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.     

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).     

Synthesis, structural investigations on organotin(IV) chlorin-e6 complexes, their effect on sea urchin embryonic development and induced apoptosis

Four new organotin(IV) chlorin derivatives, [chlorin=chlorin-e(6)=21H,23H-porphine-2-propanoic acid, 18-carboxy-20-(carboxymethyl)-8-ethenyl-13-ethyl-2,3-di-hydro-3,7,12,17-tetramethyl-(2S-trans)-], with formula (R(2)Sn)(3)(chlorin)(2).2H(2)O (R=Me, n-Bu) and (R(3)Sn)(3)chlorin.2H(2)O (R=Me, Ph) have been synthesized. The solid state and solution phase structures have been investigated by FT-IR, (119)Sn M?ssbauer, (1)H and (13)C NMR spectroscopy. In the solid state, (R(2)Sn)(3)(chlorin)(2).2H(2)O complexes contain six coordinated Sn(IV), in a skew trapezoidal environment by forming trans-R(2)SnO(4) polymeric units. As far as (R(3)Sn)(3)chlorin.2H(2)O complexes are concerned, Sn(IV) is five coordinated in a polymeric (oligomeric) trigonal bipyramidal environment and eq-R(3)SnO(2) units, in the solid state. In saturated solutions, a polymeric structure comparable to the solid phase, with carboxylate groups of the ligand behaving in monoanionic bidentate fashion bridging Sn(IV) atoms, was detected for the (Me(3)Sn)(3)chlorin.2H(2)O complex, while in more diluted ones a tetrahedral configuration for the trimethyltin(IV) moieties was observed. Cytotoxic activity of the novel organotin(IV) chlorin was investigated in order to assay the effect on sea urchin embryonic development. The results obtained demonstrated that (n-Bu(2)Sn)(3)(chlorin)(2).2H(2)O and (Ph(3)Sn)(3)chlorin.2H(2)O exerted the antimitotic effect on the early stages of sea urchin development. In addition, the cytotoxic effect exerted by (n-Bu(2)Sn)(3)(chlorin)(2).2H(2)O appeared with necrosis of the blastomeres, which were clearly destroyed. After treatment with (Ph(3)Sn)(3)chlorin.2H(2)O, a programmed cell death was triggered, as shown by light microscope observations through morphological assays. The apoptotic events in 2-cell stage embryos revealed: (i) DNA fragmentation, with the TUNEL reaction (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling); (ii) phosphatidylserine translocation in the membrane, with Annexin-V assay and (iii) cytoplasm blebbing, with the TUNEL reaction. The results demonstrated that the novel compound (Ph(3)Sn)(3)chlorin.2H(2)O was the most toxic derivative, by exerting antimitotic effect very early and by triggering apoptosis in the 2-cell stage of sea urchin embryonic development.     

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.     

Coordination properties of adenosine-5'-monophosphate and related ligands towards Me2Sn(IV)2+ in aqueous solution

The coordination of Me2Sn(IV)2+ to adenosine-5'-monophosphate (AMP) and the related compounds D-ribose-5-phosphate (R5P), D-glucose-1-phosphate (G1P) and D-glucose-6-phosphate (G6P) in aqueous solution was investigated by means of potentiometric titration, and 1H-, 31P-NMR and M?ssbauer spectroscopic methods in the pH range 2-11 (I=0.1 M NaClO4, 298 K). The complex of AMP and Me2Sn(IV)2+ precipitated at low pH was characterised by elemental analysis, FT-IR and M?ssbauer spectroscopic methods. From a comparison of the pK values obtained in the presence and absence of metal ion and the stability constants for the different systems, the coordination of [N] is excluded, while bidentate coordination of the phosphate group is presumed. M?ssbauer spectroscopic measurements recorded in the glassy state confirmed bidentate coordination of the phosphate and the formation of mixed hydroxo complexes in the weakly acidic, neutral and strongly basic pH range. With increasing pH, the phosphate groups were replaced by the deprotonated alcoholic [O] atoms of the sugar moiety. The solid complex proved to be tbp structure with bidentate phosphate coordination.     

