Available online at www.sciencedirect.
com
ScienceDirect
Chemical product design – recent advances and
perspectives
Lei Zhang1, Haitao Mao1, Qilei Liu1 and Rafiqul Gani2,3
Chemical industry is continuously looking for opportunities to
manufacture the necessary commodity chemicals as well as to
convert them into higher value-added chemicals-based
products. Development of these chemicals-based products
involves not only their design and/or selection but also their
sustainable manufacturing through an appropriate chemical
process, its marketing and its disposal as waste. This perspective
paper considers mainly computer-aided methods and tools
suitable for chemicals-based product development. The
advantage of computer-aided design methods and tools is that it
is possible to quickly identify promising candidates that can be
further investigated and verified through focused experiment-
based techniques to obtain the final optimal design. The
disadvantage of using these models and/or data-based
approaches is that their application ranges are limited to the
available models, data and knowledge related to the currently
known products. Another complexity that needs to be considered
is the multiscale and multidisciplinary nature of chemicals-based
product design problems. Therefore, to find new and innovative
chemicals-based products, systematic computer-aided
methods and tools, capable of managing this complexity are
needed. In this paper, the frontiers of model and/or data-based
methods for systematic chemical product design and application
are presented. Various computer-aided design methods and
tools including experiment-based, knowledge-based, rule-based
and model-based approaches are briefly reviewed. Perspectives
including challenges and opportunities in computer-aided
chemicals-based product design are discussed.
Addresses
1
Institute of Chemical Process Systems Engineering, School of Chemical
Engineering, Dalian University of Technology, Dalian 116024, China
2
PSE for SPEED, Skyttemosen 6, DK-3450 Allerød, Denmark
3
State Key Laboratory of Industrial Control Technology, College of
Control Science and Engineering, Zhejiang University, Hangzhou
310027, China
Corresponding authors: Zhang, Lei (keleiz@dlut.edu.cn),
Gani, Rafiqul (rgani2018@gmail.com)
Current Opinion in Chemical Engineering 2019, 27:22–34
This review comes from a themed issue on Frontiers of chemical
engineering
Edited by Rafiqul Gani and Lei Zhang
For a complete overview see the Issue and the Editorial
Available online 22nd November 2019
https://doi.org/10.1016/j.coche.2019.10.005
2211-3398/ã 2019 The Author(s). Published by Elsevier Ltd. This is an
open access article under the CC BY-NC-ND license (http://creative-
commons.org/licenses/by-nc-nd/4.0/).
Current Opinion in Chemical Engineering 2020, 27:22–34
Introduction
Current global business environment encourages a short
time-to-market for any potential chemical product
(through this paper, ‘chemical product’ will mean
‘chemicals-based product’). Therefore, the focus has
been shifting from process design for business-to-busi-
ness (B2B) chemicals to product and process design for
business-to-consumer (B2C) products [1
]. In chemical
product design, we try to find a single chemical or a
chemicals-based mixture or blend that exhibits or
enhances certain desirable and/or specified functional
properties of the product. Nowadays, chemical product
design is being regarded as a new paradigm in chemical
engineering [2]. During last three decades, efforts have
been made to develop databases, design methods and
associated software tools for chemical products. However,
because of the multiscale and multidisciplinary nature of
many chemical product design problems, various other
disciplines such as computational chemistry, thermody-
namics, material science, chemical engineering, industrial
engineering, electronic engineering, data science and
artificial intelligence also need to be incorporated within
the design methods and associated software tools.
Traditionally, chemical products are designed and
developed through heuristic rule-based and/or trial-
and-error experiment-based approaches. Although these
kind of approaches often lead to safe and reliable prod-
uct designs, it is not practically feasible to evaluate all
alternatives [3
] or to obtain the optimal solution.
Recently, the use of model-based design methods has
been gaining increased attention as they have the poten-
tial to generate and/or screen feasible product candidates
in a much larger design space, and at the same time,
reduce the time and costs for their development. If
necessary data are available and the models giving reli-
able estimations for product properties and functions are
available, it is possible to develop and use model-based
chemical product design approaches with the advances
in computer-aided technologies.
A framework for chemical product design is shown in
Figure 1. For a given product design problem, the
product needs are first identified and then translated
to a set of corresponding target properties. Next, an
analysis of the available data, models, need for experi-
ments is made. According to the analysis, a mathematical
representation of the synthesis-design problem is estab-
lished, consisting of an objective function (related to cost
and/or product performance criteria) and constraints
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 Chemical product design – recent advances and perspectives Zhang et al. 23

Figure 1

Chemical Mathematical models

products • Objective functions (Min/Max properties/Process variables/Economic indicators)
s.t Algorithms
Identify 1) Model parameter constraints; 2) Economic models; 5) process models
product needs 3) Property models; 4) Product performance models;

Translate needs
Structure-property relationship Transmission and reaction process Solution approaches
to properties

Analyze available
data, models, etc.

Product •Database
design model •Experiments
•Heuristics
Time-scale

Physico-chemical property-related Process-related

Economic Modeling at •Theoretical models
mesoscale
analysis Group Mixing rules (Nano-objects)
•Data-driven models
contribution (Molecules/
methods Mixtures)
Process
Molecular Process unit
(Groups) simulation
PBM and CFD simulation
Dynamics Phase (Process)
Prototyping Quantum (Atoms) equilibrium
simulation (Process unit)
(Mass/energy
Mechanics (Thermo-
transfer)
dynamics)
(Electrons)

Product Multiscale chemistry/chemical engineering mechanism study

launch Length-scale

Current Opinion in Chemical Engineering

Framework for chemical product design (Figure adopted from Uhlemann et al. [4
] with permission from Wiley).

representing the translated needs to target properties, Many review articles focusing on chemical product design
the process model equations as well as product-process problems have been published. In the text below, only
structural conditions. Note that the constraints are repre- those published after 2000 are considered. Zhang et al.
sented by a set of models: property models, process [1
,3
] reviewed various aspects of integrated product-
models, economic models, environmental impact mod- process design. Recently, Uhlemann et al. [4
] reviewed
els, models for sustainability indices and many more. the past, present and future for product design and
Algorithms are needed to solve the mathematical prob- engineering. Gani [5] reviewed aspects of product and
lem, and from the solution, the optimal product candi- process design using Computer-Aided Molecular Design
dates are obtained, which could be further analyzed for (CAMD) techniques, while Grossmann [6] introduced
economic analysis, prototyping, and finally, launch to the chemical product design as one of the future challenges
market. To formulate a product design problem, rela- of chemical engineering. Ng et al. [7
] reviewed the
tionships between product ingredients/structures and development, challenges and future opportunities of
product properties need to be established first through chemical product design using CAMD tools. Gani and
a set of process-property models. These models should Ng [8
] reviewed chemical product design focusing on
preferably be predictive and could be developed through product conceptualization. Austin et al. [9
] reviewed the
a combination of techniques such as Quantum Mechan- tools, applications and solution techniques for CAMD.
ics (QM), Molecular Dynamics (MD), Group Contribu- Butler et al. [10
] summarized recent progress on molec-
tion (GC), and Quantitative Structural Property Rela- ular and materials design using machine learning meth-
tionship (QSPR) for property models; and Finite ods. Gani [11
] reviewed the group contribution-based
Element (FE), Computational Fluid Dynamics property estimation methods for product design. Ng and
(CFD), and steady state-dynamic lumped for process Gani [12] proposed directions for research and teaching
models, including product performance models. Also, for chemical product design.
machine learning based models coupled with available
data could help to establish the needed process-property This perspective paper focuses on systematic computer-
models if sufficient data-knowledge is not available. aided methods and associated software tools for versatile

