Mary Gates Research Scholarship Winter 2022 CONFIDENTIAL

Applicant: Aalto, Jonathan Destroy by January 1, 2025

Investigating Supramolecular Cages as Redox Mediators for Organic Electrosynthesis

As we face the effects of climate change and industrial pollution, it is important that we

lower the energy consumption of chemical synthesis and reduce hazardous byproducts. Many

organic reactions involve oxidation and reduction, and in recent years electrochemistry has been

solidified as a promising route toward cleaner, more energy efficient redox reactions. [1] In organic

electrochemistry, a voltage is applied to an electrolyte solution, which can then induce the gain or

loss of electrons between the electrodes and dissolved reactants. For many reactions,

electrochemical synthesis can replace traditional chemical oxidants and reductants, which are often

expensive, toxic, or difficult to regenerate. However, the energy barriers for electron transfer

between dissolved reactants and a solid electrode can be high, and a common problem is for

reaction products to build up on the surface of electrodes. As products accumulate, substrates can

no longer access the surface and the reaction ceases. One solution to these problems is the addition

of redox mediators to electrochemical environments.

Redox mediators are compounds that are readily oxidized or reduced at electrode surfaces

while maintaining their solubility and structure. [2] These mediators can then transfer their charge

to substrates in solution, often against potential gradients (Fig. 1). This enables reactions to occur

away from the electrode surface, preventing build-up, and to occur at lower voltages, which

conserves energy and reduces the likelihood of side-reactions. Redox mediators are generally

compounds with a large range of accessible redox states. Buckminsterfullerene – a hollow,

spheroidal structure consisting of sixty carbon atoms connected by single and double bonds – is

one such compound. [3] The objective of my research is to investigate the application of

supramolecular cages as redox mediators.

Jonathan Aalto Page 1

Mary Gates Research Scholarship Winter 2022 CONFIDENTIAL
Applicant: Aalto, Jonathan Destroy by January 1, 2025

Supramolecular cages are macromolecules formed from the self-assembly of ligands in

solution. These typically take the form of platonic solids like cubes and tetrahedra, with organic

ligands along each edge and metal cations on vertices. [4] Supramolecular cages produce unique

chemical microenvironments within their cavities, similar to enzyme active sites. Because ligand

structure and metal identity can be adjusted to meet specific charge, size, and functional group

needs, these cavities can be tuned to catalyze a variety of reactions, often with regio- or stereo-

selectivity. To date, nearly all supramolecular cage catalysis has been directed toward redox-

neutral catalysis. In this project, I will test the ability of an iron-based supramolecular cage to

mediate the electrochemical reduction of three classes of organic molecules. If successful, this

research may introduce new electrocatalytic pathways for the synthesis of chemical feedstocks.

The supramolecular cage I will be testing is highly redox-active. It consists of iron(II)

vertices and perylene bisimide ligands, which self-assemble into discrete tetrahedra with 39 nm

edge lengths (Fig. 2). [5] According to the literature, this cage displays seven reversible

oxidation/reduction events between +18 and -16 charged species (Fig. 2c). While the cyclic

voltammogram (CV) of this cage has been reported, its ability to catalyze electrochemical

reduction reactions has not yet been explored. Based on the CV, I hypothesize that the reduced

cage should be able to mediate the reductions of aldehydes (-1.3 to -2.7 V), ketones (-1.4 to -2.8

V), and alkyl halides (-1.1 to -2.9 V), as well as carboxylic acids and nitriles (Fig. 3). [6] My first

goal is to synthesize the cage ligand according to previously reported procedures. [7] For each step

of the synthesis, I will assess product purity using nuclear magnetic resonance spectroscopy

(NMR). Once synthesized, I will react the ligand with an iron(II) salt to form the cage.

After confirming structure and purity of the cage using NMR and mass spectrometry, I will

investigate whether my redox-active cage can catalyze the electrochemical reduction of three

Jonathan Aalto Page 2

Mary Gates Research Scholarship Winter 2022 CONFIDENTIAL
Applicant: Aalto, Jonathan Destroy by January 1, 2025

classes of organic compounds: vicinal dibromides, perfluoroalkyl iodides, and aldehydes (Fig. 4).

First, I will perform cyclic voltammetry (CV) to ensure that the cage redox profile matches that

which was reported in the literature. I will also perform CV on the following three model substrates

to determine their redox potentials: 1) the vicinal dibromide compound erythro-ethyl-2,3-dibromo-

3-phenylpropanoate, 2) perfluorohexyl iodide, and 3) 4-nitrobenzaldehyde (Fig. 4). The dibromide

substrate was chosen because it can be successfully reduced using other redox mediators, such as

fullerene. [3] This well-studied reaction should allow us to compare the activity of the iron cage

to that of a known redox mediator. Using microscale-CV, I will measure the onset potential of

dibromide reduction in solutions containing pure dibromide, dibromide with catalytic fullerene,

and dibromide with catalytic iron cage. I will then perform the catalysis on a larger sample to

assess the yield, reaction rate, and product purity on a preparative scale. Together, these

experiments will allow me to compare the outcomes of cage-mediated dibromide reduction with

analogous unmediated and fullerene-mediated conditions.

