R. Barbieri

The antitumor activity of di-n-butyltin(IV) glycylglycinate, and the correlation with the structure of dialkyltin(IV) glycylglycinates in solution

The in vivo activity of Bu2nSnGlyGly, Na(Cl2GaGlyGly), and ClGaGlyGly (GlyGly2- = glycylglycinate) has been investigated in connection with a number of tumors. Positive results have been obtained only for the Bu2nSnIV complex in the case of leukemia P-388. In order to try to interpret the pharmacological data on a molecular basis, the nature of the species present in solutions of AlK2Sn GlyGly complexes, as well as the reactivity of aqueous Me2SnGlyGly, have been studied. The presence of chelated species (I), Figure 1, in organic solvents, and the equilibrium (I) in equilibrium (II), Figure 1, in water and mixed water-organic solvent systems, have been inferred from conductance measurements, as well as from studies by Mössbauer (in frozen solution), 1H, 13C, and 119Sn NMR, and ir spectroscopy. Moreover, solvated (II) would release AlK2SnIV moieties, as evidenced by the slow formation of (Me2SnO)n from aqueous Me2Sn GlyGly. The involvement of (I) and (II) in the transportation of these drugs across cell membranes is discussed.

Complexes of organometallic compounds V. Diphenyltin(IV) and triphenyltin(IV) oxinates

Abstract The complexes formed between diphenyltin(IV) and triphenyltin(IV) cations and 8-quinolinol were prepared and studied spectrophotometrically in ethanol solution. It was shown that diphenyltin dioxinate is very probably a chelate complex, with a coordination number of six for the tin atom, and that triphenyltin oxinate probably is not a chelate complex, and has a coordination number of four for the tin atom. Triphenyltin oxinate has been prepared in the solid state for the first time.

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

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).

Studies on adducts of organotin(IV) halides with bis(acetylacetone)ethylenediimine

The solid state configuration of 1/1 adducts, formed by mono-, di- and tri-organotin(IV) halides with the potentially tetradentate ligand bis(acetylacetone)ethylenediimine, has been investigated. The infrared spectra suggest that the neutral ligand coordinates SnIV through N (or O) atoms of the H-bonded acetylacetoneimine moieties. The skeletal vibrations associated to Sn-C and Sn-Cl bonds are consistent with square planar configurations of the organotin(IV) halide moieties, where SnCl3 and C3Sn groups would be T-shaped, and Alk2SnCl2 would have trans-dialkyl, trans-dichloro arrangements. The latter configuration is supported by the magnitude of the quadrupole splittings. Measurements of the temperature dependence of the Debye-Waller factor, as obtained by Mossbauer spectroscopy for the (CH3)3SnCl adduct, indicate a polymeric structure. An octahedral type configuration is then proposed, in which the planar organotin(IV) halide moieties are bridged by the ligand, axially coordinating tin(IV).

The interaction of native DNA with dimethyltin(IV) species.

The reaction of aqueous native DNA (calf thymus) with the solvated organotin(IV) species [(CH3)2SnCl2(C2H5OH)n], as well as with [(CH3)2Sn(OH)(H2O)n]+ and (CH3)2Sn(OH)2 (i.e., the hydrolysis products of aqueous (CH3)2SnCl2 at pH approximately 5 and pH approximately 7.4 respectively), was investigated by 119Sn Mössbauer spectroscopy. The addition of [(CH3)2SnCl2(C2H5OH)n] to DNA yielded a solid product, possibly (CH3)2Sn(DNA phosphodiester)2, where the environment of the tin atom is trans-octahedral with linear CSnC skeleton, and the equatorial atoms may consist of oxygen or nitrogen from water as well as from the nucleic acid constituents. No interaction with DNA apparently takes place due to hydrolyzed dimethyltin(IV) species, which occur in aqueous phases at approximate physiological pH values. The reaction pathway is then assumed to require weakly solvated, easily dissociable species such as [(CH3)2SnCl2(C2H5OH)n], which would imply in vivo reactivity of cellular DNA with organotins from hydrophobic sites.

Complexes of organometallic compounds XXVIII. The solution chemistry of bis(acetylacetone)ethylenediimine adducts of organotin(IV) halides

Abstract The nature of methanol solutions of a series of bis(acetylacetone)ethylenediimine adducts of organotin(IV) halides has been studied by electronic and PMR spectroscopy and by osmometry and conductivity. Effectively complete dissociation to the free ligand and solvated organotin(IV) halide moieties is inferred.