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.     

Synthesis, structure, spectroscopic properties and biological activity of mixed diorganotin(IV) complexes containing pyridine-2-carbaldehyde thiosemicarbazonato and diphenyldithiophosphinato ligands

Reaction of the title ligands (HPyTSC and HS(S)PPh2, respectively) with R2SnO (R = Me, Et, Bu) in ethanol (EtOH) afforded the complexes [SnMe2(PyTSC) (S2PPh2)].EtOH (1) and [SnR2(PyTSC) (S2PPh2)] (R = Et (2), Bu (3)). The structures of 1 and 2 were determined by single-crystal X-ray diffractometry. In both these complexes the tin atom is coordinated to an N,N,S-dentate thiosemicarbazonate ligand, an anisobidentate dithiophosphinato ligand and the two R groups. The coordination polyhedrons can be described as distorted pentagonal bipyramids. A comparative study of the IR spectra of 1, 2 and 3 indicates that the butyl complex has a similar structure. Multinuclear (1H, 13C, 31P and 119Sn) NMR data suggest that the structures of 1 and 2 probably remain in CDCl3 (or DMSO-d6) solution but compound 3 partially decomposes in these media. Preliminary results on the effects of the complexes on the proliferation and differentiation of FLC, CEM, U937, K562 and TOM-1 leukaemia cells, and on the clonogenic activity of K562 cells are also described.     

Synthesis, structural characterization and biological study of new organotin(IV), silver(I) and antimony(III) complexes with thioamides

An overview of our work on the synthesis and biological activity of a series of tin(IV), silver(I) and antimony(III) complexes with thioamides is reported. Organotin(IV) complexes of formulae (n-Bu)2Sn(MBZT)2 (1), Me2Sn(CMBZT)(2) (2), {(Ph3Sn)2(MNA) (Me2CO)} (3), Ph3Sn(MBZT) (4), Ph3Sn(MBZO) (5), Ph3Sn(CMBZT) (6), Ph2Sn(CMBZT)2 (7) and (n-Bu)2Sn(CMBZT)2 (8), Me2Sn(PMT)2 (9), (n-Bu)2Sn(PMT)2 (10), Ph2Sn(PMT)2 (11), Ph3Sn(PMT) (12) {where MBZT=2-mercapto-benzothiazole, CMBZT=5-chloro-2-mercapto-benzothiazole, H2MNA=2-mercapto-nicotinic acid, MBZO=2-mercapto-benzoxazole and PMTH=2-mercapto-pyrimidine} were characterized by spectroscopic (NMR, IR, Mossbauer, etc.) and X-ray diffraction techniques and their influence on the peroxidation of oleic acid was studied. They were found to inhibit strongly the peroxidation of linoleic acid by the enzyme lipoxygenase. In addition, organotin(IV) complexes were found to exhibit stronger cytotoxic activity in vitro, against leiomyosarcoma cells, than cisplatin. The antiproliferative activity of the organotin complexes studied, against leiomyosarcoma cells follow the same order of LOX activity inhibition. This is, 3>12>7>6 approximately 8 approximately 10>5 approximately 4>2>9. Thus, among organotin(IV)-CMBZT complexes, 7 exhibits higher activity than the others and this is explained by a free radical mechanism, as it is revealed by an EPR study. The results are compared with the corresponding ones found for the silver(I) complexes of formulae complexes {[Ag6(mu3-HMNA)4(mu3-MNA)2](2-).[(Et(3)NH)+]2.(DMSO)2.(H2O)} (13), {[Ag4Cl4(mu3-STHPMH2)4]n} (14), {[Ag6(mu2-Br)6(mu2-STHPMH2)4(mu3-STHPMH2)2]n} (15), {[Ag4(mu2STHPMH2)6](NO3)4}(n) (16), {[AgCl(TPTP)]4} (17), [AgX(TPTP)3] with X=Cl (18), Br (19), I (20) (where STHPMH2=2-mercapto-3,4,5,6-tetrahydro-pyrimidine, TPTP=tri(p-toly)phosphine) and those of antimony(III) complexes {[SbCl2(MBZIM)4](+).Cl(-).2H2O.(CH3OH)} (21), {[SbCl2(MBZIM)4]+.Cl(-).3H2O.(CH3CN)} (22), [SbCl3(MBZIM)2] (23), [SbCl3(EMBZIM)2] (24), [SbCl3(MTZD)2] (25), {[SbCl3(THPMT)2]} (26) and {[Sb(PMT)3].0.5(CH3OH)} (27) (where MBZIM is 2-mercapto-benzimidazole, EMBZIM=5-ethoxy-2-mercapto-benzimidazole and MTZD is 2-mercapto-thiazolidine), which they have characterized with similar techniques as in case of organotin(IV) complexes. Silver(I) and antimony(III) complexes were found to be cytotoxic against various cancer 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(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.     