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24 Frontiers of chemical engineering

chemical product design and discusses important issues,
challenges and some perspectives. The rest of the paper is
organized as follows. In Section ‘Classification of Chemi-
cal Products’, the classification of chemical products with
examples and commonly used design methods are given;
in Section ‘Model-based methods and associated software
tools for Chemical Product Design’ a collection of model-
based systematic computer-aided methods and associated
software tools used in chemical product design are sum-
marized; in Section ‘Perspectives’, the challenges and
perspectives for chemical product design are discussed.
Classification of chemical products
Zhang et al. [3
] classified chemical products as single
species products, multiple species products and devices.
Single species products are subdivided into small and large
molecules, whereas multiple species products are subdi-
vided into formulated and functional products. In this
perspective paper, a selected set of product types [13],
which could be single species and/or multiple species are
highlighted in Table 1 with examples and associated refer-
ences, the basis of their typical design methods and a list of
likely design challenges. The basis for inclusion of a prod-
uct type in Table 1 is their published application example
and the use of model-based and/or data-based design
methods in one or all steps of the design process. Obviously,
as the number of chemical product types is numerous not all
chemical product types are listed in Table 1.
Some of the challenges in design listed in Table 1 are
further discussed below. Here, only challenges A to E are
discussed in detail (as they are more developed), the rest
(F to I) are also important and are discussed in Section
‘Perspectives’ under ‘perspectives’ (as they need to be
further developed).
(A) Structure-property relationship (Absence of engineering
science and/or knowledge). While many organic chemi-
cals-based products can be routinely designed
through structure-property relationships, for some
properties and more complex chemical formulations
and materials, the theory is not well established and
so, data-driven methods such as machine learning are
finding increasing use to extract structure-property
relationships from collected data. Structure-property
relationships therefore need to play a very important
role in chemical product design, for example, in
design and/or selection of active pharmaceutical
ingredients, membranes, and catalysts. The chal-
lenge, however, is to convert the available data
and/or correlations into predictive models, for exam-
ple, in emulsified chemicals-based products and/or
other structured or functional products that require
properties, such as Krafft temperature, hydrophilic-
lipophilic balance and interfacial tension. Note that
while correlations exist for these properties, predic-
tive models needed to design the emulsifier or
detergent products are more difficult. Kontogeorgis
et al. [29] have highlighted the design of emulsified
products through a combination of predictive mod-
els, correlations and data-search, while Fung et al.
[30] highlighted the design of a detergent product
through correlations, data and experiments. The
structure of the micro-emulsion, for example, in

Table 1

Product types with examples of application, basis of design methods and challenges in design

Product type Examples Basis of typical design methods Challenges in design a

Coatings and sensors Nanoparticle-based materials [14] Heuristics, experiments A, B, C, D, G
Process fluids Solvents [15], refrigerants [16] CAMD, database, heuristics, experiments A, B, C, D, F, G, I
Fertilizers and pesticides Pesticides [17] Heuristics, experiments A, B, C, D, E, F, G, H, I
Food Food flavor and sensory [18] Regression, Artificial Neural Network (ANN), A, B, C, D, E, F, G, H, I
experiments
Healthcare Drug discovery [19] Machine learning, database, heuristics, A, B, C, D, E, F, G, H, I
experiments
Skin-protection Insect repellent lotion [20] Heuristics, database, CAMD, experiments A, B, C, D, E, F, G, H, I
Dyes and pigments Polymethine dyes [21] Expert knowledge, experiments, heuristics, A, B, C, D, E, F, G, H, I
quantum mechanics
Fragrances Perfumes [22], shampoo additives [23] Expert knowledge, database, experiments, A, B, C, D, E, F, G, H, I
machine learning
Special separations Polymers for CO2 capture and Expert knowledge, experiments, molecular A, B, C, D, E, F, G, H, I
separations [24] dynamics
Energy provider Surrogate fuels and blends [25] Heuristics, database, experiments, CAMD A, B, C, E, F, G, I
Reaction promotion Heterogeneous catalysts [26] Expert knowledge, experiments, Ab initio A, B, C, D, E, F, G, H, I
calculation, machine learning
Functional device Rechargeable batteries [27], Experiments, heuristics, expert knowledge, QM, A, B, C, D, F, G, H, I
micropower-generation devices [28] MD, meso-scale modeling, CFD
a
A. Structure-property relationship (absence of engineering science and/or knowledge); B. Multiscale complexity; C. Safety, environmental impact
and sustainability; D. Processing routes; E. Translation of needs to properties; F. Time to market; G. Feedstock availability; H. Scale-up issues; I.
Coupling product design and process engineering.

