Neutral hypoxanthine in aqueous solution: quantum chemical and Monte-Carlo studies

In order to advance in the knowledge of the hypoxanthine physicochemical properties, joint Quantum Chemical and Monte-Carlo studies of the neutral heterocycle in its N(1)–H/N(7)–H (H17) and N(1)–H/N(9)–H (H19) tautomeric forms in aqueous solution were performed. Quantum studies on hypoxanthine tautomer–water selected pairs show that both tautomeric forms have preferential sites for attractive interactions with water, which yield both common and distinctive features on the hydrogen-bond pattern of heterocycle–water. The Monte-Carlo simulations were performed with the Mobile Charges and Harmonic Oscillator potential fitted to the H17 tautomer–water interactions energies obtained with the Density Functional Theory calculations; the potential was transferable to the H19 tautomer–water case. The results for the respective tautomers aqueous solution, show no significant differences between H17 and H19 on their restricted solvation-thermodynamic properties. The same study reveals that microscopic properties such as the density of water molecules, the tautomers–water and water–water interaction energies, and the water electric dipole moment are strongly sensitive to both the respective molecular regions of each tautomer and the heterocyclic region–water intermolecular distances. Among other results, two solvation shells for each tautomer can be proposed, the first one showing distinctive location around the tautomer, in agreement with the Quantum Mechanics predictions. The H19 tautomer appears to induce a solvent reorganization at longer distances than that for H17. Such feature can be related to the comparatively higher polarization capacity of H19, as is deduced from its theoretical electric dipole moment in aqueous solution. The studies here presented are the first ones in which an approximation to the hypoxanthine–water interactions and to the structural aspects of the solvent around the solute are made for these kind of heterocycles aqueous solutions, which are of biological interest.