, which are useful in guiding
hypothesis-driven designs of new catalysts.10−12 For example,
to create structure−performance relationships, catalyst per-
formance (vertical axis) is plotted as a function of key
structural factors (horizontal axis) in order to uncover
important features of catalysts that affect their activities,
selectivities, and/or stabilities. Unfortunately, the enormous
Received: September 28, 2019
Revised: December 8, 2019
Published: December 16, 2019

© 2019 American Chemical Society 2260 DOI: 10.1021/acscatal.9b04186

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Figure 1. Description of heterogeneous catalysis from the atomic level to large-scale reactors.
amount of experimental data gathered in the study of catalyst
preparation−structure−performance relationships have not yet
been integrated into readily searchable databases. Although
recent advances in theoretical and computational chemistry
have enabled descriptions of elementary steps in catalytic
processes that have already been discovered, for the most part
they have not focused on strategies to design new catalysts.13
Therefore, the enormous amount of experimental and
theoretical data accumulated to date on various aspects of
catalysis are not that useful in predicting new catalysts or
catalytic reactions. Scaling the relationship between calculated
reaction barriers and binding energies of surface intermediates
is a promising method employed in data-intensive catalyst
design.13−15 Several studies have demonstrated how this
approach can contribute to the design of novel catalysts
based on predicted volcano trends in catalytic activity versus
binding energies of surface intermediates.14 However, the
accuracy of these models in predicting catalytic performance is
limited because of the large number of other factors involved.
Consequently, more effective relationships (descriptors) that
can be employed to analyze these processes must be devised in
order to develop more effective strategies to design novel
catalysts for important reactions.
Molecular/materials informatics has become a central
paradigm in molecular and materials science.16−29 In the
data-intensive materials design (so-called inverse design)23,24
protocol, the desired function of a new material is identified
first, and then a candidate is extracted from a computational or
experimental database using machine learning (ML) methods.
This new methodology, which is an improved version of
“quantitative structure−property relationship (QSPR) model-
ing of materials properties”,30 has been shown to be a powerful
tool for predicting the properties of substances, including those
of unknown molecules/materials. Recent success in utilizing
this approach is exemplified by the ML-assisted prediction of
physical properties of molecules/materials such as atom-
ization31,32 and formation energies,33−35 densities of states,36
band gaps,37−39 vibrational free energies,40 and melting
temperatures.41 Therefore, if a single physical property is
dominant in governing the performance of a material,
molecular/materials informatics serves as an ideal tool to
identify a novel functional material. However, catalyst design
does not fit into this category because theoretical models for
catalysis, especially heterogeneous catalysis, are not available at
this time. In contrast to those involving physical properties,
ML-assisted predictions of rates and selectivities of catalytic
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reactions are still in their infancy.42 Despite having a 30 year
history, the use of artificial intelligence (AI) for catalyst
design43−46 has had only a small impact on the discovery of
effective homogeneous or heterogeneous catalysts prepared
according to insight from data-intensive methodology. The
main barriers to employing data-intensive methods for catalyst
design are the lack of universal data sets for catalytic activities
and selectivities and the existence of only a few descriptors.
In this review, we summarize the current state of
investigations aimed at the ML-guided development of
homogeneous and heterogeneous catalysts. Recent excellent
reviews42,47−52 have described research studies of ML in
catalysis,49 pioneering investigations of ML-assisted identi-
fication of catalysts,46,53 predictions of catalytic properties by
the use of density functional theory (DFT) calculations along
with scaling relationships,13−15 and catalysis informatics.47,48 In
contrast to others, this comprehensive review covers studies of
ML-assisted theoretical and experimental investigations of
computer-aided catalyst design that have been reported in the
past decade, with a major focus on illustrating how ML, in
combination with DFT and experimental data, can be used to
identify ideal catalysts. The limitations and difficulties of ML in
catalysis research originating from the complex nature of
catalysis are also discussed. The review begins with a tutorial
overview of applications of ML in catalysis science (section 2).
This is followed by a discussion of representative studies in
which high-throughput computation and ML have been
utilized to design inorganic catalysts such as alloys, complex
metal oxides, zeolites, and inorganic−organic hybrid materials
(section 3). Representative studies focusing on high-
throughput computation to uncover important catalyst proper-
ties, including d-band centers, oxygen vacancy formation
energies (EOvac), and surface adsorption energies of molecules
and atoms, are covered in section 4. A review of ML
approaches to predict these functions is given in section 5.
These efforts are highly important because describing catalysis
as a function of a physical parameter would be necessary for
fast and efficient catalyst discovery. Illustrations of the
application of ML techniques to the characterization of
heterogeneous catalysts are provided in section 6. This
would enable more accurate and rapid characterization of the
catalysts, and eventually, automated control of these processes
in catalysis research would be possible. The discussion in
sections 7 and 8 focuses on ML treatments of experimental
data aimed at designing new heterogeneous and homogeneous
catalysts, respectively. Finally, a summary of the efforts
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Figure 2. Schematic representation of ML-aided future catalysis research.
Figure 3. ML landscape in the context of a brief overview of machine learning tasks and algorithms.
discussed in the review and future perspectives in the area of
ML-guided catalyst development (Figure 2) are given in
section 9.
2. A GUIDE TO USING MACHINE LEARNING IN
CATALYSIS RESEARCH
ML is an interdisciplinary field of study that concentrates on
developing computer algorithms that enable learning from data
without being explicitly programmed. ML emerged primarily
from the fields of computer science and statistical science, but
it now encompasses a broad range of disciplines. The
landscape of ML is briefly given Figure 3 in the form of
typical ML problems along with some common methods of
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supervised and unsupervised learning. The details of each
algorithm are covered in many excellent existing reviews.16,51
Thus, rather than just rephrasing these explanations, in this
section we highlight from a user perspective the essentials,
practices, and pitfalls of using ML in natural sciences and
specifically for catalyst development.
Particular emphasis will be given to supervised learning,
which is the most common setting used not only in catalysis
studies but also in other ML applications such as image and
speech recognition, machine translation, and medical diag-
nosis. In supervised learning, a function that maps an input to
the desired output is built without explicit modeling by
providing many examples of input−output pairs (called
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Figure 4. Caution of ‘‘garbage in, garbage out’’ in ML studies (section 2.1). Because ML is data-driven, the quality and quantity of data are essential
prerequisites for every ML study. Establishing sufficient data quality and quantity should always be prioritized over what ML algorithm is used. If
input data are of low quality, flawed, or nonsense, any ML model produces nonsense output or “garbage”.

Figure 5. Theory-driven and data-driven approaches for scientific research. Theory-driven methods try to explicitly model the inner workings of a
target phenomenon (e.g., through first-principles simulations), while data-driven methods try to precisely approximate its outer behavior observable
as data (section 2.2).

