Organometallic complexes with biological molecules. XVII. Triorganotin(IV) complexes with amoxicillin and ampicillin

Novel triorganotin(IV) complexes of two beta-lactamic antibiotics, 6-[D-(-)-beta-amino-p-hydroxyphenyl-acetamido]penicillin (=amoxicillin) and 6-[D-(-)-alpha-aminobenzyl]penicillin (=ampicillin), have been synthesized and investigated both in solid and solution states. The complexes corresponded to the general formula R(3)Sn(IV)antib*H(2)O (R=Me, n-Bu, Ph; antib=amox=amoxicillinate or amp=ampicillinate). Structural investigations about configuration in the solid state have been carried out by interpreting experimental IR and 119Sn M?ssbauer data. In particular, IR results suggested polymeric structures both for R(3)Sn(IV)amox.H(2)O and R(3)Sn(IV)amp*H(2)O. Moreover, both antibiotics appear to behave as monoanionic bidentate ligands coordinating the tin(IV) atom through ester-type carboxylate, as well as through the beta-lactamic carbonyl. Evidence that in none of these compounds water molecules were involved in coordination, was provided by thermogravimetric investigations. On the basis of 119Sn M?ssbauer spectroscopy it can be inferred that tin(IV) was pentacoordinate in all of the complexes in the solid state, showing an equatorial R(3)Sn(IV) trigonal bipyramidal (tbp) configuration. The nature of the complexes in solution state was investigated by using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, while an 119Sn spectrum was obtained for n-Bu(3)Sn(IV)amp*H(2)O. Although 1H- and 13C-NMR measurements suggested that in dimethyl sulfoxide (DMSO)-d(6) solution the polymeric structure collapsed, due to a solvolysis process of the beta-lactamic carbonyl bonding to the organometallic moiety, the complexes have been shown to maintain the same trigonal bipyramidal configuration at tin(IV) atom by the coordination of a DMSO molecule. Cytotoxic activity of these novel semisynthetic antibiotic derivatives has been tested towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia) using two different chromosome-staining techniques such as Giemsa and CMA(3). The occurrence of typical colchicinized-like (c-like) mitoses on slides obtained from animals exposed to organotin compounds, directly confirmed the high mitotic spindle-inhibiting potency of these chemicals. In addition, by comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the triorganotin(IV) complexes, structural damages such as 'achromatic lesions' and 'chromosome breakages' have been identified.     

Organometallic complexes with biological molecules. XVIII. Alkyltin(IV) cephalexinate complexes: synthesis, solid state and solution phase investigations

Dialkyltin(IV) and trialkyltin(IV) complexes of the deacetoxycephalo-sporin-antibiotic cephalexin [7-(d-2-amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid] (Hceph) have been synthesized and investigated both in solid and solution phase. Analytical and thermogravimetric data supported the general formula Alk(2)SnOHceph(.)H(2)O and Alk(3)Snceph(.)H(2)O (Alk=Me, n-Bu), while structural information has been gained by FT-IR, (119)Sn M?ssbauer and (1)H, (13)C, (119)Sn NMR data. In particular, IR results suggested polymeric structures both for Alk(2)SnOHceph(.)H(2)O and Alk(3)Snceph(.)H(2)O. Moreover, cephalexin appears to behave as monoanionic tridentate ligand coordinating the tin(IV) atom through ester-type carboxylate, as well as through beta-lactam carbonyl oxygen atoms and the amino nitrogen donor atoms in Alk(2)SnOHceph(.)H(2)O complexes. On the basis of (119)Sn M?ssbauer spectroscopy it could be inferred that tin(IV) was hexacoordinated in such complexes in the solid state, showing skew trapezoidal configuration. As far as Alk(3)Sn(IV)ceph(.)H(2)O derivatives are concerned, cephalexin coordinated the Alk(3)Sn moiety through the carboxylate acting as a bridging bidentate monoanionic group. Again, (119)Sn M?ssbauer spectroscopy led us to propose a trigonal configuration around the tin(IV) atom, with R(3)Sn equatorial disposition and bridging carboxylate oxygen atoms in the axial positions. The nature of the complexes in solution state was investigated by using (1)H, (13)C and (119)Sn NMR spectroscopy. Finally, the cytotoxic activity of organotin(IV) cephalexinate derivatives has been tested using two different chromosome-staining techniques Giemsa and CMA(3), towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia). Colchicinized-like mitoses (c-mitoses) on slides obtained from animals exposed to organotin(IV) cephalexinate compounds, demonstrated the high mitotic spindle-inhibiting potentiality of these chemicals. Moreover, structural damages such as "chromosome achromatic lesions", "chromosome breakages" and "chromosome fragments" have been identified through a comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the organotin(IV) complexes.     

