Metal Coordination and Imine−Amine Hydrogen Bonding as the Source of Strongly Shifted Adenine pKa Values

The X-ray crystal structure of a PtII complex of composition trans-[(NH3)2Pt(1,9-DimeA) (1,9-DimeAH)](ClO4)3 (2) with 1,9-DimeA = 1,9-dimethyladenine and 1,9-DimeAH+ = 1,9-dimethyladeninium)
is presented. Complex 2 forms upon deprotonation of one of the exocyclic amino groups of the adeninium
ligands in trans-[(NH3)2Pt(1,9-DimeAH)2](ClO4)4 (1), where the two nucleobases are in a head−tail
arrangement. The low pKa1 of 1 (4.1 ± 0.2) is a consequence of a combination of the effects of metal
coordination to N7 of the purine base and efficient stabilization of the deprotonated species. This feature
is supported by the results of the structure determination of 2, which displays a head−head orientation of
the two bases and intramolecular H-bonding between the imine group of 1,9-DimeA and the amino group
of 1,9-DimeAH. In the fully deprotonated species trans-[(NH3)2Pt(1,9-DimeA)2](ClO4)2 (3), the two
nucleobases are again in a head−tail arrangement. The findings are of relevance with regard to the concept
of “shifted pKa values” of nucleobases. This concept is applied to rationalize acid−base catalysis reactions
involving nucleobases of DNA and RNA which occur in the near-physiological pH range.

本文展示了由1,9-二甲基腺嘌呤（1,9-DimeA）和1,9-二甲基腺嘌呤阳离子（1,9-DimeAH+）组成的PtII配位化合物trans-[(NH3)2Pt(1,9-DimeA)(1,9-DimeAH)](ClO4)3（2）的X射线晶体结构。该化合物在去质子化trans-[(NH3)2Pt(1,9-DimeAH)2](ClO4)4（1）中的外环腺嘌呤配体氨基之一后形成，其中两个核苷酸基团呈头-尾排列。化合物1的低pKa1值（4.1 ± 0.2）是金属与嘌呤碱基N7配位效应与去质子物种高效稳定化的综合结果。这一特征得到了化合物2的结构测定结果的支持，该结果显示两个碱基呈头-头取向，并且在1,9-二甲基腺嘌呤的亚胺基和1,9-二甲基腺嘌呤阳离子的氨基之间存在分子内氢键。在完全去质子化的物种trans-[(NH3)2Pt(1,9-DimeA)2](ClO4)2（3）中，两个核苷酸基团再次呈头-尾排列。这些发现与“核苷酸基团pKa值偏移”的概念相关，该概念被应用于解释发生在近生理pH范围内的DNA和RNA核苷酸基团参与的酸碱催化反应。