Current Opinion in Chemical Engineering 2020, 27:22–34 www.sciencedirect.com

 Chemical product design – recent advances and perspectives Zhang et al. 25
design of fat-free margarine, needs to be established
through experiments. Similarly, for polymer-based
products not all target properties, namely, elasticity,
sheer stress, and so on, can be estimated through
predictive models. Also, the property dependence
related to arrangement of the polymer repeat units
and/or the selection of co-polymers in chemical
product design need more data so that model-based
techniques may be used. A better understanding of
the principles governing these product properties
and functions are needed to develop the necessary
models and thereby, advance the design of these
types of products. Also, to increase the application
ranges of currently available organic chemicals-based
products, computational chemistry-based methods
including QM, MD and even FE/CFD may be used
if sufficient structural information and/or data are
available to fill-in the gaps in properties that cannot
be currently reliably measured.
(B) Multiscale complexity. Multiscale approaches provide
opportunities to consider necessary system descrip-
tion and associated details for simultaneous process-
product design. For example, CFD-based model of
the crystallizer operation could be used together with
the end-user (macro-scale) property models for
design and/or selection of solvents (and/or anti-sol-
vents). Another example is the design of functional
materials, such as catalysts [26] or membranes [31],
where quantum mechanics could be employed to
design the product microstructure while a macro-
scale model is used for the process simulation and/or
design. To establish a multiscale design model,
modeling methods and tools from atom and molecu-
lar scales to equipment and process, and even enter-
prise-wide scales need to be considered together
with connections between different scales [32]. To
manage the complexity of multiscale models, model
reduction and solution strategies, together with the
derivation and use of surrogate models constitute a
challenge worth considering. As in the case of prop-
erty modelling, the application range depends on the
available process models. Models for processes such
as etching, coating, soap processing, vapor deposi-
tion, for example, are still not available.
(C) Safety, environmental impact and
sustainability. Mishandling of hazardous materials is
one of the main factors that result in industrial
catastrophe [33]. Although these are important
safety-related design issues, the challenge of system-
atic design of chemical products considering safety,
environmental impact as well as sustainability in the
early stages of the design process still needs to be
resolved. Here, the safety, environment and sustain-
ability related product (performance) property mod-
els are needed. For example, LC50 and GWP (global
warming potential) are safety and environment
related properties; VOC (volatile organic chemicals)
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is operational safety-hazards related issue, for exam-
ple, as benzene is likely to vaporize and because of
its carcinogenic properties, it is considered an unsafe
and hazardous material, which needs to be substi-
tuted with a benign chemical having similar func-
tions as benzene. Similarly, chemicals with low flash
point or auto-ignition temperatures may cause explo-
sion during operation of the process; therefore, they
also need to be replaced. A major challenge here is
the selection of appropriate EHS (environment,
hazards and safety) indexes and the definition of
their limiting values. In this respect, a general
method for chemical substitution [34] is a step in
the right direction.
(D) Synthesis routes. Two aspects of synthesis route
related to chemical product design are considered:
1) Reaction synthesis to identify the reaction path
needed to convert specified raw materials (reactants)
into the desired chemicals (products). For chemical
products, especially large molecular products, an
additional incentive (or challenge) is to determine
an easier synthesis route that can make the produc-
tion of a product candidate more sustainable and
economically feasible [3
]. Systematic guidelines for
determining the optimal synthesis route for the
conversion of a candidate product from specific
raw materials are needed, and the recent uses of
QM and machine learning based methods for syn-
thesis routes identification-selection are highly
encouraging [35]. 2) Processing routes for the pro-
duction of a chemical product. Single species rela-
tively small chemical products are also usually clas-
sified as commodity chemicals whose processing
route selection design are well established, and,
which are produced in large amounts for economic
feasibility. Examples of these types of products are
solvents and refrigerants. Blended products such as
fuel blends also require relatively simple processing
routes. However, processing routes for functional
products such as soaps or detergents are still based
on trial-and-error approach as appropriate property-
process models are still not available [2]. The pro-
cessing routes needed for the manufacture of phar-
maceutical products represent another challenge as
they need to be developed rapidly as well as they
need to be first time right [36]. Other unconventional
processing techniques namely Physical Vapor Depo-
sition (PVD)/Chemical Vapor Deposition (CVD),
etching, printing, and so on, usually need to be
considered for many functional (devices) products.
Currently, these are determined through experi-
ments with selected product candidates. That is,
the product selection-design could be based on
different design approaches, including model-based
techniques, but the product validation is through
experiment-based techniques. Another challenge is
to find new, innovative and more sustainable
Current Opinion in Chemical Engineering 2020, 27:22–34
Current Opinion in Chemical Engineering 2020, 27:22–34

26 Frontiers of chemical engineering

Table 2

List of selected commonly used methods and their associated computer-aided tools employed in chemical product design

Methods Basis Computer-aided tools Pros and cons

Experiments Trial and error [38]
Design of experiments [39]
Databases
Database search [40]
Heuristics
Heuristic rule-based design [41,42]
Model-based
(direct)
All equations representing the
mathematical problem (see Table 3)
are solved directly
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– Pros: Theory and knowledge are not needed;
Minitab (www.minitab.com) leads to safe and reliable products;
Cons: Limited test opportunities; costly; time-
consuming, no guarantee of solution optimality
NIST Chemistry webbook (www.webbook.nist.gov/chemistry/) Pros: Properties are reliable; fast generation of
PubChem (www.pubchem.ncbi.nlm.nih.gov) feasible candidates list;
ZINC (www.zinc.docking.org) Cons: Not all molecules are listed; limited
DRUGBANK (www.drugbank.ca) availability of property data; potential solutions
ProCAPD (www.pseforspeed.com/procapd) may be missed.
KIFS (Knowledge-based formulation system) [43] Pros: Lead to safe and reliable products; quick
ProCAPD (www.pseforspeed.com/procapd) and relatively inexpensive solution; easy to
apply when rules are available;
Cons: Better products may be missed;
experience, insight and knowledge are needed;
rules are sometimes contradictory; valid within
a narrow context.
ICAS – ProCAMD (www.pseforspeed.com/icas/
procamd)
ICAS – ProPred (www.pseforspeed.com/icas/
Group propred)
contribution [44] OptCAMD [44]
AMODEO (www.archimedes.cheme.cmu/edu/?
q=AMODEO)
DDBSP (www.ddbst.com/unifac-calculation)
COSMOtherm (www.cosmologic.de/products/
Thermo- cosmotherm) Pros: Global optimal solutions; no need to have
dynamics [45] SCM – COSMO-RS (www.scm.com/product/ in-depth knowledge once the model is ready;
cosmo-rs) can be applied to various kinds of problems;
Aspen Plus (www.aspentech.com/products/ Cons: Size and complexity of the model; a lot of
engineering/aspen-plus) physicochemical phenomena occurring are not
PRO/II (www.sw.aveva.com/ completely understood; lack of relevant
Process engineer-procure-construct/ property models for some products; the error of
simulation [46,47] process-engineering-and-simulation/ the property model.
pro-ii-process-engineering)
gPROMS (www.psenterprise.com/products/
gproms)
SPSS (www.ibm.com/analytics/
spss-statistics-software)
Matlab (www.mathworks.com/products/matlab.
Data-driven [19]

html)
Python: TensorFlow, Theano, Caffe, Scikit-learn,
Keras
 Chemical product design – recent advances and perspectives Zhang et al. 27

processing routes for any established process, where

occurring are not completely understood; lack

subproblems can be difficult; solution strategy

of relevant property models for some products;
multiscale techniques for process intensification [37]

Cons: A lot of physicochemical phenomena

Pros: Near optimal solutions; wide range of

Pros: Near optimal solutions; wide range of

needs to find the calculation order for the

promise significant improvements.

an extra-loop for the solution strategy.

Cons: Integration of tools for different

(E) Translation of needs to properties - The design of
chemical products depends very much on the ability
to represent the product characteristics by a set of
measurable and/or predictable properties. Much
problems can be solved;

problems can be solved;

work is needed a priori to obtain the data needed
to translate product needs to target properties. For
example, it is necessary to gather information from
Pros and cons

subproblems.
consumers in terms of basic needs (the main func-
tions of the products) and additional needs (which, if
they are fulfilled, would improve the product qual-
ity) as well as know-how to translate the consumer
needs into target properties. Usually, an expert
would be able to provide this knowledge if the
necessary data are available. Another option is to
GAMESS (www.msg.chem.iastate.edu/gamess)
Material Studio (www.3dsbiovia.com/products/

Material Studio (www.3dsbiovia.com/products/

Ansys Fluent (www.ansys.com/products/fluids/

collect necessary data from published expert-

collaborative-science/biovia-materials-studio)

collaborative-science/biovia-materials-studio)

insights, open-source databases, patents, published

articles, and so on, to prepare the translation of needs
ORCA (www.orcaforum.kofo.mpg.de)

LAMMPS (www.lammps.sandia.gov)

to properties tables in the same way that Conte et al.

