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Taylor Johnson and Emily Caputo

Department of Chemistry

Faculty Mentor: Dr. Tsanangurayi Tongesayi

ABSTRACT

Hypertension is a chronic medical condition in which the blood pressure in the arteries is
elevated. One in every three adults in the United States suffers from high blood pressure. This
condition is dangerous because it can lead to stokes, heart attacks, heart failure and kidney
disease. High blood pressure can be treated by lifestyle changes and diet changes, but is most
commonly treated with antihypertensive drugs. One type of antihypertensive drug is angiotensin-
converting enzyme (ACE) inhibitors. The function of ACEs is to cleave a dipeptide from
angiotensin I to form angiotensin II, a potent vasopressor. Angiotensin I and II comprise part of
the renin-angiotensin system (RAS) which controls blood pressure by regulating the volume of
fluids in the body. Although they are important in regulating fluids in the body, the action of
ACEs in constricting the blood vessels is a major cause of hypertension which is why they have
become drug targets in the treatment of high blood pressure.
Captopril, (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid, is an
angiotensin-converting enzyme inhibitor that prevents the conversion of angiotensin I to
angiotensin II by binding to the active site in ACE. Zinc is found at the center of the active site in
ACE. The thiol group of captopril makes a direct interaction with the zinc center, and allows for
the complex formation of captopril with ACE. The problem with the thiol group is that it is
extremely reactive and can bind to trace metals found in the body or other metal ions ingested as
part of an everyday diet. Because of the reaction of Captopril with metal ions other than Zn,
many patients taking captopril regularly may experience low efficacy of the drug.
The objective of this project is to gather information about the binding activities of Captopril
with trace metals in the stomach in comparison with toxic heavy metal ions. Aside from affecting
the bioavailability of Captopril in vivo, it is hypothesized that if these Captopril-metal complexes
are able to diffuse inside the cell, they may induce toxicity. The experiments in this project will
be performed in simulated gastric juice in order to mimic the conditions of the stomach. The
results of this project will be characterized using IR and proton NMR in order to determine
which complexes have formed.