Mono-organotin(IV) and tin(IV) derivatives of 2-mercaptopyridine and 2-mercaptopyrimidine: X-ray structures of methyl-tris(2-pyridinethiolato)tin(IV) and phenyl-tris(2-pyridinethiolato)tin(IV)·1.5CHCl3

Mono-organotin(IV) and tin(IV) derivatives of 2-mercaptopyridine (HSPy) and 2-mercaptopyrimidine (HSPym), RSnL 3 (R=Me, n-Bu, Ph; L=SPy, SPym; R=Bz=benzyl, o-CIBz, oClC 6 H 4 , p-ClC 6 H 4 , o-tolyl, p-tolyl; L=SPy), RSnCIL 2 (R=Me, n-Bu, Ph; L=SPy, SPym), RSnCI 2 L (R=Me, n-Bu; L=SPy, SPym) and SnCI 4-n L n (L=SPy, SPym; n=2,4) were obtained from RSnCI 3 or SnCI 4 and NaL or by neutralization (R=Ph,p-tolyl; L=SPy, SPym). RSnCIL 2 and RSnCI 2 L were better prepared by comproportionation of RSnCI 3 and RSnL 3 . MeSn(Spy) 3 and PhSn(SPy) 3 .1.5CHCI 3 crystals, as determined by single-crystal X-ray diffraction, are monoclinic. In the discrete monomeric RSn(SPy) 3 units, three bidentate SPy ligands together with R form a distorted pentagonal bipyramid around tin. One S and the C(R) atom are in the axial positions. Two S atoms and three N atoms form the pentagonal plane. From 119 Sn Mossbauer and IR data, analogous structures are inferred for the other solid RSnL 3 compounds, except for R=Bz, o-CIBz, o-CIC 6 H 4 and o-tolyl, in which tin would be hexacoordinated. In the compounds RSnCIL 2 and RSnCI 2 L, tin is at the center of an octahedron or a trigonal bipyramid, respectively. For Sn(SPym) 4 and SnCI 2 (SPym) 2 , the same type of octahedral structure as was previously found for Sn(Spy) 4 .HSPy and SnCI 2 (Spy) 2 is proposed. According to IR and 1 H, 13 C and 119 Sn NMR data, the solid-state molecular structures are retained in chloroform and dimethyl sulfoxide solution.

Dynamics of tin nuclei in alkyltin(IV)–deoxyribonucleic acid condensates by variable-temperature tin-119 Mössbauer spectroscopy

The dynamics of tin nuclei in the condensates SnR2(DNA monomer)2 and SnR3(DNA monomer)(R = Me or Et), freeze-dried, has been investigated by variable-temperature 119Sn Mossbauer spectroscopy. Linear functions In (At/A77.3)(T), In farel,abs(T) and 〈x2〉(T)(At= total area under the resonant peaks, fa the relative and the absolute estimates of Lamb-Mossbauer factors, and 〈x2〈 the mean-square displacements of the Mossbauer nucleus extracted from farel and faabs respectively) have been found at T 77.3 K, which indicate harmonic motions and the lack of phase transitions. The latter is also suggested by the temperature-invariant hyperfine parameters, isomer shift, nuclear quadrupole splitting (ΔE) and peak widths. From the slopes of the functions In At(T) and In farel(T), the dynamics of tin in alkyltin(IV)–DNA condensates is found to be analogous to that in organotin(IV) salts and complexes, on the assumption of effective vibrating masses, corresponding to molecular groups. The coincidence between farel,abs, as well as the related 〈x2〉, data, indicates that the negative charge on the DNA backbone phosphodiester groups is fully neutralized by alkyltin(IV) cations in SnR2(DNA monomer)2(R = Me or Et) as well as in SnEt3(DNA monomer), while only partially in SnMe3(DNA monomer) and in SnMe2(DNA monomer)2 obtained by standard procedures for DNA condensation. From the magnitude of the functions, as well as of the Debye temperatures, on fingerprint criteria, SnIVR2 moieties are assumed to bridge phosphodiester groups in toroidal condensates through interstrand bonding, while SnIVR3 would be appended to the double helix. Motions would involve SnR2(mononucleotide)2 and SnR3(mononucleotide) units as the effective vibrating masses. Two tin co-ordination sites occur for SnIVR2 moieties at the DNA surface, both trans-octahedral, and a single trigonal-bipyramidal site for SnIVR3, the organometal moieties being co-ordinated by phosphodiester and water oxygen atoms, according to ΔE rationalization by point-charge model structure simulations, as well as to Mossbauer–Zeeman spectra of the SnIVEt2– and SnIVEt3–DNA condensates.

The hydrolysis of Me2SnIV and Me3SnIV moieties monitored through 119Sn Mössbauer spectroscopy

Abstract The 119 Sn Mossbauer parameters δ, isomer shift, and Δ E , nuclear quadrupole splitting, have been determined in frozen aqueous solutions of Me 2 Sn IV and Me 3 Sn IV moieties at varying pH. The resulting functions n versus pH (where n is the average number of protons released per mole of the organotin aquocation) agree satisfactorily with functions from potentiometry. The structures of the aquocations, as well as of the hydroxides, and of the mono-hydroxo complex [Me 2 Sn(OH)(OH 2 ) n ] + , are correlated to the Δ E exp data by point-charge model calculations.

Mössbauer spectroscopy of mono-organotin(IV) derivatives

Abstract The Mossbauer parameters isomer shift, δ, and quadrupole splitting, ΔE, of mono-organotin compounds insofar investigated have been collected and tabulated. It is demonstrated that isomer shifts consistently depend on ligand electronegativities and coordination numbers, from which it is deduced that RSn IV behave much more as Sn IV rather than R 2 Sn IV and R 3 Sn IV derivatives. The changes of δ for RSn IV are then interpreted by hypotheses analogous to those advanced for Sn IV and its adducts and complexes. It is also inferred that in RSn IV compounds there is a consistent s-character in all tin-ligand atom bonds.