OpenFOAM (www.openfoam.com)

[20] did for liquid formulated products and Kalakul

Gaussian (www.gaussian.com)

Template-based design of mixtures and blends [25,51]

COMSOL (www.comsol.com)
Gromacs (www.gromacs.org)

et al. [25] did for different blended fuels. It should be

noted that this is a time-consuming work but avail-
ability of data in table avoids this extra work. For a
VASP (www.vasp.at)

VASP (www.vasp.at)

new type of chemical product not covered by the

ProCAPD (www.pseforspeed.com/procapd)

established tables (for example, in ProCAPD [25]) in

ansys-fluent)

a product design software tool, extra work would be

needed to establish the translation.

Model-based methods and associated

software tools for chemical product design
Computer-aided tools

Chemical product design problems are multidisciplinary

and multiscale in nature and therefore, they need differ-
ent methods and software tools from different disciplines
with associated different scales. These commonly used
CFD [50]
QM [48]

MD [49]

design methods and tools, as well as their pros and cons,

are listed in Table 2.

Experiments
solved in the outer-loop or off-line to

hierarchical subproblems, which are

(surrogate) models and solved in the

Traditionally, chemical products are developed through

solved with their associated tools
inner-loop (as direct method) and

General mathematical problem is

experiment-based trial-and-error methods by specialists.

generate the surrogate models
rigorous (complex) models are
The most complex subset of

For many chemical products with complex molecular

converted into simple local
equations representing the
mathematical problem are

decomposed into a set of

structure or ingredients, experiments are necessary

because when data and property models are missing, it
is impossible to use model-base approaches for the
design. The missing data or models have to be obtained
through experiments. Although experimental approaches
often lead to safe and reliable products, it is not practically
Basis

feasible to evaluate all alternatives, which is costly and

Table 2 (Continued )

time-consuming, even when DoE (Design of Experi-

ments) is adopted to accelerate the experiments. There-
fore, better products may be missed using experimental
Model-based

Model-based

approaches. Tam et al. [52] used experiments to design

(indirect)
Methods

(hybrid)

conductive inks, in which they generated the specific

surface energy model of Polyethylene terephthalate
(PET) substrate using experiments for the selection of

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28 Frontiers of chemical engineering
dispersing medium (for example tetradecane, ether, tol-
uene and cyclohexane).
Databases
When enough experimental results are available, a data-
base of properties could be established. Database search
is usually applied to the design of some simple molecular
products and ingredients selection of some formulated
products. Although databases are useful tools for pre-
selection of product candidates, they do not provide the
final design, even though they provide a fast and rela-
tively cheap option for chemical product design. A
complexity is the management of databases as different
types of chemicals and/or materials require separate
databases with their separate ontologies for knowledge
representation. For examples, separate databases are
needed for solvents, aroma compounds, active ingredi-
ents for different types of functional products, refriger-
ants, membranes, adsorbents, and many more. Since
different product types have different sets of property
requirements, their ontologies for knowledge represen-
tation are also different. For example, solvents are char-
acterized with different sets of properties than mem-
branes. Gu et al. [53] collected 197 201 natural product
structures and reported their biological activities for the
virtual screening step in drug discovery. In accordance
with the established drug database, they successfully
selected the possible natural product to treat a typical
disease using data analysis tools such as principal com-
ponent analysis. However, with their database, it is still
impossible to screen drugs with acceptable properties
including IC50, solubility, and so on, because these
properties are missing in the database and they are also
important in drug design. Similarly, Dionisio et al. [40]
established a database for consumer products, in which
more than 75 000 chemicals and more than 15 000 con-
sumer products are included. The data’s primary
intended use is for exposure, risk and safety assessments.
Although many databases are available online, only some
of the most common molecules and their physical param-
eters are, however, available, and the product design
space is limited to the size of the database.
Heuristics
Heuristic rules help to make design decisions, make
appropriate selections, which avoids the use of mathe-
matical programming-based design approaches. These
rules are commonly derived from a combination of expe-
rience, insight and available knowledge. The major diffi-
culty is that often the rules are contradictory and difficult
to apply, and only valid within a narrow product context.
Nevertheless, the heuristic rules are often simple, and
potentially promising solutions can be obtained very
rapidly and the potential search space significantly
reduced for similar problems. Wibowo and Ng [54] used
heuristics-rule-based methods for the design of cream and
paste products.
Current Opinion in Chemical Engineering 2020, 27:22–34
Model-based design approaches
In model-based design approaches, the product design
problems are formulated mathematically. Considering
the models and variables involved, the design problems
could be formulated as LP (linear programming), NLP
(non-linear programming), and MILP/MINLP (mixed-
integer linear/non-linear programming). A generic prob-
lem formulation [3
] is listed in Table 3. For process
simulation (Eq. (3)), or property prediction (Eq. (4)) with
only linear equations involved, there are no integer vari-
ables in the mathematical problem. Therefore, the design
problem is simplified to an LP problem, for example,
prediction of Hansen (dispersive) solubility parameter for
a given molecule using a GC method [55]. If nonlinear
terms are involved in Eqs. (3) or (4), the problem becomes
an NLP problem, for example, prediction of normal
melting point for a given molecule [55]. For molecular
design problems with only linear property models (Eqs.
(1), (4) and (6)), the design problem becomes an MILP
problem, for example, a surfactant design problem using
CAMD [56]. If the product design problem contains
nonlinear terms, the model is a MINLP problem, for
example, a solvent molecule design for liquid-liquid
extraction [44].
Quantum mechanics (QM). QM methods are used to estab-
lish the missing product structure-property relationships
by employing ab initio calculations. In the generic prob-
lem formulation (Table 3), when the property model (Eq.
(4)) is missing, it is possible to use QM methods to obtain
the property values. For example, computer-aided cata-
lyst design using Density Functional Theory (DFT) [57].
Another example is the reaction solvent design problem,
in which the reaction rate prediction model in different
solvent is needed, which can be obtained from QM
calculations. Austin et al. [48] used QM to directly predict
the reaction rate in different solvents for reaction solvent
design, Franco et al. [27] employed DFT calculations for
the design of rechargeable batteries, Carter [58
]
reviewed material design using model-based approaches,
including quantum mechanics. Currently, QM methods
are applied in product design mainly for property predic-
tion. However, the computation speed and the accuracy
restrict the application of QM to CAMD. One of the
future directions of QM for CAMD could be the integra-
tion of machine learning methods as a semi-empirical QM
method to accelerate the time-consuming QM calculation
for big molecules. Challenges for such machine learning
models include finding better descriptors for chemical
products and developing novel machine learning models
tailor-made for chemical product design.
Molecular dynamics (MD). Like QM, MD also provides
property prediction results through its molecular scale
simulation results, which can be used directly in product
design, or to establish QSPR models. Similarly, in the
generic problem formulation (Table 3), when the
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 Chemical product design – recent advances and perspectives Zhang et al. 29

