In silico Studies on Nuclei Magnetic Resonance Spectroscopy, Molecular Orbitals and Geometry Optimization of Antidiabetic Drug, N,N-dimethylimidodicarbonimidic Diamide (Metformin)

Abstract

N,N-dimethylimidodicarbonimidicdiamide (Metformin) is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. The in silico nuclear resonance magnetic spectroscopy of metformin was performed using ACD/I-lab. The chemical shifts of the methyl protons labelled 6 and 7 appeared as a singlet at 3.03 ppm while the chemical shifts of the amino protons labelled 3, 5, 10 and 11 appeared as a singlet at position 10.16, 6.66, 8.57 and 8.38 ppm respectively. The methyl carbons at 6 and 7 positions showed chemical shift at 38.77 ppm while the imine carbons showed chemical shifts at 158.20 and 159.10 ppm. All conformational analysis (geometry optimization) study was performed on a window based computer using Argus lab software. The metformin structure was generated by Argus lab, and minimization was performed with the semi-empirical Parametric Method 3 (PM3). The minimum potential energy was calculated by geometry convergence function in Argus lab software. Surfaces were created to visualize highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO) and electrostatic potentials (ESP) mapped density. The minimum potential energy calculated using geometry convergence function in Argus lab software was found to be 41.537840 kcal/mol. This energy minimum is the most stable conformation of the molecule.