Honors Theses

Date of Award

2026

Document Type

Undergraduate Thesis

Department

Chemistry and Biochemistry

First Advisor

Ryan Fortenberry

Second Advisor

Nathan Hammer

Third Advisor

Kristine Willett

Relational Format

Dissertation/Thesis

Abstract

The microsolvation of a 1,1-dimethyl-biguanide hydrochloride molecule in the presence of water molecules illustrates the initial interactions between the common drug metformin and water. This explicit water-solvation approach employs coupled-cluster theory with an explicit-correlation F12 correction and the cc-pVTZ-F12 basis set to determine the optimalgeometry of the molecule and to observe intermolecular interaction energies. 1,1-dimethyl-biguanide hydrochloride (an antidiabetic agent, metformin) is constantly in contact with water molecules in the human body, where it reduces intestinal glucose absorption, lowers hepatic glucose sensitivity, and improves overall insulin sensitivity to lower blood-glucose concentration. The B3LYP method with an aug-cc-pVTZ basis set is used to find an initial optimized geometry and the zero-point vibrational energies. CCSD(T)-F12/cc-pVTZ-F12 refines the geometry optimization for one water molecule systems, and CCSD(T)-F12/cc-pVDZ-F12 is employed for the metformin molecules in the presence of multiple water molecules. Four individual conformers of metformin related by rotation about the two bonds connecting the central nitrogen to the two double-bonded carbons are studied, and the process is repeated with each conformer in the presence of one or more water molecules. The data obtained from this work show that water binding changes the molecule’s shape, and the change in shape may alter the function in the body. This study may contribute to further research regarding water balance and hypohydration in diabetes mellitus patients who have been prescribed metformin.

Included in

Diseases Commons

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