# Understanding Geometric and Electronic Structure Contributions to Ground and Excited State Cu- and Ni-Catalyzed Cross-Coupling Reactions

> **NIH NIH R35** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2021 · $418,750

## Abstract

Project Summary
Developing sustainable approaches to the synthesis of molecular therapeutics will be important for the
continued evolution and success of medicinal and pharmaceutical chemistries. A major component of
drug synthesis involves transition metal catalyzed C–X (X = C, N, O, etc.) bond formation reactions.
While precious metals such as Pd are used for these reactions, first row transition metals are becoming
more widely adopted, as they are abundant and open new mechanistic pathways involving one- and
multi-electron transfer reactivity, which can potentially work in concert with ligand noninnocence and
multireference electronic structure to form transformative structure/function relationships. The merger
of thermal catalysis with photochemistry also provides new mechanistic possibilities for cross-couplings
that harness the energy of light to drive bond-formation reactions that would not occur in ground states.
However, the nature of inorganic intermediates and the important ultrafast transition metal excited state
relaxation processes in ground and excited state cross-coupling reactions are not well understood. This
proposal therefore applies physical inorganic approaches to develop a fundamental knowledge base
of the geometric and electronic structures of the critical inorganic species formed in Cu- and Ni-
catalyzed cross-coupling reactions, as well as the time and energy evolution of photoinduced electronic
states involved in excited state catalysis. This knowledge base will ultimately guide the development of
a molecular engineering approach to ligand development and catalyst discovery. We will bring new
spectroscopic methods to the field, including variable temperature variable field magnetic circular
dichroism (VTVH MCD) and X-ray absorption and emission spectroscopies, which will be critical to
quantitatively define transition metal electronic structure, including multireference character. Ultrafast
optical and X-ray spectroscopic approaches will also be used to define the key photonic energy
distribution pathways that define photocatalyst efficiency and further guide ligand perturbations to
control the excited state potential energy surfaces (PESs) of photocatalysts. Spectral features of
isolable species will be used to experimentally calibrate computational methods to define the critical
frontier molecular orbitals and bonding interactions that activate metal centers for reactivity, especially
those that are fleeting but critical to catalysis. Electronic structure calculations will also allow for the
translation of our understanding of resting states, intermediates, and excited states to reaction
coordinates in catalysis and the PESs governing relaxation pathways. In concert with collaborative
methodological studies, the proposed research will help inform chemists how to leverage the ground
and excited state electronic structures of first-row transition metal complexes and thus guide academic
and industry research toward susta...

## Key facts

- **NIH application ID:** 10273133
- **Project number:** 1R35GM142595-01
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Ryan G Hadt
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $418,750
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10273133

## Citation

> US National Institutes of Health, RePORTER application 10273133, Understanding Geometric and Electronic Structure Contributions to Ground and Excited State Cu- and Ni-Catalyzed Cross-Coupling Reactions (1R35GM142595-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10273133. Licensed CC0.

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