training data), and the obtained mapping function is used to
make a prediction (an output) for any possible input. One of
the main interests of catalysis science is often to gain a better
understanding of unclear relationships between inputs (e.g.,
the properties, compositions, and structures of catalysts) and
outputs (e.g., their activities, selectivities, and stabilities).
Unfortunately, it is not yet feasible to have an explicit
theoretical model that can perfectly describe such complicated
relationships. Instead, by the use of supervised learning, an
inferred relationship between the inputs and outputs can be
learned from given examples without explicitly knowing the
underlying principles. As a result, ML can serve as an
important tool to investigate and predict phenomena that are
difficult to explicitly model mathematically. This can open up a
new direction for scientific research on highly complex
phenomena with many uncertain intertwined factors, where
traditional trial-and-error styles are already reaching the limit.
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However, to maximize the capabilities of this new technology,
we need to have a careful understanding of what ML-acquired
mapping means, what grounds are utilized to obtain a
prediction or insight, and what types of results can be
misleading and force us to conclude nonexistent cause-and-
effect relationships.
2.1. “Data-Driven”: The Quality and Quantity of Data
Matter Most. The principle that underpins all of the ML
algorithms listed in Figure 3 is that ML is data-driven, which
means that ML models are defined only by feeding a given data
set (training data) into them. ML prediction models are
representative of such given training data. Thus, the quality
and quantity of “data” are essential prerequisites to elevate the
predictive capability of ML independent of whether a state-of-
the-art or simple ML algorithm is utilized. Realizing that data is
more important than algorithms is the first step for building
any ML application, and the fact that accurate ML is
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Figure 6. (top) Supervised learning (section 2.3). Supervised learning acquires a function mapping inputs to outputs that can be fitted to the
training data by using tuning parameters. (bottom) The bias−variance trade-off (section 2.5). Highly complex models often cause overfitting,
whereas models that are too simple can cause underfitting.
impossible with inaccurate data is often described as “garbage
in, garbage out” (Figure 4).
The first questions in every ML-based study would be what
types of and how much data ML requires. The most typical
form of data is tabular data (e.g., a spreadsheet), where each
row has numeric and non-numeric records of variables
(columns) from experimental observations, theoretical calcu-
lations, and existing databases. However, as this paper
showcases existing studies in subsequent sections, diverse
types of data are now used in ML-based studies, including time
series, images, sensor signals, texts, and structure data such as
chemical formulas, steric configurations, three-dimensional
(3D) point clouds, and atom mappings. These forms define
the information contents that ML can use for predictions, and
thus, any forms of data should be used if they characterize the
targets under study well. The size of the data set is another
major concern in ML-based studies, and it determines the
confidence or reliability of ML predictions. Technically, ML
can be applied to any small-sized data set, but the prediction
made from such a small data set would be less confident and
reliable in a statistical sense. Considering the use of any
existing data sets can help when the available data sets are very
limited.
2.2. Data-Driven and Theory-Driven Approaches. The
data-driven principle should also be contrasted with theory-
driven (or hypothesis-driven) methods (Figure 5), which are
most often used in traditional sciences. Theory-driven and
data-driven methods are based on very different principles.
Theory-driven methods try to explicitly model the inner
workings of a target phenomenon (e.g., through first-principles
simulations), while data-driven methods try to precisely
approximate its outer behavior observable as data. These two
are quite complementary, and data-driven approaches can
complement limitations of theory-driven ones such as high
computing costs, target/condition/parameter considerations,
scalability issues, complexity and uncertainty of real-world
systems, and known and unknown imperfections of currently
available theories.
The exact origins of scientific phenomena are often
unknown. As a result, studies aimed at identifying cause-and-
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effect relationships conventionally start with a hypothesis or
theory that arises from past observations and intuition. Then
data from carefully designed experiments or computer
simulations are collected to determine whether they are in
accord with the proposed hypothesis or theory. The theory-
driven approach has been employed in the field of catalysis to
gain significant insight and an atomic-level understanding of
how catalysts operate. In contrast, in the data-driven approach,
an existing data set is subjected to an unfixed mathematical
function (the ML model) that includes various tuning
parameters targeted to produce the desired outcome. Data
are used to train the ML model so that the model can produce
the defined outcome. Hence, the data-driven approach does
not encode domain-specific information, and as a result, it is
not cognizant of the underlying phenomenon before ML
training begins. Since data are always in accord with the model
after the ML training, it is generally hard to confidently assess
whether an ML model is valid.
The well-known statistician David Hand stated the following
in his keynote talk at the ACM SIGKDD Conference on
Knowledge Discovery and Data Mining (KDD ’18):54
“Theory-driven models can be wrong but data-driven models
cannot be wrong or right. Data-driven models are not trying to
describe an underlying reality but are merely intended to be
useful. So, they could be poor or useless, but not wrong.”
Fitting ML models to data is purely based on input−output
correlations, which do not imply causation. Training data points
are finite, and a limitless number of possible mappings having
the same goodness of fit can potentially exist. It is even
possible to deliberately choose a mapping that is consistent
with an expected outcome but is merely subjective and lacks
any rational basis. It requires considerable attention to avoid a
hypothesizing after the results are known (“HARKing”)
conclusion. As David Hand also stated, “If data can speak for
themselves, they can also lie for themselves. So, it’s critically
important to exercise caution, do not claim too much,
understand the data and its quality.”
2.3. Supervised Learning and an Example Workflow.
By analysis of training data, supervised learning identifies a
target function that best maps input variables X to the desired
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Figure 7. Differences in commonly used algorithms for supervised learning (section 2.3). Decision boundaries of each algorithm for classifying the
red and blue points in the leftmost plots are visualized. For exactly the same training sets (i.e., the three problems at the far left), each algorithm
forms very different decision boundaries (from different inductive biases) to interpolate the interspace for generalization beyond the given training
samples.
output variable Y (Figure 6). The training data consist of many
sample input−output pairs, and the trained ML model
corresponds to a function that fits the data to reproduce the
given input−output pairs. Because the number of input
variables can be large, X can be high-dimensional, and thus,
the fitting process can be technically nontrivial. For example,
supervised learning can be used to create a computer program
that recognizes handwritten characters without explicitly
knowing any underlying principles. In contrast, it is exceed-
ingly difficult to explicitly program the recognition process to
use visual images of handwritten characters (the input) to
determine what characters the images represent (the output).
When a process that is hard to model explicitly is encountered
but a good set of corresponding input−output examples can be
collected, it is always worth considering using the supervised
learning approach. However, it also should be emphasized that
high prediction performance currently available for the
handwritten character recognition does not directly mean
that we could understand any underlying mechanism by which
our brain recognizes characters. It should be noted that the
supervised learning setup arises in many subfields of computer
science and statistics, where many synonyms are used,
including where an input variable is called a feature, descriptor,
attribute, independent variable, predictor variable, explanatory
variable, or covariate and an output variable is called a
dependent, response, or outcome variable.
As presented in an excellent publication by Pedro
Domingos,55 the general framework of ML can be understood
in terms of “Learning = Representation + Evaluation +
Optimization”. The wide variety of ML methods displayed in
Figure 3 stem from differences in these three factors. The
aspect of representation is about the choice of an ML model
function that is tunable by using parameters, where “tunable”
means that the shape of the function is changed in various
forms by changing the values of the parameters. For example, if
we assume a linear input−output relationship, we can use Y =
f(X1, ···, Xp) = θ0 + θ1X1 + ... + θpXp with p + 1 parameters (θ0,
···, θp) for a p-dimensional input of X = (X1, ···, Xp). By changes
in the values of the parameters θ0, ..., θp, the function f can
represent any hyperplane in the p-dimensional space, but it
cannot represent nonlinear hypersurfaces. Moreover, it
requires a strong assumption that the input−output mapping
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is linear, meaning that Y needs to be a weighted sum of each
input variable (no interaction effect is considered). As
portrayed in Figure 6, a model with appropriate complexity
depending on the given data needs to be chosen or designed.
The differences among several ML algorithms in terms of
decision boundaries for binary classification in two dimensions
are displayed in Figure 7. An intuitive understanding of how
each parameter affects the decision boundaries can be gained
by viewing an interactive demo dealing with neural networks at
https://playground.tensorflow.org/.
The aspect of evaluation is about the choice of criteria for a
goodness-of-fit test of the chosen ML model function. For
example, linear regression analysis usually minimizes the least-
squares error between Y and f(X), but when Y is binary (e.g.,
−1 or +1), the use of the squared error is not appropriate, and
logistic regression is used instead. Lastly, the aspect of
optimization is about the choice of a tuning algorithm (the
optimization algorithm) that optimizes the evaluation criteria
for fitting the ML model function to the given data. For
example, in the cases of least-squares regression or several
kernel methods, optimal parameters can be obtained in a
closed form by using a matrix calculation, but for general ML
models such as neural networks, incremental parameter
updating with random initialization is often used.
Although recent advances made in the development of open-
source software such as scikit-learn and tensorflow have
provided ready access to numerous high-quality ML methods,
nonexperts would still be uncertain about what method to
choose from a long list of available algorithms. Below we
provide an outline of a typical workflow, practices, and
checkpoints from a user’s viewpoint. Another publication56
gives further details on best practices.
A. Problem and Variable Design. First, the problem under
study needs to be defined in an input−output format. Thus,
the first but crucial step is to identify or devise a set of relevant
input variables that characterize the output variables well (or
fully). Traditionally, a small number of dominant factors as
input variables is preferred, but this is not a requirement when
modern ML is used. Thousands or even millions of potentially
related factors beyond human capability can be considered as
long as they are observable. For example, each pixel value of an
image can be employed as an input variable, and in this case,
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10 000 input variables would be considered for an image of
100 × 100 pixels. This approach has not been a common
practice in conventional statistics, and regression using many
variables has not been recommended. It is often called “kitchen
sink regression” because of its high risk of overfitting and
capturing spurious correlations. At the current time, we can
consider a large number of input variables by using many
modern ML methods that can handle extremely high
dimensional data with appropriate control of the model
complexity. This would bring a practical advantage because if
any primary factor is missed, the prediction can suffer from so-
called omitted variable bias and potentially yield a spurious
correlation. However, it also should be noted that inclusion of
unnecessarily many irrelevant factors can deteriorate the
prediction capability even for state-of-the-art ML methods
such as deep learning.
B. Data Collection, Sanity Check, and Exploratory Data
Analysis. ML is purely data-driven, and consequently, the
quality and quantity of data are the key determining factors for
success. Because ML prediction models are representative of
the given training examples, it is crucial that the training data
be representative of actual situations we want to treat.
However, it is extremely difficult in general to guarantee this
natural requirement since truly desirable data are not yet
obtained and are literally “unseen”. Collecting available data
can often be plagued by unintentional “selection bias” because
any collectable data can be easily and strongly biased toward
targets that were successful in the past or that are merely easily
testable. Furthermore, indiscriminate data collection can be
plagued by errors, outliers, and noise. Thus, preliminary
exploratory data analysis (EDA) and a sanity check of the
training data are always required. EDA is often conducted by
investigating data distributions and outliers via descriptive
statistics and visualizations such as a histogram, correlation
matrix or correlogram, box plot, and various projection
methods to two or three dimensions.
C. Data Cleaning and Preprocessing. When a sufficiently
large training data set is collected, cleaning and preprocessing
are often required. Specifically, one needs to reformat
individual data into a single tabular form, remove or correct
erroneous or incomparable data points, impute missing values,
and normalize and rescale the data in order to stabilize the
numerical computation. The outcomes of several ML
algorithms such as kernel methods and neural networks can
differ according to whether any normalization, standardization,
or scaling is performed. It should also be noted that not only
input variables but also output variables can be normalized or
scaled.
D. Feature Engineering and Selection. The selection of
optimal input variables is a formidable step. ML is often used
because the underlying principle is so unclear that it cannot be
subjected to explicit programming, particularly in the case of
scientific data. Also, in many cases it is not certain what the
determining factors are. Thus, in practice it is necessary to
utilize engineering steps in order to derive new input variables,
which then need to be modified, replaced, and combined in a
human-understandable manner. In particular, crosstalk be-
tween two variables A and B can be taken it into account by
adding the product, A × B, as an interaction variable (more
generally, polynomial features). Further analysis of cases where
ML fails to predict correctly can provide new insight into
features that should be added. In more advanced cases, called
stacking or stacked generalization, ML outputs can be reused as
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new input variables (meta features). For example, out-of-
sample prediction values, principal component values,
clustering results, and hierarchical features from deep learning
models can be used.
E. Choosing, Applying, and Customizing ML Algorithms.
After a training set is properly designed and set up, several ML
algorithms are applied and evaluated.
• Performance Evaluation Measure (or “Loss Func-
tion”). First, an appropriate evaluation measure needs to
be selected. Typical choices are the prediction accuracy,
F1 score, or area under the receiver operating character-
istic curve (ROC-AUC) score for classification tasks and
the mean absolute error (MAE), mean square error
(MSE), root-mean-square error (RMSE) and root-
mean-square logarithmic error (RMSLE) for regression
tasks. Special cases like those with imbalanced classes
(e.g., 0.1% positive, 99.9% negative) can be properly
handled by customizing the evaluation measure (e.g.,
class-weighted loss or focal loss). Another example is a
case with outliers handled by a robust loss function (e.g.,
Huber loss).
• Preparation of Validation and Test Data: Also,
establishing reliable validation strategies for estimating
the prediction performance is quite important (but
notoriously difficult in general). Standard options are to
use cross-validation or to split the data into training,
validation, and test sets in order to evaluate a prediction
in an out-of-sample way. By definition, the training data
cannot be used for model evaluation. Thus, the
validation set is utilized to evaluate the hyperparameter
tuning, while the test set is used to evaluate the
prediction performance. When cross-validation is
employed, each subpart of the data needs to be further
split into training and validation sets (or perform nested
cross-validation, often called double cross-validation),
being careful not to have data leakage from the training
set into the validation or test set. We will discuss this
point more in section 2.4.
• Constant Prediction: Next, a constant prediction model
can be applied to obtain a worst-case baseline for the
given evaluation measure. For example, scikit-learn
contains DummyClassifier and DummyRegressor for
this purpose. For regression tasks, the mean target value
in the training data set is often used as the constant. R2
scores are relative measures using the MSE against this
basic reference. For classification tasks, the most
frequent class label is commonly used.
• Linear Prediction: Subsequently, a linear prediction is
applied. A common choice is logistic regression for
classification tasks and linear regression for regression
tasks. Linear prediction causes underfitting when the
input−output relationship is not linear, but in many
practical cases it can produce quite stable predictions
with a sufficient level of performance. It should also be
noted that even simple log scaling of the variables breaks
linearity. Furthermore, when interaction variables are
introduced into the model, linear prediction leads to
(partially) polynomial classification or regression con-
sidering an interaction effect. When the number of
variables is large (in particular, larger than that of
training examples), linear regression can be non-
computable or unstable without any regularization
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because of matrix noninvertibility. In this case, a
regularized linear regression technique such as LASSO
or ridge regression should be used instead. LASSO and
ridge regression for regression tasks correspond to L1-
penalized and L2-penalized linear regression, respec-
tively. Similarly, logistic regression for classification tasks
is also commonly used with L1- and L2-penalized
regularization (e.g., LogisticRegression in scikit-learn has
these options). Other common options in chemo-
informatics are partial least-squares (PLS) regression
and principal component analysis (PCA) regression,
which are linear regression with supervised or
unsupervised dimensionality reduction by linear coor-
dinate transformation, respectively.
• First-Choice Nonlinear Prediction: After performing
constant and linear predictions, we can test nonlinear
predictions. The recommended first choices for this
purpose are random forest or extra trees (and possibly k-
nearest neighbors for classification) because both are less
hyperparameter-dependent and the critical parameter is
often only the number of trees (or k for k-nearest
neighbors). For relatively large data sets, the use of extra
trees is preferred because it usually exhibits a comparable
and sometimes better performance and it requires much
less computation time.
• More Complex Nonlinear Prediction: When nonlinear
predictions perform better than linear predictions, we
can move on to more complicated models such as kernel
methods, neural networks, and gradient boosted trees
(GBDT/GBRT, including XGBoost and LightGBM).
However, these methods are sensitive to hyperparameter
tuning and can display significantly worse performance if
the hyperparameters are incorrectly set. The best
practice is to use systematic hyperparameter tuning
based on a grid or a random or more advanced search
method (e.g., model-based optimization such as
Bayesian optimization, multiarmed bandits, genetic
algorithms (GAs), and any AutoML pipelines). We
will discuss this point in more detail in section 2.5.
• Deep Learning Applicability: In cases where large data
sets of direct measurements such as images, videos, and
sensor signals are available, deep neural network (DNN)
(i.e., deep learning) models can often perform
significantly better than other methods. They can also
learn a series of nonlinear feature transformations to
convert the inputs to representations that are easier to
predict. In particular, for image observations (e.g., arising
from microscopy), convolutional network (CNN)
methods such as VGG, ResNet, and DenseNet are
widely used. Nowadays, many CNN models that are
pretrained on quite large data sets of natural images
(e.g., the ImageNet database) are available. These
pretrained CNN models can be used as handy feature
extractors for any natural images (through a series of
convolution filter banks). Futhermore, f ine-tuning of
these models by reusing the pretrained weights for
initialization or remodeling can improve the prediction
performance even when only a small number of image
observations are available for a given task.
• Bespoke ML Models: For many practical cases, it is
sufficient to select an off-the-shelf ML method from the
available list. However, consideration needs to be given
to specific constraints, including imbalanced/skewed
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data, missing data, real-time processing, domain
adaptations, and dependencies arising from time series
or structural variable correlations. When this is the case,
a customized or newly developed method is required to
meet each specific requirement.
F. Analysis of the Trained ML Models. The main use of
trained ML models is to make predictions for the target
problem, but they can also provide much additional
information. The trained ML models represent possible
approximations of the unknown input−output relationship
under study. Thus, extracting information on how strongly
each variable or each sample contributes to the prediction is
quite helpful to gain a better understanding of the problem.
Popular methods for this purpose include significance tests on
regression coefficients, decision rules extraction, variable
importance scores from PLS regression (known as VIP analysis
in chemoinformatics), feature importance scores from tree
ensemble methods such as random forests, partial dependency
plots (such as the sklearn.inspection module of scikit-learn),
(global) sensitivity analysis methods, and feature visualization
methods for DNNs (such as saliency maps and gradient-based
methods such as GradCAM, DeepLift, and SHAP). However,
it is noteworthly that forcibly projecting multivariate trends
into independent univariate contributions of individual features
always entails information loss because of the correlation
between features. These “interpretability” or “explainability”
aspects of ML algorithms have been a recent hot topic among
ML reseachers. For another example, investigating hard-to-
predict examples in detail would also give some insights into
the problem design under study and the input variable design
and engineering steps.
G. Evaluating and Maintaining Predictions. Following the
attainment of ML predictions, a further engineering effort is
sometimes needed to carefully check whether the prediction
works in the intended manner. Unfortunately, this step is not
simple because ML procedures depend not only on the
algorithm but also on the data and possibly random numbers
for model initialization. Traditional software engineering
techniques are often useless for ML-based software develop-
ment because of its data and parameter dependencies. Here we
need not only code versioning but also proper data versioning.
Moreover, in these cases debugging, testing, and requirement
definition are often more troublesome, and some data
treatments also require data infrastructure and management
along with iterative system deployment and maintenance.
2.4. Data Leakage and Data Dredging. The only
trustworthy way to estimate the prediction performance of the
trained ML model is to test it using completely unseen external
data derived from actual situations. In many cases, however,
acquiring a completely new data set in a real-world context is
costly from both a time and money perspective. Thus, some
strategy is required for simulating “unseen” data to test the ML
prediction by using available data at hand. A simple approach is
to set aside a portion of the data set for model validation and
testing by a three-way split of the data into training, validation,
and test sets. When the data set is not large, the most standard
practice is to use k-fold or leave-k-out cross-validation or
repeated random subsampling.
However, since the test data are taken from a portion of the
already obtained data, the estimated performance can some-
times be overly optimistic as a consequence of data leakage,57
which can occur when information on the test set leaks into
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Figure 8. Example of the bias−variance trade-off (section 2.5), showing how the decision boundaries of an SVM vary as two main hyperparameters,
gamma and C, are changed, in the form of underfitting and overfitting cases.
the training or validation sets in a complicated and unintended
way. For example, hyperparameter tuning based on the
performance for test data can easily cause data leakage. In
practice, test data are finite, and as a result, we can even overfit
the ML model to the given test data by tweaking the
hyperparameters. In this case, the ML prediction exhibits
“too good” performance, but in fact it has no real effect. This
kind of misuse is often called data dredging. In cases caused by
accidents, normalizing or preprocessing the entire data set
before splitting can also cause small data leakage. Because data
leakage can occur unintentionally, it should always be kept in
mind for assuring scientific reproducibility.
2.5. Bias−Variance Trade-Off and Hyperparameter
Tuning. An ML model that perfectly predicts the given
training data (with zero training error) is seemingly preferable.
However, real-world data usually contain irreducible errors that
arise from random noise factors or deterministic unpredict-
ability due to the practical impossibility of perfectly sensing all
relevant information. ML is not able to precisely predict trends
arising from completely random noise. Thus, learning every
little detail of the training data can often result in inaccurate
prediction for unseen data.
In practice, a trade-off between two sources of error, termed
the bias−variance trade-of f, should be carefully considered for
ML models to make generalizations beyond the training data.
Bias is the difference between the prediction of an ML model
and the ground-truth value to be predicted for every given
training set. A high-bias ML model often cannot capture the
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underlying trends and causes underfitting because it contains
small degrees of freedom. Variance is the expected variability of
the model prediction. A high-variance ML model often has a
large degree of freedom and, as a result, it captures every detail
of the training data, which then causes overfitting arising from
high sensitivity and variability. What is needed is a “just right”
model that balances trade-off between high-bias and high-
variance models (cf. Figure 6). Complicated nonlinear ML
models such as DNNs can sometimes have millions or even
billions of parameters (i.e., a tremendously large number of
degrees of freedom). As a result, a limitless number of
parameter settings exist that have the same goodness of fit to
the finite data. In these cases, independent of its size, the
training data alone are not sufficient to properly train a given
ML model.
To remedy this situation, the number of degrees of freedom
of the model (i.e., the model complexity) must be restricted by
using some inductive bias. Since “unseen” data can take
arbitrary values without any additional assumptions, all
supervised learning strategies rely on some inductive bias
implicitly or explicitly. For example, a penalty can be placed on
overly complex models, a perturbation can be applied to
stabilize too-variable fitting, or the size of the model
components can be explicitly limited, for example, by
restricting the number of units and layers in neural networks
or the maximum depth (or the number of leaf nodes) of
decision trees. This process, termed regularization, is often
controlled by using hyperparameter tuning. The hyperpara-
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meters, such as the strength of the penalty or perturbation and
the size, shape, or structure of the model units, should be
clearly distinguished from the model parameters that are
autotuned in the training process. In contrast, hyperparameters
control inductive bias that is not determinable from the
training data and need to be explicitly set before the model is
trained. The plots in Figure 8 demonstrate the changes in the
decision boundaries of support vector machines (SVMs) that
occur when two main hyperparameters, the kernel coefficient
(gamma) and the penalty parameter (C), are varied. For more
practical examples, studies by our group provide detailed
explanations about how to tune hyperparameters in a
systematic way.58,59
Regularization is a crucial step when a risk of overfitting
exists as a result of the use of a highly complicated nonlinear
model, an insufficient number of training samples, or a large
number of input variables. The best practice is to systemati-
cally test a predefined set of candidate values by using a grid or
random search. In recent years, advanced methods such as
Bayesian optimization, GA, and model-based optimization for
hyperparameter tuning have been developed in the ML
community. The recent concept of AutoML attempts to
automate this demanding process, and several software
packages are available for conducting typical tasks such as
hyperparameter optimization (HPO) and neural architecture
search (NAS).
2.6. Exploitation−Exploration Trade-Off and Extrap-
olation. The mechanism of prediction in supervised learning
is based on interpolating given training data. When a
prediction lies outside the region that the training data
cover, it can be quite inaccurate and baseless. The notions of
interpolation and extrapolation might be intuitively reasonable
(Figure 6), but in practice they are not simple because of high
dimensionality. In a high dimension, it is not clear whether a
specific input point is interpolative or extrapolative. For
example, tree ensemble classifiers such as random forests and
extra trees seem to be quite restricted and nonsmooth in
Figure 7 when they are compared with other nonlinear
methods. However, it is widely known that the tree ensemble
classifiers function well in a very high dimensional space (even
up to 100000−700000 features).60,61 Also, decision boundaries
of deep neural networks can be counterintuitive in an
extremely high dimension (e.g., for images) and have a widely
known problem of adversarial examples to easily fool them.62
We can conclude that prediction would be quite uncertain
when no training examples exist around a specified input point
where the prediction is made. In the materials and molecular
sciences, quantitative structure−activity relationships (QSARs)
or QSPRs have been investigated extensively, and problems
arising from the potentially huge gap between available and
unseen data have long been discussed.63,64 In particular, the
crucial importance of the “applicability domain” (AD) of an
ML model has been recognized.
A strong goal in catalysis research is the development of
genuinely new catalysts that exhibit better performance than
currently available catalysts. However, predicting high-
performance catalysts would be extrapolative because by
definition such catalysts would be dissimilar to any existing
catalysts and thus outliers in the training data. Therefore, it
would be difficult to predict a novel catalyst simply by using
supervised learning that only models an average trend in the
given data.
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The exploitation−exploration trade-of f is an established
guiding principle to learn something novel. To gain essential
knowledge and avoid overlooking possible discoveries, it is not
sufficient to perform only “exploitation” of knowns by spotting
trends seen in currently identified high-performance cata-
lystsit is also important to carry out “exploration” for
unknowns by probing potentially novel candidates with almost
no information that can be quite different from any existing
catalysts. Algorithms for balancing this trade-off include a wide
variety of model-based optimization algorithms such as
sequential experimental design, active learning, Bayesian
optimization, multiarmed bandits, black-box optimization,
and reinforcement learning. Applying metaheuristic optimiza-
tion algorithms, including evolutionary algorithms such as GA,
is another popular option. Implementing these search
algorithms by both utilizing and questioning current
assumptions and biases would be a promising approach for
carrying out automated chemical exploration and discovery
using autonomous robotic systems.65 Many practical examples
will be covered in subsequent sections and existing reviews, but
in section 7.1 (Figure 24) we also introduce an example from
our group that is based on balancing this exploitation−
exploration trade-off.66
2.7. Bayesian Inference, Generative Models, and
Inverse Design. Up to this point, we have discussed ML in
a standard setting. However, for most of the algorithms listed
in Figure 3, including neural networks and decision trees,
Bayesian versions exist where probabilistic inference is made
instead of performing function fitting by pinpointing single
best parameters.23,67 In Bayesian inference, a probability
distribution is set for parameters prior to data collection, and
it is updated every time new data are obtained. The prior
probability distribution, rewritten into the posterior distribu-
tion using Bayes’ theorem, represents the degree of certainty of
the values of the parameter, which begins with an unbiased
distribution and becomes more and more biased as the number
of observations increases. When prediction is quite certain, the
distribution would be peaked only at the specific parameter
value, but otherwise it can be quite broadly distributed over
possible values. Standard ML inference relies on optimization
for function fitting, but Bayesian inference relies on integration
required for normalizing any distribution into a probability
distribution so that the integral over its domain is equal to 1. If
a prior distribution is set arbitrarily, the corresponding
posterior distribution cannot be obtained in closed form as a
result of the integration in Bayes’ theorem. As a result of the
recent advent of numerical computation methods such as
accelerated Markov chain Monte Carlo (MCMC) and
automatic variational inference, Bayesian inference now is a
quite flexible and practical tool for statistical modeling.
In the materials sciences, Bayesian methods are often used
for the inverse design approach.67,68 Apparently, when the aim
is to predict possible inputs that give a specific desirable
output, inverse design can be executed by simply interchanging
inputs and outputs in supervised learning. However, this is not
that simple because inputs and outputs usually have a many-to-
one correspondence. For example, a limitless number of
images (inputs) can correspond to the label “dog” (output).
Similarly, an infinite number of inputs can potentially exist that
give a catalyst with a specific level of performance. However, by
the use of Bayesian methods, a probability distribution of
candidates that might give a specific level of performance can
be produced, and this distribution can be employed to generate
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samples of these catalysts. Also, a hierarchical generative
process can be specified in order to explicitly model some
latent intermediate variables that cannot be observed directly
but can characterize well the data and problem under study.
This type of statistical modeling, which is based on generative
models, is now called probabilistic programming, for which
many software packages such as Stan, PyMC3, and Edward are
available.
2.8. Use and Misuse of ML in Catalyst Identification:
Correlation and Causality. As implied by the statement
“correlation does not imply causation”, it is generally difficult
to identify any “causal” relationships on the sole basis of
observational data. Any ML-generated result can have a risk of
being an artifact arising from a spurious correlation and thus
cannot alone be considered to be scientifically conclusive.
Interventional studies are needed to more safely ensure that
ML-derived trends are real, as suggested by the statement “to
find out what happens to a system when you interfere with it
you have to interfere with it (not just passively observe it)”.69
In general, many strong and unrealistic assumptions are
required to guarantee that ML algorithms can produce causal
information from observational data. For example, formal
discussions of causal inference usually assume that all
confounders have been identified and included in the model
(i.e., that no unidentified but related factors exist). It is widely
recognized that “causality” is notoriously difficult to even
define, formalize, or quantify, but in practice there are useful
guidelines such as the Bradford Hill criteria in epidemiology to
carefully evaluate the potential gap between the observed
correlation and causality.
Although ML is based only on correlation and thus might
suffer from the potential risk of being spurious, correlation is
clearly a sign of a potential causal connection. Therefore, the
result can be quite informative and can be subjected to further
investigation using good data to assess whether it is actually
“causal”. For example, in chemoinformatics, QSAR/QSPR
studies with many descriptors are widely known to have an
enhanced risk of exhibiting chance correlations, and the
significance of the input−output correlation is often further
ensured by using computational methods such as Y-random-
ization and random-number pseudodescriptors.70 In Y-random-
ization, the prediction performance of the original ML model is
compared to that of a model built from randomly shuffled Y
values (outputs). Also, random-number pseudodescriptors can
be used instead of or in addition to the original input variables.
The performance score of the original model should be
significantly better than the randomized cases when a potential
causal connection exists between inputs and outputs. In
particular, when a large collection of input variables
(descriptors) is utilized in ML models, the risk of producing
a spurious correlation should always be assessed.
3. ML PREDICTION OF NEW MATERIALS
The discovery of new heterogeneous catalysts begins with the
discovery and structural identification of new materials.
Current approaches used to identify novel materials primarily
rely on trial-and-error synthesis combined with exhaustive
phase diagram analysis. This protocol for materials discovery is
far too slow and expensive to meet the demands for
development of new heterogeneous catalysts. Instead, a
rational and structured method that fully explores chemical-
wide space is needed. In data-driven (inverse) design of
catalysts of this type, it is required to establish a crystallo-
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graphic database of known and hypothetical structures
comprising a very large number of inorganic compounds.71
Several materials databases that contain the properties of
experimentally observed and hypothetical materials are now
available. Examples of such data sets include the Inorganic
Crystal Structure Database (ICSD),72 AtomWork,73 the
Materials Project,74 the Open Quantum Materials Database
(OQMD),75 and the Automatic Flow of Materials Discovery
Library (AFLOWLIB).76 Recent advances made in developing
high-throughput DFT calculations and ML techniques have
enabled the efficient utilization of these inorganic material
databases for crystal structure predictions and the design of
materials (Figure 9).77−82 The new methods even enable rapid
Figure 9. Schematic representation of ML-aided future materials
design. The compound database is filtered to a smaller list of
promising catalyst candidates through computational and exper-
imental methods associated with ML approaches.
in silico predictions of the structures of hypothetical materials.
When the large set of DFT-driven crystallographic data is
combined with ML, the search space of unknown compounds
is greatly expanded. In this section, we describe typical
examples of predictions of structures of catalytically important
materials using both high-throughput DFT calculations and
ML.
3.1. Alloys (Intermetallics). Intermetallic compounds
(intermetallics) are a class of substances that have defined
compositions and adopt structures distinct from those of the
component elements. Despite their importance in many areas,
including catalysis, rules for predicting intermetallics are not
well-defined, and as a result, the design of novel intermetallics
is challenging. Mar et al. applied various ML methods (e.g.,
SVM and PLS) to develop a crystal structure predictor for
binary AB intermetallics.83,84 Models were trained and
validated by classifiing 706 AB compounds with seven
structure types (NaCl, CsCl, CuAu, ZnS, TlI, NiAs, and β-
FeB) extracted from a crystallographic database. The data were
split into a training set and a validation set, and the best
descriptors and a better model were selected. SVM was found
to be a better model, giving a sensitivity of 94.2%, specificity of
92.7%, and accuracy of 93.2%. The ML method used to obtain
quantitative predictions of hypothetical compounds led to the
identification of the new compound RhCd, which was
predicted by SVM to have a CsCl-type structure (0.918
probability). The authors synthesized RhCd and demonstrated
that it has a CsCl-type structure. This finding suggests that the
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Figure 10. (a) Schematic overview of text extraction and database construction. (b) A hierarchical neural network assigns labels (“MATERIAL”) to
words one at a time by converting them to embedding and heuristic vector representations and outputting them to a classifier. (c) A grammatical
parse of a sentence is used to resolve word-level labels (below the colored bars) into sequential word-chunk-level labels (above the colored bars),
followed by resolution into word-chunk relations (curved arcs). (d, e) Calcination and hydrothermal (d) temperature and (e) time kernel density
estimates for TiO2. From ref 86. CC BY 4.0.

ML method can be an accurate predictor of a crystal structure
of an intermetallic.
3.2. Metal Oxides. Ceder et al. explored the ternary oxide
(A x B y O z ) chemical space in a search for previously
uncharacterized compounds using ML methods along with
high-throughput DFT calculations. 85 In this effort, a
probabilistic model was built from the ICSD and then used
to identify new compositions that would likely to form a
ternary oxide. The most likely crystal structure of each
composition was predicted using the same probabilistic model.
Finally, the stabilities of these substances were determined
using DFT. The high efficiency of this method is demonstrated
by the observation that 355 new compounds were identified
within ca. 55 days following initiation of computing using 400
Intel Xeon 5140 2.33 GHz cores.
The ability to identify what structure types result from
synthetic routes would be an important tool in the materials
sciences. However, finding this type of specific information is
difficult because of the fact that different synthetic methods
can generate the same types of products. An excellent ML-
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based method was developed recently by Olivetti and co-
workers that overcomes this problem.86,87 In that approach,
aggregated synthesis parameters were first computed using
data extracted from over 640 000 publications by using natural
language processing (NLP) and ML algorithms. Then a set of
tabulated and collated synthesis parameters associated with 30
known oxide systems were input into the treatment. An
overview of the approaches employed to transform human-
readable publications into machine-readable synthesis planning
resources and synthesis parameters is given in Figure 10.
Notably, direct human intervention is not involved in
implementing this method. Rather, an automated text
processing method downloads articles, extracts key synthesis
information, codifies this information into a database, and
subsequently aggregates the data into material system types.
Scientific validation of the scheme was carried out by briefly
comparing the aggregated data in the provided data set to
known parameters. For example, frequent use of temperatures
close to the anatase-to-rutile phase transformation for TiO2
were observed (Figure 10). Additional patterns showed that
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Figure 11. (a) Schematic representation of self-assembly of the {Mo120Ce6} wheel from basic building blocks in polyhedron mode. (b) Schematic
diagram of the three exploration methods used. (c) Explorations of crystallization space using the three methods. The exploration is computed as
the volume of the convex envelope of the experiments leading to crystals. (d) Average prediction accuracies between the classes of crystals and
noncrystals for the three methods, using a random forest classifier. From ref 89. CC BY 4.0.

