Tuesday, July 1, 2025 7/1/2025

Investigation of a Pterin-Dithiolene Model Complex for the Molybdenum Cofactor

Award Number: R15GM081848
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/06/2007
PERIOD OF PERFORMANCE END DATE: 01/31/2019

Group Awards By:

View Award Description

Investigation of a Pterin-Dithiolene Model Complex for the Molybdenum Cofactor - Summary/Abstract Molybdenum (Mo) is critical to the health of nearly every organism on earth. Humans have an absolute requirement for several molybdenum enzymes and one in particular is critical for proper embryo development to maturity. Inherited diseases in humans result in compromised molybdenum enzymes causing pervasive neurological problems at best and infant fatalities at worst. Despite fifty years' of research on molybdenum enzymes, the function and certain structural aspects of the unique ligand chelating Mo in these proteins remain a mystery. This ligand is a pterin-substituted dithiolene chelate and is found only in molybdenum and the related tungsten enzymes. Human diseases resulting from molybdoenzyme disfunction have been linked to errors in the pterin-dithiolene biosynthetic path which underscores the pivotal role of the ligand in enzyme function. This project will undertake a detailed study of the chemical behavior and reactivity of a Mo-pyranopterin- dithiolene model complex designed to be nearly identical to the Mo site in the enzymes. The goal is to understand how conformation and redox changes at the pterin influence the electronic structure of the entire pterin-dithiolene ligand coordinated to Mo in the enzymes. Of particular interest is establishing the pyran ring reactivity towards scission and how the gamut of known pterin redox chemistry is altered when pterin is fused to a pyran ring and a dithiolene ligand. Specific objectives are: (a) to determine those factors that influence pyran ring cyclization and cleavage on pterin-dithiolene ligands chelated to Mo; (b) to understand the redox chemistry and properties of pyranopterin dithiolene ligands using chemical and electrochemical methods; (c) to probe the electronic effects of pterins at different levels of reduction on the Mo-dithiolene unit; and (d) to accomplish full spectroscopic and structural characterization of all model compounds. The results are critical to a complete understanding of how the Mo site functions and how the pterin-dithiolene might be involved in dysfunctional enzymes. It is expected that these studies will: a) reveal what chemical reactivity exists for pterin-dithiolene ligands within the Mo enzymes, and this understanding will b) provide insights for how the protein environment could influence pterin behavior; (c) provide spectroscopic and structural benchmarks to aid interpretation of similar results from the enzymes and (d) describe fundamental chemistry of the active site chemistry of Mo and W enzymes to be exploited for possible future therapies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2019 ( Subtotal = -$3,558 )
2019	2014	BRYN MAWR COLLEGE	101 N MERION AVE	BRYN MAWR	PA	19010	DELAWARE	USA	Biomedical Research and Research Training	000	2	6/10/2019	COMPETING CONTINUATION	-$3,558
														Subtotal = -$3,558

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2014	BRYN MAWR COLLEGE	101 N MERION AVE	BRYN MAWR	PA	19010	DELAWARE	USA	Biomedical Research and Research Training	000	2	1/31/2018	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $284,660 )
2014	2014	BRYN MAWR COLLEGE	MERION DRIVE	BRYN MAWR	PA	19010	DELAWARE	USA	Biomedical Research and Research Training	000	2	1/22/2014	COMPETING CONTINUATION	$284,660
														Subtotal = $284,660

Issue Date FY: 2011 ( Subtotal = $0 )
2011	2007	BRYN MAWR COLLEGE	MERION DRIVE	BRYN MAWR	PA	19010	DELAWARE	USA	Biomedical Research and Research Training	000	1	7/21/2011	NEW	$0
														Subtotal = $0

Issue Date FY: 2010 ( Subtotal = $0 )
2010	2007	BRYN MAWR COLLEGE	MERION DRIVE	BRYN MAWR	PA	19010	DELAWARE	USA	Academic Research Enhancement Award	001	1	8/9/2010	NEW	$0
2010	2007	BRYN MAWR COLLEGE	MERION DRIVE	BRYN MAWR	PA	19010	DELAWARE	USA	Academic Research Enhancement Award	000	1	1/18/2010	NEW	$0
														Subtotal = $0

Issue Date FY: 2007 ( Subtotal = $210,933 )
2007	2007	BRYN MAWR COLLEGE	MERION DRIVE	BRYN MAWR	PA	19010	DELAWARE	USA	Academic Research Enhancement Award	000	1	8/6/2007	NEW	$210,933
														Subtotal = $210,933

Grand Total All Awards = $492,035

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigation of a Pterin-Dithiolene Model Complex for the Molybdenum Cofactor

Award Number: R15GM081848

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/06/2007

PERIOD OF PERFORMANCE END DATE: 01/31/2019

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer