# Subproject Investigator: Dong Wang

> **NIH NIH P20** · UNIVERSITY OF MONTANA · 2020 · $214,735

## Abstract

Project Summary:
Title: M2O2 "Diamond Core": the Next Generation of Biomimetic Transition-metal Catalyst for Effective and
Selective Aliphatic Hydrocarbon Functionalization.
The selective installation of functional groups onto inert aliphatic carbon centers is a key step in many metabolic
transformations, and finds many uses in the synthesis of pharmaceuticals, clinical reagents, materials and
agrochemicals. For example, the halogenated biomolecules and drug candidates are expected to be more
metabolically stable and have improved target-binding affinities. The introduction of the azide group, on the other
hand, provides a convenient way to access a variety of functionalities through redox chemistry and the
azide-alkyne cycloaddition reaction (“click chemistry”). In biological systems the functionalization of C–H bonds
is catalyzed by metalloenzymes that utilize mono- or multi-nuclear active sites and employ earth-abundant
transition metals. One representative example is the α-ketoglutarate dependent nonheme halogenase SyrB2
that activates O2 as the natural oxidant and specifically converts a C–H bond to a C–Cl bond through a
high-valent Cl–FeIV=O intermediate. A recent development has even shown that SyrB2 could carry out aliphatic
C–N bond formation reactions, suggesting that this radical-based reaction pathway might be considered as a
universal strategy for aliphatic C–H bond functionalization. While this enzymatic strategy appears highly
attractive in designing biomimetic catalytic systems; great challenges exist for synthetic systems, which lack the
enzymatic scaffold, in controlling the transfer of the functional group selectively onto the target carbon center.
Competition between the functional group –X and the –OH group generated by the initial C–H bond cleavage
from the substrate normally resulted in a reaction mixture composed of multiple products.
In order to tackle these challenges, the proposed research is inspired by natural metalloenzymes that utilize
dinuclear active sites possessing a specific M2(µ-O)2 “diamond core” structure, and recent biomimetic studies
showing that the M2(µ-O)2 “diamond core” could be activated to release higher oxidizing ability upon interacting
with Lewis bases. The proposed dinuclear synthetic catalysts would have a M2(µ-O)2 “diamond core”, where the
two metals function in a cooperative manner in the catalytic cycle. This project also integrates attractive features
of high-valent metal-oxo chemistry for late-transition metals (Co, Ni) as active C–H bond cleaving oxidants.
Specifically, the project contains three aims. The goal of the first aim is to design and evaluate the catalytic
system, including synthesizing and characterizing ligands and catalysts, optimizing experimental conditions,
expanding the substrate scope and the identity of the functional group, and investigating the reaction mechanism
and the ligand effect on the catalytic activity. In the second aim, efforts will be devoted to the indepen...

## Key facts

- **NIH application ID:** 10004089
- **Project number:** 5P20GM103546-10
- **Recipient organization:** UNIVERSITY OF MONTANA
- **Principal Investigator:** Dong Wang
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $214,735
- **Award type:** 5
- **Project period:** 2011-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004089

## Citation

> US National Institutes of Health, RePORTER application 10004089, Subproject Investigator: Dong Wang (5P20GM103546-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10004089. Licensed CC0.

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