Synthesis and structural studies by infrared and Mössbauer spectroscopy of adducts of tin(IV) and organotin(IV) derivatives with 2,2′-azopyridine

A number of complexes have been prepared by the reaction between 2,2′-azopyridine(AZP) and tin(IV) halides and organotin(IV) halides, and characterized by elemental analysis and infrared and variable temperature ¹¹⁹Sn Mössbauer spectroscopies. All of the new compounds have 1:1 stoichiometry, with the AZP ligand occupying two coordination sites by bonding through one of the ring and one of the azo group nitrogen atoms, to give rise to distorted octahedral structures. In the diorganotin complexes the two organic groups occupy trans positions. The infrared and Mössbauer spectroscopic data suggest that these compounds are monomeric in the solid state.     

Synthesis, characterization and crystal structures of homo- and hetero-substituents containing trans six-coordinate tin(IV) complexes of H2tmtaa (5,14-dihydro-6,8,15,17-tetramethyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine), and the solid state NMR spectra study of Sn

The reaction of Sn(tmtaa)Cl₂ (H₂tmtaa=5,14-dihydro-6,8,15,17-tetramethyldi-benzo[b,i][1,4,8,11]tetraazacyclotetradecine) and ammonium thiocyanate or sodium azide under a mild condition resulted in trans six-coordinate tmtaa tin(IV) complexes, Sn(tmtaa)X₂ (X=NCS, 1; X=N₃, 2). However, the treatment of Sn(tmtaa)Cl₂ and sodium picrate produced Sn(tmtaa)(Cl)(OC₆H₂ (2,4,6-3NO₂)) (3). Only one chloro atom of Sn(tmtaa)Cl₂ was substituted because of low nucleophilicity of the 2,4,6-trinitrophenolic anion in 3. Furthermore, because of the steric hindrance between the 2,4,6-trinitrophenolic group and the tmtaa ligand, which has a non-planar, saddle-shaped conformation, two chloro atoms cannot be substituted by two 2,4,6-trinitrophenolic groups simultaneously. All complexes were characterized by IR spectra, UV spectra, mass spectra, NMR spectra and elemental analyses, as well as DSC measurements. X-ray crystal structures of 1 and 3 reveal that the complexes retain the characteristic saddle-shaped configuration of H₂tmtaa but have adopted the trans geometry. Solid state ¹¹⁹Sn NMR spectroscopy was used to study the bonding environment in the series of six-coordinate trans Sn(IV) tmtaa complexes. It can be found that the ¹¹⁹Sn chemical shifts of the Sn(IV) tmtaa complexes are almost not influenced by the substituents.     

Theoretical investigations on the hydrolysis pathway of tin verdoheme complexes: elucidation of tin’s ring opening inhibition role