hydrothermal reactions occur in the narrow temperature range
between 100 and 200 °C, which confirmed that hydrothermal
reactions are more likely to occur than calcination when long
time periods are utilized.
Studies of catalysis by polyoxometalates (POMs) are
extremely important in catalysis. The group headed by Cronin,
who is a leader in the field of automated chemical synthesis,88
constructed a workflow for crystallization of the new POM
cluster Na6[Mo120Ce6O366H12(H2O)78]·200H2O that pos-
sesses a trigonal-ring-type architecture (Figure 11).89 Synthesis
and crystallization of this substance were probed by an ML
algorithm. The obtained results were compared with those
arising from experimentation. The ML-based approach was
able to cover approximately 9 times more crystallization space
than that of a random search and approximately 6 times more
than a search conducted by humans. This expansion increased
the crystallization prediction accuracy from 77.1 ± 0.9% for a
human search to 82.4 ± 0.7%. Cronin and co-workers
suggested that this outcome might be a consequence of the
fact that the ML-based method is untied to prior chemical
knowledge and is more “adventurous” in that it performs
“jumps” in chemical space directly into what are believed to be
boundaries between crystals and noncrystals.
3.3. Zeolites. Zeolites are crystalline aluminosilicate
materials having a network of linked pores and cavities. For
decades, these materials have been used in a large number of
industrial catalytic processes, and consequently, a large
demand exists for the synthesis of new zeolites that display
high catalytic performances. ML algorithms have been used to
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discover complex patterns embedded in the large amount of
data accumulated for zeolites.90,91 For example, in pioneering
studies of ML applications to zeolite research, Blaisten-Barojas
et al.92−94 developed a knowledge-based model that is able to
classify and predict topological types of zeolites with high
accuracy using a nine-dimensional feature vector, including
topological descriptors obtained by computations, together
with some physical and chemical properties of zeolites.
Alkaline desilication of zeolites is a conventional method
employed to prepare mesoporous zeolites, and the conditions
utilized strongly influence important properties of zeolites,
such as the micro- and mesopore volumes, Si/Al ratio, and
acidity, and their consequent influence on the activities,
selectivities, and durabilites of zeolite catalysts. However, it is
difficult to define the optimal desilication conditions that
should be used to produce a catalyst tailored for a specific
application. Blay et al. showed that perturbation theory
combined with ML (PTML) is a powerful approach for
predicting the effect of desilication conditions on the
properties of ZSM-5 zeolites.95 Accordingly, the PTML models
enable prediction of the properties of a query material or
compound starting with the properties for a reference and then
adding PT operators to measure deviations from the reference.
This method can be used to study large data sets with multiple
inputs obtained from experiments. In the approach, a PTML
model was first constructed using 1019 data sets for various
ZSM-5 zeolites (H-ZSM-5, NH4-ZSM-5, Na-ZSM-5, Na,K-
ZSM-5, etc.) collected from the literature. The data set
contains information about the effect of preparation and
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treatment conditions on eight properties, including the BET
surface area, mesopore volume, micropore volume, Si/Al molar
ratio, etc. The model was found to have a high accuracy (R2 =
0.98) in an external validation series, demonstrating that the
PTML method is useful for the rational design of alkaline-
desilicated zeolites. In the model, the sizes of the mesopores in
the alkaline-treated zeolites (z axis in Figure 12) are described
Figure 12. (a) Schematic workflow used to develop the PTML
model. (b) Predicted values of εk(mi, cj)pred = mesopore size for >1000
data points. Reproduced from ref 95. Copyright 2018 American
Chemical Society.
by the micropore and mesopore volumes before treatment.
This map will be helpful for designing rational methods to
prepare new zeolites with desired mesopore sizes.
The mechanical stabilities (elastic properties) play an
essential role in the selection of feasible zeolite structures.
However, determination of the elastic properties of crystalline
materials using DFT-based energy calculations requires a great
computational cost. Consequently, Evans and Coudert96
developed ML methods to efficiently predict the elastic
properties of pure silica zeolites employing a DFT-calculated
accurate training set of elastic properties. The ML approach
based only on geometric parameters of the zeolites (structure,
porosity, and local geometry) is able to predict bulk and shear
moduli of zeolites with high accuracies. The methodology was
employed to predict elastic responses of 590 448 hypothetical
zeolites. The availability of this large database enabled an
assessment of stability trends in zeolites.
Zeolite BEA is typically synthesized using of a number of
organic structure-directing agents (OSDAs). Daeyaert et al.
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described a new ML approach to aid the computational design
of synthesizable OSDAs for use in the preparation of zeolite
beta (Figure 13).97 Models to predict stabilization energies
using a neural network were trained and validated using a data
set of 4781 putative BEA zeolite OSDAs. The stabilization
energies in BEA were produced through MD calculations. This
effort led to the identification of 3062 promising OSDAs, 469
of which were predicted to stabilize the zeolite structure better
than known compounds. The use of ML in this case sped up
the computation by a factor of 350. Recently, Olivetti and co-
workers extended the automatic data extraction approach
developed for metal oxides (see above) to prediction of the
crystallization of zeolite structures.98 This method was used to
synthesize Ge-containing zeolites to investigate relationships
between the synthesis parameters and the resulting topology.
3.4. Inorganic−Organic Hybrid Materials. Inorganic−
organic hybrid materials, including organically templated metal
oxides and metal−organic frameworks (MOFs), have attracted
much attention because they possess characteristics that can be
controlled at the molecular level. Such unique features make
inorganic−organic hybrids suitable for use as catalysts.
Nevertheless, the formation of these materials is not perfectly
understood, and as a result, the development of new materials
currently relies primarily on the results of exploratory synthetic
investigations. However, the ML method developed by
Raccuglia et al. allows prediction of the success of reactions
between organic and inorganic building blocks by using data
from failed experiments (Figure 14).99 Using this approach,
the authors were able to predict reaction outcomes of
crystallization of templated vanadium selenites. The training
set came from information arising from “dark” reactions,
specifically from unsuccessful or failed hydrothermal syntheses.
When applied to hydrothermal synthesis with commercially
available and previously untested organic building blocks, the
ML model outperformed conventional human approaches and
successfully predicted experimental conditions for the for-
mation of a new organically templated inorganic compound
with a notable success rate (89%).
4. SCALING RELATIONSHIPS FOR REACTIONS ON
SURFACES
Describing catalytic activity as a function of a physical
parameter without carrying out extensive trial-and-error
experimentation has been a general strategy for catalyst design.
Important contributions have been made by employing surface
properties related to catalysis such as work function,100,101 d-
band center,102 coordination number (CN),103 surface
energy,104 and strain105 as descriptors of catalyst properties.
In these efforts, the most widely explored examples involve
establishing scaling relationships between the adsorption
energies of reactants and intermediates using the d-band
model and between activation and reaction energies, called
Brønsted−Evans−Polanyi relationships (Figure
15).13−15,104,106−111 On the basis of the set of linear
relationships, reactivity trends for a target catalytic reaction
can be readily derived from adsorption energies of reactants
without having to utilize tedious activation barrier calculations
and full analysis of the steps involved in the reaction. By using
the scaling relationships strategy, Nørskov and co-workers
predicted and experimentally verified that bimetal catalysts
such as NiZn would be applicable for selective hydrogenation
of acetylene112 and that NiGa would be applicable to CO2
hydrogenation.113
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Figure 13. (a) Scatter plots of MD- vs ML-predicted stabilization energies for the OSDAs in the validation set. (b) Top five OSDA substances
predicted by model 1b. The scores are ML-determined binding energies in kJ/(mol of Si). From ref 97. CC BY 4.0.

Figure 14. Schematic representation of the three hypotheses generated from the developed model together with representative structures for each
hypothesis. The experimental conditions required for the formation of single crystals depend on the properties of the amine. Reproduced with
permission from ref 99. Copyright 2016 Springer Nature.

Despite its importance in catalysis, the role played by
electronic structures in determining adsorption energies on
semiconducting and insulating oxide surfaces is still a matter of
debate. Hence, in silico discovery of metal oxide catalysts is
quite rare. In silico prediction of new catalysts using
computationally low-cost descriptors could be possible in the
future if comprehensive data sets containing quantitative
descriptors for many reactants on many unknown surfaces
were available. This section describes the results of recent
studies aimed at determining relationships between electronic
properties and adsorption energies on metal oxide surfaces.
4.1. Scaling Relationships between Adsorption
Energies. Extensive studies of the adsorption of atoms and
2274
molecules on metal oxide surfaces have shown that scaling
relationships exist for adsorption energies despite the structural
and electronic complexities of metal oxide surfaces. Fernández
et al. performed DFT calculations on the adsorption of AHx
intermediates and bare A atoms (A = O, S, N) on various
transition metal oxide, nitride, and sulfide surfaces.114 The
same linear relationship was found to exist between adsorption
energies of AHx and A on surfaces of both metal oxides and
pure metals. The trends in adsorption energies can be
understood by using a modified version of the d-band
model115 and by “Fermi softness”,109 which is defined as the
sum of the density of states weighted by the derivative of the
Fermi−Dirac distribution function at a certain nonzero
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Figure 15. Schematic representation of volcano plots and scaling relationships for reactions on surfaces.
temperature. Calle-Vallejo et al. reported that the adsorption
energies of O, OH, and OOH are linearly related to the
number of outer electrons at the adsorption sites of metal,
monoxide, and perovskite surfaces.116 Although this effort
found that the number of outer electrons can be a simple and
efficient descriptor, van Santen et al. pointed out that
experimental data on perovskite LaXO3 compounds do not
follow this trend but instead show double-peaked volcano-type
behavior for the third-row reducible metal oxides, which is
most likely to be due to the high spin-state stabilization of d5
electron systems.5 Recently, scaling relationships were reported
to exist between the adsorption energies of various molecules
containing atoms bearing lone-pair electrons across a wide
variety of materials.117 Moreover, our group recently
investigated the adsorption of a number of molecules on
TiO2 surfaces employing DFT calculations together with
statistical approaches.118 We observed linear relationships
between the highest occupied molecular orbital (HOMO)
levels of the molecules and the adsorption energies. ML-based
statistical analysis indicates that the dipole moment of the
molecule also plays a role in molecular adsorption. It should be
noted that adsorption energies on metal oxide surfaces are
significantly affected by the presence of surface vacancies,
dopants, and coadsorbed molecules. Therefore, further
consideration is required in order to describe more precisely
the activities and selectivities of working metal oxide catalysts.
4.2. Oxygen Vacancy Formation Energy as a
Descriptor for the Catalytic Behavior of Metal Oxides.
Defects play a significant role in governing the properties of
catalysts. Various kinds of extended and point defects
introduced into structures of catalysts largely govern their
physical and chemical properties. In particular, point defects in
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metal oxide surfaces such as oxygen vacancies have dominant
effects on the properties of heterogeneous catalysts.119,120 The
energies required to form the oxygen defects in metal oxide
catalysts are typically used to rationalize and predict the
performance of these catalysts.108
Oxygen vacancy formation in ABO3 perovskites has been
extensively investigated using DFT computations because it
controls the electrocatalytic activity.121−123 Using DFT
calculations, Chen and Ciucci systematically investigated the
dependence of the stability and electronic and ionic
conductivity on substitutions of A and B sites of BaFeO3.124
They found that EOvac is reduced by the presence of Na, K, Ca,
Sr, and Pb in the A site and Cu, Ni, Zn, and Ag in the B site.
The value of EOvac was found to be linearly correlated with the
occupied O p-band center, which is related to the basicity of
the oxygen atoms. Emery et al. used high-throughput DFT to
search for novel perovskites that promote thermochemical
water splitting (TWS).125 They screened 5329 calculated
perovskites on the basis of the stabilities and vacancy
formation energies and identified 139 potential candidates
for TWS.
Kumar et al. studied oxidative coupling reactions of CH4 on
various metal oxide surfaces.108 These reactions begin with
abstraction of the H atom from a C−H bond of CH4 by a
lattice oxygen atom, which leads to the formation of a CH3
radical. They reported that this process takes place more
readily for highly reducible oxides and that the activation
energy to cleave the C−H bond is linearly correlated with
EOvac. The CH3 radical intermediate is converted to the desired
C2 hydrocarbons by radical coupling or to undesired methoxy
species by absorption to surface oxygen leading to the eventual
formation of CO or CO2. Thus, adsorption of CH3 radical
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regulates the selectivity for C2 hydrocarbon production. The
adsorption energy of methyl radical is also linearly correlated
with EOvac. Surfaces activating the C−H bond more easily bind
methyl radical more strongly. The authors proposed that metal
oxides like TbOx that can exist in multiple oxidation states
could overcome the intrinsic competitive processes by
changing the oxygen atmosphere.
Although theoretical studies of the formation of oxygen
vacancies on metal oxides have been conducted recently,
research on surface defects is still rare, and the number of
investigated surfaces remains limited despite the obvious
importance of oxygen vacancies for catalytic activity. There-
fore, studies that provide EOvac values and reveal the physical
factors determining EOvac are highly desirable. In this context,
our group recently determined EOvac values of various
semiconducting and insulating oxide surfaces using DFT
calculations with comparable structure models at the same
computational level.126 A further investigation aimed at
providing a deep understanding of the formation of oxygen
vacancies found that the band gap, formation energy of the
bulk, and electron affinity of a metal oxide are important
properties that govern EOvac. The reason why these electronic
properties determine EOvac is that electrons enter the defect
state(s) after removal of oxygen, which could be in the
conduction band for most cases. It is worth mentioning here
that use of ML for statistical analysis to assess the physical
basis of this relationship would perhaps be more meritorious
than predicting physical property values themselves.127
Although limitations associated with variety of the metal
oxide surfaces and computational accuracy exist, the
information would be helpful for catalysis researchers.
4.3. Understanding Acid−Base Properties of Metal
Oxides. Solid acids and bases have been employed to catalyze
various reactions, and the role of the properties of these solids
in governing the catalytic performance has been investigated
extensively.128 An early computational study of the acid−base
properties of the γ-Al2O3 surface found that the energies of
occupied and unoccupied orbitals can be employed to rank
surface Lewis acid and base sites, respectively.129 Jenness et al.
computed the adsorption energies of alcohols, diethyl ether,
and water and the activation barriers for ethanol dehydration
and etherification promoted by several Lewis acid sites on γ-
Al2O3 surfaces.130 The results showed that energies of
unoccupied s-band centers can be used as descriptors to
evaluate the Lewis acidities of the Al3+ sites. These descriptors
correlate the adsorption energies with the barriers for ethanol
dehydration in a quantitative manner but describe the barrier
for ethanol etherification only qualitatively because of the
bimolecular nature of the process. Very recently, the occupied
p-band center of O and unoccupied s-band center of Al were
employed to evaluate the reactivity for C−H bond activation of
CH4 over γ-Al2O3 surfaces.131
In a study of n-butane oxidation over vanadium phosphorus
oxides, Wang et al. identified the active site for this reaction
among 15 possible VO and PO sites in total.111 Both V
O and PO sites abstract a H atom from n-butane in what
can be viewed as a proton-coupled electron transfer process in
which V5+ and oxygens serve as electron and proton acceptors,
respectively. Thus, the activity of the PO sites is lowered by
increasing the distance between V5+ and these sites. The results
showed that a linear relationship exists between the centers of
the energies of the PO lone-pair bands and the energies for
reaction at the PO sites. Accordingly, the study demon-
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strated that energies of the s- and p-band centers are useful for
rapid screening of potential active sites of metal oxide catalysts.
Brønsted acid sites (BASs) in zeolite micropores are formed
by protonation of oxygen atoms linking neighboring silicon
and aluminum atoms for charge balancing. The presence of
BASs in the confined environment is a crucial factor governing
the catalytic properties of many zeolite catalysts.132 Pidko and
co-workers determined the acid strength of various zeolites
using the adsorption energies of probe molecules such as NH3,
CO, pyridine, etc.133 The acid strength obtained by the
adsorption energy calculations of NH3 was found to be
correlated with the activation barrier of isobutene protonation
in FAU zeolites. Matsuoka et al. screened 933 613 structures in
a database of hypothetical zeolites to identify chemically
feasible members that have strong Brønsted acidity.134 Density,
ring counting, and average ring sizes were used to eliminate
unsuitable candidates. To assess the Brønsted acid strength,
they introduced a new structural descriptor called b, which is
the distance between barycenters of the two triangles
connecting O atoms linked to T atoms in the acid site. This
parameter can be calculated for pure silica with low
computational cost, although the correlation between b and
the Brønsted acid strength is weak. They confirmed by using
DFT calculations that six out of 12 final candidates contain a
strongly acidic Brønsted site. This encouraging result suggests
that even nonquantitatively accurate structural descriptors
might be sufficient for screening purposes where speed is more
important than accuracy.
5. ML PREDICTION OF DFT-DERIVED FUNCTIONS
FOR CATALYSIS
As described above, the activity orders of different catalysts are
correlated with physical parameters such as adsorption
energies and values of d-band centers, which can be
determined with less computational cost than activation
energies for reactions. Recent efforts focusing on these
descriptor-based approaches for analysis of trends across the
periodic table and reaction mechanisms as well as recent
developments in computer technology have developed
effective screening platforms for the discovery of novel
catalysts. However, the costs of these approaches, which are
normally based on first-principles calculations, are still high. If
DFT-derived values were to be predictable using ML with
widely available descriptors, it would be possible to quickly
predict trends in catalytic activity. The investigations discussed
in this section exemplify how fast calculations of catalytically
important parameters (e.g., adsorption energies, d-band
centers, bond strengths between metals and supports) can be
carried out using ML models.
5.1. Adsorption Energies. Several recent reports have
described ML predictions of adsorption energies of reactants
and surface intermediates. In a pioneering work, Yildirim and
co-workers showed that neural network models can be
employed to predict the adsorption energies of O2 and CO
on Au2 to Au10 clusters using the size and charge of the cluster,
the number of unpaired electrons, and the CN as
descriptors.135 ML of DFT-derived adsorption energies on
metal (alloy) surfaces,136−144 low-symmetry Pt nanopar-
ticles,145 and metal cation sites in zeolites146 were also
determined using different descriptors and ML models. Virtual
screening by utilizing the artificial neural network model for
the adsorption energy of CO on core−shell alloy surfaces
(Cu3B-A@Cu) indentified new catalyst candidates for selective
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Figure 16. Combinatorial challenge of identifying surfaces and active sites for bimetallic catalysts. (A) Ni/Ga intermetallic compounds synthesized
experimentally and identified as the lower hull by the Materials Project database. (B) 40 identified facets/terminations. (C) 583 adsorption
configurations identified as having unique average coordination of bonding metal atoms. (D) High-throughput methods developed to catalog and
evaluate necessary thermodynamic quantities. Reproduced from ref 149. Copyright 2017 American Chemical Society.
CO2 electrochemical reduction to form C2 species.137 The
group of Asahi described how adsorption energies of N, O, and
NO on Rh1−xAux alloy nanoparticles can be predicted using a
Bayesian linear regression model and a multidimensional
structural descriptor.147,148 By combining this information with
a kinetic model, those researchers were able to predict the rates
of NO decomposition by the Rh1−xAux alloy nanoparticles as a
function of composition and particle size. Nørskov et al.
described a systematic ML-aided discovery approach for
identifying NiGa bimetallic catalysts that are active for the
electrochemical reduction of CO2 (Figure 16).149 Also, Tran
and Ulissi demonstrated how ML-assisted theoretical screening
can be used to discover new intermetallic catalysts (Figure
17).150 By screening various alloys, they uncovered 258
candidate surfaces across 102 alloys for inducing H2 evolution
and 131 surfaces across 54 alloys for promoting CO2
reduction. For the purpose of experimental validation, the
top candidates were used as catalysts for the electrochemical
H2 evolution, CO2 reduction, and O2 evolution reactions.
Our group also developed a simple ML model for efficient
prediction of adsorption energies of CH4-related species,
including CH3, CH2, CH, C, and H, on Cu-based alloys
(Figure 18).151 The ML model developed was demonstrated
to predict DFT-derived adsorption energies using 12
descriptors that are readily obtained for selected elements. It
was also shown that the top three descriptors for doped metals,
including melting point, surface energy, and group in the
periodic table, can be employed to predict the adsorption
energies with comparable accuracies. Moreover, differences
between the adsorption energies of CH3 and CH2 (ECH3 −
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ECH2) were predicted to make selective catalysts that can
enable the efficient use of CH4.
Ni2P is known to be an effective catalyst for the
electrochemical hydrogen evolution reaction (HER). Rappe
et al. carried out virtual screening of Ni2P(0001) surfaces
doped at P sites with different concentrations of nonmetal
dopants (B, C, N, O, Si, S, As, Se, and Te).152 This process led
to the development of a regularized random forest ML
algorithm to quantify the relative importance of DFT-derived
descriptors of the surface structure on determining the free
energies of H atom adsorption (ΔGH) on the catalyst
candidates. The results showed that the Ni−Ni bond length
is the most important descriptor for the HER activity, with
shorter Ni−Ni bonds giving higher HER activities.
By using DFT, O’Connor et al. were able to calculate
energies for adsorption of various early and late transition
metals such as V, Mn, Fe, Co, Ni, Cu, Ru, Rh, Pd, Ag Ir, Pt,
and Au on several reducible and irreducible oxide supports
such as CeO2(111), MgO(100), CeO2(110), ZnO(100),
TbO2(111), α-Al2O3(0001), and TiO2(011).153 DFT together
with an ML method based on LASSO regression was
employed to identify descriptors that predict interaction
strengths between oxide supports and single metal atoms.
The results demonstrated that the adsorption energies are
correlated with properties of both the metal and the support,
namely, the metal oxidation enthalpies, support reducibilities,
and enthalpies of metal−metal interactions.
5.2. d-Band Centers. Our group used ML to predict d-
band centers, which are widely employed as general and
versatile descriptors for a variety of reactions occurring over
heterogeneous transition metal catalysts.58,59 The d-band
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Figure 17. CO2 reduction activity map for bimetallics. A visualization of two-component intermetallics with surfaces that have low-coverage CO
adsorption energy (ΔECO) values within the range of −0.77 to −0.57 eV is shown. White shading indicates an absence of enumerated surfaces; gray
shading indicates that all of the ΔECO values are outside the range of −0.77 to −0.57 eV; colored shading indicates possible activity. The ΔECO
values used to create the upper half of this map were calculated using DFT, and the values used to create the bottom half were calculated using the
surrogate machine learning model. Reproduced with permission from ref 150. Copyright 2018 Springer Nature.

model assumes that chemisorption is dominantly governed by
d electrons of transition metals.14 The approach involves linear
scaling between the adsorption energy of a given adsorbate and
the energy of the d-band center relative to the Fermi level. The
higher the energies of the d states are relative to the Fermi
level, the emptier are the antibonding states and the larger is
the adsorption energy of an adsorbed species on a surface.
Thus, we demonstrated that the d-band centers for
monometallic and bimetallic surfaces having two different
structures (overlayers on clean metal surfaces and surface
impurities) can be predicted by employing an ML method
(gradient boosting regression) (Figure 19).
5.3. Band Gaps. For the most part, experimental databases
contain information about crystal structures of materials. It is
much more difficult to access information about the electronic
structures of compounds. For example, band gaps in the
Materials Project database have been calculated using the
generalized gradient approximation (GGA) functional by
Perdew, Burke, and Ernzerhof (PBE) and GGA PBE+U for
some of the compounds. Therefore, the band gaps of
semiconductors are underestimated because of the only
2278
approximate description of the exchange−correlation func-
tionals, the missing derivative discontinuity, and the self-
interaction error.154 Although use of the GW approach and
hybrid functionals usually gives reasonable results, these
methods are often computationally too expensive. It would
be desirable to obtain the band gap, which is a key property for
the treatment of (photo)catalysts and other relevant
applications such as solar absorbers and transparent con-
ductors, with sufficiently high accuracy at a reasonable
computational cost.
In this regard, Dey and co-workers predicted the band gaps
of over 227 new chalcopyrite compounds using the band gaps
of 44 chalcopyrites reported in the literature.37 Subsequently,
the group headed by Tanaka determined prediction models of
G0W0 band gaps for 270 inorganic compounds employing
Kohn−Sham band gaps, cohesive energies, crystalline volumes
per atom, and other fundamental information about the
constituent elements as descriptors.38 As determined using
support vector regression, the best model had an RMSE of
0.24 eV, showing that the method is useful for screening a large
set of materials. Band gaps of double perovskites have also
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Figure 18. (a) Representative adsorption model for CH3 on Cu-based alloys. (b) DFT-derived adsorption energies of CH3, CH2, CH, C, and H on
Cu-based alloys. (c) Average RMSEs to predict the adsorption energies of CH3 by 100 rounds of random leave-25%-out trials with various ML
models. (d) Correlation maps of the 12 descriptors. (e) Feature-importance scores of the descriptors for the extra tree regression prediction of the
adsorption energies of CH3. Reproduced from ref 151. Copyright 2018 American Chemical Society.

