# Mechanistic Investigation into Modern Catalytic Reactions

> **NIH NIH R35** · STATE UNIVERSITY OF NY,BINGHAMTON · 2022 · $232,080

## Abstract

Project Summary: Mechanistic understanding of emerging catalytic methodologies is an important factor
in the successful application of novel transformations to the synthesis of pharmaceuticals and other high-
value chemicals. Despite this, there is a significant lag between new reaction discovery and its
mechanistic description. This research program addresses this challenge in two important areas of
contemporary catalysis – photoredox catalysis and biocatalysis by engineered enzymes.
 Photocatalysts harness the power of visible light to generate highly reactive radical intermediates
that can be strategically channeled to participate in a variety of valuable bond-formations. There are a
variety of photophysical approaches for the detection and characterization of these open-shell
intermediates. However, experimental probes of the transition state geometry, of key bond-forming and
bond-breaking events in photoredox catalysis, are virtually non-existent. In this context, this research
program establishes 13C kinetic isotope effects as the elusive experimental probe of the transition state
geometry of photoredox reactions. In addition to shedding light on these complex reaction mechanisms,
this measurement serves as an important experimental benchmark to calibrate theoretical methods to
accurately evaluate the rate- and selectivity-determining steps in these reactions.
 Directed evolution of cytochromes P450 has led to the discovery of carbene- and nitrene-transfer
activity of these heme-containing enzymes. Mechanistic investigations of these systems have largely
been limited to theoretical studies due to the inherent challenges associated with conducting standard
physical organic experiments in enzymatic systems. This program utilizes a newly developed
intramolecular 13C kinetic isotope effect technique along with classical kH/kD experiments to gain insight
into the transition state geometry of C–C and C–N bond-forming steps in these reactions. High-level
QM/MM calculations and MD simulations are also utilized to interpret experimental findings and
understand the origin of selectivity in these biocatalytic reactions.

## Key facts

- **NIH application ID:** 10501633
- **Project number:** 1R35GM147183-01
- **Recipient organization:** STATE UNIVERSITY OF NY,BINGHAMTON
- **Principal Investigator:** Jennifer Hirschi
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $232,080
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501633

## Citation

> US National Institutes of Health, RePORTER application 10501633, Mechanistic Investigation into Modern Catalytic Reactions (1R35GM147183-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10501633. Licensed CC0.

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