When Tautomers Matter: UV‐Vis Absorption Spectra of Hypoxanthine in Aqueous Solution from Fully Atomistic Simulations

Abstract

The UV‐Vis spectrum of the solvated purine derivative Hypoxanthine (HYX) is investigated using the Quantum Mechanics/Fluctuating Charges (QM/FQ) multiscale approach combined with a sampling of configurations through atomistic Molecular Dynamics (MD) simulations. Keto 1H7H and 1H9H tautomeric forms of HYX are the most stable in aqueous solution and form different stable complexes with the surrounding water molecules, ultimately affecting the electronic absorption spectra. The final simulated spectrum resulting from the combination of the individual spectra of tautomers agrees very well with most of the characteristics in the measured spectrum. The importance of considering the effect of the solute tautomers and, in parallel, the contribution of the different solvent arrangements around the solute when modeling spectral properties, is highlighted. In addition, the high quality of the computed spectra leads to suggesting an alternative way for acquiring tautomeric populations from combined computational/experimental spectra.

The Role of Hydrogen Bonding in the Raman Spectral Signals of Caffeine in Aqueous Solution

“…This is carried out using the NBO analysis [54][55][56] in the NBO7 program [92]. Similar QM/FQ NBO analyses have been conducted for common pharmaceuticals [51,67] and hypoxanthine [48] in solution. Conventional bond critical points (BCP) of the electron density and localized Natural BCPs topological descriptors are computed with the Natural BCP (NBCP) analysis as implemented in NBO7 [92].…”

“…Such features are all integrated into Quantum Mechanics/Fluctuating Charges (QM/FQ) computational protocols developed during the last years in our research group [44][45][46]. By following the protocol, we have previously studied the absorption spectra of caffeine and similar xanthines [47,48] and so far we have also computed RR spectroscopies on solvated amides [49], dipeptides [50], anionic ibuprofen [51], contaminants [52], doxorubicin (DOX) and DOX-DNA [53] complexes. As a general finding, we have seen that the multiscale QM/FQ protocols outperform implicit and non-polarizable QM/Molecular Mechanics approaches, and this is due to the atomistic treatment of the solvent molecules and thus of the solute-solvent interactions.…”