Development of novel mixed-ligand oxotechnetium [SNS/S] complexes as potential 5-HT1A receptor imaging agents

The "3 + 1" ligand system [SN(R)S/S combination] was applied in order to synthesize neutral mixed-ligand oxotechnetium complexes of the general formula 99mTcO[SN(R)S]/[S] as potential 5-HT1A receptor imaging agents. The complexes are carrying the 1-(2-methoxyphenyl)piperazine moiety, a fragment of the true 5-HT1A antagonist WAY 100635, either on the monodentate ligand [S] or on the tridentate ligand [SN(R)S]. The complexes MO[EtN(CH2CH2S)2] [o-MeOC6H4N(CH2CH2)2NCH2CH2S] (3), MO[o- MeOC6H4N(CH2CH2)2N(CH2)3N(CH2CH2S)2][PhS] (6) and MO[o-MeOC6H4N(CH2CH2)2N(CH2)3N(CH2CH2S)2] [PhCH2CH2S] (9), where M = 99mTc, were prepared at tracer level using 99mTc glucoheptonate as precursor. For structural characterization, the analogous oxorhenium (M = Re, 1, 4 and 7, respectively) and oxotechnetium (M = 99gTc, 2, 5 and 8, respectively) complexes were prepared by ligand exchange reactions. All products were characterized by elemental analysis and spectroscopic methods. Complexes 1, 4 and 7 were further characterized by crystallographic analysis. For 1, the coordination geometry about rhenium can be described as trigonally distorted square pyramidal (tau = 0.36), while for 4 and 7, as distorted trigonal bipyramidal (tau = 0.66 and tau = 0.61, respectively). The coordination sphere about oxorhenium in all complexes is defined by the SNS donor atom set of the tridentate ligand and the sulfur atom of the monodentate coligand. The structure of the 99mTc complexes 3, 6 and 9 was established by comparative HPLC using authentic oxorhenium and oxotechnetium samples. The binding affinity of oxorhenium compounds for the 5-HT1A receptor subtype was determined in rat brain hippocampal preparations (IC50 = 6-31 nM). Preliminary tissue distribution data in healthy mice revealed the ability of all three 99mTc complexes to cross the intact blood-brain barrier (0.49-1.15% ID at 1 min p.i.). In addition, complexes 6 and 9 showed significant brain retention. These promising results have demonstrated that the SNS/S mixed-ligand system can be used in the development of 99mTc complexes as potential 5-HT1A receptor imaging agents.     

