Atomistic nature of the DPT tautomerisation of the biologically important C•C* DNA base mispair containing amino and imino tautomers of cytosine: a QM and QTAIM approach

A theoretical study of tautomerisation of the biologically important cytosine center dot cytosine* (C center dot C*) DNA mismatch with a propeller-like structure (vertical bar C4N3N3C4 vertical bar = 32.4 degrees; C-1 symmetry) and cis-oriented N1H glycosidic bonds, formed by the amino and imino tautomers of the C nucleobase, via the asynchronous concerted double proton transfer (DPT) along two H-bonds through the transition state (TSC center dot C*<-> C*center dot C) (vertical bar C4N3N3C4 vertical bar = 48.5 degrees; C-1 symmetry) into the C*center dot C mispair was carried out for the first time. It was established that the C center dot C*/C*center dot C DNA base mispair is associated by the antiparallel N4H center dot center dot center dot N4 (6.66 kcal mol(-1)), N3H center dot center dot center dot N3 (6.47 kcal mol(-1)) H-bonds and the O2 center dot center dot center dot O2 van der Waals (vdW) contact (0.33 kcal mol(-1)), while the zwitterionic TSC center dot C*<-> C*center dot C is stabilized by the parallel N4(+)H center dot center dot center dot N4(-) (13.55 kcal mol(-1)), N3(+)H center dot center dot center dot N3(-) (13.20 kcal mol(-1)) H-bonds and the O2(+)center dot center dot center dot O2(-) vdW contact (0.60 kcal mol(-1)). It was shown that the C center dot C* <-> C*center dot C tautomerisation via the DPT is assisted by the O2 center dot center dot center dot O2 vdW contact, that in contrast to the two others N4H center dot center dot center dot N4 and N3H center dot center dot center dot N3 H-bonds exists along the entire intrinsic reaction coordinate (IRC) range. The positive values of the Grunenberg's compliance constants (30.919 and 21.384 angstrom mdyn(-1) for C center dot C*/C*center dot C and TSC center dot C*<-> C*center dot C, respectively) indicate that the O2 center dot center dot center dot O2 vdW contact is a stabilizing closed-shell interaction. It was found that the middle N3H center dot center dot center dot N3 H-bond is anti-cooperative with the upper N4H center dot center dot center dot N4 H-bond and cooperative with the lower O2 center dot center dot center dot O2 vdW contact. The 9 key points, which can be considered as electron-topological "fingerprints" of the asynchronous concerted C center dot C* <-> C*center dot C tautomerisation process via the DPT were revealed along the IRC and examined in detail. It was shown that the C center dot C*/C*center dot C base mispair is a thermodynamically and dynamically stable structure. Its lifetime is equal to 1.53 x 10(-7) s at the MP2/cc-pVQZ//B3LYP/6-311++G(d,p) level of theory in vacuum. All 6 low-frequency intermolecular vibrations are able to develop during this time span.