Theoretical and experimental studies on 2-(2-methyl-5-nitro-1-imidazolyl)ethanol

In this work, we report a combined experimental and theoretical study on molecular structure, vibrational spectra, natural bond orbital (NBO) and UV spectral analysis of [2-(2-methyl-5-nitro-1-imidazolyl) ethanol] (Metronidazole-MTD). The FT-IR solid phase (4000-400 cm-1) liquid phase, and FT-Raman spectra (3500-50 cm-1) of MTD were recorded. The molecular geometry, harmonic vibrational frequencies and bonding features of MTD in the ground state have been calculated using the density functional method B3LYP with 6-311G(d,p) as basis set. The assignments of the vibrational spectra have been carried out with the help of the Gauss view program package. Stability of the molecule arising from hyperconjugative interactions and charge delocalization have been analyzed using natural bond orbital analysis. The results show that charge in electron density (ED) in the σ* and π* antibonding orbitals and second order stabilization energies E2 confirms the occurrence of Intramolecular Charge Transfer (ICT) within the molecule. The UV spectrum was measured in ethanol solution. The energy and oscillator strength calculated by Time-Dependent Density Functional Theory (TD-DFT) results complement the experimental findings. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the Gauge Independent Atomic Orbital (GIAO) method and compared with experimental results.  Finally the results of calculations were applied to simulate Infrared and Raman spectra of the title compound which show good agreement with observed spectra

Identification of Important Chemical Features of 11β-Hydroxysteroid Dehydrogenase Type1 Inhibitors: Application of Ligand Based Virtual Screening and Density Functional Theory

11β-Hydroxysteroid dehydrogenase type1 (11βHSD1) regulates the conversion from inactive cortisone to active cortisol. Increased cortisol results in diabetes, hence quelling the activity of 11βHSD1 has been thought of as an effective approach for the treatment of diabetes. Quantitative hypotheses were developed and validated to identify the critical chemical features with reliable geometric constraints that contribute to the inhibition of 11βHSD1 function. The best hypothesis, Hypo1, which contains one-HBA; one-Hy-Ali, and two-RA features, was validated using Fischer’s randomization method, a test and a decoy set. The well validated, Hypo1, was used as 3D query to perform a virtual screening of three different chemical databases. Compounds selected by Hypo1 in the virtual screening were filtered by applying Lipinski’s rule of five, ADMET, and molecular docking. Finally, five hit compounds were selected as virtual novel hit molecules for 11βHSD1 based on their electronic properties calculated by Density functional theory