Stress degradation, structural optimization, molecular docking, ADMET analysis of tiemonium methylsulphate and its degradation products

Abstract

Attempts have been taken to study stress degradation of tiemonium methylsulphate (TMS). Quantum mechanical approach was applied to investigate the structural information, protein binding affinity and pharmacokinetic properties of the TMS and degradation products. Forced degradation study revealed that TMS degraded significantly under acid hydrolysis and photolytic degradation conditions than basic, thermal or oxidative conditions. Density functional theory (DFT) with B3LYP/6-31G+ (d, p) has been employed to optimize the structures. Frontier molecular orbital features (HOMO–LUMO) gap, hardness, softness), dipole moment, atomic partial charge, electrostatic potential and thermodynamic properties (electronic energy, enthalpy, Gibb's free energy) are investigated for optimization of degradation products. Molecular docking has been performed against muscarinic acetylcholine receptor protein 5DSG to search the binding affinity and mode(s). ADMET calculation predicts that all the products are non-carcinogenic and safe for oral administration.

Keywords

• tiemonium methylsulphate
• stress degradation
• uplc method
• dft
• molecular docking
• admet