# Multimetallic Catalysis in Biology and Synthesis

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $388,275

## Abstract

The proposed work focuses on (a) understanding how natural multimetallic clusters operate as
active sites in metalloenzymes, and (b) using synthetic multimetallic clusters for productive
chemical synthesis. Many metalloenzymes feature multimetallic clusters as active sites for
catalyzing multielectron/multiproton transformations of gaseous small molecules, including
cases of environmental significance to human health like atmospheric regulation of carbon
dioxide and nitrous oxide. In many cases, these multimetallic clusters have unusual
compositions and geometries, and so the chemical reactivity patterns have not been mapped
out in laboratory settings. This proposal aims to achieve that for several multimetallic active
sites, including the tetrametallic active site of nitrous oxide reductase and the heterobimetallic
active site of carbon monoxide dehydrogenase, using synthetic model studies based on the PI’s
established expertise in this area. Additionally, lessons about how these natural multimetallic
clusters operate will be applied to develop synthetic multimetallic catalysts for C-C and C-X
bond-forming reactions of relevance to pharmaceutical synthesis. The benefits of developing
this catalytic paradigm for synthetic organic chemistry include emergence of reactivity and
selectivity patterns that are complementary to established mononuclear catalyst systems, as
well as the advancement of a bio-inspired tool to design earth-abundant metal catalysts that
improve the sustainability of synthetic technologies in the pharmaceutical industry.

## Key facts

- **NIH application ID:** 10402390
- **Project number:** 5R35GM140850-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Neal P Mankad
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $388,275
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402390

## Citation

> US National Institutes of Health, RePORTER application 10402390, Multimetallic Catalysis in Biology and Synthesis (5R35GM140850-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10402390. Licensed CC0.

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