NMR and X-ray Structural Characterization of a Cisplatin Analogue Able To Slow Down the Pt−N7 Rotation of a Coordinated Guanine Base by a Billion-Fold Times: 2,2′-Bipiperidine(dimethylmalonato)platinum(II) Complex

The synthesis and the NMR and X-ray structural characterization of a cisplatin analogue designed to reduce the Pt−N7 rotation of a coordinated guanine base by a billion times are reported. The [Pt(dmm){(±)-bip}] (dmm = dimethylmalonato; bip = 2,2′-bipiperidine) complex crystallizes in the C2/m space group, which contemplates a mirror plane bisecting the bip and dmm ligands. Because the bip moiety (R,R or S,S configuration at the 2,2′-carbon atoms) does not have planes of symmetry, the requirements of the crystal symmetry are satisfied by a statistical disorder made of bip molecules of R,R or S,S configurations alternating at the same crystallographic site. Such an unexpected arrangement has been permitted by a “quasi planarity” of the bip ligand [maximum deviation from the mean plane through the C and N atoms of 0.2927(9) Å], which allows bip molecules of different chiralities to fit in the same space. The bip array of heavy atoms is overlaid, from both sides, by a layer of “quasi axial” (C)H and (N)H atoms (six per side). Those on one side are hydrogen-bonded to the dmm oxygen atoms of another complex molecule joined in a pair. The distance between the average platinum coordination planes is as short as 3.498(1) Å, comparable to those found in crystals of the [PtCl2(bipy)] complex (bipy = 2,2′-bipyridine) and of graphite, in which, however, all atoms of each unit are rigorously coplanar and there are no out-of-plane hydrogen atoms. The NMR data show a net chemical shift separation between geminal methylene protons, with the “quasi axial” protons being always at higher field with respect to the “quasi equatorial” ones. This is in accordance with a rigid bip ligand frame and the inability of the bip methylene protons adjacent to the coordinated nitrogen to rotate away from a cis-G base (G = guanine) during G rotation around the Pt−N7 bond.

本文报道了一种顺铂（cisplatin）类似物的合成、核磁共振波谱法（Nuclear Magnetic Resonance, NMR）表征与X射线结构表征，该类似物旨在将配位鸟嘌呤碱基的Pt−N7键旋转速率降低十亿倍。该[Pt(dmm){(±)-bip}]（其中dmm为二甲基丙二酸根（dimethylmalonato），bip为2,2'-联哌啶（2,2′-bipiperidine））配合物以C2/m空间群（space group）结晶，其晶胞中包含一个平分bip与dmm配体的镜面（mirror plane）。由于bip片段（2,2'-碳原子处具有R,R或S,S构型）不存在对称面，晶体对称性的要求通过统计无序（statistical disorder）得以满足：同一晶体学位点（crystallographic site）上交替排布R,R与S,S构型的bip分子。这种非预期的排布源于bip配体的准平面性（quasi planarity）[通过其C、N原子的平均平面的最大偏差为0.2927(9)埃（Å）]，使得不同手性的bip分子可容纳于同一空间位点中。bip配体的重原子阵列两侧均被一层准轴向（quasi axial）(C)H与(N)H原子覆盖（每侧各六个原子）。其中一侧的氢原子与成对结合的另一配合物分子的dmm配体氧原子形成氢键（hydrogen bond）。铂配位平面（platinum coordination planes）的平均间距仅为3.498(1)埃，与[PtCl2(bipy)]（其中bipy为2,2'-联吡啶（2,2′-bipyridine））配合物晶体及石墨（graphite）中的间距相当，但后两者中每个结构单元的所有原子均严格共面（coplanar），且无平面外氢原子。核磁共振数据显示偕亚甲基质子（geminal methylene protons）间存在显著的化学位移（chemical shift）分离：准轴向（quasi axial）质子始终相较于准平伏（quasi equatorial）质子处于更高场。这与刚性的bip配体骨架相符，也说明在鸟嘌呤（guanine）绕Pt−N7键旋转的过程中，与配位氮原子相邻的bip亚甲基质子无法偏离顺式鸟嘌呤碱基的方位。