Polynuclear diorganotin(IV) complexes with arylhydroxamates: Syntheses, structures and in vitro cytotoxic activities

Series of polynuclear diorganotin(IV) complexes with di-halogenbenzohydroxamate ligands (substituents=2,4-Cl(2), 2,4-F(2), 3,4-F(2), 2,5-F(2), 2,6-F(2)), formulated as the polymeric [R(2)SnL](n)a (1:1) and the tetranuclear [R(4)Sn(2)(HL)(2)(L)](2)b (2:3) (HL=arylhydroxamate), were prepared and characterized by FT-IR, (1)H, (13)C, (119)Sn NMR spectroscopies, elemental analyses and melting point measurements. X-ray diffraction analyses were also carried out for the representative complexes [Me(2)Sn{2,4- F(2)C(6)H(3)C(O)NO}](n)2a and [n-Bu(4)Sn(2){2,4- F(2)C(6)H(3)C(O)NHO}(2) {2,4-F(2)C(6)H(3)C(O)NO}] (2)1b and show that the ligated mono- and di-basic forms, HL and L, of the arylhydroxamic acid (H(2)L) display the oxamic and oximic tautomeric forms, respectively. These compounds exhibit in vitro cytotoxicities toward human leukemic promyelocites HL-60, BGC-823, BEL-7402 and KB cell lines which, in some cases, are identical to, or even higher than, that of "cisplatin". The polymeric diorganotin/hydroxamato complexes a containing the long carbon chain butyl ligands are the most active ones, and the dependence of the antitumor activity of the complexes on various factors, namely the nuclearity, the organic ligand, the type, position and number of the X ring substituents, is also discussed.     

Characterization and crystal structure of cadmium(II) halide complexes with amino acids and their derivatives: VII. Crystal structures of aquadibromo(3-aminopropanoic acid)cadmium(II), dichloro(4-aminobutanoic acid)cadmium(II), diaquabis(aminohexanoic acid)cadmium(II) tetrachlorocadmium(II), and dibromo(azetidine-3-carboxylic acid)cadmium(II)

Seven cadmium complexes: [CdX2(Hapro)(H2O)n] (X: Cl(1), Br(2)), [CdX2(Hgaba)] (X: Cl(3), Br(4)), [Cd(Hahex)2(H2O)2][CdCl4] (5), and [CdX2(Haze-3)](H2O)n (X: Cl(6), Br(7)) have been prepared and investigated by means of IR and FT Raman spectra. The crystal and molecular structures of 2, 3, 5 and 7 were determined by a single-crystal X-ray diffraction method. In complex 2, the cadmium atom is in a distorted octahedral geometry, ligated by two carboxyl oxygen atoms of Hapro, a water molecule, and three bromine atoms; one is terminal and each of the other two is bridging two cadmium atoms to make a polymer. The structure of 3 consists of one-dimensional polymers bridged by two chlorine atoms and a carboxyl group. The carboxyl oxygen atoms of Hgaba coordinate forkedly to two cadmium atoms. The cadmium atom of [Cd(Hahex)2(H2O)2]2+ in complex 5 is in a distorted octahedral geometry, ligated by four carboxyl oxygen atoms of two molecules of Hahex and by two water molecules. [Cd(Hahex)2(H2O)2]2+ exists between two layers which are formed of infinite [CdCl4]2- chains. The carboxyl oxygen atoms of Hahex coordinate to the same cadmium atom. In complex 7, the cadmium atom is ligated by two carboxyl oxygen atoms and four bridging bromine atoms to make a polymer.     

Synthesis and characterization of binuclear molybdenum-polycarboxylate complexes with sulfur bridges

A group of four binuclear sulfur-bridged molybdenum-polycarboxylato complexes with homocitrate, citrate, cysteine, ethylenediaminetetraacetate ligands, respectively, have been synthesized and characterized. These complexes were prepared in order to study the interaction of Mo and homocitrate in the FeMo-co of nitrogenases. In the structures of K4(NH4)2[Mo2O2S2(C6H4O7)2].10H2O (2), (NH4)2[Mo2O2S2(C3H5SNO2)2].5H2O (3) and (NH4)2[Mo2O2S2(C10H12N2O8)].3.5H2O (4), molybdenum (V) atom adopts a distorted octahedral arrangement through a terminal oxygen atom, two bridging sulfur atoms and three atoms from the ligand (hydroxyl, alpha-, beta-carboxylates, sulfide or amine). The coordination mode of homocitrate ligand in K5(NH4)[Mo2O2S2(C7H5O7)2].3H2O.CH3OH (1) has been proposed in a tridentate fashion via its hydroxyl and a pair of carboxylate groups (alpha-, beta-carboxylates). The electrochemical properties of these complexes have been discussed.     

