Density functional theory studies on a non-covalent interaction system: hydrogen-bonded dimers of zoledronate

A computational study was carried out to characterize the hydrogen-bonded dimers of Zoledronate (ZOL), which is used widely in treating skeletal diseases. The stable conformations, hydrogen bonding interactions, IR spectra, thermodynamic properties, and electronic characteristics of nine possible ZOL dimers were studied using density functional theory (DFT) at the B3LYP/6-311++G** level. The stability of dimers was determined according to the analyses of total electronic energies and hydrogen bonding interactions. The results showed that both the number and intensity of hydrogen bonds played an important role in determining the stability order of dimers, and the hydrogen bonding interactions in dimers resulted in a red shift of hydroxyl vibration with a corresponding increase in intensity. The calculated thermodynamic properties illustrated that the dimerization process can take place spontaneously at room temperature. Natural bond orbital and atoms in molecules analyses revealed that the nature of hydrogen bonding interactions was attributed to the interactions from lone pair orbital n(A) to the antibonding orbital σ*(D-H), and the interactions were closed-shell interactions in hydrogen-bonded dimers of ZOL. Graphical abstract Changes in Gibbs free energy and infrared spectra of ZL in the dimerization process.