Table 3

Generic problem formulation of chemical product design model

No. Equation Explanation Example Solution strategies

n o
1 min=max F obj ¼ F CTY þ f ðxÞ
2 b1 ðxÞ ¼ 0
3 b2 ðx; Y Þ ¼ 0
4 b3 ðx; Y Þ  u ¼ 0
5 l1  g1 ðx; Y Þ  u1
6 l2  g2 ðx; Y Þ  u2
7 l3  p1 ðx; Y Þ  u3
Objective function. Minimizing or
maximizing a certain required
function. CTY represents the linear
part, f ðxÞ represents linear/nonlinear
part. x  0 represents a vector of
continuous variables for product
and/or process design variables.
Equality constraints related to
specifications for process design.
Equality
constraints related to the process
model equations. Y ¼ 0 or 1
represents binary decision
variables.
Equality constraints related to the
product model equations. u
represents product properties.
Inequality constraints related to
process design specifications.
Inequality constraints related to
product design constraints.
Design constraints related to
process intensification.
Maximizing product
performance; minimizing
cost; and so on.
Operating pressure/
temperature; utility usage;
and so on.
Mass and energy balance
equations, and so on.
Molecular/mixture property
models; and so on.
Sustainability indicators;
process environmental
impacts; and so on.
Target property constraints;
and so on.
Intensified equipment design
variables; unit operation
reduction; and so on.
Direct: all equations are
solved simultaneously;
Indirect: Eqs. (3) or (4) are
solved with local (surrogate)
models in the inner loop and
rigorous model off-line;
Hybrid: different tools
representing different
subsets are solved
sequentially, including
candidate generation,
property estimation (different
subsets of linear and
nonlinear), process
simulation, and product
performance analysis.

property model (Eq. (4)) is missing, it is possible to use
MD calculations to obtain the property values. The
advantage of MD and QM methods is that properties
as a function of the molecular structure can be predicted
as the building blocks allow one to represent different
structural differences. MD methods have already been
applied to systems involving drug delivery, gas adsorp-
tion, polymer design evaluation, and so on. Al-Qattan et al.
[49] designed carbon-nanotube-based targeted drug
delivery using MD. Kupgan et al. [24] used MD to design
 z et al. [59]
polymers for CO2 capture and separations. Sled
reviewed drug design using MD. However, as in the case
of QM methods, the computation speed and accuracy still
restrict its application to CAMD. Although several works
have already been proposed to integrate MD and CAMD
methods [60], these problems are not solved yet. Surro-
gate modeling methods derived from MD simulation can
be a future direction to accelerate the integrated product
design model without losing its accuracy.
Group contribution (GC). Group contribution methods are
some of the most commonly used property prediction
methods for CAMD (see Eq. (4) in Table 3). Although,
GC methods have been mainly applied to small mole-
cules [55] and mixtures [61], recent developments have
extended applications to amino acids [34], acid dissocia-
tion [62] and activity coefficients of ionic liquids [63].
Even though high computation speed and acceptable
accuracy have been achieved by GC methods, there
are limitations, such as, missing group interaction param-
eters, questionable accuracy for large multifunctional
molecules, and inability to distinguish isomers [11
].
Future directions for the GC methods include developing
GC+ methods for predicting missing group parameters
through lower scale property models; expanding GC
methods to complex chemical systems and developing
GC methods for equations of state.
Thermodynamic models. Thermodynamic models are com-
monly used to predict phase equilibrium, specifically
activity coefficients and fugacity coefficients for phase
equilibrium-based separation, to evaluate product stabil-
ity, and/or to predict functional properties (as a function of
temperature, pressure, and/or composition). An important
issue for use of thermodynamic models in chemical
product design is their representation by a large number
of nonlinear equations, which are difficult to solve when
integrated into the product design model (see Eq. (3) in
Table 3). Chao et al. [46] applied UNIFAC-IL model for
extraction ionic liquid design. Scheffczyk et al. [64] devel-
oped a COSMO-CAMD framework for liquid-liquid
extraction solvent design. Schilling et al. [65] developed
a 1-stage CoMT-CAMD model for working fluid design
of ORC process using PC-SAFT.
Population-based model (PBM) and Computational fluid
dynamics (CFD). PBM is based on partial differential
equations that are employed to simulate dynamics of