I will repeat this process for the reduction of perfluorohexyl iodide to perfluorohexene.

Perfluoroalkenes are commonly used in the synthesis of fluoropolymers, such as Teflon. [8]

Currently, however, perfluoroalkyl halides cannot be reduced to alkenes directly on a large scale

due to adsorption of reduced intermediates on the electrode surface, causing electrode passivation.

If, as we hypothesize, the iron cage can stabilize the intermediates of this reaction within the

tetrahedral cavity, this would prevent these species from adsorbing to the electrode. I also intend

to investigate the reduction of carbonyls to alcohols. Currently, aldehydes such as furfural and 5-

hydroxymethyl furfural can be obtained in large quantities from biomasses, but diversifying these

compounds into other chemicals is difficult due to the energy barriers involved in reducing

aromatic-adjacent carbonyl groups. [9] The reduction of 4-nitrobenzaldehyde will serve as a proof

Jonathan Aalto Page 3

Mary Gates Research Scholarship Winter 2022 CONFIDENTIAL
Applicant: Aalto, Jonathan Destroy by January 1, 2025

of concept for supramolecular redox-mediated catalysis of these types of reactions. Together, these

model substrates will allow me to assess how supramolecular cages influence electrochemical

reactions, and whether unique product selectivity or stabilization of intermediates can be observed.

Throughout this project, I will be assisted by Kathleen Snook, a graduate student, and

Assistant Professor Dianne Xiao. Kathleen will help me draft experiment plans and provide advice

while I run experiments. I will be regularly discussing my findings with Kathleen, and at the end

of each month I will present my progress at meetings with Professor Xiao.

Contributing to research has long been a dream of mine. When I decided to commit to

chemistry in my freshman year, I became eager to explore the field hands-on. I developed an

interest for extended structures and porous materials during Chem 165, and Professor Xiao’s lab

seemed like a perfect fit. I have been able to shadow Kathleen on many reactions and lab

procedures, and Professor Xiao has always given fantastic feedback and project coordination. Over

the past four months I have worked with Kathleen on the synthesis of catechol-based

supramolecular cages, and I am excited to transfer what I have learned to this new project. I am

happy to be working on research with such great potential to benefit the environment, and as I

intend to pursue graduate school, this experience is a great way to prepare for future research.

Being named a Mary Gates Scholar would be a great honor that would enhance my

applications to graduate programs and provide valuable financial support. I am responsible for

much of my housing and textbook costs, and such funds would allow me to continue my current

research unhindered. Working in the Xiao lab has been an incredibly fulfilling part of my UW

experience, with each day offering new skills to learn and new opportunities to improve. As I

continue my research journey, I am eager to see where this new project takes me.

Jonathan Aalto Page 4

Mary Gates Research Scholarship Winter 2022 CONFIDENTIAL
Applicant: Aalto, Jonathan Destroy by January 1, 2025

Figure 1: Redox Mediators (Med) in

Reductive Electrochemistry [2]

Figure 2: Iron-PBI Cage (a), PBI Ligand (b), and Figure 4: Targeted Electrocatalysis Reactions
CV Scan (c) [5]
a
a

References:
[1] – Chem. Soc. Rev. 2021, 50, 7941-8002,
doi.org/10.1039/D1CS00223F
b [2] – Chem. Soc. Rev. 2014, 43, 2492-2521,
doi.org/10.1039/C3CS60464K
[3] – J. Electroanal. Chem. 1996, 411, 115-119,
doi.org/10.1016/0022-0728(96)04583-4
[4] – Nature Catalysis. 2020, 3, 969-984,
doi.org/10.1038/s41929-020-00528-3
c [5] J. Am. Chem. Soc. 2013, 135, 41, 15656-15661,
doi.org/10.1021/ja4083039
[6] – J. Org. Chem. 2021, 86, 15875-15885,
doi.org/10.1021/acs.joc.1c01520
[7] – Macromol. Chem. Phys. 1994, 195, 1905-1911
doi.org/10.1002/macp.1994.021950602
[8] – Chemosphere 2005, 58, 1471-1496,
doi.org/10.1016/j.chemosphere.2004.11.078
[9] – ACS Catal. 2016, 6, 6704-6717,
doi.org/10.1021/acscatal.6b01861

Figure 3: Reduction Voltages for

Organic Compounds [6]

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