# Computational Models for New Developments in Radical Chemistry

> **NIH NIH R01** · COLORADO STATE UNIVERSITY · 2024 · $304,186

## Abstract

Project Abstract
The goal of this project is to develop new understanding and predictive models for the formation, reactivity, and
selectivity of organic radical and diradical intermediates. Triplet diradicals can undergo a variety of
transformations that are not accessible in the singlet ground state. However, developing efficient photocatalytic
triplet energy transfer processes, particularly in an enantioselective fashion, remains an enduring goal. We will
show that computational approaches can be leveraged to develop general principles for substrate and sensitizer
design to harness triplet-state reactivity. We will use computation to target the mechanism-guided discovery of
unexplored reactivity in the triplet state, such as homolytic aromatic substitution, and the design of chiral Lewis
acids to promote asymmetric photocatalytic cyclizations. We will also develop a qualitative and quantitative
understanding of the factors controlling the reaction rates and site selectivities of radical homolytic substitution,
such as hydrogen and halogen atom transfer reactions. These conceptual insights will be used to rationalize
experimental observations and underpin the development of new radical reagents for site-selective C(sp3)-H
chlorination. The development of quantitative models, aided by new physical-organic parameters, can be used
to accelerate this process. Machine learning models grounded in mechanistic understanding will provide new
tools to parametrize substrates and reagents to accelerate reaction discovery and optimization. We will employ
this strategy to predict the site-selectivity of P450 oxidation small molecules and to establish general workflows
to predict the metabolic degradation pathways.

## Key facts

- **NIH application ID:** 10907794
- **Project number:** 5R01GM151533-02
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Robert Scott Paton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $304,186
- **Award type:** 5
- **Project period:** 2023-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907794

## Citation

> US National Institutes of Health, RePORTER application 10907794, Computational Models for New Developments in Radical Chemistry (5R01GM151533-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10907794. Licensed CC0.

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