Figure 19. ML prediction of the d-band center values for 11 metals (Au, Pt, Ir, Ag, Pd, Rh, Ru, Cu, Ni, Co, and Fe) and their pairwise bimetals for
two types of structures (overlayer-covered or 1% metal-doped metal surfaces). Reproduced with permission from ref 58. Copyright 2016 Royal
Society of Chemistry.

been predicted using ML methods.39 In addition, ML
predictions have recently been made for the band edges of
MXenes, which are 2D layered transition metal carbides and
nitrides such as graphene and molybdenum disulfide.
Determination of accurate positions of the band edges of
these novel materials is extremely important because they have
promise in catalysis applications, in particular as photocatalysts
and eletrocatalysts. Mishra et al.155 developed an ML model
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for determining the band edges with GW level accuracy having
a minimum RMSE of 0.12 eV. They also found that
electronegativity differences between transition metals and
functional groups play a crucial role in tuning the electronic
properties and positioning the band edges of MXenes.
5.4. Surface Phase Diagrams. Surface phase diagrams are
of great importance to understand the surface chemistry
occurring in (electro)catalysis, where various adsorbates and
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Figure 20. (a) Workflow scheme of the ELSIE algorithm, which consists of two steps. In the first step, the absorption species is identified and used
to narrow the number of candidate computed reference spectra. In the second step, the spectral matching ensemble yields a list of computational
spectra rank-ordered by their similarity to the target spectrum. (b) Performance of the ELSIE algorithm on 19 test spectra. From ref 162. CC BY
4.0.

coverages exist at varying applied potentials. These diagrams
are typically made by employing intuition, an approach that
has the risk of missing complex configurations and coverages at
potentials of interest. Cluster expansion methods showing
higher accuracy are often difficult to implement for treatment
of new surfaces. The group of Nørskov employed an ML
approach to address these issues.156 The free energies of all
possible adsorbate surface coverages were predicted for a finite
number of adsorption sites using a Gaussian process regression
(GPR) model. The results showed that a simple, rational, and
systematic approach could be implemented to obtain free
energy diagrams at relatively low computational costs. The
Pourbaix diagram for the IrO2(110) surface having nine
coverages from fully oxygenated to fully hydrogenated can be
reconstructed using only 20 electronic structure relaxations,
compared to ca. 90 required when typical search approaches
are utilized. The authors also extended this method to the
MoS2 surface and obtained similar efficiencies.
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6. ML PREDICTION FOR CATALYST
CHARACTERIZATION
Spectroscopic and microscopic analysis of catalysts requires
efforts by experienced experts. If an ML model can be
constructed for a large number of catalysts and surface
reactions from various types of spectroscopy and microscopy
data, rapid identification of active sites, intermediates, and
products would be possible.157 Although various ML-assisted
spectroscopic analysis methods have been described,158−160
the discussion in this section focuses on the current status of
ML-assisted analysis of various spectroscopy and microscopy
data that are closely related to heterogeneous catalysis.
6.1. XAFS. X-ray absorption fine structure (XAFS) is a
widely used technique for determining the local atomic
structures of catalytic materials. XAFS is divided into two
regimes: X-ray absorption near-edge structure (XANES) and
extended X-ray absorption fine structure (EXAFS). XANES
gives a fingerprint of coordination chemistry and the oxidation
states of X-ray-absorbing atoms of a material, and EXAFS
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provides information on the CN of neighboring atoms and
their distances. Quantitative XANES analysis is typically
difficult to carry out. Moreover, XANES analysis relies mainly
on manual comparison of measured and reliable reference
spectra. However, existing databases of XAFS spectra are
limited in terms of the number of reference spectra, energy
resolution, and signal-to-noise ratio.161 Zheng et al. recently
constructed a large database of computed reference XANES
(more than 800 000 K-edge spectra for more than 40 000
compounds) and developed an algorithm called Ensemble-
Learned Spectra Identification (ELSIE) for the automatic
identification of matching spectra for any experimental XANES
spectra.162,163 The algorithm combines 33 weak learners
composed of a set of preprocessing steps (peak shifting/
alignment, spectra normalization, feature transformation, etc.)
and a similarity measure (Figure 20). The approach attained
up to 84.2% accuracy in identifying the correct coordination
environment and oxidation state of a test set of 19 K-edge
XANES spectra covering a variety of materials. The XANES
database and ELSIE algorithm have recently been integrated
into the Materials Project database,74 which is available to all
materials scientists.
Kiyohara et al. developed a data-driven approach based on
the clustering and decision tree method to “predict” and
“interpret” oxygen K-edge XANES/electron-loss near-edge
structure (ELNES) spectra of oxides.164 The “prediction”
proposes candidate spectra for a target oxide from a
theoretically calculated spectral database on the basis of
geometric and element input information such as bond length,
bond angle, and valence state, while the “interpretation”
suggests material information for the target spectrum. This
methodology operated well in making an actual prediction and
interpretation for the target SiO2 polymorph among 32 SiO2
polymorphs. Suzuki et al. showed how to estimate materials
parameters (charge, symmetry, the crystal field parameter
10Dq, etc.) for manganese oxide from experimental Mn L2,3
XANES spectra.165 A spectral data set was first prepared by
theoretical simulation using various parameters. Then the
similarity values between the individual spectra and the
reference spectrum were calculated to construct a statistical
learning model for estimating the material’s parameters from
its spectrum. A discrete value, for example the charge of Mn, is
then estimated from the measured spectrum using dimension-
ality reduction, and its 10Dq (continuous value) is determined
using the regression model obtained from the similarity of the
spectra.
Timoshenko et al. described an approach for determination
of the 3D geometry of Pt nanoparticle catalysts (1−3 nm size)
supported on γ-Al2O3 that employs a supervised ML method
and an artificial neural network.166 The artificial neural
network was trained using theoretically calculated XANES
data for Pt nanoparticles having different shapes and sizes,
which are represented as the average CNs for the first four
coordination shells {C1, C2, C3, C4}. The artificial neural
network displayed high performance for predicting correct CN
values {C1, C2, C3, C4} for experimental XANES spectra of the
supported Pt nanoparticles, and thus, it is useful for obtaining
their 3D structures. These researchers also utilized a modified
artificial neural network method that included the effect of the
bond distance R ({C1, C2, C3, C4, R}) to obtain 3D structures
of subnanometer Cu clusters (Cu4, Cu12, C20) deposited on a
ZnO or ZrO2 substrate under a reactive atmosphere.167
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Akai et al. applied sparse modeling based on l1 regularization
to EXAFS oscillations analysis of Cu foil. In this approach,
simplified basis functions based on a single-scattering
approximation for the EXAFS oscillation are used instead of
plane-wave basis functions for the Fourier transform (FT).168
Consequently, the radial structure function takes a discrete
spectrum and increases its intensity with increasing distance
from the X-ray absorbing atom, suggesting the possibility of
analysis of the CN at much higher shells. The Debye−Waller
factor can also be obtained directly without prior assumptions
about the atomic-scale local structure.
An ML-based approach that can classify the local
coordination environments of the absorbing atom from
simulated K-edge XANES spectra was demonstrated recently
by Carbone and co-workers.169 The fidelity and robustness of
the developed ML method were demonstrated by high average
accuracy (86%) across the wide chemical space of oxides in
eight 3d transition metal families. Lamberti et al. also applied
ML techniques to simulate XANES spectra in order to
investigate molecular adsorption on open metal sites (Ni2+) of
a MOF material.170 It should also be mentioned that automatic
oxidation threshold recognition was demonstared by using ML
and experimental XAFS spectra by the group of Takahashi.171
Although several successful examples are available for ML
prediction of XAFS spectra, most of the studies used
computationally derived (well-behaved) data sets as inputs.
This is mainly because proper energy alignments are required
for ML modeling of XAFS spectra, and thus, it is difficult to
obtain a sufficiently large number of experimental data sets for
this purpose. Improvements in the accuracy of theoretical
simulations are strongly desired.
6.2. TEM/STEM. It has become increasingly common to
record atomically resolved transmission electron microscopy
(TEM) and scanning TEM (STEM) images of catalytic
materials and to monitor their atomic dynamics during
reactions. However, because the amount of TEM/STEM
data available has significantly increased recently and their
interpretation often requires a great deal of time for
nonexperts, it is highly desired to have automated analysis
tools that can be utilized to identify and classify the local
structures such as atoms (atomic columns), defects, dopants,
and phases.
Madsen et al. showed that deep convolutional neural
networks can be used to directly identify atoms (atomic
columns) of Au nanoparticles supported on CeO2 in high-
resolution TEM (HRTEM) images.172 In this protocol, the
network is trained using simulated TEM images of 500 Au
nanoparticles. Because the network should be able to recognize
both atomically flat and rough surfaces, the training data set
includes both types of nanoparticles. Nanoparticles are initially
cut from a regular crystal, keeping random numbers of layers in
directions with low Miller indices (the ⟨100⟩, ⟨110⟩, and ⟨111⟩
directions), and then a random number of additional atoms are
added to the particle to make it more rough. Subsequently,
each particle is aligned into the ⟨110⟩ or ⟨111⟩ zone axis and
rotated a random amount around the zone axis. It is finally
tilted 0−5° away from the zone axis. Figure 21a shows TEM
images of CeO2-supported Au nanoparticles in an oxygen
atmosphere and the corresponding analysis using the neural
network. As can be seen, the network can confidently identify
the atoms in the nanoparticle, and in particular, the surface
atoms at the corners of the nanoparticle appear and disappear
again. The same CeO2-supported Au nanoparticle in vacuum
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Figure 21. (a) Top row: Successive experimental TEM images of a
Au particle on CeO2 in a 4.5 Pa O2 atmosphere. Middle row: Output
images given by the neural network from the images above. Bottom
row: Atoms identified by using the neural network are marked as
black circles overlaid on the original image. (b) Surface dynamics of
Au nanoparticles on CeO2 influenced by the gaseous atmosphere. The
occurrence is the percentage of frames where the neural network
identified an atomic column at a possible site. The event is the
percentage of frames where a site was previously occupied but is
unoccupied in the frame immediately after, or vice versa. Reproduced
with permission from ref 172. Copyright 2018 Wiley-VCH Verlag
GmbH & Co. KGaA.
and in an oxygen atmosphere is shown in Figure 21b. In the
oxygen atmosphere, many surface and corner atoms are
present part of the time, indicating the occurrence of surface
diffusion.
Ziatdinov et al. used DNN to locate atomic species and
defects in atomically resolved STEM images.173 For this
purpose, they developed a “weakly supervised” approach that
employs coordinates of all atomic species and types of defects
to identify various defects that are not part of the initial
training set. This technique was used to interpret atomic and
defect transformations, including switching between different
coordinations of Si dopants in graphene and the formation of a
peculiar Si dimer with mixed threefold and fourfold
coordination.
Vasudevan et al. used the deep convolutional neural
networks technique for automatic determination of the Bravais
lattice symmetry seen in atomically resolved STEM and STM
images.174 The deep convolutional neural network was trained
to identify this type of lattice symmetry when a 2D fast FT of
the input image is given and then applied to sequential STEM
images recorded during electron-beam decomposition of Mo-
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doped WS2. The method allowed tracking and determination
of the rate of growth of voids (defects). Belianinov et al.
proposed an approach to separate mixed phases, symmetries,
and defects that is based on multivariate statistical analysis of
the coordination spheres of individual atoms, represented by
an array of values that correspond to a variety of metrics
(distances, angles, etc.) between an atom and its nearest or
next-nearest neighbors.175 A k-means clustering analysis was
performed for the two-phase (M1 and M2) mixed STEM
image of Mo−V−Te−Ta oxide. The analysis enabled clear
distinction of different areas of the image based on the
similarity of the chemical neighborhoods of their constituent
atoms and also predictions of the existence of a third phase in
addition to the original two phases.
6.3. Nanoscale Elemental Analysis Using STEM-EDX
and EELS. Advances in STEM have enabled comprehensive
energy-dispersive X-ray (EDX)/electron energy-loss (EELS)
spectral data sets from a specified region of interest (ROI) to
be obtained. The spectrometers collect a set of spectra, each
from a subnanometer area of the sample, by using the
subnanometer electron probe scanning over the two-dimen-
sional ROI. However, because of the presence of heteroge-
neous volumes in which spatial overlap of different phases exist
within the beam path, the STEM-EDX signals from different
depths in the beam path are mixed. Therefore, they need to be
separated to determine the compositions of the individual
phases. Rossouw et al. applied a blind source separation
method based on PCA and independent component analysis
(ICA) to analyze EDX spectral images (SIs) of core−shell
nanoparticles in order to determine the number of phases in an
analyzed volume (core, shell, and supporting film).176 Figure
22a,c−e contain HAADF STEM images of FePt@Fe3O4 core−
shell nanoparticles supported on carbon and the respective
EDX elemental maps. It is clear that the particles consist of Pt-
rich cores surrounded by Fe oxide shells. However, it is
difficult to tell whether the particles contain a monometallic Pt
core with a surrounding Fe oxide shell or Fe makes an alloy
with Pt to form a bimetallic core. The scree plot in Figure 22b
suggests that the sample is composed of three principal phases.
The spatial distribution of the independent components
IC#0−IC#2 (Figure 22f−h) and the corresponding spectra
(Figure 22i) show that IC#2, IC#1, and IC#0 represent the
carbon support, Fe oxide shells, and bimetallic FePt cores,
respectively. The small Cu peaks in all components likely
originate from the Cu mesh support. More recently, Shiga et al.
developed a new non-negative matrix factorization (NMF)
method for automatic resolution and extraction of constituent
chemical components in STEM-EDX/EELS SI data.177 The
method uses an extended NMF model with two penalty terms,
namely, a prior automatic relevance determination (ARD) that
optimizes the number of components and a soft orthogonal
constraint that resolves each spectral component. An assess-
ment of the method employing both phantom and real STEM-
EDX/EELS SI data sets demonstrated that the prior ARD
successfully identified the correct number of physically
meaningful components.
7. ML PREDICTION OF EXPERIMENTAL DATA FOR
HETEROGENEOUS CATALYSTS
Experimentally produced data (conversion, selectivity, reaction
rate) for reactions promoted using different catalyst
compositions or different reaction conditions can be utilized
to construct ML models for predicting reaction data. Although
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Figure 22. ICA of a cluster of bimetallic FePt nanoparticle seeds coated by Fe3O4 shells. (a) HAADF-STEM image of the nanoparticles. (b) Scree
plot of the first 50 principal components displaying the first three components lying above the noise. (c−e) Element maps of (c) Pt, (d) Fe, and (e)
O. (f−h) The IC maps (f) IC#0, (g) IC#1, and (h) IC#2 and (i) the corresponding IC spectra. Reproduced from ref 176. Copyright 2015
American Chemical Society.

Figure 23. Proposed ML method considering elemental features as representative input instead of the catalyst compositions themselves. As
elemental descriptors, 11 physical properties that are readily available from chemical handbooks and the periodic table (atomic number, atomic
weight, period, group, melting point, atomic radius, electronegativity, boiling point, enthalpy of fusion, density, and ionization energy) were
employed for each element. Reproduced with permission from ref 66. Copyright 2019 Wiley-VCH Verlag GmbH & Co. KGaA.

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Figure 24. (a) Comparison of 90%/10% training (blue)/test (red) error plots for three representation models of catalyst performance predictions
for OCM (C2 yield): conventional ML methods using (i) only catalyst compositions and (ii) catalyst compositions + experimental conditions and
(iii) proposed ML method using catalyst compositions + experimental conditions. (b) Top 20 descriptors to predict the C2 yield. (c) Top 20
promising candidate catalysts worth testing next. Reproduced with permission from ref 66. Copyright 2019 Wiley-VCH Verlag GmbH & Co.
KGaA.

most of the studies mentioned above focused on building ML
models from computationally derived (well-behaved) data sets,
developing approaches to use ML with “real world”
experimental catalysis data would be more useful because the
computational costs to obtain accurate theoretical models for
heterogeneous catalysis are currently prohibitively high. The
dynamic nature of catalytically active sites/fields makes the
modeling even more difficult. Even though excellent efforts
have been conducted to create databases of surface reaction
energetics, such as CatApp178 and Catalysis-Hub.org,179 the
accuracies and varieties of methods developed to capture the
complex phenomena of heterogeneous catalysis are not yet
adequate. After a brief overview of previous studies, this
section summarizes recent examples of efforts focusing on ML-
assisted prediction of catalytic reaction data.
Hattori et al. described pioneering studies of artificial
intelligence approaches to catalyst design that use an expert
system or neural network. 43−46 Subsequently, several
groups180−186 reported approaches for investigating and
optimizing catalyst compositions using neural network, GA,
or SVM methods, which have been summarized in previous
reviews.4,30,187,188 Because the concepts and a tutorial overview
of this general approach are described in reviews by
Rothenberg,4,188 we only summarize progress made in this
area in the past decade.
7.1. CH4 Conversion. Because of the large amount of CH4
that is available from natural sources, it is strongly desired to
develop processes for direct and indirect conversion of this
substance into value-added products. Among the methods
devised for direct conversion of CH4 to value-added chemicals,
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oxidative coupling of CH4 (OCM) to produce C2 products
such as C2H6 and C2H4 is the most popular. Catalysts for
OCM reactions have been analyzed and predicted by several
groups using a database consisting of nearly 2000 data sets on
catalyst compositions and their performances collected from
diverse published data.189−193 Very recently, our group
reported a statistical analysis and a proposal of novel
heterogeneous catalysts for OCM using ML treatment of
literature data.66 This effort led to the development of a novel
ML method considering elemental features as input
representations instead of inputting catalyst compositions
directly (Figure 23). Effective analysis of literature data by
ML methods has the capability to provide valuable
information. Nevertheless, utilization of literature data has
obstacles such as bias from prior published data, low sample
counts for many elements, and lack of composition overlaps.
The newly developed method has the potential to guide
catalyst design and discovery, including those that promote
reactions where limited catalyst composition overlap exists in
the given data. The prediction accuracy of this approach is
higher than those of conventional methods using catalyst
compositions as input (Figure 24). Among various state-of-the-
art ML models developed, gradient boosting regression with
XGBoost displayed the highest level of performance to predict
catalytic performance. In order to determine quantitatively the
most important input variables for prediction of the catalytic
performance, a feature importance score was also obtained.
Moreover, a catalyst optimization procedure that uses ML as
“surrogate” models identified the top 20 promising catalyst
candidates. This investigation provided fundamental knowl-
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Figure 25. Performance of the training and test sets for the model describing the conversion of 5-ethoxymethylfurfural to the corresponding
unsaturated alcohol. Reproduced with permission from ref 201. Copyright 2012 Royal Society of Chemistry.
edge about catalytic processes. Moreover, it has the potential of
being used to identify truly novel heterogeneous catalysts
where the reported data are limited and biased because they
are very noisy and inconsistent as a consequence of variations
arising from the use of different instruments, procedures, and
platforms.
Currently, CH4 is industrially converted through autother-
mal or catalytic steam reforming to form synthesis gas (a
mixture of H2 and CO), which then is used for large-scale
manufacture of methanol and higher-molecular-weight hydro-
carbons. Although these processes are already industrially
viable, they suffer from harsh reaction conditions. Thus, better
catalysts are needed. The Yildirim group constructed 5508
experimental data points for steam reforming of CH4 (SRM)
using 81 publications appearing between 2004 and 2014.194
The database was analyzed using decision trees to extract
correlations, heuristics, and trends that are not identifiable
using only the naked eye. Analysis of the performance variable
showed that Ni, Ru, Rh, and Pt are the most frequently used
active metals and that they are normally supported on Al2O3,
CeO2, or ZrO2 employing impregnation methods. In addition,
the analysis determined the ranges of catalyst preparation and
operational conditions employed that lead to high CH4
conversion. More recently, the same group extracted knowl-
edge for the dry reforming of CH4 (DRM) reaction from
literature experimental data employing data mining tools.195 A
database having 5521 data points was constructed from 101
papers reported between 2005 and 2014.
7.2. CO Oxidation. Günay and Yildirim performed a
systematic analysis of experimental data for CO oxidation
reactions reported between 2000 and 2012 using combinations
of various data mining tools.196 The decision tree classification
formulated some simple rules needed for high conversion. The
same group reported neural network analysis of the results of
experimental CO oxidation reactions over Cu- and Au-based
catalysts.197,198 The original data set was collected from
publications by different groups. The analysis was successful in
the experimental region that contained many data points,
whereas the conditions with smaller data sets were not easily
generalized.
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A database containing 4360 experimental data points on the
Pt- or Au-catalyzed water gas shift reaction (WGS), which
converts CO and H2O to CO2 and H2, was also constructed by
the Yildirim group using data obtained from publications
appearing between 2002 and 2012.199 The database was
analyzed using three mining tools to extract key information.
Specifically, (1) decision trees were used to determine the
empirical rules and conditions that allow for high CO
conversion, (2) artificial neural networks were used to provide
the relative importance of a variety of experimental variables
and their effects on the catalytic activity, and (3) SVMs were
used to predict outcomes of reactions performed under
unstudied conditions.
7.3. Friedel−Crafts Reaction. Omata devised a method
for predicting the activities of heteropolyacid catalysts
supported on active carbon to promote a Friedel−Crafts
reaction that utilizes GPR.200 Additives that enhance activity
were predicted using the regression model and verified through
experimentation. The influence of physicochemical properties
on the activity was estimated by employing GPR. The most
influential properties were found to be density, atomic weight,
and ionic radius of the additive element. It is significant that
this approach uncovered the excellent effect of Pt addition on
this process.
7.4. Utilization of Biomass. Rothenberg et al. reported
experimental data on the hydrogenation of 5-ethoxymethyl-
furfural, an important intermediate to obtain industrial
chemicals from sugars, promoted by different Al2O3-supported
metal catalysts under various conditions.201 The obtained data
were compared with the results of studies of 48 bimetallic
catalysts and rationalized by an effective model that applied
catalyst descriptors based on Slater-type orbitals. In this
approach, each metal is described using four parameters: the
distance of the orbital peak from the metal atom center, the
height of the peak, the peak skewness, and the peak width at
half height. The authors then applied these descriptors to
modeling of the reaction data using multivariate methods. In
spite of the inherent complexity of the reaction pathway, the
models developed in this way reasonably described the
performances of the catalysts (Figure 25).
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Figure 26. (a) Loading magnitudes for the 14 descriptors identified using factor analysis. (b) Relative importance of descriptor variables for the
penalized regression models (elastic nets, LASSO, LAR). Descriptors are sorted by median (gold bars). The bar color indicates the sign of the
coefficient: positive (light gray) and negative (dark gray). (c) Heat map of relative OER activity predictions for ABO3 perovskites using LAR and
data obtained from the Materials Project. Reproduced from ref 206. Copyright 2015 American Chemical Society.