In order to obtain a better molecular understanding of inhibitory role of tin metal in the verdoheme ring opening process, hydrolysis of three possibly six, five, and four coordinate verdoheme complexes of tin(IV) and (II) have been studied using DFT method. The results of calculations indicate that, in excellent accord with experimental reports, hydrolysis of different possibly coordinated tin(IV) and (II) verdohemes does not lead to the opening of the macrocycle. Contrary to iron and zinc verdohemes, in five and four coordinate verdoheme complexes of tin(IV) and (II), formation of open ring helical complexes of tin are unfavorable both thermodynamically and kinetically. In these pathways, coordination of hydroxide nucleophile to tin metal due to the highly charged, exclusive oxophilicity nature of the Sn center, and high affinity of Sn to increase coordination state are proposed responsible as inhibiting roles of tin via the ring opening. While, in saturated six coordinate tin(IV) and (II) verdoheme complexes the ring opening of tin verdohemes is possible thermodynamically, but it is not predicted to occur from a kinetics point of view. In the six coordinate pathway, tin plays no coordination role and direct addition of hydroxide nucleophile to the positive oxo-carbon centers and formation of closed ring hydroxy compounds is proposed for preventing the verdoheme ring opening. These key points and findings have been corroborated by the results obtained from atomic charge analysis, geometrical parameters, and molecular orbital calculations. In addition, the results of inhibiting ring opening reaction of tin verdoheme complexes could support the great interest of tin porphyrin analogues as pharmacologic means of chemoprevention of neonatal jaundice by the competitive inhibitory action of tin porphyrins on heme oxygenase.     

Diorganotin(IV) N-acetyl-l-cysteinate complexes: Synthesis, solid state, solution phase, DFT and biological investigations

Diorganotin(IV) complexes of N-acetyl-l-cysteine (H₂NAC; (R)-2-acetamido-3-sulfanylpropanoic acid) have been synthesized and their solid and solution-phase structural configurations investigated by FTIR, Mössbauer, ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy. FTIR results suggested that in R₂Sn(IV)NAC (R = Me, Bu, Ph) complexes NAC²⁻ behaves as dianionic tridentate ligand coordinating the tin(IV) atom, through ester-type carboxylate, acetate carbonyl oxygen atom and the deprotonated thiolate group. From ¹¹⁹Sn Mössbauer spectroscopy it could be inferred that the tin atom is pentacoordinated, with equatorial R₂Sn(IV) trigonal bipyramidal configuration. In DMSO-d₆ solution, NMR spectroscopic data showed the coordination of one solvent molecule to tin atom, while the coordination mode of the ligand through the ester-type carboxylate and the deprotonated thiolate group was retained in solution. DFT (Density Functional Theory) study confirmed the proposed structures in solution phase as well as the determination of the most probable stable ring conformation. Biological investigations showed that Bu₂SnCl₂ and NAC2 induce loss of viability in HCC cells and only moderate effects in non-tumor Chang liver cells. NAC2 showed lower cytotoxic activity than Bu₂SnCl₂, suggesting that the binding with NAC²⁻ modulates the marked cytotoxic activity exerted by Bu₂SnCl₂. Therefore, these novel butyl derivatives could represent a new class of anticancer drugs.     

Spectral analysis and in vitro cytotoxicity profiles of novel organotin(IV) esters of 2-maleimidopropanoic acid

Six novel triorganotin(IV) 2-maleimidopropanoato complexes: R₃SnOCOCH₃(CH)(COCH)₂, (R: Me(1), Et(2), n-Pr(3), n-Bu(4), Ph(5), Bz(6) have been synthesized. Their solid-state configuration has been determined by FT IR and ^119mSn Mössbauer spectroscopy. The tin(IV) atom is five-coordinated in all the complexes with 2-maleimidopropanoic acid behaving as a monoanionic bidentate ligand coordinating the tin(IV) atom through a chelating or bridging carboxylate group. The solution-state configuration has been elucidated by means of ¹H-, ¹³C- and ¹¹⁹Sn-NMR spectroscopy which assigned a tetrahedron. Elemental analysis and FAB MS data also supported a 1:1 metal to ligand stoichiometry. The title complexes have been screened in vitro for anti-tumour, anti-fungal, anti-leishmanial and urease inhibition activities and displayed promising results.     

