# Structure/Function Correlations Over Copper Enzymes

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $589,893

## Abstract

Project Summary
Cu (along with Fe) enzymes play dominant roles in O2 activation in Nature. They are important in melanogenesis,
neurochemistry, metal ion metabolism, proton pumping, bioremediation, ROS generation, a range of disease
states, and can be utilized in biofuel cells for implantable devices. On a molecular level these can reduce O2 by
1,2, possibly 3 and 4 electrons to accomplish a range of functions, including H-atom abstraction from both weak
and strong C-H bonds, electrophilic activation by 2 as well as 1 Cu center, and the coupling of O2 reduction to
water to Fe metabolism by the multicopper oxidases and proton pumping by the heme-copper oxidases. Oxygen-
activating Cu enzymes are divided into five classes based on structure and type of reaction with the mononuclear
Cu class further divided based on the redox active states of the Cu and the oxygen. Our studies use the
combination of kinetics on the enzymes to obtain intermediates, application of a wide range of spectroscopies to
define these, parallel model studies and the coupling of the results of these kinetic, spectroscopic and model
studies to electronic structure calculations to define frontier molecular orbitals and reaction coordinates in
catalysis. Innovative aspects of this research effort include the development of new spectroscopic methods, the
analyses of the unique spectral features often exhibited by Cu/O2 intermediates in terms of their geometric and
electronic structures and the coupling of these data to electronic structure calculations for development of
experimentally validated reaction coordinates. These studies define the reaction mechanisms of each class and
subclass on a molecular level (important in the design of drugs, devices and catalysts) and by parallel studies
over the classes develop general insight into structure/function correlations over oxygen utilization in Nature.

## Key facts

- **NIH application ID:** 9953871
- **Project number:** 2R01DK031450-40
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** EDWARD I SOLOMON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $589,893
- **Award type:** 2
- **Project period:** 1982-01-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953871

## Citation

> US National Institutes of Health, RePORTER application 9953871, Structure/Function Correlations Over Copper Enzymes (2R01DK031450-40). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953871. Licensed CC0.

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