# Computation and Development of New, Enabling Synthetic Methods

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2021 · $545,731

## Abstract

PROJECT SUMMARY/ABSTRACT
Summary
 The overall objective of this research program is to develop analyses, tools, and methods to achieve new,
more effective reagents, catalysts, and biological ligands.
 One focus will be on state-of-the-art computation methods to understand stereoselectivity, chemoselectivity,
and reactivity at the molecular level with the aim of designing new, more effective reagents, catalysts, and
biological ligands. The control of selectivity and reactivity are essential features of efficient synthesis, yet our
molecular level understanding of how fundamental interactions perturb these aspects is only rudimentary.
Further, many aspects of how these same fundamental interactions govern binding in a biological context are
incompletely understood.
 Another focus will be on oxidative coupling of fragments via C-C, C-O, and C-N bond formation by means of
C–H activation chemistry. Catalyst libraries will be designed for study of biomimetic reactions using two guiding
principles: 1) matching catalyst oxidation potentials with the oxidation potentials of the substrates under
consideration and 2) selecting metals that can utilize oxygen to regenerate the catalytic species. These libraries
will be deployed in a high-throughput microscale format to discover reactivity patterns heretofore unimagined.
From the data obtained, reaction “profiles” will be constructed and new inferences about reactivity, selectivity,
and mechanism will be made, which will be tested experimentally.
 The fundamental hallmark of this proposal is the ability to access new reaction patterns to construct important
organic structures in an efficient and rational manner. Computation and mechanistic understanding gives us the
tools to solve problems and posit hypotheses. High throughput microscale experimentation permits rational
hypotheses to be interrogated broadly and to facilitate optimization of the many interdependent variables in the
possible reaction space.
Relevance
 The fundamental hallmark of this proposal is the ability to design new reactions and catalysts via computation
and mechanistic study. The goal is to construct important organic structures in an efficient and rational manner.
New synthetic methods greatly increase access to untapped chemical space, leading to materials and
pharmaceuticals that benefit society. To achieve this goal, investigations will focus on obtaining an improved
understanding of reactivity and selectivity. The development of new oxidative coupling chemistry is a particular
focus due to increases in efficiency from lower step counts and smaller waste streams. The challenge in this
area is selectivity in any given transformation due the numerous C–H bonds present in a typical organic molecule.
Use of biomimetic processes leads to bioactive natural products and natural product-like cores, desirable entities
in medicinal chemistry. Invaluable training, absent outside of industrial settings, will be afforded to graduate
students and o...

## Key facts

- **NIH application ID:** 10190968
- **Project number:** 5R35GM131902-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Marisa C Kozlowski
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $545,731
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190968

## Citation

> US National Institutes of Health, RePORTER application 10190968, Computation and Development of New, Enabling Synthetic Methods (5R35GM131902-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190968. Licensed CC0.

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