Giuseppe Ruisi

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.

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.

Synthesis of diorganotin(IV) complexes with nucleosides and their characterization by Mössbauer and infrared spectroscopy

Abstract A number of new complexes of R 2 Sn IV with adenosine, guanosine, inosine, cytidine and uridine were synthesized by reaction of ribonucleosides with diorganotin oxide in hot methanol. The complexes were characterized by infrared and 119 Sn Mossbauer spectroscopy as O(2′), O(3′) (diorganostannylene) nucleosides; the occurence of dimers with three-co-ordinate oxygen atoms is inferred on the basis of spectroscopic data.

Diorganotin(IV)–2‐mercaptopyrimidine complexes

The complexes formed between the diorganotin(IV) moieties, R 2 Sn(IV), and the ligand 2-mercaptopyrimidine, (H)SPym, were investigated. Complexes R 2 SnHal(SPym) and R 2 Sn(SPym) 2 [R = Me, i Pr, n Bu, i Bu, t Bu, cyclohexyl(Cy), Ph] were synthesized, and characterized by elemental analysis. In the solid state, chelation of SPym through S and N donors was established by IR spectroscopy, and the nature of the environment of tin centers was investigated by 119 Sn Mossbauer spectroscopy. From the dynamics of 119 Sn nuclei determined by variable-temperature measurements on representative compounds [Me 2 SnCl(SPym) and Cy 2- SnBr(SPym)], as well as by point-charge model treatment of nuclear quadrupole splitting parameters, it was inferred that Me 2 SnCl-(SPym) may assume a trans-Me 2 octahedral coordination geometry around tin in a monodimensional polymer, or a monomeric trigonal-bipyramidal structure (distorted). The latter type of structure was assigned to the other R 2 SnHal(SPym) species, while R 2 Sn(SPym) 2 complexes assume a trans-octahedral, or skew trapezoidal, tin environment. In CHCl 3 -CDCl 3 solutions, monomeric species occur (according to vapor-pressure osmometry), where 1 H and 13 C NMR spectroscopic parameters of SPym indicate the persistence of Sn chelation by S and N donor atoms. The Me 2 SnCl(SPym) species assume trigonal-bipyramidal structures with a chelating SPym ligand, in CDCl 3 and C 2 H 5 OH solutions, according to the coupling constants 1 J( 119 Sn, 13 C), as well as IR and 119 Sn Mossbauer spectroscopic data. 119 Sn NMR parameters fully correspond with data for the homologous complexes with 2-mercaptopyridine.

The binding of trialkyltin(IV) moieties to rat haemoglobin, and the structure of model systems, studied by tin-119 Mössbauer spectroscopy

The configuration of the tin environment in binding sites of microcrystalline SnR3–rat haemoglobin complexes (R = Me, Et, or Bun), as well as in model systems consisting of SnIVR3 moieties in aqueous media and in organic solutions (mimicking hydrophilic and hydrophobic zones of the globin respectively) has been investigated by 119Sn Mossbauer spectroscopy, through the point-charge model rationalization of the experimental nuclear quadrupole splitting, ΔE, measured at 77.3 K, and eventually by Mossbauer–Zeeman spectra taken at 4.2 K in a transverse magnetic field of 6 T. A distorted trigonal-bipyramidal (tbp) structure SnR3(Sthiol)( Nhet) has been inferred for the haemoglobin complexes, where the ligand atoms (axial) would come from a cysteine and histidine side chain respectively, according to previous biochemical work. Moreover, the occurrence of a strong Sn–S bond (with a C–Sn–S angle consistently larger than 90°), as well as of a weak N → Sn co-ordinative interaction, has been proposed. The aqueous model systems [SnIVMe3 and SnIVEt3 derivatives at pH 7.40, eventually in presence of N-(2- hydroxyethyl)piperazine-N′-ethane-2- sulphonic acid (Hepes) buffer, which were reacted with cysteine] have evidenced the formation of quasi-regular ternary tbp complexes SnR3(Sthiol)(Nam)(the ligand atoms being axially located, coming from cysteine and Hepes respectively) where the N →Sn interaction is consistently lower than Sn–S. Slow-rate reactivities in aqueous solutions of SnR3 cysteinates are also reported and commented upon. Essentially regular tbp species SnIVR3(SPh)(Nhet)(Nhet from 1 -methylimidazole; R = Me, Bun, or Ph) have been identified in benzene solution. The distortion of the tbp binding site in the haemoglobin complexes has then been assumed to be peculiar to the SnR3-globin system. Comments based on crystalline derivatives with Sn–S bonds have been accordingly reported.