Potentiometric and spectroscopic studies on the dimethyltin(IV) complexes of 2-hydroxyhippuric acid

Equilibrium and spectroscopic (1H, 13C NMR and 119Sn M?ssbauer) studies in aqueous solution are reported for dimethyltin(IV) complexes of 2-hydroxyhippuric acid (Sal-Gly). Below pH 4, oxygen-coordinated complexes MLH and ML are formed. In the pH range 5-8.5, the species MLH(-1), predominates at any metal-to-ligand ratio. The ligand exchange of this species is slow on the NMR time scale, which allows its structural characterization by NMR spectroscopy: the coordination polyhedron around the tin atom is distorted trigonal bipyramidal, with tridentate [O-,N-,COO-] coordination of Sal-Gly, involving two equatorial methyl groups. The NMR results reveal that the main cause of the distortion of the polyhedron is the large CH3-Sn-CH3 angle of 136+/-4 degrees. The presented results supplement the data available on the dimethyltin(IV)-promoted amide deprotonation of peptides, and provide further arguments for the fundamental role of the carboxylate as an anchoring group in this process.     

Interaction of tributyltin(IV) chloride and a related complex [Bu(3)Sn(LSM)] with rat leukocytes and erythrocytes: Effect on DNA and on plasma membrane

The discovery of the antitumor activity of cisplatin led several research groups to investigate the possible therapeutic applications of other metal-based compounds. Organotin(IV) complexes have been developed from organotin compounds that were employed in industry and agriculture as stabilizers and pesticides, respectively. A careful choice of the ligand coordinated to an organotin(IV) fragment can modulate the activity of the organotin(IV) complex and minimize its drawbacks. With this aim, the tributyltin(IV) complex [Bu(3)Sn(LSM)] (LSM=bis(1-methyl-1H-imidazol-2-ylthio)acetate) was synthesized and its in vitro effects on rat blood cells were compared with those of the analogous tributyltin(IV) compound without the anionic ligand. Comet-assay results show that both the tributyltin(IV) chloride (TBTC) and the complex [Bu(3)Sn(LSM)] can induce DNA damage in leukocytes, but a stronger effect was observed in the presence of the organotin(IV) complex. Moreover, lipid-hydroperoxide formation in leukocyte plasma membranes increases more in the presence of [Bu(3)Sn(LSM)] compared with TBTC, while TBTC can change the lipid order and packing of leukocytes and, partially, erythrocyte plasma membranes. The treatment of whole blood with these two compounds shows a preferential oxidative effect of TBTC on erythrocyte plasma membranes and erythrocyte oxidative processes, which influence the induction of DNA damage in leukocytes. The different hydrophobic characters and the different extents of steric hindrance of TBTC and [Bu(3)Sn(LSM)] influence the capacity of the two compounds to cross the plasma membrane and affect the pathways that lead to DNA damage.     

Synthesis,characterization and in vitro cytotoxicity of new organotin(IV) derivatives of N-methylglycine

The synthesis and characterization of new coordination compounds of some diorganotins(IV) with N-methylglycine (sarcosine) are reported; all these derivatives mainly tend to assume a chelate structure. As single crystals were not obtained, a large number of experimental techniques were used to accomplish a definitive characterization and determination of their structure. Results obtained by (1)H/(119)Sn NMR, FT-IR and (119)mSn-M?ssbauer spectroscopy and thermogravimetric analysis allow us to deduce the pentacoordination for 1:1 (Sn/sarcosine) derivatives [R(2)SnCl(2)(Sar)](+)Cl(-) (R=Me, n-Bu) in a trigonal-bipyramidal structure, and the hexacoordination for 1:2 complexes [R'(2)Sn(Sar)(2)](2+)2Cl(-) (R'=Me, n-Bu, Ph) in an octahedral structure; however, the probability of partially or totally non-chelate structures for some adducts increases with the steric hindrance of the R/R' groups and the number of the sarcosine molecules bound to the tin atom, so that they give rise to fluxional equilibria in solution. Finally, the synthesized compounds have been tested for in vitro cytotoxic activity against human adenocarcinoma HeLa cells showing, in some cases, strong activity even at low concentration.     

