Brüning Wolfgang, Freisinger Eva, Sabat Michal, Sigel Roland K O, Lippert Bernhard
Fachbereich Chemie Universität Dortmund, 44221 Dortmund, Germany.
Chemistry. 2002 Oct 18;8(20):4681-92. doi: 10.1002/1521-3765(20021018)8:20<4681::AID-CHEM4681>3.0.CO;2-P.
A series of complexes obtained from the reaction of trans-[(CH3NH2)2PtII] with unsubstituted cytosine (CH) and its anion (C), respectively, has been prepared and isolated or detected in solution: trans-[Pt(CH3NH2)2(CH-N3)Cl]Cl.H2O (1), trans-Pt(CH3NH2)2(CH-N3)22 (1a), trans-[Pt(CH3NH2)2(C-N3)2].2H2O (1b), trans-Pt(CH3NH2)2(CH-N3)2(2).2DMSO (1c), trans-[Pt(CH3NH2)2(CH-N1)2] (NO3)(2).3H2O (2a), trans-[Pt(CH3NH2)2(C-N1)2].2H2O (2b), trans-Pt(CH3NH2)2(CH-N1)(CH-N3)2 (3a), trans-[Pt(CH3NH2)2(C-N1)(C-N3)] (3b), and trans-[Pt(CH3NH2)2(N1-CN3)(N3-C-N1)Cu(OH)]ClO(4).1.2H2O (4). X-ray crystal structures of all these compounds, except 3a and 3b, are reported. Complex 2a is of particular interest in that it contains the rarer of the two 2-oxo-4-amino tautomer forms of cytosine, namely that with the N3 position protonated. Since the effect of PtII on the geometry of the nucleobase is minimal, bond lengths and angles of CH in 2a reflect, to a first approximation, those of the free rare tautomer. Compared to the preferred 2-oxo-4-amino tautomer (N1 site protonated) of CH, the rare tautomer in 2a differs particularly in internal ring angles (7-11 sigma). Formation of compounds containing the rare CH tautomers on a preparative scale can be achieved by a detour (reaction of PtII with the cytosine anion, followed by cytosine reprotonation) or by linkage isomerization (N3-->N1) under alkaline reaction conditions. Surprisingly, in water and over a wide pH range, N1 linkage isomers (3a, 2a) form in considerably higher amounts than can be expected on the basis of the tautomer equilibrium. This is particularly true for the pH range in which the cytosine is present as a neutral species and implies that complexation of the minor tautomer is considerably promoted. Deprotonation of the rare CH tautomers in 2a occurs with pKa values of 6.07 +/- 0.18 (1 sigma) and 7.09 +/- 0.11 (1 sigma). This value compares with pKa 9.06 +/- 0.09 (1 sigma) (average of both ligands) in 1a.
分别通过反式-[(CH₃NH₂)₂PtII]与未取代的胞嘧啶(CH)及其阴离子(C)反应得到了一系列配合物，并对其进行了制备、分离或在溶液中检测：反式-[Pt(CH₃NH₂)₂(CH-N₃)Cl]Cl·H₂O (1)、反式-Pt(CH₃NH₂)₂(CH-N₃)₂₂ (1a)、反式-[Pt(CH₃NH₂)₂(C-N₃)₂]·2H₂O (1b)、反式-Pt(CH₃NH₂)₂(CH-N₃)₂(2)·2DMSO (1c)、反式-Pt(CH₃NH₂)₂(CH-N₁)₂(2)·3H₂O (2a)、反式-[Pt(CH₃NH₂)₂(C-N₁)₂]·2H₂O (2b)、反式-Pt(CH₃NH₂)₂(CH-N₁)(CH-N₃)₂ (3a)、反式-[Pt(CH₃NH₂)₂(C-N₁)(C-N₃)] (3b)以及反式-[Pt(CH₃NH₂)₂(N₁-CN₃)(N₃-C-N₁)Cu(OH)]ClO(4)·1.2H₂O (4)。报道了除3a和3b之外所有这些化合物的X射线晶体结构。配合物2a特别引人关注，因为它包含胞嘧啶两种较罕见的2-氧代-4-氨基互变异构体形式中的一种，即N₃位置质子化的那种。由于PtII对核碱基几何结构的影响极小，2a中CH的键长和键角在一级近似下反映了游离罕见互变异构体的键长和键角。与CH的优选2-氧代-4-氨基互变异构体（N₁位点质子化）相比，2a中的罕见互变异构体在内环角度上尤其不同（相差7 - 11西格玛）。通过迂回方法（PtII与胞嘧啶阴离子反应，随后胞嘧啶再质子化）或在碱性反应条件下通过连接异构化（N₃→N₁）可实现制备规模的含有罕见CH互变异构体的化合物的形成。令人惊讶的是，在水和较宽的pH范围内，N₁连接异构体（3a、2a）的形成量比基于互变异构体平衡预期的量高得多。对于胞嘧啶以中性物种存在的pH范围尤其如此，这意味着次要互变异构体的络合作用得到了显著促进。2a中罕见CH互变异构体的去质子化发生时的pKa值为6.07±0.18（1西格玛）和7.09±0.11（1西格玛）。该值与1a中的pKa 9.06±0.09（1西格玛）（两个配体的平均值）相比。
