Exploring the molecular interactions of dorzolamide hydrochloride in aqueous solutions: a comprehensive study using thermophysical techniques and molecular simulations across various temperatures

Abstract

This research begins with the initial assessment of key physical properties—density ( ρ), speed of sound ( u), and refractive index ( nD ) in binary aqueous solutions of dorzolamide hydrochloride. These properties were measured in solutions with varying molalities, ranging from 0.0 to 0.0276, under standard atmospheric conditions and at temperatures between 300.15 and 320.15 K. From these measurements, we were able to calculate a range of important parameters, including the apparent molar volume ( Vϕ), its limiting values ([Formula: see text]), limiting apparent molar expansivity ([Formula: see text]), Helper’s constant ([Formula: see text]), apparent molar isentropic compression ( κϕ), and its limiting values ([Formula: see text]), specific refraction ( RD), molar refraction ( RM), and hydration number ( nh). These calculated values provided insights into the strong interactions between the solute and solvent in the liquid system. They also shed light on the presence of various molecular interactions, such as inter- and intramolecular hydrogen bonds, dipole–dipole, and dipole-induced-dipole interactions, as well as the ability of the solute to influence the structure of the surrounding water molecules. Additionally, we derived the densities of dorzolamide hydrochloride solutions from molecular dynamics (MD) simulations, which showed a strong correlation with our experimental findings, underscoring the reliability of MD simulations in such studies. In the end, our combined study on dorzolamide hydrochloride in water demonstrates that it shapes structures because it has lower volumetric properties and stronger hydrogen bonds in MD simulations. More alchemical free energy calculations show that there are big changes in solvation energies. This is important for understanding how dorzolamide hydrochloride works in water.