Synthesis, crystal structures, cytotoxicity and qualitative structure-activity relationship (QSAR) of cis-bis{5-[(E)-2-(aryl)-1-diazenyl]quinolinolato}di-n-butyltin(IV) complexes, (n)Bu2Sn(L)2

A series of cis-bis{5-[(E)-2-(aryl)-1-diazenyl]quinolinolato}di-n-butyltin(IV) complexes has been synthesized and characterized by ¹H-, ¹³C-, ¹¹⁹Sn NMR, ESI-MS (electrospray ionization mass spectrometry), IR and ^119mSn Mössbauer spectroscopic techniques in combination with elemental analyses. The structures of four di-n-butyltin(IV) complexes, viz., ⁿBu₂Sn(L³)₂ (3), ⁿBu₂Sn(L⁴)₂ (4), ⁿBu₂Sn(L⁵)₂ (5) and ⁿBu₂Sn(L⁷)₂ · 0.5C₆H₆ (7) (LH = 5-[(E)-2-(aryl)-1-diazenyl)quinolin-8-ol) were determined by single crystal X-ray diffraction. In general, the complexes were found to adopt a distorted cis-octahedral arrangement around the tin atom. These complexes retain their solid-state structure in non-coordinating solvent as evidenced by ¹¹⁹Sn and ¹³C NMR spectroscopic results. The in vitro cytotoxicity of di-n-butyltin(IV) complexes (3-8) is reported against seven well characterized human tumour cell lines. The basicity of the two quinolinolato donor N and O atoms of the ligands are discussed in relation to the cytotoxicity data.     

An in vitro comparative assessment with a series of new triphenyltin(IV) 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoates endowed with anticancer activities: structural modifications, analysis of efficacy and cytotoxicity involving human tumor cell lines

Four new triphenyltin(IV) complexes of composition Ph₃SnLH (where LH = 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoate) (1-4) were synthesized and characterized by spectroscopic (¹H, ¹³C and ¹¹⁹Sn NMR, IR, ¹¹⁹Sn Mössbauer) techniques in combination with elemental analysis. The ¹¹⁹Sn NMR spectroscopic data indicate a tetrahedral coordination geometry in non-coordinating solvents. The crystal structures of three complexes, Ph₃SnL¹H (1), Ph₃SnL³H (3), Ph₃SnL⁴H (4), were determined. All display an essentially tetrahedral geometry with angles ranging from 93.50(8) to 124.5(2)°; ¹¹⁹Sn Mössbauer spectral data support this assignment. The cytotoxicity studies were performed with complexes 1-4, along with a previously reported complex (5) in vitro across a panel of human tumor cell lines viz., A498, EVSA-T, H226, IGROV, M19 MEL, MCF-7 and WIDR. The screening results were compared with the results from other related triphenyltin(IV) complexes (6-7) and tributyltin(IV) complexes (8-11) having 2-/4-[(E)-2-(aryl)-1-diazenyl]benzoates framework. In general, the complexes exhibit stronger cytotoxic activity. The results obtained for 1-3 are also comparable to those of its o-analogs i.e. 4-7, except 5, but the advantage is the former set of complexes demonstrated two folds more cytotoxic activity for the cell line MCF-7 with ID₅₀ values in the range 41-53 ng/ml. Undoubtedly, the cytotoxic results of complexes 1-3 are far superior to CDDP, 5-FU and ETO, and related tributyltin(IV) complexes 8-11. The quantitative structure-activity relationship (QSAR) studies for the cytotoxicity of triphenyltin(IV) complexes 1-7 and tributyltin(IV) complexes 8-11 is also discussed against a panel of human tumor cell lines.     