The Yildirim group conducted a statistical analysis of
catalytic transesterification reactions by employing artificial
neural network and decision tree techniques. The aims were to
estimate important variables affecting conversion of fatty acid
and suitable ranges of these variables.202 For this purpose, a
database of 1324 data points was constructed from the
experimental results reported in 31 publications. Importantly,
artificial neural network analysis showed that the most
important variable to obtain high conversion of the fatty acid
was the reaction time, followed by the catalyst loading,
alcohol/oil molar ratio, reaction temperature, and type of
support, each of which have a similar relative importance of
about 10%.
7.5. Oxidative Dehydrogenation of Butane. The
oxidative dehydrogenation of butane to form butenes and
butadiene can also be accurately modeled employing heuristic
descriptor models. Rothenberg et al.203 synthesized and
experimentally tested 15 bimetallic mixed oxides supported
on Al2O3 in order to construct a descriptor model. The results
obtained utilizing data from this study to assess 1711 mixed
oxide catalysts in silico led to the prediction of six new
bimetallic oxides, which were then experimentally synthesized
and tested. The correlation between the predicted and
experimental results was excellent, showing the power of
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these low-cost predictive models. The wide operational range
of the model was demonstrated by its use in uncovering not
only catalysts that have expected high performances but also
those expected to have low activities. It is important to note
that an understandable bias exists for including only “good”
results in publications because articles often exclude
descriptions of badly performing catalysts. However, models
developed to predict the performance of catalysts should be
based on a wide range of data, highlighting the importance of
including both “good” and “bad” candidates in publications.
7.6. Reduction of CO2. Several new catalysts for CO2
hydrogenation to form higher-molecular-weight hydrocarbons
(CO2-based Fischer−Tropsch synthesis) were devised by
Baerns and co-workers, who applied an evolutionary strategy
using a GA.204 Among those predicted are Fe-based catalysts
modified using K and Zn or Cu, which promote high CO2
conversions combined with high selectivity toward C5−C15
hydrocarbons and low CH4 formation. Moreover, it was
demonstrated that TiO2 is required as a support in order to
obtain low CH4 selectivities.
Experimental data on the electrocatalytic reduction of CO2
(471 data points) were collected and used for statistical
analysis by Günay and co-workers.205 The collected data were
first examined by exploratory analysis using box-and-whisker
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Figure 27. Chemoinformatics-guided optimization protocol. (A) Generation of a large in silico library of catalyst candidates. (B) Calculation of
robust chemical descriptors. (C) Selection of a universal training set (UTS). (D) Acquisition of experimental selectivity data. (E) Application of
ML to use moderate- to low-selectivity reactions to predict high-selectivity reactions. Reproduced with permission from ref 226. Copyright 2019
American Association for the Advancement of Science.
plots. Subsequently, decision tree analysis was carried out to
identify the importance of the variables and conditions that
lead to higher reduction efficiencies and rates as well as
selectivities for product formation. It was found that Cu
contents less than 71% are the main requirement to realize
high Faradaic efficiency while Cu contents less than 13% are
essential for high production rates. The topmost factor
determining the selectivity was found to be the Sn content.
The most important variables for obtaining high Faradaic
efficiency were also identified to be the Cu content, applied
potential, TGP-H-60-type diffusion layer, filterpress cell,
Nafion 117-type membrane, and KHCO3 in the anolyte and
catholyte. The CO2 flow rate and applied potential were
identified to be the most highly significant input variables to
maximize the production rate. Moreover, Cu contents less than
52% and Sn contents higher than 15% were found to be the
most important factors for obtaining the highest rate and
selectivity for formic acid production.
7.7. Oxygen Evolution Reaction. Hong and co-workers
demonstrated how statistical learning approaches can be
utilized to investigate ambiguities in the reported descriptors
for oxygen evolution reaction (OER) catalytic performance.206
The authors found through aggregation of 101 observations of
51 perovskites reported in the literature and their own
experimental data that 14 descriptors of metal−oxygen bond
strengths can be grouped into five basic descriptor families,
including electrostatics, metal−oxygen covalency, structure,
transition metal electron occupancy, and exchange interactions
(Figure 26). Electron occupancy and covalency have the
strongest influence on the OER catalytic performance. The
charge-transfer energy (covalency) and the number of d
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electrons were found to be the most important, while other
factors, including the M−O−M bond angle, optimum eg
occupancy, and tolerance factor were determined to be
secondary descriptors. Figure 26c contains estimates of the
relative OER activities made using the best-performing model
(least angle regression, LAR) for ABO3 perovskites from the
Materials Project. More recently, Palkovits and Palkovits also
developed ML models using literature data to forecast OER
catalysts.207 They used a data set consisting of more than 6000
catalysts with four features represented by composition to
predict overpotentials at 10 mA/cm2.
7.8. Photocatalytic Water Splitting. ML techniques
could serve as a powerful tool in the field of photocatalysis.208
The Yildirim group constructed and analyzed a database
containing 540 cases from 151 published articles on photo-
catalytic water splitting reacions over perovskites using data
mining.209 Important factors to achieve efficient H2 generation
were revealed by association rule mining. Decision tree analysis
also identified useful heuristics for future investigations.
Moreover, they developed predictive models using random
forest regression.
8. ML PREDICTION OF EXPERIMENTAL DATA FOR
HOMOGENEOUS CATALYSTS
Homogeneous catalysts, generally organocatalysts and organo-
metallic catalysts, play essential roles in industry, especially for
promoting synthetically useful reactions in a highly selective
manner. Most organocatalysts and organometallic catalysts
have been discovered through serendipity or trial-and-error
studies rather than by rational design, which is often too
resource intensive and intellectually frustrating. As a result of
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Figure 28. (a) General catalytic cycle for C−C cross-coupling reactions. (b) Reference volcano plot for the reaction. Region I corresponds to
reductive elimination, region II to transmetalation, and region III to oxidative addition. Good catalyst candidates should fall into the middle region.
(c) Database having 25 116 molecular transition metal catalyst candidates. Each complex comprises one out of six transition metals and a
combination of two out of 91 ligands. Each ligand was written in SMILES notation, and all possible L1−M−L2 combinations were constructed.
SMILES strings were then converted into Cartesian coordinates. (d) Histogram ranking of the five most identified ligands that appear on the
volcano plateau. The histogram is scaled relative to the Pd/oxazole ligand combination. (e) Estimated prices of the catalysts (for 1 mmol in U.S.
dollars) in the selected range of −32.1 to −23.0 kcal/mol. From ref 227. CC BY-NC 3.0.

the drawbacks of these approaches, increasing attention has
been given to the development of predictive strategies that can
provide insights into the connection between structure and
function. To predict reactivity trends (linear free energy
relationships) of organic reactions, semiquantitative descriptors
have been established that are based on steric and electronic
properties of the substituents (i. e., Hammett and related
substituent parameters).210 Because the outcomes of reactions
catalyzed by transition metal complexes strongly depend on
the nature of the ligands, well-known ligand descriptors such as
cone angles and electronic parameters have been estab-
lished.211 As discussed in excellent reviews by Fey and co-
workers,212−214 modern organometallic chemistry has estab-
lished DFT-derived ligand descriptors to identify how steric
and electronic properties affect the properties of complexes.
Because homogeneous catalysts are generally well-defined
molecules composed of transition metal centers and ligands
(organometallic complexes), DFT calculations of descriptors
for homogeneous catalysis are relatively simpler than those for
heterogeneous catalysts. Accumulated experimental data
derived from ligand screening of organometallic catalysts in
combination with calculated ligand descriptors serve as
databases for the learning phase of ML-assisted catalyst design.
Sigman, 2 1 5 − 2 1 9 Fey, 2 1 2 − 2 1 4 Rothenberg, 2 2 0 −2 2 2 and
others223,224 have extensively utilized QSAR to correlate
input data (ligand descriptors and reaction conditions) and
output data (conversion, yield, selectivity, etc.) using conven-
tional algorithms such as PLS, multivariate linear regression
(MLR), PCA, GA, SVM, and artificial neural networks. These
authors demonstrated the success of predictive modeling of
homogeneous catalysts. Very recent progress has been made in
this area as a result of the increasing availability of descriptor-
computation methods and modern ML algorithms. This
section discusses several examples of efforts aimed at the
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design of homogeneous catalysts using ML models together
with DFT or simple computationally derived descriptors.
8.1. Organocatalysis. Enantioselective organocatalysis is a
useful synthetic method for the synthesis of enantiomerically
pure or enriched chiral compounds. Enantioselectivity in these
processes arises from a difference in free energy between
competing transition states leading to different enantiomers
(ΔΔG⧧). Various factors, including electronic and steric
interactions between the catalyst and substrate, are important
in governing ΔΔG⧧ and thus the level of enantioselectivity.
However, the effect of these factors on ΔΔG⧧ is not yet
quantitively predictable and understood, making data-intensive
discovery of new enantioselective organocatalysts challenging.
Sigman et al. developed MLR models for predicting the
enantiomeric excess (% ee) for enantioselective cross-
dehydrogenative C−N coupling reactions of various amide-
group-containing substrates promoted by various chiral
phosphoric acid derivatives as catalysts.225 Among the large
number of steric and vibrational terms initially examined, four
were statistically selected as molecular descriptors for which
ΔΔG⧧ predictions were validated experimentally. The results
demonstrated the success of a data-intensive method for
deriving a mechanistic model for predicting enantioselectivities
of organocatalyst-promoted reactions.
Zahrt et al. developed averaged steric occupancy (ASO)
descriptors of catalyst structures, which include 3D informa-
tion and are responsible for induction of enantioselectivity
(Figure 27).226 They demonstrated accurate predictive
modeling of enantioselectivities (ΔΔG⧧) in N,S-acetal-forming
processes with SVM and deep feed-forward neural networks
using ASOs as readily calculable descriptors for large
compound libraries. These examples serve to demonstrate
the potential of data-driven approaches for optimization of
chiral organocatalysts.
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Figure 29. Tungsten-catalyzed epoxidation reactions of 1-octene (1) using previously unverified phosphonic acid derivatives as catalysts. (a)
Comparison of predicted and experimental yields. (b) Plot of experimental vs predicted yields. Reproduced with permission from ref 228.
Copyright 2018 The Chemical Society of Japan.

Figure 30. Flowchart for CatVS. User-defined substrates are merged into a reaction template together with ligands from a predefined library,
followed by an automated conformational search using TSFF parameters and Boltzman averaging of the free energies calculated for the ensembles
of the diastereomeric transition states. FF, force field. Reproduced with permission from ref 230. Copyright 2018 Springer Nature.

