Conformational distributions of tetrahydro-2-turoic acid in water at different pH values by their IR and vibrational circular dichroism spectra.

Infrared (IR) and vibrational circular dichroism (VCD) spectra of tetrahydro-2-furoic acid (THFA) in aqueous solutions under several different pH conditions were recorded. To interpret the IR and VCD spectra of THFA obtained in highly acidic and basic aqueous solutions, extensive and systematic conformational searches were conducted to acquire the low-energy minima for both the neutral and deprotonated forms of THFA species, as well as their hydrated clusters. This was accomplished by using the conformer-rotamer ensemble sampling tool (CREST) with an implicit solvation model for water. The CREST candidates were further optimized at the B3LYP-D3BJ/def2-TZVP level of theory. The simulated VCD spectra of the neutral THFA conformers in the polarizable continuum model (PCM) of water alone exhibit little agreement with the experimental data under highly acidic conditions. Applying the clusters-in-a-liquid solvation model by considering the monohydrate THFA conformers in the PCM of water, significantly improved agreement with the experimental data. Similarly, the deprotonated THFA species solvated with one to four explicit water molecules in the PCM of water were considered. While the IR and VCD spectra of the deprotonated THFA monohydrate conformers offer the best agreement with the experimental data, other larger hydrated clusters, particularly the dihydrates, also contribute to the spectra. Through the synergistic combined experimental and theoretical approach used in the study, comprehensive conformational distributions of the predominant THFA species across various pH conditions were extracted.