Poster Title

Theoretical Calculation of the Electron Density Distribution of 1-Methyl-2-Mercaptoimidazole (MMI)

Grade Level at Time of Presentation

Sophomore

Institution

Western Kentucky University

KY House District #

24

KY Senate District #

5

Department

Dept. of Chemistry

Abstract

The thyroid gland is responsible for producing hormones that regulate both gene expression and metabolism. Hyperthyroidism, caused by above average levels of thyroid hormones, can lead to serious conditions such as cardiovascular disease, osteoporosis, or even infertility if left untreated. The most common treatment for hyperthyroidism, 1-methyl-2-mercaptoimidazole (MMI) works to block the synthesis of the thyroid hormone thyroxine (T4) by inhibiting thyroid peroxidase (TPO), a key enzyme in the synthesis pathway. This study looked to facilitate further research on the mechanisms of action of MMI and other thiourea-based compounds by examining the molecular structure and electronic properties that are helpful in modeling enzyme-substrate docking experiments that simulate the drug’s biological activity.

The electronic structure of the MMI molecule has been determined using advanced quantum mechanical techniques and the computing facilities at WKU’s High-Performance Computing Center. Quantum mechanical molecular wavefunctions, total energies, and electron density distributions of MMI have been calculated with large basis sets using three different theoretical approaches. Theoretical electron distributions were compared directly with a previous experimental determination of the electron density obtained from high-resolution, low-temperature single-crystal x-ray measurements. The theoretical and experimental electron distributions show excellent agreement within the estimated uncertainties of the experiment except in the sulfur lone pair region, where less lone pair density is observed compared with the experiment. The topologies of the theoretical densities were analyzed using the Quantum Theory of Atoms in Molecules (QTAIM) formalism which identifies critical point features of the topology which are characteristic of the atomic properties and bonding network present in a molecule. The energies of the N-H…S and C-H…S hydrogen bonds were also determined from theoretical calculations on molecule pairs, and compared with approximate estimates obtained from values of the bond critical point parameters.

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Theoretical Calculation of the Electron Density Distribution of 1-Methyl-2-Mercaptoimidazole (MMI)

The thyroid gland is responsible for producing hormones that regulate both gene expression and metabolism. Hyperthyroidism, caused by above average levels of thyroid hormones, can lead to serious conditions such as cardiovascular disease, osteoporosis, or even infertility if left untreated. The most common treatment for hyperthyroidism, 1-methyl-2-mercaptoimidazole (MMI) works to block the synthesis of the thyroid hormone thyroxine (T4) by inhibiting thyroid peroxidase (TPO), a key enzyme in the synthesis pathway. This study looked to facilitate further research on the mechanisms of action of MMI and other thiourea-based compounds by examining the molecular structure and electronic properties that are helpful in modeling enzyme-substrate docking experiments that simulate the drug’s biological activity.

The electronic structure of the MMI molecule has been determined using advanced quantum mechanical techniques and the computing facilities at WKU’s High-Performance Computing Center. Quantum mechanical molecular wavefunctions, total energies, and electron density distributions of MMI have been calculated with large basis sets using three different theoretical approaches. Theoretical electron distributions were compared directly with a previous experimental determination of the electron density obtained from high-resolution, low-temperature single-crystal x-ray measurements. The theoretical and experimental electron distributions show excellent agreement within the estimated uncertainties of the experiment except in the sulfur lone pair region, where less lone pair density is observed compared with the experiment. The topologies of the theoretical densities were analyzed using the Quantum Theory of Atoms in Molecules (QTAIM) formalism which identifies critical point features of the topology which are characteristic of the atomic properties and bonding network present in a molecule. The energies of the N-H…S and C-H…S hydrogen bonds were also determined from theoretical calculations on molecule pairs, and compared with approximate estimates obtained from values of the bond critical point parameters.