8.2. Organometallic Catalysis. Rothenberg et al. devised
a QSAR approach for selecting catalysts and reaction
conditions for promoting Heck cross-coupling reactions.220
Correlations between catalyst precursors, ligands, substrates,
and reaction conditions in a data set of 412 Heck cross-
coupling reactions based on a set of defined and calculated
steric and electronic descriptors were analyzed using various
regression methods. Becuase of the complex nature of the
Heck cross-coupling reaction, nonlinear methods such as
classification trees and neural networks were found to be
superior to simple linear regression methods in modeling and
predicting the catalytic performance. The models were used to
predict the catalytic activities of 60 000 combinations of virtual
catalysts as well as reaction conditions.
Although volcano plots are frequently used to understand or
predict trends in heterogeneous catalysts, their application to
homogeneous catalysts is relatively rare. Corminboeuf et al.
applied a volcano plot approach to ML-assisted prediction of
homogeneous catalysts for C−C cross-coupling reactions
(Figure 28).227 The computed energies for the oxidative
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addition step, ΔE(Rxn A), were machine-learned using simple
molecular descriptors, including SMILES notation of ligands in
vast libraries of Pd-, Pt-, Ni-, Cu-, Au-, and Ag-based
organometallic catalysts combined with 91 ligands. Figure
28b shows the volcano relationship between the reaction free
energy and ΔE(Rxn A), which indicates that good catalysts
should fall into the region −32.1 kcal/mol < ΔE(Rxn A) <
−23.0 kcal/mol. Out-of-sample ML predictions made using a
total of 18 062 compounds led to the identification of 557
catalyst candidates falling into this ideal thermodynamic
window. Considering the price estimation of <$10/mmol,
the authors recommended 37 catalysts, including earth-
abundant Cu and less common ligands as well as a large
number of Pd−phosphine complexes.
Tungstate-catalyzed epoxidation reactions of alkenes with
H2O2 are significantly accelerated by phosphonic acid
cocatalysts. Yada et al. demonstrated an ML model (LASSO)
for predicting the yields of epoxidation of 1-octene using 14
types of phosphonic acids (Figure 29).228 Vibrational and
electronic descriptors of phosphonic acids (HOMO−LUMO
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gaps, NBO charges, and frequencies and intensities of the IR
modes, especially [P(O)(OH)2] vibrations) were calculated
using DFT. The established model was used to predict yields
of reactions promoted by previously unstudied phosphonic
acids. The success of the model was verified by comparing
predicted and experimental results for eight types of
phosphonic acids.
The group headed by Doyle used two easily calculable ligand
descriptors, percent buried volume and cone angle, to predict
yields of Ni-catalyzed Suzuki coupling reactions of acetals with
boronic acids to form benzylic ethers.229 The model suggested
a new concept for ligand design in which remote steric
hindrance is used to predict the effectiveness of a ligand.
Rosales et al. developed an automated method for rapid virtual
screening of substrate and ligand libraries for asymmetric
catalyzed processes (Figure 30).230 A quantum-guided
molecular mechanics (Q2MM) method was used for
automated calculation of transition state force fields, which
were then used as descriptors for an ML model to predict the
stereoselectivities of organic reactions. Predictive computa-
tional ligand selection was shown by using a virtual ligand
screen of a library of diphosphine ligands for the Rh-catalyzed
asymmetric hydrogenation of enamides. The high selectivities
of predicted substrate−ligand combinations were verified
experimentally. Predictive modeling was also applied to make
predictions about isomerization reactions of alkenes promoted
by zipper Ru catalysts231 and catalytic regioselective difluori-
nation reactions of alkenes.232
Recently, Amar et al. developed a new ML-based method for
rational selection of solvents.233 Rational solvent selection has
a large impact on the performance of catalytic processes and
remains a formidable task in process development. The
developed ML method enabled the rapid identification of
promising solvents for asymmetric hydrogenation, outperform-
ing those identified by human intuition in terms of
diastereomeric excess and conversion. They found optimal
operating conditions and successfully explored an idea that
uses mixed solvents to attain a range of experimental space not
accessible with pure solvents. More recently, Yamaguchi et al.
found that a regression technique, molecular field analysis, is
highly effective for designing molecules in asymmetric
catalysis.234 The analysis using intermediate structures in an
enantiodetermining step allowed for extraction and visual-
ization of important 3D structural information to improve the
enantioselectivity. In addition, they experimentally confirmed
that the newly designed substrate obtained using their method
exhibited improved enantioselectivity.
9. CONCLUSIONS AND FUTURE OUTLOOK
For the most part, discovering and optimizing catalysts/
catalysis are still empirically driven. It is true that ML-assisted
development of real catalysts remains in its infancy despite the
fact that this approach has had success in molecular and
materials science. Nevertheless, little doubt exists that ML will
become a valuable addition to the toolkit for generating
knowledge about and designing catalysts in the future. Not
only first-principles-calculated data but also experimental data
for specific catalytic reactions are required in order to use ML
for practical discovery of new catalysts. This is especially true
for heterogeneous catalysts, for which adequate theoretical
models are currently unavailable. Thus, ML-predicted data
cannot directly lead to the design of novel catalysts. Although
“catalysis informatics” is highly related to materials informatics
2290
Review
and chemoinformatics, it is distinguished by the fact that
catalysis is a dynamic event controlled by the structures and
chemical nature of catalytically active sites. Moreover, the time-
dependent nature of catalysis makes data representation and
analysis more challenging. It would be beneficial for future
investigations in this area to aim at bridging the gap between
simplified descriptor-based screening and complex real models
in a manner that considers dynamics during catalytic events.
Although high-throughput or combinatorial methods, which
have been applied successfully to relevant fields including
materials synthesis, serve as powerful tools to discover novel
catalysts and catalytic processes,53,136,235−243 at the current
time these experiments have not been explored fully. As a
consequence, there is a lack of good and refined data to guide
ML. Although text- and data-mining approaches also
demonstrate promise to accelerate research in this area,87,188
catalytic reactions are not only highly dependent on specified
experimental conditions such as temperature, reactant
concentration, and flow rate but also effected by unstated
conditions such as the shape and volume of the reactor. Also,
approaches tend to be biased toward successful examples
reported previously. Direct use of the ML technique could
result in discovery of only a narrow range of finely tuned
variations of previously studied catalysts because ML builds
predictive models that are representative of the given training
data. Therefore, published data might not serve as good
training sets for ML predictions. In this sense, experimental
data need to be generated under the same or at least
comparable reaction conditions. Also, coupling data science
with theoretical and experimental approaches could lead to
new methods for discovering catalysts to ensure “closing the
loop”.
Another aim of catalysis research is to establish more
accurate and lower-computational-cost calculations of tran-
sition states for catalyzed reactions. Although calculations of
this type are generally performed using first-principles
electronic structure methods and as a result are computation-
ally expensive, use of ML can significantly reduce costs.244−251
In addition, the artificial-force-induced reaction (AFIR)
methodology in the global reaction route mapping strategy
can be employed for automatic and unbiased searches of
complex reaction pathways.252,253 The AFIR approach locates
local minima and transition states of reaction paths without
guessing. Therefore, it can find both unanticipated and
anticipated reaction pathways. Ultimately, integration of
these methods with existing chemical and physical models
should greatly accelerate the automated design, discovery, and
optimization of catalysts as well as catalytic processes and lead
to the establishment of “catalysis informatics”.
■ AUTHOR INFORMATION
Corresponding Authors
*E-mail: ichigaku.takigawa@riken.jp (I.T.).
*E-mail: kshimizu@cat.hokudai.ac.jp (K.S.).
ORCID
Takashi Toyao: 0000-0002-6062-5622
Takashi Kamachi: 0000-0001-9281-0454
Ichigaku Takigawa: 0000-0001-5633-995X
Ken-ichi Shimizu: 0000-0003-0501-0294
Notes
The authors declare no competing financial interest.
DOI: 10.1021/acscatal.9b04186
ACS Catal. 2020, 10, 2260−2297
ACS Catalysis
■ ACKNOWLEDGMENTS
The preparation of this review and studies described that were
carried out by the authors were supported by the Japanese
Ministry of Education, Culture, Sports, Science, and
Technology (MEXT) within the projects Elements Strategy
Initiative To Form Core Research Center and Integrated
Research Consortium on Chemical Sciences (IRCCS) and by
JST-CREST Project JPMJCR17J3.
■ REFERENCES
(1) Schlögl, R. Heterogeneous Catalysis. Angew. Chem., Int. Ed.
2015, 54, 3465−3520.
(2) Nørskov, J. K.; Bligaard, T.; Rossmeisl, J.; Christensen, C. H.
Towards the Computational Design of Solid Catalysts. Nat. Chem.
2009, 1, 37−46.
(3) Matera, S.; Schneider, W. F.; Heyden, A.; Savara, A. Progress in
Accurate Chemical Kinetic Modeling, Simulations, and Parameter
Estimation for Heterogeneous Catalysis. ACS Catal. 2019, 9, 6624−
6647.
(4) Ras, E. J.; Rothenberg, G. Heterogeneous Catalyst Discovery
Using 21st Century Tools: A Tutorial. RSC Adv. 2014, 4, 5963−5974.
(5) van Santen, R. A.; Tranca, I.; Hensen, E. J. M. Theory of Surface
Chemistry and Reactivity of Reducible Oxides. Catal. Today 2015,
244, 63−84.
(6) Liu, L.; Corma, A. Metal Catalysts for Heterogeneous Catalysis:
From Single Atoms to Nanoclusters and Nanoparticles. Chem. Rev.
2018, 118, 4981−5079.
(7) Bruix, A.; Margraf, J. T.; Andersen, M.; Reuter, K. First-
Principles-Based Multiscale Modelling of Heterogeneous Catalysis.
Nat. Catal. 2019, 2, 659−670.
(8) Ishikawa, S.; Zhang, Z.; Ueda, W. Unit Synthesis Approach for
Creating High Dimensionally Structured Complex Metal Oxides as
Catalysts for Selective Oxidations. ACS Catal. 2018, 8, 2935−2943.
(9) Sehested, J. Industrial and Scientific Directions of Methanol
Catalyst Development. J. Catal. 2019, 371, 368−375.
(10) Pelletier, J. D. A.; Basset, J. M. Catalysis by Design: Well-
Defined Single-Site Heterogeneous Catalysts. Acc. Chem. Res. 2016,
49, 664−677.
(11) Toyao, T.; Hakim Siddiki, S. M. A.; Kon, K.; Shimizu, K. The
Catalytic Reduction of Carboxylic Acid Derivatives and CO2 by Metal
Nanoparticles on Lewis-Acidic Supports. Chem. Rec. 2018, 18, 1374−
1393.
(12) Grajciar, L.; Heard, C. J.; Bondarenko, A. A.; Polynski, M. V.;
Meeprasert, J.; Pidko, E. A.; Nachtigall, P. Towards Operando
Computational Modeling in Heterogeneous Catalysis. Chem. Soc. Rev.
2018, 47, 8307−8348.
(13) van Santen, R. A.; Neurock, M.; Shetty, S. G. Reactivity Theory
of Transition-Metal Surfaces: A Brønsted−Evans−Polanyi Linear
Activation Energy−Free-Energy Analysis. Chem. Rev. 2010, 110,
2005−2048.
(14) Nørskov, J. K.; Abild-Pedersen, F.; Studt, F.; Bligaard, T.
Density Functional Theory in Surface Chemistry and Catalysis. Proc.
Natl. Acad. Sci. U. S. A. 2011, 108, 937−943.
(15) Hammer, B.; Nørskov, J. Theoretical Surface Science and
Catalysis. Adv. Catal. 2000, 45, 71.
(16) Butler, K. T.; Davies, D. W.; Cartwright, H.; Isayev, O.; Walsh,
A. Machine Learning for Molecular and Materials Science. Nature
2018, 559, 547−555.
(17) Butler, K. T.; Frost, J. M.; Skelton, J. M.; Svane, K. L.; Walsh, A.
Computational Materials Design of Crystalline Solids. Chem. Soc. Rev.
2016, 45, 6138−6146.
(18) Fujinami, M.; Seino, J.; Nukazawa, T.; Ishida, S.; Iwamoto, T.;
Nakai, H. Virtual Reaction Condition Optimization Based on
Machine Learning for a Small Number of Experiments in High-
Dimensional Continuous and Discrete Variables. Chem. Lett. 2019,
48, 961−964.
(19) Szymkuć, S.; Gajewska, E. P.; Klucznik, T.; Molga, K.; Dittwald,
P.; Startek, M.; Bajczyk, M.; Grzybowski, B. A. Computer-Assisted
2291
Review
Synthetic Planning: The End of the Beginning. Angew. Chem., Int. Ed.
2016, 55, 5904−5937.
(20) Segler, M. H. S.; Preuss, M.; Waller, M. P. Planning Chemical
Syntheses with Deep Neural Networks and Symbolic AI. Nature 2018,
555, 604−610.
(21) Coley, C. W.; Thomas, D. A.; Lummiss, J. A. M.; Jaworski, J.
N.; Breen, C. P.; Schultz, V.; Hart, T.; Fishman, J. S.; Rogers, L.; Gao,
H.; Hicklin, R. W.; Plehiers, P. P.; Byington, J.; Piotti, J. S.; Green, W.
H.; Hart, A. J.; Jamison, T. F.; Jensen, K. F. A Robotic Platform for
Flow Synthesis of Organic Compounds Informed by AI Planning.
Science 2019, 365, eaax1566.
(22) Tabor, D. P.; Roch, L. M.; Saikin, S. K.; Kreisbeck, C.; Sheberla,
D.; Montoya, J. H.; Dwaraknath, S.; Aykol, M.; Ortiz, C.; Tribukait,
H.; Amador-Bedolla, C.; Brabec, C. J.; Maruyama, B.; Persson, K. A.;
Aspuru-Guzik, A. Accelerating the Discovery of Materials for Clean
Energy in the Era of Smart Automation. Nat. Rev. Mater. 2018, 3, 5−
20.
(23) Sanchez-Lengeling, B.; Aspuru-Guzik, A. Inverse Molecular
Design Using Machine Learning: Generative Models for Matter
Engineering. Science 2018, 361, 360−36.
(24) Zunger, A. Inverse Design in Search of Materials with Target
Functionalities. Nat. Rev. Chem. 2018, 2, 0121.
(25) Ward, L.; Agrawal, A.; Choudhary, A.; Wolverton, C. A
General-Purpose Machine Learning Framework for Predicting
Properties of Inorganic Materials. npj Comput. Mater. 2016, 2, 16028.
(26) Ramprasad, R.; Batra, R.; Pilania, G.; Mannodi-Kanakkithodi,
A.; Kim, C. Machine Learning in Materials Informatics: Recent
Applications and Prospects. npj Comput. Mater. 2017, 3, 54.
(27) Rajan, K. Materials Informatics: The Materials “Gene” and Big
Data. Annu. Rev. Mater. Res. 2015, 45, 153−169.
(28) Nandy, A.; Duan, C.; Janet, J. P.; Gugler, S.; Kulik, H. J.
Strategies and Software for Machine Learning Accelerated Discovery
in Transition Metal Chemistry. Ind. Eng. Chem. Res. 2018, 57, 13973−
13986.
(29) Duan, C.; Janet, J. P.; Liu, F.; Nandy, A.; Kulik, H. J. Learning
from Failure: Predicting Electronic Structure Calculation Outcomes
with Machine Learning Models. J. Chem. Theory Comput. 2019, 15,
2331−2345.
(30) Le, T.; Epa, V. C.; Burden, F. R.; Winkler, D. A. Quantitative
Structure−Property Relationship Modeling of Diverse Materials
Properties. Chem. Rev. 2012, 112, 2889−2919.
(31) Rupp, M.; Tkatchenko, A.; Müller, K.-R.; von Lilienfeld, O. A.
Fast and Accurate Modeling of Molecular Atomization Energies with
Machine Learning. Phys. Rev. Lett. 2012, 108, 058301.
(32) Pilania, G.; Wang, C.; Jiang, X.; Rajasekaran, S.; Ramprasad, R.
Accelerating Materials Property Predictions Using Machine Learning.
Sci. Rep. 2013, 3, 2810.
(33) Meredig, B.; Agrawal, A.; Kirklin, S.; Saal, J. E.; Doak, J. W.;
Thompson, A.; Zhang, K.; Choudhary, A.; Wolverton, C.
Combinatorial Screening for New Materials in Unconstrained
Composition Space with Machine Learning. Phys. Rev. B: Condens.
Matter Mater. Phys. 2014, 89, 094104.
(34) Faber, F.; Lindmaa, A.; Von Lilienfeld, O. A.; Armiento, R.
Crystal Structure Representations for Machine Learning Models of
Formation Energies. Int. J. Quantum Chem. 2015, 115, 1094−1101.
(35) Ubaru, S.; Miȩdlar, A.; Saad, Y.; Chelikowsky, J. R. Formation
Enthalpies for Transition Metal Alloys Using Machine Learning. Phys.
Rev. B: Condens. Matter Mater. Phys. 2017, 95, 214102.
(36) Schütt, K. T.; Glawe, H.; Brockherde, F.; Sanna, A.; Müller, K.
R.; Gross, E. K. U. How to Represent Crystal Structures for Machine
Learning: Towards Fast Prediction of Electronic Properties. Phys. Rev.
B: Condens. Matter Mater. Phys. 2014, 89, 205118.
(37) Dey, P.; Bible, J.; Datta, S.; Broderick, S.; Jasinski, J.; Sunkara,
M.; Menon, M.; Rajan, K. Informatics-Aided Bandgap Engineering for
Solar Materials. Comput. Mater. Sci. 2014, 83, 185−195.
(38) Lee, J.; Seko, A.; Shitara, K.; Nakayama, K.; Tanaka, I.
Prediction Model of Band Gap for Inorganic Compounds by
Combination of Density Functional Theory Calculations and
DOI: 10.1021/acscatal.9b04186
ACS Catal. 2020, 10, 2260−2297
ACS Catalysis
Machine Learning Techniques. Phys. Rev. B: Condens. Matter Mater.
Phys. 2016, 93, 115104.
(39) Pilania, G.; Mannodi-Kanakkithodi, A.; Uberuaga, B. P.;
Ramprasad, R.; Gubernatis, J. E.; Lookman, T. Machine Learning
Bandgaps of Double Perovskites. Sci. Rep. 2016, 6, 19375.
(40) Legrain, F.; Carrete, J.; van Roekeghem, A.; Curtarolo, S.;
Mingo, N. How the Chemical Composition Alone Can Predict
Vibrational Free Energies and Entropies of Solids. Chem. Mater. 2017,
29, 6220−6227.
(41) Seko, A.; Maekawa, T.; Tsuda, K.; Tanaka, I. Machine Learning
with Systematic Density-Functional Theory Calculations: Application
to Melting Temperatures of Single- and Binary-Component Solids.
Phys. Rev. B: Condens. Matter Mater. Phys. 2014, 89, 054303.
(42) Goldsmith, B. R.; Esterhuizen, J.; Bartel, C. J.; Sutton, C.; Liu,
J.-X. Machine Learning for Heterogeneous Catalyst Design and
Discovery. AIChE J. 2018, 64, 2311−2323.
(43) Hattori, T.; Kito, S.; Murakami, Y. Integration of Catalyst
Activity Pattern (INCAP) Artificial Intelligence Approach in Catalyst
Design. Chem. Lett. 1988, 17, 1269−1272.
(44) Hattori, T.; Kito, S. Artificial Intelligence Approach to Catalyst
Design. Catal. Today 1991, 10, 213−222.
(45) Kito, S.; Hattori, T.; Murakami, Y. Estimation of the Acid
Strength of Mixed Oxides by a Neural Network. Ind. Eng. Chem. Res.
1992, 31, 979−981.
(46) Hattori, T.; Kito, S. Neural Network as a Tool for Catalyst
Development. Catal. Today 1995, 23, 347−355.
(47) Medford, A. J.; Kunz, M. R.; Ewing, S. M.; Borders, T.;
Fushimi, R. Extracting Knowledge from Data through Catalysis
Informatics. ACS Catal. 2018, 8, 7403−7429.
(48) Takahashi, K.; Takahashi, L.; Miyazato, I.; Fujima, J.; Tanaka,
Y.; Uno, T.; Satoh, H.; Ohno, K.; Nishida, M.; Hirai, K.; Ohyama, J.;
Nguyen, T. N.; Nishimura, S.; Taniike, T. The Rise of Catalyst
Informatics: Towards Catalyst Genomics. ChemCatChem 2019, 11,
1146−1152.
(49) Kitchin, J. R. Machine Learning in Catalysis. Nat. Catal. 2018,
1, 230−232.
(50) Li, Z.; Wang, S.; Xin, H. Toward Artificial Intelligence in
Catalysis. Nat. Catal. 2018, 1, 641−642.
(51) Schlexer Lamoureux, P.; Winther, K.; Garrido Torres, J. A.;
Streibel, V.; Zhao, M.; Bajdich, M.; Abild-Pedersen, F.; Bligaard, T.
Machine Learning for Computational Heterogeneous Catalysis.
ChemCatChem 2019, 11, 3581−3601.
(52) Freeze, J. G.; Kelly, H. R.; Batista, V. S. Search for Catalysts by
Inverse Design: Artificial Intelligence, Mountain Climbers, and
Alchemists. Chem. Rev. 2019, 119, 6595−6612.
(53) Caruthers, J. M.; Lauterbach, J. A.; Thomson, K. T.;
Venkatasubramanian, V.; Snively, C. M.; Bhan, A.; Katare, S.;
Oskarsdottir, G. Catalyst Design: Knowledge Extraction from High-
Throughput Experimentation. J. Catal. 2003, 216, 98−109.
(54) Hand, D. J. Data Science for Financial Applications. In
Proceedings of the 24th ACM SIGKDD International Conference on
Knowledge Discovery and Data Mining (KDD ’18); ACM: New York,
2018.
(55) Domingos, P. A Few Useful Things To Know about Machine
Learning. Commun. ACM 2012, 55, 78−87.
(56) Wujek, B.; Hall, P.; Güneş, F. Best Practices for Machine
Learning Applications; SAS Paper SAS2360-2016; SAS Institute: Cary,
NC, 2 01 6. ht t ps : / / s u p p o r t . s a s. co m / r e s o u r c e s / pa p e r s /
proceedings16/SAS2360-2016.pdf.
(57) Kaufman, S.; Rosset, S.; Perlich, C. Leakage in Data Mining:
Formulation, Detection, and Avoidance. In Proceedings of the 17th
ACM SIGKDD International Conference on Knowledge Discovery and
Data Mining (KDD ’11); ACM: New York, 2011; pp 556−563.
(58) Takigawa, I.; Shimizu, K.; Tsuda, K.; Takakusagi, S. Machine-
Learning Prediction of the d-Band Center for Metals and Bimetals.
RSC Adv. 2016, 6, 52587−52595.
(59) Takigawa, I.; Shimizu, K.; Tsuda, K.; Takakusagi, S. Machine
Learning Predictions of Factors Affecting the Activity of Heteroge-
neous Metal Catalysts. Nanoinformatics 2018, 45−64.
2292
Review
(60) Caruana, R.; Karampatziakis, N.; Yessenalina, A. An Empirical
Evaluation of Supervised Learning in High Dimensions. In Proceedings
of the 25th International Conference on Machine Learning (ICML ’08);
ACM: New York, 2008; pp 96−103.
(61) Fernández-Delgado, M.; Cernadas, E.; Barro, S.; Amorim, D.
Do We Need Hundreds of Classifiers to Solve Real World
Classification Problems? J. Mach. Learn. Res. 2014, 15, 3133−3181.
(62) Nguyen, A.; Yosinski, J.; Clune, J. Deep Neural Networks Are
Easily Fooled: High Confidence Predictions for Unrecognizable
Images. In 2015 IEEE Computer Society Conference on Computer Vision
and Pattern Recognition (CVPR); IEEE, 2015.
(63) Cherkasov, A.; Muratov, E. N.; Fourches, D.; Varnek, A.;
Baskin, I. I.; Cronin, M.; Dearden, J.; Gramatica, P.; Martin, Y. C.;
Todeschini, R.; Consonni, V.; Kuz’min, V. E.; Cramer, R.; Benigni, R.;
Yang, C.; Rathman, J.; Terfloth, L.; Gasteiger, J.; Richard, A.;
Tropsha, A. QSAR Modeling: Where Have You Been? Where Are
You Going To? J. Med. Chem. 2014, 57, 4977−5010.
(64) Tropsha, A. Best Practices for QSAR Model Development,
Validation, and Exploitation. Mol. Inf. 2010, 29, 476−488.
(65) Gromski, P. S.; Henson, A. B.; Granda, J. M.; Cronin, L. How
to Explore Chemical Space Using Algorithms and Automation. Nat.
Rev. Chem. 2019, 3, 119−128.
(66) Suzuki, K.; Toyao, T.; Maeno, Z.; Takakusagi, S.; Shimizu, K.;
Takigawa, I. Statistical Analysis and Discovery of Heterogeneous
Catalysts Based on Machine Learning from Diverse Published Data.
ChemCatChem 2019, 11, 4537−4547.
(67) Ghahramani, Z. Probabilistic Machine Learning and Artificial
Intelligence. Nature 2015, 521, 452−459.
(68) Noh, J.; Kim, J.; Stein, H. S.; Sanchez-Lengeling, B.; Gregoire, J.
M.; Aspuru-Guzik, A.; Jung, Y. Inverse Design of Solid-State Materials
via a Continuous Representation. Matter 2019, 1, 1370−1384.
(69) Box, G. E. P. Use and Abuse of Regression. Technometrics 1966,
8, 625−629.
(70) Rücker, C.; Rücker, G.; Meringer, M. Y-Randomization and Its
Variants in QSPR/QSAR. J. Chem. Inf. Model. 2007, 47, 2345−2357.
(71) Hill, J.; Mulholland, G.; Persson, K.; Seshadri, R.; Wolverton,
C.; Meredig, B. Materials Science with Large-Scale Data and
Informatics: Unlocking New Opportunities. MRS Bull. 2016, 41,
399−409.
(72) Belsky, A.; Hellenbrandt, M.; Karen, V. L.; Luksch, P. New
Developments in the Inorganic Crystal Structure Database (ICSD):
Accessibility in Support of Materials Research and Design. Acta
Crystallogr., Sect. B: Struct. Sci. 2002, 58, 364−369.
(73) Xu, Y.; Yamazaki, M.; Villars, P. Inorganic Materials Database
for Exploring the Nature of Material. Jpn. J. Appl. Phys. 2011, 50,
11RH02.
(74) Jain, A.; Ong, S. P.; Hautier, G.; Chen, W.; Richards, W. D.;
Dacek, S.; Cholia, S.; Gunter, D.; Skinner, D.; Ceder, G.; Persson, K.
A. Commentary: The Materials Project: A Materials Genome
Approach to Accelerating Materials Innovation. APL Mater. 2013,
1, 011002.
(75) Saal, J. E.; Kirklin, S.; Aykol, M.; Meredig, B.; Wolverton, C.
Materials Design and Discovery with High-Throughput Density
Functional Theory: The Open Quantum Materials Database
(OQMD). JOM 2013, 65, 1501−1509.
(76) Curtarolo, S.; Setyawan, W.; Wang, S.; Xue, J.; Yang, K.; Taylor,
R. H.; Nelson, L. J.; Hart, G. L. W.; Sanvito, S.; Buongiorno-Nardelli,
M.; Mingo, N.; Levy, O. AFLOWLIB.ORG: A Distributed Materials
Properties Repository from High-Throughput Ab Initio Calculations.
Comput. Mater. Sci. 2012, 58, 227−235.
(77) Wicker, J. G. P.; Cooper, R. I. Will It Crystallise? Predicting
Crystallinity of Molecular Materials. CrystEngComm 2015, 17, 1927−
1934.
(78) Bassman, L.; Rajak, P.; Kalia, R. K.; Nakano, A.; Sha, F.; Sun, J.;
Singh, D. J.; Aykol, M.; Huck, P.; Persson, K.; Vashishta, P. Active
Learning for Accelerated Design of Layered Materials. npj Comput.
Mater. 2018, 4, 74.
DOI: 10.1021/acscatal.9b04186
ACS Catal. 2020, 10, 2260−2297
ACS Catalysis
(79) Graser, J.; Kauwe, S. K.; Sparks, T. D. Machine Learning and
Energy Minimization Approaches for Crystal Structure Predictions: A
Review and New Horizons. Chem. Mater. 2018, 30, 3601−3612.
(80) Jha, D.; Ward, L.; Paul, A.; Liao, W.-k.; Choudhary, A.;
Wolverton, C.; Agrawal, A. ElemNet: Deep Learning the Chemistry of
Materials From Only Elemental Composition. Sci. Rep. 2018, 8,
17593.
(81) Aykol, M.; Hegde, V. I.; Hung, L.; Suram, S.; Herring, P.;
Wolverton, C.; Hummelshøj, J. S. Network Analysis of Synthesizable
Materials Discovery. Nat. Commun. 2019, 10, 2018.
(82) Braham, E. J.; Cho, J.; Forlano, K. M.; Watson, D. F.; Arròyave,
R.; Banerjee, S. Machine Learning-Directed Navigation of Synthetic
Design Space: A Statistical Learning Approach to Controlling the
Synthesis of Perovskite Halide Nanoplatelets in the Quantum-
Confined Regime. Chem. Mater. 2019, 31, 3281−3292.
(83) Oliynyk, A. O.; Mar, A. Discovery of Intermetallic Compounds
from Traditional to Machine-Learning Approaches. Acc. Chem. Res.
2018, 51, 59−68.
(84) Oliynyk, A. O.; Adutwum, L. A.; Harynuk, J. J.; Mar, A.
Classifying Crystal Structures of Binary Compounds AB through
Cluster Resolution Feature Selection and Support Vector Machine
Analysis. Chem. Mater. 2016, 28, 6672−6681.
(85) Hautier, G.; Fischer, C. C.; Jain, A.; Mueller, T.; Ceder, G.
Finding Natures Missing Ternary Oxide Compounds Using Machine
Learning and Density Functional Theory. Chem. Mater. 2010, 22,
3762−3767.
(86) Kim, E.; Huang, K.; Tomala, A.; Matthews, S.; Strubell, E.;
Saunders, A.; McCallum, A.; Olivetti, E. Machine-Learned and
Codified Synthesis Parameters of Oxide Materials. Sci. Data 2017, 4,
170127.
(87) Kim, E.; Huang, K.; Saunders, A.; McCallum, A.; Ceder, G.;
Olivetti, E. Materials Synthesis Insights from Scientific Literature via
Text Extraction and Machine Learning. Chem. Mater. 2017, 29,
9436−9444.
(88) Caramelli, D.; Salley, D.; Henson, A.; Camarasa, G. A.; Sharabi,
S.; Keenan, G.; Cronin, L. Networking Chemical Robots for Reaction
Multitasking. Nat. Commun. 2018, 9, 3406.
(89) Duros, V.; Grizou, J.; Xuan, W.; Hosni, Z.; Long, D. L.; Miras,
H. N.; Cronin, L. Human versus Robots in the Discovery and
Crystallization of Gigantic Polyoxometalates. Angew. Chem., Int. Ed.
2017, 56, 10815−10820.
(90) Moliner, M.; Román-Leshkov, Y.; Corma, A. Machine Learning
Applied to Zeolite Synthesis: The Missing Link for Realizing High-
Throughput Discovery. Acc. Chem. Res. 2019, 52, 2971−2980.
(91) Muraoka, K.; Sada, Y.; Miyazaki, D.; Chaikittisilp, W.; Okubo,
T. Linking Synthesis and Structure Descriptors from a Large
Collection of Synthetic Records of Zeolite Materials. Nat. Commun.
2019, 10, 4459.
(92) Yang, S.; Lach-hab, M.; Vaisman, I. I.; Blaisten-Barojas, E.
Identifying Zeolite Frameworks with a Machine Learning Approach. J.
Phys. Chem. C 2009, 113, 21721−21725.
(93) Carr, D. A.; Lach-hab, M.; Yang, S.; Vaisman, I. I.; Blaisten-
Barojas, E. Machine Learning Approach for Structure-Based Zeolite
Classification. Microporous Mesoporous Mater. 2009, 117, 339−349.
(94) Lach-hab, M.; Yang, S.; Vaisman, I. I.; Blaisten-Barojas, E.
Novel Approach for Clustering Zeolite Crystal Structures. Mol. Inf.
2010, 29, 297−301.
(95) Blay, V.; Yokoi, T.; González-Díaz, H. Perturbation Theory−
Machine Learning Study of Zeolite Materials Desilication. J. Chem.
Inf. Model. 2018, 58, 2414−2419.
(96) Evans, J. D.; Coudert, F. X. Predicting the Mechanical