Spectral analysis and in vitro cytotoxicity profiles of novel organotin(IV) esters of 2-maleimidopropanoic acid

Six novel triorganotin(IV) 2-maleimidopropanoato complexes: R3SnOCOCH3(CH)(COCH)2, (R: Me(l), Et(2), n-Pr(3), n-Bu(4), Ph(5), Bz(6) have been synthesized. Their solid-state configuration has been determined by FT IR and lI9mSn M?ssbauer spectroscopy. The tin(IV) atom is five-coordinated in all the complexes with 2-maleimidopropanoic acid behaving as a monoanionic bidentate ligand coordinating the tin(IV) atom through a chelating or bridging carboxylate group. The solution-state configuration has been elucidated by means of 1H-, 13C- and 119Sn-NMR spectroscopy which assigned a tetrahedron. Elemental analysis and FAB MS data also supported a 1:1 metal to ligand stoichiometry. The title complexes have been screened in vitro for anti-tumour, anti-fungal, anti-leishmanial and urease inhibition activities and displayed promising results.     

Synthetic, spectral, thermal and antimicrobial studies on some mixed 1,3-dithia-2-stannacyclopentane derivatives with dialkyldithiocarbamates

1,3-dithia-2-stannacyclopentane derivatives with dialkyldithiocarbamates of the types SCH(2)CH(2)SSn[S(2)CNR(2)]Cl (I) and SCH(2)CH(2)SSn[S(2)CNR(2)](2) (II) (where R = CH(3), C(2)H(5) and -CH(2)-CH(2)-) have been synthesized by the reaction of 2,2-dichloro-1,3-dithia-2-stannacyclopentane and sodium/ammonium salts of dialkyldithiocarbamates in 1:1 and 1:2 molar ratios, respectively, in anhydrous benzene. These newly synthesized derivatives have been characterized by elemental analyses (C, H, N, S and Sn), thermal [thermogravimetry (TG) and differential thermal analyses (DTA)] as well as spectral [UV, IR and multinuclear NMR ((1)H, (13)C and (119)Sn)] studies. The monodentate behaviour of the dialkyldithiocarbamate ligands was confirmed by IR and (119)Sn NMR spectral data and distorted tetrahedral structures have been suggested for both type (I) and (II) compounds. The free ligands and their tin complexes have also been screened for their antibacterial and antifungal activities. These results made it desirable to delineate a comparison between free ligands and their tin complexes. These exhibit higher antibacterial effect than some of the previously investigated antibiotics.     

Synthesis, spectroscopy (IR, multinuclear NMR, ESI-MS), diffraction, density functional study and in vitro antiproliferative activity of pyrazole-beta-diketone dihalotin(IV) compounds on 5 melanoma cell lines

Novel 4-acylpyrazolon-5-ato-dihalotin(IV) complexes, [Q2SnX2], (X = F, Cl, Br or I); HQ = HQ(CHPh2) (1,2-dihydro-3-methyl-1-phenyl-4-(2,2-diphenylacetyl)pyrazol-5-one), HQ(Bn) (1,2-dihydro-3-methyl-1-phenyl-4-(2-phenylacetyl)pyrazol-5-one) or HQ(CF3,py) (4-(2,2,2-trifluoroacetyl)-1,2-dihydro-3-methyl-1-(pyridin-2-yl)pyrazol-5-one) have been synthesized and characterized by spectroscopic (IR, 1H, 13C, 19F and 119Sn NMR, electrospray ionisation mass spectrometry (ESI-MS)), analytical and structural methods (X-ray and density functional theory). 119Sn chemical shifts depend on the nature of the halides bonded to tin. Isomer conversion, detected in solution by NMR spectroscopy, is related to the acyl moiety bulkiness while the cis(Cl)-cis(acyl)-trans(pyrazolonato) scheme is found in the solid state. The in vitro antiproliferative tests of three derivatives on three human melanoma cell lines (JR8, SK-MEL-5, MEL501) and two melanoma cell clones (2/21 and 2/60) show dose-dependent decrease of cell proliferation in all cell lines. The activity correlates with the nature of the substituent on position 1 of pyrazole, decreasing in the order pyridyl>Ph>methyl. The activity for (Q(CF3,py))2SnCl2 on the SK-MEL-5 cell line is IC50 = 50 microM.     