119mSn Mössbauer studies on tin compounds

Information extracted from 119Sn Mossbauer spectroscopy of tin compounds essentially concerns (1) the valence state in inorganic derivatives, (2) structure and bonding in the m et al. environment (mainly in organotins) and (3) the dynamics of tin nuclei, the latter possibly correlated to the nature of the substrate (mono- or polymeric). Measurements are effected on solids (crystalline as well as amorphous), gels and solutions (frozen to glassy phases). It then appears that Mossbauer spectroscopic measurements give information analogous, or complementary, to data gained from other spectroscopic techniques, such as NMR spectroscopy, X-ray diffractometry, neutron diffraction, etc. There are advantages, as well as disadvantages, in the data extracted from Mossbauer spectroscopy: the first concerns, inter alia, the easy experimental procedures, the simple and inexpensive instrumentation, the possibility of obtaining information about the m et al. properties in high molecular weight systems; the second lies essentially in the time needed to collect a spectrum (∼1 day). In fact, the circumstance that the absorber samples must contain Sn at the milligram level [about 0.5(mg119Sn)cm-2], and the near impossibility of quantitative Sn analysis, are common to other widely employed spectroscopic techniques.

Synthesis, characterization, crystal structures and in vitro antistaphylococcal activity of organotin(IV) derivatives with 5,7-disubstituted-1,2,4-triazolo(1,5-a)pyrimidine

New organotin(IV) complexes of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp) with 1:1 and/or 1:2 stoichiometry were synthesized and investigated by X-ray diffraction, FT-IR and (119)Sn Mössbauer in the solid state and by (1)H and (13)C NMR spectroscopy, in solution. Moreover, the crystal and molecular structures of Et(2)SnCl(2)(dbtp)(2) and Ph(2)SnCl(2)(EtOH)(2)(dptp)(2) are reported. The complexes contain hexacoordinated tin atoms: in Et(2)SnCl(2)(dbtp)(2) two 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine molecules coordinate classically the tin atom through N(3) atom and the coordination around the tin atom shows a skew trapezoidal structure with axial ethyl groups. In Ph(2)SnCl(2)(EtOH)(2)(dptp)(2) two ethanol molecules coordinate tin through the oxygen atom and the 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N(3), to the OH group of the ethanol moieties; Ph(2)SnCl(2)(EtOH)(2)(dptp)(2) has an all-trans structure and the C-Sn-C fragment is linear. On the basis of Mössbauer data, the 1:2 diorganotin(IV) complexes are advanced to have the same structure of Et(2)SnCl(2)(dbtp)(2), while Me(2)SnCl(2)(dptp)(2) to have a regular all-trans octahedral structure. A distorted cis-R(2) trigonal bipyramidal structure is assigned to 1:1 diorganotin(IV) complexes. The in vitro antibacterial activities of the synthesized complexes have been tested against a group of reference pathogen micro-organisms and some of them resulted active with MIC values of 5μg/mL, most of all against staphylococcal strains, which shows their inhibitory effect.

Mono-aryltin(IV) and mono-benzyltin(IV) complexes with pyridine-2-carboxylic acid and 8-hydroxyquinoline. X-ray structure of p-chloro-phenyl-tris(8-quinolinato)tin(IV)·2CHCl3

Abstract Complexes RSn(O2CPy)3·2H2O and RSn(Ox)3, (PyCOOH=pyridine-2-carboxylic acid, HOx=8-hydroxyquinoline, R=o- and p-Tolyl, o- and p-ClC6H4=o- and p-ClPh, o-ClC6H4CH2=o-ClBenzyl; besides, R=Ph in RSn(Ox)3) have been synthesized and characterized by elemental analysis and determination of molecular weights in CHCl3 solutions. The structure of p-ClPhSn(Ox)3·2CHCl3 has been determined by X-ray diffractometry. The 7-coordinated tin atom of the monomeric compound is in the center of a pentagonal bipyramid formed by (p-ClPh)C and O and N atoms of the chelating Ox− ligands. The latter type of structure would hold for all complexes according to 119Sn Mossbauer (including the determination of the dynamics of 119Sn nuclei) and IR spectroscopy in the solid state; the ligand −O2CPy appears to chelate Sn through one oxygen atom of the COO− group and the N atom, although the occurrence of one chelating and two monodentate PyCO2− ligands (through COO−), and coordination by the H2O molecules to Sn cannot be excluded. In CDCl3 and CHCl3 solutions, the persistence of the pentagonal bipyramidal species is assumed, in line with 1H-, 13C-, 119Sn-NMR and UV–vis spectroscopic studies.

Syntheses, Mössbauer and infrared spectroscopic investigations on tin(II) chloride adducts with purine and pyrimidine bases and nucleosides

Abstract The synthesis of two types of tin(II) complex SnCl2·L·CH3OH (L = adenosine, cytidine and inosine) and SnCl2·L2·CH3OH (L = adenine and cytosine) are described. The complexes are characterised by their infrared and 119Sn Mossbauer data. The Mossbauer shift data suggest that the bonds between tin(II) chloride and the donor atoms of the ligands are relatively weak.

The interaction of DNA with organotin(IV) salts and complexes

Ethanol solutions of AlknSnCl4−n (Alk = Me, Et; n = 1–3) added to aqueous calf thymus DNA provoke DNA condensation (even in the presence of added cysteine) possibly through charge neutralization of DNA phosphodiesters by organotin(IV) cations. The structures of tin bonding environments in binary and ternary condensed systems organotin(IV)-DNA and ligand-organotin(IV)-DNA are determined through point-charge model treatment of the 119Sn Mössbauer parameter Δ, while the possible interchain interaction DNA-tin is inferred from the dynamics of 119Sn nuclei through vtMs.