A near-infrared spectroscopic study of the conformational equilibria of lidocaine molecules in a highly concentrated lidocaine solution in supercritical CO2

Abstract

In this work, we studied conformational equilibria of molecules of lidocaine in its highly concentrated solutions in scCO2 at the CO2 density values ranging from ∼1.5 to ∼2.0 of the critical value along the isotherm of 35 °C. The study was based on analyzing the spectral band related to the first overtone of the stretching vibrations of the lidocaine molecule N–H fragment. To determine the key factor affecting the formation of intermolecular hydrogen bonds between the lidocaine molecules in the solution we divided our experiment into two stages. First, in the pressure range of 100–180 bar we analyzed the spectra evolution associated with an increase in the concentration of the saturated solution. Then, in the pressure range of 180–300 bar we analyzed the spectra evolution for a solution, where the lidocaine concentration, which was reached at 180 bar, remained constant.We found that the probability of intermolecular hydrogen bond formation considerably increased with lidocaine concentration growth, which, in turn, led to a rise in the population of lidocaine molecules without an intramolecular hydrogen bond. We concluded that the formation of intermolecular hydrogen bonds caused redistribution of the conformer fractions with and without an intramolecular hydrogen bond. Finally, we showed that the key factor affecting the formation of intermolecular hydrogen bonds between the molecules of lidocaine in its solution in scCO2 is the solute concentration rather than the pressure.