A series of ten oxygen and sulfur heterocyclic compounds that are potential antithrombotic agents are to be synthesize using proven synthetic organic pathways. These compounds, similar in structure to some naturally occurring heterocyclic substances found in garlic, will be purified and characterized, and the structures of the rings of these compounds will be determined using far-infrared and low-frequency Raman spectroscopy. Blood platelet aggregation inhibition properties of these substances will be measured using a Chrono-Log Model 540 VS Whole Blood Aggregometer. Also, state-of-the-art FT-Raman Spectroscopy, using near-infrared laser excitation and fiber optics remote sensing will be used to examine the changes in the blood-platelet membrane that control and prevent platelet aggregation. A correlation study will be performed to look for a possible connection between the molecular structure of these ring compounds and their ability to prevent platelet aggregation. The long term objective of the study is to obtain a better understanding of the forces that are present in small heterocyclic ring molecules, and how and why these substances affect blood platelet aggregation. The study, when completed, will reveal a possible link between the structure of the inhibitor and it s ability to prevent blood platelet aggregation. These studies will provide information useful in the design of drugs that can be used in place of heparin and aspirin to limit blood clotting, possibly with fewer side effects.
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