Tautomerism of Inosine in Water: Is It Possible?

Syn- and anti-conformers of four tautomer structures of inosine were studied in the gas phase and in solvent water to investigate the possibility of hydrogen bonding and tautomeric conversion. It was found that in the gas phase and in water solution the most stable is the syn-conformer of the 6-keto tautomer followed by its anti-conformer and syn-conformer of the 6-enol form. In the gas phase, the percent content of syn- and anti-conformers is 83.77 and 12.86%, respectively, whereas syn-enol tautomer is calculated to be 2.54%. However, in water solution the syn-conformer of the keto tautomer is 99.9%. The water-assisted proton transfer process in inosine was investigated using ab initio MP2 and SCS-MP2 quantum chemical approaches. Solute-solvent clusters containing an inosine molecule and five water molecules embedded in the "bulk" solvent treated as polarizable continuum (the CPCM/MP2/6-31+G(d,p) level of theory) were explored. The energy barrier of the water-assisted proton transfer reaction in inosine is found to be 12.9 kcal mol and the rate constant ( k = 6.68 × 101 s) is sufficiently large to generate the 6-enol tautomer. From the reaction profile of the proton transfer we can conclude that the process is realized through the asynchronous concerted mechanism.