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30 Frontiers of chemical engineering
particulate systems, such as crystallization, deposition,
granulation, drying, polymerization, fermentation, and
so on. PBM describes the time evolutions and distribu-
tions of the particulate processes by predicting particle
properties, such as particle size distribution, growth and
breakage. Therefore, PBM is a useful tool for combined
product-process design. For example, crystallization
product engineering via distribution shaping control
[66], and polymerization modeling and optimization
[67]. CFD is a numerical tool to analyze and solve
problems that involve fluid flows to study, for example,
the effect of velocity, pressure, temperature and density
of a moving fluid. As in specific chemical products, fluids
are often involved in the product synthesis step, and/or
product application process, CFD tools could be used to
evaluate the fluid flow-related functions. That is, CFD is
used more in process design issues related to product
design. For example, a crystallizer design problem [68], a
fluidized bed polymerization reactor design problem [69]
can benefit from the use of CFD tools. Two of the
challenges for the application of PBM-based and CFD-
based methods in product design problems are the size
and complexity of the models, including large number of
nonlinear/nonconvex equations, which may cause diffi-
culties in modeling and solution of the model equations.
Another challenge is to understand the principal phe-
nomena and mechanisms involved in the process (coagu-
lation, aggregate and breakage, etc.) as well as their
dependence on parameters namely flow regime, particle
size, solids concentration, mixing effect, and so on. A good
understanding is fundamental towards making an appro-
priate selection of the mathematical equations and
obtaining a successful model that can be solved in rea-
sonable time to give reliable and useful results [70].
Process simulation. Process simulation tools help to evalu-
ate the processing route (process flowsheet) and its oper-
ating conditions needed to manufacture the designed
chemical product as well as to evaluate the performance
of the product (see Table 2). For example, to evaluate the
performance of a designed solvent (single species prod-
uct), a solvent-based extraction process needs to be
simulated [64], while the manufacturing of the solvent
in this case is evaluated through standard process simula-
tion tools. In the case of a hand lotion design, the selection
of pre-emulsification and homogenization equipment and
their operating conditions [71], however, need special
models that are not available in standard process simula-
tion tools. Similarly, in design of a crystallizer operation to
match a specified particle size distribution or solvent-
based biphasic reactor operation, special process models
are needed for evaluation of the processing route. That is,
the use of commercial process simulators is limited by the
process models available in the simulator library and
therefore, verification of the product performance, includ-
ing drug delivery, protection through coatings, fuel per-
formance, and so on, still needs to be done through
Current Opinion in Chemical Engineering 2020, 27:22–34
carefully designed experiments. The main reason for this
is a lack of data and theory associated with the develop-
ment of process models for evaluation of the product
(target) functions and their corresponding processing
routes.
Perspectives
Chemical products have been playing an important role in
sustaining modern society. However, although its meth-
ods have been studied for several decades, it is still a
research topic not fully developed and most products are
still developed through experiment-based trial-and-error
approaches. The systematic model and/or data-based
methods and associated software tools should be able
to make a major contribution to chemical product design,
and thereby, significantly reduce the design and devel-
opment time and cost. Some perspectives for chemical
product design are given below:
Development of property prediction models. The library of
reliable models and property data need to be enlarged.
These models can be developed from three directions:
theoretical-based, data-driven and their combination.
However, for some of the product types and their prop-
erties, the theoretical-based models are too complex and
difficult to be implemented for a computer-aided design
tool. Therefore, it is not currently possible to use them in
chemical product design problems. Instead, with the
availability of method and tools from data science, devel-
opment of data-driven models could be considered.
Multiscale modeling of chemical product design
problems. Multiscale modeling methods and tools are
needed for certain product design problems. For exam-
ple, for designing a crystallizer, or designing a solvent for
crystallization, multiscale modeling can be used for estab-
lishing a better design model with additional details,
where quantum mechanics models (electrons level) are
used for structural optimization and obtaining missing
force field parameters for MD simulation; with the opti-
mized molecular structure, MD models (atoms level) are
used to predict the crystal growth rate; then, thermody-
namic models are used to predict the solid-liquid equi-
librium; on the basis of the predicted crystal growth rate,
population balance model and CFD simulation are used
to simulate the flow distribution as well as crystal size
distribution; finally, a crystallizer is designed using pro-
cess unit simulation. However, the goals of product
design in future are to be able to solve problems in fast
and efficient way, to accelerate the product design and
development process, and to release early to the market.
Therefore, effective solution algorithms need to be
developed to solve the large-scale nonlinear and noncon-
vex optimization problems. Here, model reduction tech-
niques could also be considered. Combination of different
solution methods is also a possible direction to accelerate
the solution speed. For example, using machine learning
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 Chemical product design – recent advances and perspectives Zhang et al. 31
methods to replace the time-consuming QM calculation
[72], and using group contribution methods to fast obtain
the s-profiles of the COSMO-RS model [73].
Processing route synthesis. It is still difficult to consider
simultaneously the manufacturing process (processing
route and techniques) of the product together with
product design. This is because of a number of reasons,
such as problem size and complexity, the lack of appro-
priate models, and/or data [12]. In some cases, for
example, refrigerant cycle [16] and solvent-based
extraction [64], where the production of the chemical
product is neglected (or the products are assumed to be
available), but the design or selection of the product and
its application process have been successfully consid-
ered. For products where the application of the product
(to verify its function) is difficult to model, for example,
drug delivery, systems with coating [74], emulsion for-
mation with breakage and coalescence [71], it is still
difficult to design such products with model-based
approaches. However, recent progress in process model-
ing indicates good advances [75]. For formulated pro-
ducts or blends where the process to make them are
usually designed through experiments (for example,
soaps, detergents, etc.), the main issue is to understand
how the changes in microstructure (such as droplet
deformation, breakup, or coalescence, changes in crystal
size or distribution, and structure realignment) effect
the product properties and processing conditions [2] so
that appropriate model-based solution methods could be
developed.
Solving practical problems of significance. Although com-
puter-aided product design methods and tools have been
developed for decades, there are only few works
reported that solved practical industrial problems.
Therefore, efforts are needed to promote the use of
various product design tools based on different design
methods for industrial problem solution. For example,
Fung and Ng [76] proposed rules to select chemicals for
granular products such as tablets and capsules in the
form of a database search and then test them through a
combination of models and experiments. An indoor air
purifier is designed using heuristic rules, models and
experiments [13]. It should also be pointed out that
through the integration of latest model-based product
design techniques, such as ProCAPD [25] and Opt-
CAMD [44], models, heuristic-rules, as well as experi-
mental approaches, the application range of chemical
product design can be extended. At the same time, more
reliable, fast and sustainable product design tools that
does not need long-term maintenance, need to be devel-
oped. A chemical product simulator like a process simu-
lator could also help so that teaching, training as well as
design-analysis of at least some chemical products can be
routinely done by the combined effort from academia
and industry.
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Conclusions
In this perspective paper, computer-aided methods and
tools suitable for chemical product design in a multidis-
ciplinary and multiscale point of view have been dis-
cussed, and the challenges and perspectives for chemical
product design have been presented. In the current state,
these methods and tools mainly focus on certain types of
products, such as small molecules and liquid formulations
and blends. However, the research scope is continuously
expanding to wider application ranges, such as larger and
more complex molecules, polymers, membranes, drugs,
catalysts, and many more. Integration of models and data
from different disciplines has allowed to reduce the gap in
the understanding of relationships between product
structure and their performances. Although greater suc-
cess has been achieved for chemical product design, there
are still many challenges and opportunities that are yet to
be resolved. Such task are as follows: a) Identification of
the product needs, their translation into property targets,
for all types of products; b) Management of the complex-
ity associated with the handling of multiple scales in the
chemical products that need them; c) Increasing the
ability to find best processing route for a given chemical
product; and d) Improving the possibility to find novel,
better and more innovative chemical products faster and
more reliably.
To address the above issues, current and future efforts are
needed to integrate methods and tools from different
disciplines, adopt modeling from a multiscale point of
view, and encourage collaboration between academia and
industries. The following are some insights needed to
achieve the above goals.

Better understanding of the principles governing prod-
uct properties and functions for various types of chem-
ical products. The multidisciplinary nature of the
design problem and the interaction between scales
in generating solutions must be understood.

Integrating model-based and data-driven property pre-
diction techniques to establish quantitatively accurate
product structure-property relationships.

Developing multiscale approaches, which provide
opportunities to generate better solutions when data
and models are missing in the literature, and experi-
ments cannot be performed for safety or other reasons.

Developing hybrid systems involving data, heuris-
tics, model-based methods and experiments into a
generic framework through problem-specific design
workflows.
Although designing better and more versatile products
will continue to be a challenge, and the product portfolio
that can be handled by currently available computer-
aided tools need to be expanded. With continued
developments in multidisciplinary theories, computing
Current Opinion in Chemical Engineering 2020, 27:22–34
32 Frontiers of chemical engineering
technologies, mathematical models and algorithms, the
prototype chemical product simulator (ProCAPD), which
is comparable to the existing process simulators need to
be further developed, so that it is possible to design
rapidly and efficiently better products safer, have higher
quality, and are more sustainable and environment-
friendly, and verified through focused experiments.
Conflict of interest statement
Nothing declared.
Acknowledgements
Lei Zhang, Haitao Mao and Qilei Liu are grateful for the financial support
of National Nature Science Foundation of China (21808025).
References and recommended reading
Papers of particular interest, published within the period of review,
have been highlighted as

of special interest
1. Zhang L, Fung KY, Wibowo C, Gani R: Advances in chemical

product design. Int Rev Chem Eng 2018, 34:319-340.
This article provides an overview of current state and challenges of all
related aspects for chemical product design.
2. Hill M: Product and process design for structured products.
AIChE J 2004, 50:1656-1661.
3. Zhang L, Babi DK, Gani R: New vistas in chemical product and

process design. Annu Rev Chem Biomol 2016, 7:557-582.
This article reviews the challenges and perspectives for chemical product
and process design.
4. Uhlemann J, Costa R, Charpentier JC: Product experiments

design and engineering in chemical engineering: past, present
state and future. Chem Eng Technol 2019, 42(11):2258-2274
http://dx.doi.org/10.1002/ceat/201900236.
This article discusses status and challenges of product design and
engineering and maps academic and industry perspectives.
5. Gani R: Chemical product design: challenges and
opportunities. Comput Chem Eng 2004, 28:2441-2457.
6. Grossmann IE: Challenges in the new millennium: product
discovery and design, enterprise and supply chain
optimization, global life cycle assessment. Comput Chem Eng
2004, 29:29-39.
7. Ng LY, Chong FK, Chemmangattuvalappil NG: Challenges and

