Barbieri R, Musmeci M T
Department of Inorganic Chemistry, University of Palermo, Italy.
J Inorg Biochem. 1988 Feb;32(2):89-108. doi: 10.1016/0162-0134(88)80018-7.
In the context of a study of the molecular basis of the antileukemia (murine) activity of diorganotin (IV) compounds, the interaction with rat hemoglobin (selected as a model protein) of the representative terms dimethyltin dichloride, dimethyltin glycylglycinate (Me2SnGlyGly), and dimethyltin L-cysteinate (Me2Sn-Cys) has been investigated by 119Sn Mössbauer spectroscopy. In order to possibly determine the reaction pathway, aqueous model systems in Hepes buffer at pH 7.4 were also considered. The structural characteristics of reactants and products were advanced on the basis of semiempirical calculations of Mössbauer nuclear quadrupole splitting parameters, delta E, by the point-charge model approach. In aqueous Hepes at pH 7.4, evidence was obtained for the formation of the five-coordinated species, trigonal bipyramidal type (tbp), Me2Sn(OH)2.Hepes(II), Me2Sn(OH)(GlyGly).Hepes(III), and Me2Sn(OH)Cys(IV) (see Fig. 1). Equatorial groups or atoms would be the Me radicals, as well as OH, N(peptide), and S(thiol), respectively. Hepes would coordinate to tin in axial position through the tertiary amino nitrogen, while cysteine would behave as a bidentate chelating agent, with an axially located amino group. Species (II), (III), and (IV) react with cysteine in aqueous Hepes at pH 7.4, yielding Me2Sn(OH)Cys(IV), as well as Me2SnCys2(V), where tin would be embedded into a tbp structure due to one cysteine probably chelating (equatorial S thiol and axial amino nitrogen), and one monodentate through S thiol. Species (II), (III), and (IV) react analogously with rat hemoglobin, primarily through the S thiol of a cysteine side chain, yielding pellets where the environment of tin could be tetrahedral, such as in Me2Sn(OH)(S thiol), (VI), and tetrahedral (IX) or tbp (V) in Me2Sn(Cys)(S thiol), where Cys would act either as chelating or monodentate. Further reaction of (VI) and (IX) could involve imidazole nitrogen atoms, N het, of histidine side chains, forming tetrahedral Me2Sn(S thiol)(N het), (VIII), or tbp Me2Sn(OH)(S thiol)(N het), (VII), and Me2Sn(Cys)(S thiol)(N het), (V) (see Figs. 1 and 5).
在一项关于二有机锡（IV）化合物抗白血病（鼠类）活性分子基础的研究中，通过¹¹⁹Sn穆斯堡尔光谱研究了代表性化合物二氯化二甲基锡、二甲基锡甘氨酰甘氨酸（Me₂SnGlyGly）和二甲基锡L-半胱氨酸（Me₂Sn-Cys）与大鼠血红蛋白（选为模型蛋白）的相互作用。为了可能确定反应途径，还考虑了pH 7.4的Hepes缓冲液中的水相模型体系。基于点电荷模型方法对穆斯堡尔核四极分裂参数δE进行半经验计算，提出了反应物和产物的结构特征。在pH 7.4的水相Hepes中，获得了形成五配位物种的证据，即三角双锥型（tbp）的Me₂Sn(OH)₂.Hepes(II)、Me₂Sn(OH)(GlyGly).Hepes(III)和Me₂Sn(OH)Cys(IV)（见图1）。赤道基团或原子分别为甲基基团、OH、N（肽）和S（硫醇）。Hepes将通过叔氨基氮在轴向位置与锡配位，而半胱氨酸将作为双齿螯合剂，氨基位于轴向。物种（II）、（III）和（IV）在pH 7.4的水相Hepes中与半胱氨酸反应，生成Me₂Sn(OH)Cys(IV)以及Me₂SnCys₂(V)，其中由于一个半胱氨酸可能螯合（赤道S硫醇和轴向氨基氮）且一个通过S硫醇单齿配位，锡将嵌入tbp结构。物种（II）、（III）和（IV）与大鼠血红蛋白的反应类似，主要通过半胱氨酸侧链的S硫醇，生成小球，其中锡的环境可能是四面体，如在Me₂Sn(OH)(S硫醇)（VI）中，以及在Me₂Sn(Cys)(S硫醇)中为四面体（IX）或tbp（V），其中半胱氨酸将作为螯合剂或单齿配体起作用。（VI）和（IX）的进一步反应可能涉及组氨酸侧链的咪唑氮原子N het，形成四面体Me₂Sn(S硫醇)(N het)（VIII）或tbp Me₂Sn(OH)(S硫醇)(N het)（VII）以及Me₂Sn(Cys)(S硫醇)(N het)（V）（见图1和5）。
