# Merging Computation and Experiment to Understand and Develop Asymmetric Open-Shell Radical Cross-Couplings

> **NIH NIH R35** · UNIV OF MARYLAND, COLLEGE PARK · 2021 · $93,073

## Abstract

PROJECT SUMMARY/ABSTRACT
 Despite advances in high-throughput screening methods leading to a surge in the discovery of catalytic
reactions, our knowledge of the molecular-level interactions in the rate- and selectivity-determining steps of
catalytic reactions involving highly unstable and reactive open-shell intermediates is rudimentary. These
knowledge gaps prevent control, suppression or enhancement, of competing reaction channels that can drive
development of new catalytic reactions. Built on strong computational and experimental preliminary results, this
program seeks to understand and guide design of new sustainable, catalytic, and asymmetric transformations.
 Overall, our goals are to develop predictive models of reactivity and selectivity of first-row, open-shell
transition metal-catalyzed carbon-carbon bond formations that can be adapted by the organic, organometallic,
and bio(in)organic community in the synthesis of medicinally-active compounds. To accomplish this
overarching goal, we have identified two areas of research for the next 5 years and plans for beyond. In the
first area, we will use combined experimental and computational tools to understand and develop new
asymmetric iron-catalyzed radical cascade/cross-coupling reactions. In the second area, through collaborative
efforts, we will target the synthesis of quaternary centers via metallophotoredox-catalyzed cross-couplings.
These reactions proceed through carbon-centered radical intermediates, open-shell organometallic species,
and photoexcited electronic state species where evaluating the mechanisms has been historically hampered
by the inherent complexity associated with the high reactivity and instability of these species. High-level
quantum mechanical calculations, rigorously calibrated against experimental data, will be used to interrogate
the mechanisms and to guide the development of new catalysts and reagents for currently sluggish or
unselective reactions. In addition, we will exploit selected potential energy surfaces susceptible to dynamic
effects, single-electron transfers, and intersystem crossings to gain a deeper understanding of the factors
determining product selectivity and inform catalyst and reaction design. Overall, these efforts will push the
limits of accurate molecular modeling of increasing complex catalytic reactions and potentially impact the fields
of organic, bio(in)organic, and transition-metal catalysis.

## Key facts

- **NIH application ID:** 10201676
- **Project number:** 5R35GM137797-02
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Osvaldo Gutierrez
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $93,073
- **Award type:** 5
- **Project period:** 2020-07-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201676

## Citation

> US National Institutes of Health, RePORTER application 10201676, Merging Computation and Experiment to Understand and Develop Asymmetric Open-Shell Radical Cross-Couplings (5R35GM137797-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201676. Licensed CC0.

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