Properties of Zeolite Frameworks by Machine Learning. Chem. Mater.
2017, 29, 7833−7839.
(97) Daeyaert, F.; Ye, F.; Deem, M. W. Machine-Learning Approach
to the Design of OSDAs for Zeolite Beta. Proc. Natl. Acad. Sci. U. S. A.
2019, 116, 3413−3418.
(98) Jensen, Z.; Kim, E.; Kwon, S.; Gani, T. Z. H.; Román-Leshkov,
Y.; Moliner, M.; Corma, A.; Olivetti, E. A Machine Learning
2293
Review
Approach to Zeolite Synthesis Enabled by Automatic Literature Data
Extraction. ACS Cent. Sci. 2019, 5, 892−899.
(99) Raccuglia, P.; Elbert, K. C.; Adler, P. D. F.; Falk, C.; Wenny, M.
B.; Mollo, A.; Zeller, M.; Friedler, S. A.; Schrier, J.; Norquist, A. J.
Machine-Learning-Assisted Materials Discovery Using Failed Experi-
ments. Nature 2016, 533, 73−76.
(100) Vayenas, C. G.; Bebelis, S.; Ladas, S. Dependence of Catalytic
Rates on Catalyst Work Function. Nature 1990, 343, 625−627.
(101) Shen, X.; Pan, Y.; Liu, B.; Yang, J.; Zeng, J.; Peng, Z. More
Accurate Depiction of Adsorption Energy on Transition Metals Using
Work Function as One Additional Descriptor. Phys. Chem. Chem.
Phys. 2017, 19, 12628−12632.
(102) Ruban, A.; Hammer, B.; Stoltze, P.; Skriver, H. L.; Nørskov, J.
K. Surface Electronic Structure and Reactivity of Transition and
Noble Metals. J. Mol. Catal. A: Chem. 1997, 115, 421−429.
(103) Calle-Vallejo, F.; Tymoczko, J.; Colic, V.; Vu, Q. H.; Pohl, M.
D.; Morgenstern, K.; Loffreda, D.; Sautet, P.; Schuhmann, W.;
Bandarenka, A. S. Finding Optimal Surface Sites on Heterogeneous
Catalysts by Counting Nearest Neighbors. Science 2015, 350, 185−
189.
(104) Zhuang, H.; Tkalych, A. J.; Carter, E. A. Surface Energy as a
Descriptor of Catalytic Activity. J. Phys. Chem. C 2016, 120, 23698−
23706.
(105) Kitchin, J. R.; Nørskov, J. K.; Barteau, M. A.; Chen, J. G. Role
of Strain and Ligand Effects in the Modification of the Electronic and
Chemical Properties of Bimetallic Surfaces. Phys. Rev. Lett. 2004, 93,
156801.
(106) Greeley, J. Theoretical Heterogeneous Catalysis: Scaling
Relationships and Computational Catalyst Design. Annu. Rev. Chem.
Biomol. Eng. 2016, 7, 605−635.
(107) Calle-Vallejo, F.; Loffreda, D.; Koper, M. T. M.; Sautet, P.
Introducing Structural Sensitivity into Adsorption−Energy Scaling
Relations by Means of Coordination Numbers. Nat. Chem. 2015, 7,
403−410.
(108) Kumar, G.; Lau, S. L. J.; Krcha, M. D.; Janik, M. J. Correlation
of Methane Activation and Oxide Catalyst Reducibility and Its
Implications for Oxidative Coupling. ACS Catal. 2016, 6, 1812−1821.
(109) Huang, B.; Xiao, L.; Lu, J.; Zhuang, L. Spatially Resolved
Quantification of the Surface Reactivity of Solid Catalysts. Angew.
Chem., Int. Ed. 2016, 55, 6239−6243.
(110) Capdevila-Cortada, M.; Vilé, G.; Teschner, D.; Pérez-Ramírez,
J.; López, N. Reactivity Descriptors for Ceria in Catalysis. Appl. Catal.,
B 2016, 197, 299−312.
(111) Wang, P.; Fu, G.; Wan, H. How High Valence Transition
Metal Spreads Its Activity over Nonmetal Oxoes: A Proof-of-Concept
Study. ACS Catal. 2017, 7, 5544−5548.
(112) Studt, F.; Abild-Pedersen, F.; Bligaard, T.; Sørensen, R. Z.;
Christensen, C. H.; Nørskov, J. K. Identification of Non-Precious
Metal Alloy Catalysts for Selective Hydrogenation of Acetylene.
Science 2008, 320, 1320−1322.
(113) Studt, F.; Sharafutdinov, I.; Abild-Pedersen, F.; Elkjær, C. F.;
Hummelshøj, J. S.; Dahl, S.; Chorkendorff, I.; Nørskov, J. K.
Discovery of a Ni-Ga Catalyst for Carbon Dioxide Reduction to
Methanol. Nat. Chem. 2014, 6, 320−324.
(114) Fernández, E. M.; Moses, P. G.; Toftelund, A.; Hansen, H. A.;
Martínez, J. I.; Abild-Pedersen, F.; Kleis, J.; Hinnemann, B.;
Rossmeisl, J.; Bligaard, T.; Nørskov, J. K. Scaling Relationships for
Adsorption Energies on Transition Metal Oxide, Sulfide, and Nitride
Surfaces. Angew. Chem., Int. Ed. 2008, 47, 4683−4686.
(115) Vojvodic, A.; Hellman, A.; Ruberto, C.; Lundqvist, B. I. From
Electronic Structure to Catalytic Activity: A Single Descriptor for
Adsorption and Reactivity on Transition-Metal Carbides. Phys. Rev.
Lett. 2009, 103, 146103.
(116) Calle-Vallejo, F.; Inoglu, N. G.; Su, H. Y.; Martínez, J. I.; Man,
I. C.; Koper, M. T. M.; Kitchin, J. R.; Rossmeisl, J. Number of Outer
Electrons as Descriptor for Adsorption Processes on Transition
Metals and Their Oxides. Chem. Sci. 2013, 4, 1245−1249.
(117) Kakekhani, A.; Roling, L. T.; Kulkarni, A.; Latimer, A. A.;
Abroshan, H.; Schumann, J.; Aljama, H.; Siahrostami, S.; Ismail-Beigi,
DOI: 10.1021/acscatal.9b04186
ACS Catal. 2020, 10, 2260−2297
ACS Catalysis
S.; Abild-Pedersen, F.; Nørskov, J. K. Nature of Lone-Pair-Surface
Bonds and Their Scaling Relations. Inorg. Chem. 2018, 57, 7222−
7238.
(118) Kamachi, T.; Tatsumi, T.; Toyao, T.; Hinuma, Y.; Maeno, Z.;
Takakusagi, S.; Furukawa, S.; Takigawa, I.; Shimizu, K. Linear
Correlations between Adsorption Energies and HOMO Levels for the
Adsorption of Small Molecules on TiO2 Surfaces. J. Phys. Chem. C
2019, 123, 20988−20997.
(119) Ruiz Puigdollers, A.; Schlexer, P.; Tosoni, S.; Pacchioni, G.
Increasing Oxide Reducibility: The Role of Metal/Oxide Interfaces in
the Formation of Oxygen Vacancies. ACS Catal. 2017, 7, 6493−6513.
(120) Jia, J.; Qian, C.; Dong, Y.; Li, Y. F.; Wang, H.; Ghoussoub, M.;
Butler, K. T.; Walsh, A.; Ozin, G. A. Heterogeneous Catalytic
Hydrogenation of CO2 by Metal Oxides: Defect Engineering −
Perfecting Imperfection. Chem. Soc. Rev. 2017, 46, 4631−4644.
(121) Lee, Y.-L.; Kleis, J.; Rossmeisl, J.; Yang, S.-H.; Morgan, D.
Prediction of Solid Oxide Fuel Cell Cathode Activity with First-
Principles Descriptors. Energy Environ. Sci. 2011, 4, 3966−3970.
(122) Curnan, M. T.; Kitchin, J. R. Effects of Concentration, Crystal
Structure, Magnetism, and Electronic Structure Method on First-
Principles Oxygen Vacancy Formation Energy Trends in Perovskites.
J. Phys. Chem. C 2014, 118, 28776−28790.
(123) Staykov, A.; Téllez, H.; Akbay, T.; Druce, J.; Ishihara, T.;
Kilner, J. Oxygen Activation and Dissociation on Transition Metal
Free Perovskite Surfaces. Chem. Mater. 2015, 27, 8273−8281.
(124) Chen, C.; Ciucci, F. Designing Fe-Based Oxygen Catalysts by
Density Functional Theory Calculations. Chem. Mater. 2016, 28,
7058−7065.
(125) Emery, A. A.; Saal, J. E.; Kirklin, S.; Hegde, V. I.; Wolverton,
C. High-Throughput Computational Screening of Perovskites for
Thermochemical Water Splitting Applications. Chem. Mater. 2016, 28,
5621−5634.
(126) Hinuma, Y.; Toyao, T.; Kamachi, T.; Maeno, Z.; Takakusagi,
S.; Furukawa, S.; Takigawa, I.; Shimizu, K. Density Functional Theory
Calculations of Oxygen Vacancy Formation and Subsequent
Molecular Adsorption on Oxide Surfaces. J. Phys. Chem. C 2018,
122, 29435−29444.
(127) Pankajakshan, P.; Sanyal, S.; De Noord, O. E.; Bhattacharya,
I.; Bhattacharyya, A.; Waghmare, U. Machine Learning and Statistical
Analysis for Materials Science: Stability and Transferability of
Fingerprint Descriptors and Chemical Insights. Chem. Mater. 2017,
29, 4190−4201.
(128) Tanabe, K.; Hölderich, W. F. Industrial Application of Solid
Acid-Base Catalysts. Appl. Catal., A 1999, 181, 399−434.
(129) Digne, M.; Sautet, P.; Raybaud, P.; Euzen, P.; Toulhoat, H.
Use of DFT to Achieve a Rational Understanding of Acid-Basic
Properties of γ-Alumina Surfaces. J. Catal. 2004, 226, 54−68.
(130) Jenness, G. R.; Christiansen, M. A.; Caratzoulas, S.; Vlachos,
D. G.; Gorte, R. J. Site-Dependent Lewis Acidity of γ-Al2O3 and Its
Impact on Ethanol Dehydration and Etherification. J. Phys. Chem. C
2014, 118, 12899−12907.
(131) Cholewinski, M. C.; Dixit, M.; Mpourmpakis, G. Computa-
tional Study of Methane Activation on γ-Al2O3. ACS Omega 2018, 3,
18242−18250.
(132) Bhan, A.; Iglesia, E. A Link between Reactivity and Local
Structure in Acid Catalysis on Zeolites. Acc. Chem. Res. 2008, 41,
559−567.
(133) Liu, C.; Tranca, I.; van Santen, R. A.; Hensen, E. J. M.; Pidko,
E. A. Scaling Relations for Acidity and Reactivity of Zeolites. J. Phys.
Chem. C 2017, 121, 23520−23530.
(134) Matsuoka, T.; Baumes, L.; Katada, N.; Chatterjee, A.; Sastre,
G. Selecting Strong Brønsted Acid Zeolites through Screening from a
Database of Hypothetical Frameworks. Phys. Chem. Chem. Phys. 2017,
19, 14702−14707.
(135) Davran-Candan, T.; Günay, M. E.; Yildirim, R. Structure and
Activity Relationship for CO and O2 Adsorption over Gold
Nanoparticles Using Density Functional Theory and Artificial Neural
Networks. J. Chem. Phys. 2010, 132, 174113.
2294
Review
(136) Li, Z.; Wang, S.; Chin, W. S.; Achenie, L. E.; Xin, H. High-
Throughput Screening of Bimetallic Catalysts Enabled by Machine
Learning. J. Mater. Chem. A 2017, 5, 24131−24138.
(137) Ma, X.; Li, Z.; Achenie, L. E. K.; Xin, H. Machine-Learning-
Augmented Chemisorption Model for CO2 Electroreduction Catalyst
Screening. J. Phys. Chem. Lett. 2015, 6, 3528−3533.
(138) Noh, J.; Back, S.; Kim, J.; Jung, Y. Active Learning with Non-
Ab Initio Input Features toward Efficient CO2 Reduction Catalysts.
Chem. Sci. 2018, 9, 5152−5159.
(139) Andersen, M.; Levchenko, S. V.; Scheffler, M.; Reuter, K.
Beyond Scaling Relations for the Description of Catalytic Materials.
ACS Catal. 2019, 9, 2752−2759.
(140) Jäger, M. O. J.; Morooka, E. V.; Federici Canova, F.;
Himanen, L.; Foster, A. S. Machine Learning Hydrogen Adsorption
on Nanoclusters through Structural Descriptors. npj Comput. Mater.
2018, 4, 37.
(141) Back, S.; Yoon, J.; Tian, N.; Zhong, W.; Tran, K.; Ulissi, Z. W.
Convolutional Neural Network of Atomic Surface Structures to
Predict Binding Energies for High-Throughput Screening of Catalysts.
J. Phys. Chem. Lett. 2019, 10, 4401−4408.
(142) Chowdhury, A. J.; Yang, W.; Walker, E.; Mamun, O.; Heyden,
A.; Terejanu, G. A. Prediction of Adsorption Energies for Chemical
Species on Metal Catalyst Surfaces Using Machine Learning. J. Phys.
Chem. C 2018, 122, 28142−28150.
(143) Hoyt, R. A.; Montemore, M. M.; Fampiou, I.; Chen, W.;
Tritsaris, G.; Kaxiras, E. Machine Learning Prediction of H
Adsorption Energies on Ag Alloys. J. Chem. Inf. Model. 2019, 59,
1357−1365.
(144) García-Muelas, R.; López, N. Statistical Learning Goes beyond
the D-Band Model Providing the Thermochemistry of Adsorbates on
Transition Metals. Nat. Commun. 2019, 10, 4687.
(145) Gasper, R.; Shi, H.; Ramasubramaniam, A. Adsorption of CO
on Low-Energy, Low-Symmetry Pt Nanoparticles: Energy Decom-
position Analysis and Prediction via Machine-Learning Models. J.
Phys. Chem. C 2017, 121, 5612−5619.
(146) Göltl, F.; Müller, P.; Uchupalanun, P.; Sautet, P.; Hermans, I.
Developing a Descriptor-Based Approach for CO and NO Adsorption
Strength to Transition Metal Sites in Zeolites. Chem. Mater. 2017, 29,
6434−6444.
(147) Jinnouchi, R.; Asahi, R. Predicting Catalytic Activity of
Nanoparticles by a DFT-Aided Machine-Learning Algorithm. J. Phys.
Chem. Lett. 2017, 8, 4279−4283.
(148) Jinnouchi, R.; Hirata, H.; Asahi, R. Extrapolating Energetics
on Clusters and Single-Crystal Surfaces to Nanoparticles by Machine-
Learning Scheme. J. Phys. Chem. C 2017, 121, 26397−26405.
(149) Ulissi, Z. W.; Tang, M. T.; Xiao, J.; Liu, X.; Torelli, D. A.;
Karamad, M.; Cummins, K.; Hahn, C.; Lewis, N. S.; Jaramillo, T. F.;
Chan, K.; Nørskov, J. K. Machine-Learning Methods Enable
Exhaustive Searches for Active Bimetallic Facets and Reveal Active
Site Motifs for CO2 Reduction. ACS Catal. 2017, 7, 6600−6608.
(150) Tran, K.; Ulissi, Z. W. Active Learning across Intermetallics
To Guide Discovery of Electrocatalysts for CO2 Reduction and H2
Evolution. Nat. Catal. 2018, 1, 696−703.
(151) Toyao, T.; Suzuki, K.; Kikuchi, S.; Takakusagi, S.; Shimizu, K.;
Takigawa, I. Toward Effective Utilization of Methane: Machine
Learning Prediction of Adsorption Energies on Metal Alloys. J. Phys.
Chem. C 2018, 122, 8315−8326.
(152) Wexler, R. B.; Martirez, J. M. P.; Rappe, A. M. Chemical
Pressure-Driven Enhancement of the Hydrogen Evolving Activity of
Ni2P from Nonmetal Surface Doping Interpreted via Machine
Learning. J. Am. Chem. Soc. 2018, 140, 4678−4683.
(153) O’Connor, N. J.; Jonayat, A. S. M.; Janik, M. J.; Senftle, T. P.
Interaction Trends between Single Metal Atoms and Oxide Supports
Identified with Density Functional Theory and Statistical Learning.
Nat. Catal. 2018, 1, 531−539.
(154) Castelli, I. E.; Hüser, F.; Pandey, M.; Li, H.; Thygesen, K. S.;
Seger, B.; Jain, A.; Persson, K. A.; Ceder, G.; Jacobsen, K. W. New
Light-Harvesting Materials Using Accurate and Efficient Bandgap
Calculations. Adv. Energy Mater. 2015, 5, 1400915.
DOI: 10.1021/acscatal.9b04186
ACS Catal. 2020, 10, 2260−2297
ACS Catalysis
(155) Mishra, A.; Satsangi, S.; Rajan, A. C.; Mizuseki, H.; Lee, K. R.;
Singh, A. K. Accelerated Data-Driven Accurate Positioning of the
Band Edges of MXenes. J. Phys. Chem. Lett. 2019, 10, 780−785.
(156) Ulissi, Z. W.; Singh, A. R.; Tsai, C.; Nørskov, J. K. Automated
Discovery and Construction of Surface Phase Diagrams Using
Machine Learning. J. Phys. Chem. Lett. 2016, 7, 3931−3935.
(157) Timoshenko, J.; Frenkel, A. I. ”Inverting” X-ray Absorption
Spectra of Catalysts by Machine Learning in Search for Activity
Descriptors. ACS Catal. 2019, 9, 10192−10211.
(158) Liu, J.; Osadchy, M.; Ashton, L.; Foster, M.; Solomon, C. J.;
Gibson, S. J. Deep Convolutional Neural Networks for Raman
Spectrum Recognition: A Unified Solution. Analyst 2017, 142, 4067−
4074.
(159) Ito, K.; Obuchi, Y.; Chikayama, E.; Date, Y.; Kikuchi, J.
Exploratory Machine-Learned Theoretical Chemical Shifts Can
Closely Predict Metabolic Mixture Signals. Chem. Sci. 2018, 9,
8213−8220.
(160) Ghosh, K.; Stuke, A.; Todorović, M.; Jørgensen, P. B.;
Schmidt, M. N.; Vehtari, A.; Rinke, P. Deep Learning Spectroscopy:
Neural Networks for Molecular Excitation Spectra. Adv. Sci. 2019, 6,
1801367.
(161) Asakura, K.; Abe, H.; Kimura, M. The Challenge of
Constructing an International XAFS Database. J. Synchrotron Radiat.
2018, 25, 967−971.
(162) Zheng, C.; Mathew, K.; Chen, C.; Chen, Y.; Tang, H.; Dozier,
A.; Kas, J. J.; Vila, F. D.; Rehr, J. J.; Piper, L. F. J.; Persson, K. A.; Ong,
S. P. Automated Generation and Ensemble-Learned Matching of X-
ray Absorption Spectra. npj Comput. Mater. 2018, 4, 12.
(163) Mathew, K.; Zheng, C.; Winston, D.; Chen, C.; Dozier, A.;
Rehr, J. J.; Ong, S. P.; Persson, K. A. Data Descriptor: High-
Throughput Computational X-ray Absorption Spectroscopy. Sci. Data
2018, 5, 180151.
(164) Kiyohara, S.; Miyata, T.; Tsuda, K.; Mizoguchi, T. Data-
Driven Approach for the Prediction and Interpretation of Core-
Electron Loss Spectroscopy. Sci. Rep. 2018, 8, 13548.
(165) Suzuki, Y.; Hino, H.; Kotsugi, M.; Ono, K. Automated
Estimation of Materials Parameter from X-ray Absorption and
Electron Energy-Loss Spectra with Similarity Measures. npj Comput.
Mater. 2019, 5, 39.
(166) Timoshenko, J.; Lu, D.; Lin, Y.; Frenkel, A. I. Supervised
Machine-Learning-Based Determination of Three-Dimensional Struc-
ture of Metallic Nanoparticles. J. Phys. Chem. Lett. 2017, 8, 5091−
5098.
(167) Timoshenko, J.; Halder, A.; Yang, B.; Seifert, S.; Pellin, M. J.;
Vajda, S.; Frenkel, A. I. Subnanometer Substructures in Nano-
assemblies Formed from Clusters under a Reactive Atmosphere
Revealed Using Machine Learning. J. Phys. Chem. C 2018, 122,
21686−21693.
(168) Akai, I.; Iwamitsu, K.; Igarashi, Y.; Okada, M.; Setoyama, H.;
Okajima, T.; Hirai, Y. Sparse Modeling of an Extended X-ray
Absorption Fine-Structure Spectrum Based on a Single-Scattering
Formalism. J. Phys. Soc. Jpn. 2018, 87, 074003.
(169) Carbone, M. R.; Yoo, S.; Topsakal, M.; Lu, D. Classification of
Local Chemical Environments from X-ray Absorption Spectra Using
Supervised Machine Learning. Phys. Rev. Mater. 2019, 3, 033604.
(170) Guda, A. A.; Guda, S. A.; Lomachenko, K. A.; Soldatov, M. A.;
Pankin, I. A.; Soldatov, A. V.; Braglia, L.; Bugaev, A. L.; Martini, A.;
Signorile, M.; Groppo, E.; Piovano, A.; Borfecchia, E.; Lamberti, C.
Quantitative Structural Determination of Active Sites from In Situ and
Operando XANES Spectra: From Standard Ab Initio Simulations to
Chemometric and Machine Learning Approaches. Catal. Today 2019,
336, 3−21.
(171) Miyazato, I.; Takahashi, L.; Takahashi, K. Automatic
Oxidation Threshold Recognition of XAFS Data Using Supervised
Machine Learning. Mol. Syst. Des. Eng. 2019, 4, 1014−1018.
(172) Madsen, J.; Liu, P.; Kling, J.; Wagner, J. B.; Hansen, T. W.;
Winther, O.; Schiøtz, J. A Deep Learning Approach to Identify Local
Structures in Atomic-Resolution Transmission Electron Microscopy
Images. Adv. Theory Simul. 2018, 1, 1800037.
2295
Review
(173) Ziatdinov, M.; Dyck, O.; Maksov, A.; Li, X.; Sang, X.; Xiao, K.;
Unocic, R. R.; Vasudevan, R.; Jesse, S.; Kalinin, S. V. Deep Learning
of Atomically Resolved Scanning Transmission Electron Microscopy
Images: Chemical Identification and Tracking Local Transformations.
ACS Nano 2017, 11, 12742−12752.
(174) Vasudevan, R. K.; Laanait, N.; Ferragut, E. M.; Wang, K.;
Geohegan, D. B.; Xiao, K.; Ziatdinov, M.; Jesse, S.; Dyck, O.; Kalinin,
S. V. Mapping Mesoscopic Phase Evolution during E-Beam Induced
Transformations via Deep Learning of Atomically Resolved Images.
npj Comput. Mater. 2018, 4, 30.
(175) Belianinov, A.; He, Q.; Kravchenko, M.; Jesse, S.; Borisevich,
A.; Kalinin, S. V. Identification of Phases, Symmetries and Defects
through Local Crystallography. Nat. Commun. 2015, 6, 7801.
(176) Rossouw, D.; Burdet, P.; De La Peña, F.; Ducati, C.; Knappett,
B. R.; Wheatley, A. E. H.; Midgley, P. A. Multicomponent Signal
Unmixing from Nanoheterostructures: Overcoming the Traditional
Challenges of Nanoscale X-ray Analysis via Machine Learning. Nano
Lett. 2015, 15, 2716−2720.
(177) Shiga, M.; Tatsumi, K.; Muto, S.; Tsuda, K.; Yamamoto, Y.;
Mori, T.; Tanji, T. Sparse Modeling of EELS and EDX Spectral
Imaging Data by Nonnegative Matrix Factorization. Ultramicroscopy
2016, 170, 43−59.
(178) Hummelshøj, J. S.; Abild-Pedersen, F.; Studt, F.; Bligaard, T.;
Nørskov, J. K. CatApp: A Web Application for Surface Chemistry and
Heterogeneous Catalysis. Angew. Chem., Int. Ed. 2012, 51, 272−274.
(179) Winther, K. T.; Hoffmann, M. J.; Boes, J. R.; Mamun, O.;
Bajdich, M.; Bligaard, T. Catalysis-Hub.Org, an Open Electronic
Structure Database for Surface Reactions. Sci. Data 2019, 6, 75.
(180) Holeňa, M.; Baerns, M. Feedforward Neural Networks in
Catalysis: A Tool for the Approximation of the Dependency of Yield
on Catalyst Composition, and for Knowledge Extraction. Catal. Today
2003, 81, 485−494.
(181) Serra, J. M.; Corma, A.; Chica, A.; Argente, E.; Botti, V. Can
Artificial Neural Networks Help the Experimentation in Catalysis?
Catal. Today 2003, 81, 393−403.
(182) Huang, K.; Zhan, X. L.; Chen, F. Q.; Lü, D. W. Catalyst
Design for Methane Oxidative Coupling by Using Artificial Neural
Network and Hybrid Genetic Algorithm. Chem. Eng. Sci. 2003, 58,
81−87.
(183) Umegaki, T.; Watanabe, Y.; Nukui, N.; Omata, K.; Yamada,
M. Optimization of Catalyst for Methanol Synthesis by a
Combinatorial Approach Using a Parallel Activity Test and Genetic
Algorithm Assisted by a Neural Network. Energy Fuels 2003, 17, 850−
856.
(184) Omata, K.; Watanabe, Y.; Hashimoto, M.; Umegaki, T.;
Yamada, M. Simultaneous Optimization of Preparation Conditions
and Composition of the Methanol Synthesis Catalyst by an All-
Encompassing Calculation on an Artificial Neural Network. Ind. Eng.
Chem. Res. 2004, 43, 3282−3288.
(185) Corma, A.; Serra, J. M.; Serna, P.; Valero, S.; Argente, E.;
Botti, V. Optimisation of Olefin Epoxidation Catalysts with the
Application of High-Throughput and Genetic Algorithms Assisted by
Artificial Neural Networks (Softcomputing Techniques). J. Catal.
2005, 229, 513−524.
(186) Baumes, L. A.; Serra, J. M.; Serna, P.; Corma, A. Support
Vector Machines for Predictive Modeling in Heterogeneous Catalysis:
A Comprehensive Introduction and Overfitting Investigation Based
on Two Real Applications. J. Comb. Chem. 2006, 8, 583−596.
(187) Le, T. C.; Winkler, D. A. Discovery and Optimization of
Materials Using Evolutionary Approaches. Chem. Rev. 2016, 116,
6107−6132.
(188) Rothenberg, G. Data Mining in Catalysis: Separating
Knowledge from Garbage. Catal. Today 2008, 137, 2−10.
(189) Zavyalova, U.; Holena, M.; Schlögl, R.; Baerns, M. Statistical
Analysis of Past Catalytic Data on Oxidative Methane Coupling for
New Insights into the Composition of High-Performance Catalysts.
ChemCatChem 2011, 3, 1935−1947.
(190) Kondratenko, E. V.; Schlüter, M.; Baerns, M.; Linke, D.;
Holena, M. Developing Catalytic Materials for the Oxidative
DOI: 10.1021/acscatal.9b04186
ACS Catal. 2020, 10, 2260−2297
ACS Catalysis
Coupling of Methane through Statistical Analysis of Literature Data.
Catal. Sci. Technol. 2015, 5, 1668−1677.
(191) Takahashi, K.; Miyazato, I.; Nishimura, S.; Ohyama, J.
Unveiling Hidden Catalysts for the Oxidative Coupling of Methane
Based on Combining Machine Learning with Literature Data.
ChemCatChem 2018, 10, 3223−3228.
(192) Schmack, R.; Friedrich, A.; Kondratenko, E. V.; Polte, J.;
Werwatz, A.; Kraehnert, R. A Meta-Analysis of Catalytic Literature
Data Reveals Property-Performance Correlations for the OCM
Reaction. Nat. Commun. 2019, 10, 441.
(193) Ohyama, J.; Nishimura, S.; Takahashi, K. Data Driven
Determination of Reaction Conditions in Oxidative Coupling of
Methane via Machine Learning. ChemCatChem 2019, 11, 4307−4313.
(194) Baysal, M.; Günay, M. E.; Yıldırım, R. Decision Tree Analysis
of Past Publications on Catalytic Steam Reforming to Develop
Heuristics for High Performance: A Statistical Review. Int. J. Hydrogen
Energy 2017, 42, 243−254.
(195) Ş ener, A. N.; Günay, M. E.; Leba, A.; Yıldırım, R. Statistical
Review of Dry Reforming of Methane Literature Using Decision Tree
and Artificial Neural Network Analysis. Catal. Today 2018, 299, 289−
302.
(196) Günay, M. E.; Yildirim, R. Knowledge Extraction from
Catalysis of the Past: A Case of Selective CO Oxidation over Noble
Metal Catalysts between 2000 and 2012. ChemCatChem 2013, 5,
1395−1406.
(197) Günay, M. E.; Yildirim, R. Neural Network Analysis of
Selective CO Oxidation over Copper-Based Catalysts for Knowledge
Extraction from Published Data in the Literature. Ind. Eng. Chem. Res.
2011, 50, 12488−12500.
(198) Günay, M. E.; Yildirim, R. Developing Global Reaction Rate
Model for CO Oxidation over Au Catalysts from Past Data in
Literature Using Artificial Neural Networks. Appl. Catal., A 2013, 468,
395−402.
(199) Odabaşi, Ç .; Günay, M. E.; Yildirim, R. Knowledge Extraction
for Water Gas Shift Reaction over Noble Metal Catalysts from
Publications in the Literature between 2002 and 2012. Int. J. Hydrogen
Energy 2014, 39, 5733−5746.
(200) Omata, K. Screening of New Additives of Active-Carbon-
Supported Heteropoly Acid Catalyst for Friedel−Crafts Reaction by
Gaussian Process Regression. Ind. Eng. Chem. Res. 2011, 50, 10948−
10954.
(201) Ras, E. J.; Louwerse, M. J.; Rothenberg, G. New Tricks by
Very Old Dogs: Predicting the Catalytic Hydrogenation of HMF
Derivatives Using Slater-Type Orbitals. Catal. Sci. Technol. 2012, 2,
2456−2464.
(202) Alper Tapan, N.; Yıldırım, R.; Günay, M. E. Analysis of Past
Experimental Data in Literature to Determine Conditions for High
Performance in Biodiesel Production. Biofuels, Bioprod. Biorefin. 2016,
10, 422−434.
(203) Madaan, N.; Shiju, N. R.; Rothenberg, G. Predicting the
Performance of Oxidation Catalysts Using Descriptor Models. Catal.
Sci. Technol. 2016, 6, 125−133.
(204) Rodemerck, U.; Holeňa, M.; Wagner, E.; Smejkal, Q.;
Barkschat, A.; Baerns, M. Catalyst Development for CO2 Hydro-
genation to Fuels. ChemCatChem 2013, 5, 1948−1955.
(205) Günay, M. E.; Türker, L.; Tapan, N. A. Decision Tree Analysis
for Efficient CO2 Utilization in Electrochemical Systems. J. CO2 Util.
2018, 28, 83−95.
(206) Hong, W. T.; Welsch, R. E.; Shao-Horn, Y. Descriptors of
Oxygen-Evolution Activity for Oxides: A Statistical Evaluation. J. Phys.
Chem. C 2016, 120, 78−86.
(207) Palkovits, R.; Palkovits, S. Using Artificial Intelligence To
Forecast Water Oxidation Catalysts. ACS Catal. 2019, 9, 8383−8387.
(208) Masood, H.; Toe, C. Y.; Teoh, W. Y.; Sethu, V.; Amal, R.
Machine Learning for Accelerated Discovery of Solar Photocatalysts.
ACS Catal. 2019, 9, 11774−11787.
(209) Can, E.; Yildirim, R. Data Mining in Photocatalytic Water
Splitting over Perovskites Literature for Higher Hydrogen Production.
Appl. Catal., B 2019, 242, 267−283.
2296
Review
(210) Hansch, C.; Leo, A.; Taft, R. W. A Survey of Hammett
Substituent Constants and Resonance and Field Parameters. Chem.
Rev. 1991, 91, 165−195.
(211) Tolman, C. A. Steric Effects of Phosphorus Ligands in
Organometallic Chemistry and Homogeneous Catalysis. Chem. Rev.
1977, 77, 313−348.
(212) Fey, N.; Orpen, A. G.; Harvey, J. N. Building Ligand
Knowledge Bases for Organometallic Chemistry: Computational
Description of Phosphorus(III)-Donor Ligands and the Metal-
Phosphorus Bond. Coord. Chem. Rev. 2009, 253, 704−722.
(213) Fey, N. The Contribution of Computational Studies to
Organometallic Catalysis: Descriptors, Mechanisms and Models.
Dalton Trans. 2010, 39, 296−310.
(214) Jover, J.; Fey, N. The Computational Road to Better Catalysts.
Chem. - Asian J. 2014, 9, 1714−1723.
(215) Milo, A.; Neel, A. J.; Toste, F. D.; Sigman, M. S. A Data-
Intensive Approach to Mechanistic Elucidation Applied to Chiral
Anion Catalysis. Science 2015, 347, 737−743.
(216) Sigman, M. S.; Harper, K. C.; Bess, E. N.; Milo, A. The
Development of Multidimensional Analysis Tools for Asymmetric
Catalysis and Beyond. Acc. Chem. Res. 2016, 49, 1292−1301.
(217) Reid, J. P.; Sigman, M. S. Comparing Quantitative Prediction
Methods for the Discovery of Small-Molecule Chiral Catalysts. Nat.
Rev. Chem. 2018, 2, 290−305.
(218) Santiago, C. B.; Guo, J. Y.; Sigman, M. S. Predictive and
Mechanistic Multivariate Linear Regression Models for Reaction
Development. Chem. Sci. 2018, 9, 2398−2412.
(219) Bess, E. N.; Bischoff, A. J.; Sigman, M. S. Designer Substrate
Library for Quantitative, Predictive Modeling of Reaction Perform-
ance. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 14698−14703.
(220) Burello, E.; Farrusseng, D.; Rothenberg, G. Combinatorial
Explosion in Homogeneous Catalysis: Screening 60,000 Cross-
Coupling Reactions. Adv. Synth. Catal. 2004, 346, 1844−1853.
(221) Hageman, J. A.; Westerhuis, J. A.; Frü hauf, H. W.;
Rothenberg, G. Design and Assembly of Virtual Homogeneous
Catalyst Libraries - Towards In Silico Catalyst Optimisation. Adv.
Synth. Catal. 2006, 348, 361−369.
(222) Maldonado, A. G.; Rothenberg, G. Predictive Modeling in
Homogeneous Catalysis: A Tutorial. Chem. Soc. Rev. 2010, 39, 1891−
1902.
(223) Kreutz, J. E.; Shukhaev, A.; Du, W.; Druskin, S.; Daugulis, O.;
Ismagilov, R. F. Evolution of Catalysts Directed by Genetic
Algorithms in a Plug-Based Microfluidic Device Tested with
Oxidation of Methane by Oxygen. J. Am. Chem. Soc. 2010, 132,
3128−3132.
(224) Occhipinti, G.; Bjørsvik, H. R.; Jensen, V. R. Quantitative
Structure-Activity Relationships of Ruthenium Catalysts for Olefin
Metathesis. J. Am. Chem. Soc. 2006, 128, 6952−6964.
(225) Milo, A.; Neel, A. J.; Toste, F. D.; Sigman, M. S. A Data-
Intensive Approach to Mechanistic Elucidation Applied to Chiral
Anion Catalysis. Science 2015, 347, 737−743.
(226) Zahrt, A. F.; Henle, J. J.; Rose, B. T.; Wang, Y.; Darrow, W. T.;
Denmark, S. E. Prediction of Higher-Selectivity Catalysts by
Computer-Driven Workflow and Machine Learning. Science 2019,
363, eaau5631.
(227) Meyer, B.; Sawatlon, B.; Heinen, S.; Von Lilienfeld, O. A.;
Corminboeuf, C. Machine Learning Meets Volcano Plots: Computa-
tional Discovery of Cross-Coupling Catalysts. Chem. Sci. 2018, 9,
7069−7077.
(228) Yada, A.; Nagata, K.; Ando, Y.; Matsumura, T.; Ichinoseki, S.;
Sato, K. Machine Learning Approach for Prediction of Reaction Yield
with Simulated Catalyst Parameters. Chem. Lett. 2018, 47, 284−287.
(229) Wu, K.; Doyle, A. G. Parameterization of Phosphine Ligands
Demonstrates Enhancement of Nickel Catalysis via Remote Steric
Effects. Nat. Chem. 2017, 9, 779−784.
(230) Rosales, A. R.; Wahlers, J.; Limé, E.; Meadows, R. E.; Leslie,
K. W.; Savin, R.; Bell, F.; Hansen, E.; Helquist, P.; Munday, R. H.;
Wiest, O.; Norrby, P. O. Rapid Virtual Screening of Enantioselective
Catalysts Using CatVS. Nat. Catal. 2019, 2, 41−45.
DOI: 10.1021/acscatal.9b04186
ACS Catal. 2020, 10, 2260−2297
ACS Catalysis Review

