Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Akademika Zabolotnoho Str., 03680 Kyiv, Ukraine.
Phys Chem Chem Phys. 2013 Dec 14;15(46):20091-104. doi: 10.1039/c3cp52644e.
A theoretical study of tautomerisation of the biologically important cytosine·cytosine* (C·C*) DNA mismatch with a propeller-like structure (|C4N3N3C4| = 32.4°; C1 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·C*↔C*·C) (|C4N3N3C4| = 48.5°; C1 symmetry) into the C*·C mispair was carried out for the first time. It was established that the C·C*/C*·C DNA base mispair is associated by the antiparallel N4H···N4 (6.66 kcal mol(-1)), N3H···N3 (6.47 kcal mol(-1)) H-bonds and the O2···O2 van der Waals (vdW) contact (0.33 kcal mol(-1)), while the zwitterionic TSC·C*↔C*·C is stabilized by the parallel N4(+)H···N4(-) (13.55 kcal mol(-1)), N3(+)H···N3(-) (13.20 kcal mol(-1)) H-bonds and the O2(+)···O2(-) vdW contact (0.60 kcal mol(-1)). It was shown that the C·C* ↔ C*·C tautomerisation via the DPT is assisted by the O2···O2 vdW contact, that in contrast to the two others N4H···N4 and N3H···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 Å mdyn(-1) for C·C*/C*·C and TSC·C*↔C*·C, respectively) indicate that the O2···O2 vdW contact is a stabilizing closed-shell interaction. It was found that the middle N3H···N3 H-bond is anti-cooperative with the upper N4H···N4 H-bond and cooperative with the lower O2···O2 vdW contact. The 9 key points, which can be considered as electron-topological "fingerprints" of the asynchronous concerted C·C* ↔ C*·C tautomerisation process via the DPT were revealed along the IRC and examined in detail. It was shown that the C·C*/C*·C base mispair is a thermodynamically and dynamically stable structure. Its lifetime is equal to 1.53 × 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.
首次对具有桨状结构（|C4N3N3C4|=32.4°；C1 对称）和顺式取向的 N1H 糖苷键的生物重要胞嘧啶·胞嘧啶*（C·C*）DNA 错配的互变异构化进行了理论研究，该错配由 C 核碱基的氨基和亚氨基互变异构体通过异步协同双质子转移（DPT）形成，通过过渡态（TSC·C*↔C*·C）（|C4N3N3C4|=48.5°；C1 对称）进入 C*·C 错配。结果表明，C·C*/C*·C DNA 碱基错配由反平行 N4H···N4（6.66 kcal mol(-1)）、N3H···N3（6.47 kcal mol(-1)）氢键和 O2···O2 范德华（vdW）接触（0.33 kcal mol(-1)）稳定，而 zwitterionic TSC·C*↔C*·C 则由平行 N4(+)H···N4(-)（13.55 kcal mol(-1)）、N3(+)H···N3(-)（13.20 kcal mol(-1)）氢键和 O2(+)···O2(-) vdW 接触（0.60 kcal mol(-1)）稳定。结果表明，C·C*↔C*·C 互变异构通过 DPT 得到 O2···O2 vdW 接触的辅助，与另外两个 N4H···N4 和 N3H···N3 氢键不同，它沿着整个固有反应坐标（IRC）范围存在。Grunenberg 顺应常数的正值（C·C*/C*·C 和 TSC·C*↔C*·C 分别为 30.919 和 21.384 Å mdyn(-1)）表明 O2···O2 vdW 接触是一种稳定的闭壳相互作用。结果发现，中间的 N3H···N3 氢键与上部的 N4H···N4 氢键呈反协同作用，与下部的 O2···O2 vdW 接触呈协同作用。沿着 IRC 揭示并详细检查了 9 个关键点，它们可以被认为是通过 DPT 进行异步协同 C·C*↔C*·C 互变异构过程的电子拓扑“指纹”。结果表明，C·C*/C*·C 碱基错配是一种热力学和动力学稳定的结构。在真空的 MP2/cc-pVQZ//B3LYP/6-311++G(d,p)理论水平下，其寿命等于 1.53×10(-7)s。在此期间，所有 6 个低频率的分子间振动都能够发展。