opportunities in computer-aided molecular design. Comput
Chem Eng 2015, 81:115-129.
This paper highlights the significant developments, current challenges
and future opportunities in field of chemical product design using com-
puter-aided molecular design tools.
8. Gani R, Ng KM: Product design – molecules, devices,

functional products and formulated products. Comput Chem
Eng 2015, 81:71-79.
In this paper, the challenges for designing molecules, devices, functional
and formulated products as well as the approaches to meet these
challenges have been identified.
9. Austin ND, Sahinidis NV, Trahan DW: Computer-aided molecular

design: an introduction and review of tools, applications, and
solution techniques. Chem Eng Res Des 2016, 116:2-26.
This article introduces and reviews the field of computer-aided molecular
design (CAMD).
10. Butler KT, Daview DW, Carwright H, Isayev O, Walsh A: Machine

learning for molecular and materials science. Nature 2018,
559:547-555.
This article summarizes recent progress in machine learning for the
chemical sciences.
11. Gani R: Group contribution-based property estimation

methods: advances and perspectives. Curr Opin Chem Eng
2019, 23:184-196.
Current Opinion in Chemical Engineering 2020, 27:22–34
This perspective paper gives a brief overview on the state of the art in
group-contribution-based property estimation methods and their further
development and use.
12. Ng KM, Gani R: Chemical product design: advances in and
proposed directions for research and teaching. Comput Chem
Eng 2019, 126:147-156.
13. Seider WD, Lewin DR, Seader JD, Widagdo S, Gani R, Ng KM:
Product and Process Design Principles: Synthesis, Analysis and
Design. 4th ed.. Wiley; 2017.
14. Portehault D, Delacroix S, Gouget G, Grosjean R, Chan-
Chang THC: Beyond the compositional threshold of
nanoparticle-based materials. Acc Chem Res 2018, 51:930-939.
15. Zhou T, Lyu Z, Qi Z, Sundmacher K: Robust design of optimal
solvents for chemical reactions – a combined experimental
and computational strategy. Chem Eng Sci 2015, 137:613-625.
16. Cignitti S, Mansouri SS, Woodley JM, Abildskov J: Systematic
optimization-based integrated chemical product-process
design framework. Ind Eng Chem Res 2018, 57:677-688.
17. Yang R, Xu T, Fan J, Zhang Q, Ding M, Huang M, Deng L, Lu Y,
Guo Y: Natural products-based pesticides: design, synthesis
and pesticidal activities of novel fraxinellone derivatives
containing N-phenylpyrazole moiety. Ind Crop Prod 2018,
117:50-57.
18. Yu P, Low MY, Zhou W: Design of experiments and regression
modelling in food flavor and sensory analysis: a review. Trends
Food Sci Technol 2018, 71:202-215.
19. Lavecchia A: Machine-learning approaches in drug discovery:
methods and applications. Drug Discov Today 2015, 20:318-
331.
20. Conte E, Gani R, Ng KM: Design of formulated products: a
systematic methodology. AIChE J 2010, 57:2431-2449.
21. Bricks JL, Kachkovskii AD, Slominskii YL, Gerasov AO, Popov SV:
Molecular design of near infrared polymethine dyes: a review.
Dye Pigment 2015, 121:238-255.
22. Teixeira MA, Rodrı́guez O, Gomes P, Mata V, Rodrigues AE:
Chapter 1 – a product engineering approach in the perfume
industry. Perfume Engineering. Oxford: Butterworth-Heinemann;
2013, 1-13.
23. Zhang L, Mao H, Liu L, Du J, Gani R: A machine learning based
computer-aided molecular design/screening methodology for
fragrance molecules. Comput Chem Eng 2018, 115:295-308.
24. Kupgan G, Abbott LJ, Hart KE, Colina CM: Modeling amorphous
microporous polymers for CO2 capture and separations. Chem
Rev 2018, 118:5488-5538.
25. Kalakul S, Zhang L, Fang Z, Choudhury HA, Intikhab S, Elbashir N,
Eden MR, Gani R: Computer aided chemical product design –
ProCAPD and tailor-made blended products. Comput Chem
Eng 2018, 116:37-55.
26. Goldsmith BR, Esterhuizen J, Liu JX, Bartel CJ, Sutton C: Machine
learning for heterogeneous catalyst design and discovery.
AIChE J 2018, 64:2311-2323.
27. Franco AA, Rucci A, Brandell D, Frayret C, Gaberscek M,
Jankowski P, Johansson P: Boosting rechargeable batteries
R&D by multiscale modeling: myth or reality? Chem Rev 2019,
119:4569-4627.
28. Mitsos A, Hencke MM, Parton PI: Product engineering for man-
portable power generation based on fuel cells. AIChE J 2005,
51:2199-2219.
29. Kontogeorgis GM, Mattei M, Ng KM, Gani R: An integrated
approach for the design of emulsified products. AIChE J 2019,
65:75-86.
30. Fung KY, Wibowo C, Ng KM: Chapter 8 product-centered
process synthesis and development: detergents. Comput
Aided Chem Eng 2007, 23:239-274.
31. Yeo J, Jung GS, Martı́n-Martı́nez FJ, Beem J, Qin Z, Buehler MJ:
Multiscale design of graphyne-based materials for high-
www.sciencedirect.com
 Chemical product design – recent advances and perspectives Zhang et al. 33
performance separation membranes. Adv Mater 2019, 31
(42):1805665 http://dx.doi.org/10.1002/adma.201805665.
32. Li J, Huang W: From multiscale to mesoscience: addressing
mesoscales in mesoregimes of different levels. Annu Rev
Chem Biomol 2018, 9:3.1-3.20.
33. Ten JY, Hassim MH, Ng DKS, Chemmangattuvalappil NG: A
molecular design methodology by the simultaneous
optimization of performance, safety and health aspects. Chem
Eng Sci 2017, 159:140-153.
34. Jhamb S, Liang X, Gani R, Kontogeorgis GM: Systematic model-
based methodology for substitution of hazardous chemicals.
ACS Sustain Chem Eng 2019, 7:7652-7666.
35. Coley CW, Green WH, Jensen KF: Machine learning in
computer-aided synthesis planning. Acc Chem Res 2018,
51:1281-1289.
36. Srai JS, Badman C, Krumme M, Futran M, Johnston C: Future
supply chains enabled by continuous processing—
opportunities and challenges. May 20–21, 2014 continuous
manufacturing symposium. J Pharm Sci 2015, 104:840-849.
37. Babi DK, Holtbruegge J, Lutze P, Górak A, Woodley JM, Gani R:
Sustainable process synthesis-intensification. Comput Chem
Eng 2015, 81:218-244.
38. Cussler EL, Moggridge GD: Chemical Product Design.
Cambridge, ME: Cambridge University Press; 2011.
 R: Design of Experiments in Chemical Engineering: a Practical
39. Lazic
Guide. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA; 2004.
40. Dionisio KL, Phillips K, Price PS, Grulke CM, Williams A, Biryol D,
Hong T, Issaacs KK: The chemical and products database, a
resource for exposure-relevant data on chemicals in
consumer products. Sci Data 2018, 5:180125.
41. Tam SK, Fung KU, Poon GSH, Ng KM: Product design: metal
nanoparticle-based conductive inkjet inks. AIChE J 2016,
62:2740-2753.
42. Boone K, Camarda K, Spencer P, Tamerler C: Antimicrobial
peptide similarity and classification through rough set theory
using physicochemical boundaries. BMC Bioinformatics 2018,
19:469-479.
43. Lee CKH, Choy KL, Chan YN: A knowledge-based ingredient
formulation system for chemical product development in the
personal care industry. Comput Chem Eng 2014, 65:40-53.
44. Liu Q, Zhang L, Liu L, Du J, Tula AK, Eden M, Gani R: OptCAMD:
an optimization-based framework and tool for molecular and
mixture product design. Comput Chem Eng 2019, 124:285-301.
45. Liu Q, Zhang L, Liu L, Du J, Meng Q, Gani R: Computer-aided
reaction solvent design based on transition state theory and
COSMO-SAC. Chem Eng Sci 2019, 202:300-317.
46. Chao H, Song Z, Cheng H, Chen L, Qi Z: Computer-aided design
and process evaluation of ionic liquids for n-hexane-
methylcyclopentane extractive distillation. Sep Purif Technol
2018, 196:157-165.
47. Shirahata H, Badr S, Dakessian S, Sugiyama H: Alternative
generation and multiobjective evaluation using a design
framework: case study on sterile filling processes of
biopharmaceuticals. Comput Chem Eng 2019, 123:286-299.
48. Austin ND, Sahinidis NV, Konstantinov IA, Trahan DW: COSMO-
based computer-aided molecular/mixture design: a focus on
reaction solvents. AIChE J 2018, 64:104-122.
49. Al-Qattan MN, Deb PK, Tekade RK: Molecular dynamics
simulation strategies for designing carbon-nanotube-based
targeted drug delivery. Drug Discov Today 2018, 23:235-250.
50. Hernández B, Fraser B, Juan LM, Martı́n M: Computational Fluid
Dynamics (CFD) modeling of swirling flows in industrial
counter-current spray-drying towers fouling conditions. Ind
Eng Chem Res 2018, 57:11988-12002.
51. Yunus NA, Gernaey KV, Woodley JM, Gani R: A systematic
methodology for design of tailor-made blended products.
Comput Chem Eng 2014, 66:201-213.
www.sciencedirect.com
52. Tam SK, Fung KY, Poon GSH, Ng KM: Product design: metal
nanoparticle-based conductive inkjet inks. AIChE J 2016,
62:2740-2753.
53. Gu J, Gui Y, Chen L, Yuan G, Lu HZ, Xu X: Use of natural products
as chemical library for drug discovery and network
pharmacology. PLoS One 2013, 8:e62839.
54. Wibowo C, Ng KM: Product-oriented process synthesis and
development: creams and pastes. AIChE J 2001, 47:2746-2767.
55. Marrero J, Gani R: Group-contribution based estimation of pure
component properties. Fluid Phase Equilib 2001:183-184.
56. Zhang L, Cignitti S, Gani R: Generic mathematical programming
formulation and solution for computer-aided molecular
design. Comput Chem Eng 2015, 78:79-84.
57. Nørskov JK, 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.
58. Carter EA: Challenges in modeling materials properties

