A 119sn mössbauer spectroscopic study on the interaction of dimethyltin(IV) derivatives with rat hemoglobin, and of related model systems in aque

Abstract 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 (Me 2 SnGlyGly), and dimethyltin l -cysteinate (Me 2 SnCys) has been investigated by 119 Sn Mossbauer 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 Mossbauer nuclear quadrupole splitting parameters, ΔE, 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 bipyramldal type (tbp), Me 2 Sn(OH) 2 .·Hepes(II), Me 2 Sn(OH)(GlyGly)·Hepes(III), and Me 2 Sn(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 Me 2 Sn(OH)Cys(IV), as well as Me 2 SnCys(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 Me 2 Sn(OH)(S thiol), (VI), and tetrahedral (IX) or tbp (V) in Me 2 Sn(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 Me 2 Sn(S thiol)(N het), (VIII), or tbp Me 2 Sn(OH)(S thiol)(N het), (VII), and Me 2 Sn(Cys)(S thiol)(N het), (V) (see Figs. 1 and 5).