(231) Landman, I. R.; Paulson, E. R.; Rheingold, A. L.; Grotjahn, D. (250) Takahashi, K.; Miyazato, I. Rapid Estimation of Activation
B.; Rothenberg, G. Designing Bifunctional Alkene Isomerization Energy in Heterogeneous Catalytic Reactions via Machine Learning. J.
Catalysts Using Predictive Modelling. Catal. Sci. Technol. 2017, 7, Comput. Chem. 2018, 39, 2405−2408.
4842−4851. (251) Garrido Torres, J. A.; Jennings, P. C.; Hansen, M. H.; Boes, J.
(232) Banerjee, S.; Sreenithya, A.; Sunoj, R. B. Machine Learning for R.; Bligaard, T. Low-Scaling Algorithm for Nudged Elastic Band
Predicting Product Distributions in Catalytic Regioselective Reac- Calculations Using a Surrogate Machine Learning Model. Phys. Rev.
tions. Phys. Chem. Chem. Phys. 2018, 20, 18311−18318. Lett. 2019, 122, 156001.
(233) Amar, Y.; Schweidtmann, A. M.; Deutsch, P.; Cao, L.; Lapkin, (252) Sameera, W. M. C.; Kumar Sharma, A.; Maeda, S.;
A. Machine Learning and Molecular Descriptors Enable Rational Morokuma, K. Artificial Force Induced Reaction Method for
Solvent Selection in Asymmetric Catalysis. Chem. Sci. 2019, 10, Systematic Determination of Complex Reaction Mechanisms. Chem.
6697−6706. Rec. 2016, 16, 2349−2363.
(234) Yamaguchi, S.; Sodeoka, M. Molecular Field Analysis Using (253) Sugiyama, K.; Sumiya, Y.; Takagi, M.; Saita, K.; Maeda, S.
Intermediates in Enantio-Determining Steps Can Extract Information Understanding CO Oxidation on the Pt(111) Surface Based on a
for Data-Driven Molecular Design in Asymmetric Catalysis. Bull. Reaction Route Network. Phys. Chem. Chem. Phys. 2019, 21, 14366−
Chem. Soc. Jpn. 2019, 92, 1701−1706. 14375.
(235) Sasmaz, E.; Mingle, K.; Lauterbach, J. High-Throughput
Screening Using Fourier-Transform Infrared Imaging. Engineering
2015, 1, 234−242.
(236) Katare, S.; Caruthers, J. M.; Delgass, W. N.;
Venkatasubramanian, V. An Intelligent System for Reaction Kinetic
Modeling and Catalyst Design. Ind. Eng. Chem. Res. 2004, 43, 3484−
3512.
(237) Yamada, Y.; Kobayashi, T. Utilization of Combinatorial
Method and High Throughput Experimentation for Development of
Heterogeneous Catalysts. J. Jpn. Pet. Inst. 2006, 49, 157−167.
(238) Diamond, G. M.; Hall, K. A.; Lapointe, A. M.; Leclerc, M. K.;
Longmire, J.; Shoemaker, J. A. W.; Sun, P. High-Throughput
Discovery and Optimization of Hafnium Heteroaryl-Amido Catalysts
for the Isospecific Polymerization of Propylene. ACS Catal. 2011, 1,
887−900.
(239) Kondratyuk, P.; Gumuslu, G.; Shukla, S.; Miller, J. B.;
Morreale, B. D.; Gellman, A. J. A Microreactor Array for Spatially
Resolved Measurement of Catalytic Activity for High-Throughput
Catalysis Science. J. Catal. 2013, 300, 55−62.
(240) Gumuslu, G.; Kondratyuk, P.; Boes, J. R.; Morreale, B.; Miller,
J. B.; Kitchin, J. R.; Gellman, A. J. Correlation of Electronic Structure
with Catalytic Activity: H2−D2 Exchange across CuxPd1−x Compo-
sition Space. ACS Catal. 2015, 5, 3137−3147.
(241) Kitchin, J. R.; Gellman, A. J. High-Throughput Methods
Using Composition and Structure Spread Libraries. AIChE J. 2016,
62, 3826−3835.
(242) Renom-Carrasco, M.; Lefort, L. Ligand Libraries for High
Throughput Screening of Homogeneous Catalysts. Chem. Soc. Rev.
2018, 47, 5038−5060.
(243) Isbrandt, E. S.; Sullivan, R. J.; Newman, S. G. High
Throughput Strategies for the Discovery and Optimization of
Catalytic Reactions. Angew. Chem., Int. Ed. 2019, 58, 7180−7191.
(244) Wellendorff, J.; Lundgaard, K. T.; Møgelhøj, A.; Petzold, V.;
Landis, D. D.; Nørskov, J. K.; Bligaard, T.; Jacobsen, K. W. Density
Functionals for Surface Science: Exchange-Correlation Model
Development with Bayesian Error Estimation. Phys. Rev. B: Condens.
Matter Mater. Phys. 2012, 85, 235149.
(245) Snyder, J. C.; Rupp, M.; Hansen, K.; Müller, K. R.; Burke, K.
Finding Density Functionals with Machine Learning. Phys. Rev. Lett.
2012, 108, 253002.
(246) Pozun, Z. D.; Hansen, K.; Sheppard, D.; Rupp, M.; Müller, K.
R.; Henkelman, G. Optimizing Transition States via Kernel-Based
Machine Learning. J. Chem. Phys. 2012, 136, 174101.
(247) Peterson, A. A. Acceleration of Saddle-Point Searches with
Machine Learning. J. Chem. Phys. 2016, 145, 074106.
(248) Ulissi, Z. W.; Medford, A. J.; Bligaard, T.; Nørskov, J. K. To
Address Surface Reaction Network Complexity Using Scaling
Relations Machine Learning and DFT Calculations. Nat. Commun.
2017, 8, 14621.
(249) Koistinen, O. P.; Dagbjartsdóttir, F. B.; Á sgeirsson, V.;
Vehtari, A.; Jónsson, H. Nudged Elastic Band Calculations
Accelerated with Gaussian Process Regression. J. Chem. Phys. 2017,
147, 152720.

2297 DOI: 10.1021/acscatal.9b04186

ACS Catal. 2020, 10, 2260−2297