without experimental input. Science 2008, 321:800-803.
This perspective reviews current quantum mechanics–based materials
modeling approaches and their successes and limitations and offers a
view to the future.
 z P, Caflisch A: Protein structure-based drug design: from
59. Sled
docking to molecular dynamics. Curr Opin Struct Biol 2018,
48:93-102.
60. Liang X, Zhang X, Zhang L, Liu L, Du J, Zhu X, Ng KM: Computer-
aided polymer design: Iintegrating group contribution and
molecular dynamics. Ind Eng Chem Res 2019, 58(34):15542-
15552 http://dx.doi.org/10.1021/acs.iecr.9b02769.
61. Gmehling J, Constantinescu D, Schmid B: Group contribution
methods for phase equilibrium calculations. Annu Rev Chem
Biomol Eng 2015, 6:267-292.
62. Zhou T, Jhamb S, Liang X, Sundmacher K, Gani R: Prediction of
acid dissociation constants of organic compounds using
group contribution methods. Chem Eng Sci 2018, 183:95-105.
63. Dong Y, Huang S, Guo Y, Lei Z: COSMO-UNIFAC model for ionic
liquids. AIChE J 2019 http://dx.doi.org/10.1002/aic.16787.
64. Scheffczyk J, Fleitmann L, Schwarz A, Lampe M, Bardow A,
Leonhard K: COSMO-CAMD: a framework for optimization-
based computer-aided molecular design using COSMO-RS.
Chem Eng Sci 2017, 159:84-92.
65. Schilling J, Lampe M, Gross J, Bardow A: 1-stage CoMT-CAMD:
An approach for integrated design of ORC process and
working fluid using PC-SAFT. Chem Eng Sci 2017, 159:217-
230.
66. Nagy ZK: A population balance model approach for
crystallization product engineering via distribution shaping
control. Comput Aided Chem Eng 2008, 25:139-144.
67. Kiparissides C: Challenges in particulate polymerization
reactor modeling and optimization: a population balance
perspective. J Process Control 2006, 16:205-224.
68. Kougoulos E, Jones AG, Wood-Kaczmar M: CFD modelling of
mixing and heat transfer in batch cooling crystallizers: aiding
the development of a hybrid predictive compartmental model.
Chem Eng Res Des 2005, 83:30-39.
69. Chen XZ, Shi DP, Gao X, Luo ZH: A fundamental CFD study of
the gas–solid flow field in fluidized bed polymerization
reactors. Powder Technol 2011, 205:276-288.
70. Jeldres RI, Fawell PD, Florio BJ: Population balance modelling
to describe the particle aggregation process: a review. Powder
Technol 2018, 326:190-207.
71. Fung KY, Ng KM, Zhang L, Gani R: A grand model for chemical
product design. Comput Chem Eng 2016, 91:15-27.
72. Smith JS, Isayev O, Roitberg AE: ANI-1: an extensible neural
network potential with DFT accuracy at force field
computation cost. Chem Sci 2017, 8:3192-3203.
Current Opinion in Chemical Engineering 2020, 27:22–34
34 Frontiers of chemical engineering
73. Mu T, Rarey J, Gmehling J: Group contribution prediction of
surface charge density profiles for COSMO-RS(OI). AIChE J
2007, 53:3231-3240.
74. Amoozgar Z, Yeo Y: Recent advances in stealth coating of
nanoparticle drug delivery systems. Wiley Interdiscipl Rev
Nanomed Nanobiotechnol 2012, 4:219-233.
Current Opinion in Chemical Engineering 2020, 27:22–34
75. Lutze P, Babi DK, Woodley JM, Gani R: Phenomena based
methodology for process synthesis incorporating process
intensification. Ind Eng Chem Res 2013, 52:7127-7144.
76. Fung KY, Ng KM: Product-centered processing:
pharmaceutical tablets and capsules. AIChE J 2003, 49:1193-
1215.
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