Synthesis,vibrational and mössbauer spectra studies of complexes of organotin chlorides and 2-pyridinecarboxaldehyde thiosemicarbazone

The complex formation between organotin chlorides and 2-pyridinecarboxaldehyde thiosemicarbazone (PT) has been investigated. In only one case is a substitution reaction observed whereas in all other cases, 1:1 addition complexes are formed. The solid state configurations of the complexes have been studied by ^119mSn Mössbauer and far infrared spectroscopy. The chelating ligand (PT) functions as a bidentate ligand towards diorganotin chlorides giving octahedral coordination geometry around the tin atom.     

A 119Sn M?ssbauer spectroscopic study on the interaction of dimethyltin (IV) derivatives with rat hemoglobin, and of related model systems in aqueous solution

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 M?ssbauer 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 M?ssbauer 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).     

Characterization of diorganotin(IV) complexes with captopril. The first crystallographically authenticated metal complex of this anti-hypertensive agent

Diorganotin(IV) complexes R(2)Sn(cap) (capH(2)=N-[(S)-3-mercapto-2-methylpropionyl]-L-proline; R=Me, Et, n-Bu and t-Bu) were prepared and characterised. The FTIR and Raman spectra demonstrated that the organotin(IV) moieties interact with the [S] atom of the ligand, while the other coordination sites are the carboxylate and the amide -CO groups. M?ssbauer Delta data showed that the diorganotin(IV) compounds adopt slightly distorted trigonal-bipyramidal (tbp) geometry. A single-crystal X-ray study was performed on the compound Me(2)Sn(cap): the Sn atom is five-coordinated in a distorted tbp environment, with two [O] atoms in the axial positions and the [S] and two [C] atoms in the equatorial (eq) plane. Each cap ligand coordinates to two different Sn atoms, and infinite zigzag chains are formed, directed parallel to each other and to the b axis of the unit cell. NMR (CDCl(3)) of the Me(2)Sn(IV) and n-Bu(2)Sn(IV) complexes indicated the presence of different oligomeric species.     

Di- and triorganotin(IV) carboxylates derived from triorganotin(IV) iodide with mixed organic groups on tin: Cyclic, hexameric triorganotin(IV) carboxylates

The reaction of ethyldiphenyltin(IV) iodide with silver benzoate in ethanol results in the formation of bis(benzoato)ethylphenyltin(IV), EtPhSn[OC(O)C₆H₅]₂ (1), by the cleavage of a phenyl group bound to tin. The reaction of ethyldiphenyltin(IV) iodide with silver acetate provides acetatoethyldiphenyltin(IV), EtPh₂SnOC(O)CH₃ (2). Similarly, the reaction of diphenylpropyltin(IV) iodide with silver acetate affords acetatodiphenyl-n-propyltin(IV), Ph₂PrSnOC(O)CH₃ (3). These three complexes were characterized by elemental analysis, mass spectrometry, and infrared spectroscopy (IR), as well as ¹H, ¹³C, and ¹¹⁹Sn NMR. The molecular structures of three complexes were also verified by single-crystal X-ray analyses. The X-ray structures show that 1 adopts a skew-trapezoidal bipyramidal structure, while 2 and 3 are rare, cyclic hexameric structures.     

Synthesis and crystal structure of macrocyclic di-n-butyltin(IV) complex with 2-mercapto-4-methyl-5-thiazoleacetic acid, {[n-Bu2Sn(O2CCH2C4H3NS)SS(C4H3NSCH2CO2)Sn n-Bu2]O}2

A novel macrocyclic di-n-butyltin(IV) complex 1 was synthesized by the reaction of di-n-butyltin(IV) oxide and 2-mercapto-4-methyl-5-thiazoleacetic acid. Characterization of the complex 1 was achieved using elemental analysis, IR, ¹H, ¹³C and ¹¹⁹Sn NMR spectra and X-ray diffraction. X-ray data of the complex 1 revealed that it is an unusual macrocycle containing the bridging-S-S-linkages and tetranuclear ladder based on a planar four-membered Sn₂O₂ ring. In the so-called ladder structure, there are two distinct tin environments, the endocyclic tin atom is best described as five-coordinate and the exocyclic tin atom as six-coordinate.