Computational evaluation on the molecular conformation, vibrational spectroscopy, NBO analysis and molecular docking of betaxolol and betaxolol-chlorthalidone cocrystals

Abstract

In this work, we will report a combined experimental and theoretical study on the molecular structures of betaxolol and betaxolol. HCl drug in monomeric and dimeric forms, and in combination with chlorthalidone. Geometry optimizations were carried out in the gas phase by B3LYP-D3BJ/6–311++G(d,p) level of DFT. The electronic properties were performed by time-dependent DFT (TD-DFT) approach. Global reactivity descriptors (ionization potential, electron affinity, electronegativity, electrophilicity index, global hardness, global softness and chemical potential) were predicted with the help of HOMO/LUMO energy values. Experimental FT-IR spectrum of betaxolol was recorded and compared with the computed values obtained by the same level of DFT. Detailed vibrational assignments of the vibrational spectrum have been made on the basis of potential energy distribution (PED) analysis. Molecular electrostatic potential map (MEP), topology analysis (AIM, ELF, LOL) and reduced density gradient (RDG) were used to detect the possible electrophilic and nucleophilic sites as well as hydrogen bonding, which elucidated the important role of the isopropylamino-2-propanol moiety of the betaxolol structure in the biological activity of the drug to block β1-adrenergic receptors. Cocrystals of betaxolol–chlorthalidone were prepared and the structure was tested by X-ray powder diffraction. Stability of the molecular structures and hydrogen bonding interactions in pure betaxolol and in betaxolol-chlorthalidone cocrystals were investigated by NBO analysis. The biological activity of the molecule in terms of molecular docking has been analyzed theoretically.