Tautomerism of Inosine in Water: Is It Possible?

Abstract

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–1 and the rate constant (k = 6.68 × 101 s–1) 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.

Tautomerism of cytosine, cytidine, and deoxycytidine: Proton transfer through water bridges

“…However, the energy difference between the syn-and anti-conformers of CydA is 6.32 kcal mol À1 while these between syn-and anti-conformers of CydB are 3.34-3.77 kcal mol À1 . As we noted in our previous paper [8] the energy barrier of the rotation around the glycosidic bond in inosine is 4.33 kcal mol À1 . That is why the syn-, anti-, and syn-clinal conformers of the cytidine tautomers should coexist in gas phase.…”

“…To consider the impact of the non‐specific (long‐range) solvent effects on the investigated complexes, the structure of the six cytosine‐water clusters in the reaction field of water as implicit solvent was optimized at CPCM/MP2/6–31 + G ( d , p ) level. We have successfully used such а cluster‐continuum model to study the mechanism of water‐assisted proton transfer reactions [8].…”

“…Therefore, it is higher in energy and less preferred in isolated form [6]. Nucleosides are known to have complex conformational structure in isolated state [7, 8].…”

Self‐catalytic mechanism of prebiotic reactions: From formamide to purine bases

“…Spin‐component‐scaled MP2 method has been successfully used for the investigation of the reaction mechanism of tautomeric conversions [ 100,101 ] or chalcone formation. [ 102 ] Galvao et al [ 100 ] reported that the value of the energy gap between cis ‐2‐hydroxypyridine and 2‐pyridone, calculated at SCS‐MP2/aug‐cc‐pVTZ level is closer to the experimental value than the one calculated at CCSD(T)/aug‐cc‐pVTZ level.…”

“…In addition, the SCS‐MP2 method has the advantage of lower computational cost than QCISD(T) and CCSD(T) methods. We have shown in our previous papers [ 101,102 ] that the calculations at the SCS‐MP2 level increase the energy barriers compared with the MP2 ones.…”