Synthesis, characterization and crystal structures of the organotin(IV) compounds with the Schiff base ligands of pyruvic acid thiophene-2-carboxylic hydrazone and salicylaldehyde thiophene-2-carboxylic hydrazone

A series of organotin (IV) compounds of the type [R₃SnL]₂, R is Me (1), Bu (2), [R₂SnL]₂, R is Ph (3), Me (4), Bu (5), L is pyruvic acid thiophene-2-carboxylic hydrazone, and R₂SnL, R is Me (6), Bu (7), Ph (8), L is salicylaldehyde thiophene-2-carboxylic hydrazone have been synthesized in 1:1 molar ratio. All compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR and ¹¹⁹Sn NMR spectra. The crystal structure of compounds 1, 3, 4, 8 have been determined by X-ray single crystal diffraction analyses, study found that the compounds 1 and 3 are rendered one-dimensional chain structure and the tin atoms are five-coordinated in a distorted trigonal-bipyramidal geometry. The compound 4 has a dimeric structure and the central tin atom is rendered seven-coordinate in a distorted pentagonal-bipyramid configuration. While the compound 8 is a monomer in which the tin atom adopts five-coordinated in distorted trigonal-bipyramidal geometry.     

Characterization studies and cytotoxicity assays of Pt(II) and Pd(II) dithiocarbamate complexes by means of FT-IR, NMR spectroscopy and mass spectrometry

The precursors [M(ESDTM)Cl(2)] (M=Pt(II), Pd(II); ESDTM=EtO(2)CCH(2)(CH(3))NCS(2)Me, S-methyl(ethylsarcosinedithiocarbamate)) were synthesized as previously reported [J. Inorg. Biochem. 83 (2001) 31] and used to obtain [M(ESDT)Cl](n) (ESDT=ethylsarcosinedithiocarbamate anion) species. The complexes formed through reaction between [M(ESDT)Cl](n) and the two chiral amino-alcohols synephryne (Syn) and norphenylephrine (Nor) have been synthesized, with the ultimate goal of preparing mixed dithiocarbamate/amino metal complexes of the type [M(ESDT)(Am)Cl] (Am=Syn, Nor). These compounds have been isolated, purified and characterized by means of FT-IR, mono- and bidimensional NMR spectroscopy and mass spectrometry ESI/MS (electronspray mass spectra). The experimental data suggest that in all cases coordination of the dithiocarbamate ligand (ESDT) takes a place through the two sulfur atoms, the -NCSS moiety acting as a symmetrical bidentate chelating group, in a square-planar geometry around the M(II) ion, while the other two coordination positions are occupied by the chlorine atom and the amino-alcohol ligand, respectively. In particular, synephrine and norphenylephrine appear to be bound to the metal atom through the amino nitrogen atom by means of a dative bond. Finally, the biological activity of the new complexes has been studied by MTT (tetrazolio salt reduction) test and by detecting the inhibition of DNA synthesis and of clonal growth in various cancer cell lines. All Pd(II) derivatives showed a noticeable activity very close to that of cisplatin, used as reference drug. Moreover, they showed significantly reduced cross-resistance to cisplatin in a pair of cell lines (2008/C13*) with known acquired cisplatin resistance mechanisms.     

Synthesis, structural characterization and influence on the phagocytic activity of human neutrophils of thiazoline and thiazine derivative ligands and their zinc(II) complexes

The zinc(II) complexes dichloro[2-(3,4-dichlorophenyl)imino-kappaN-(2-thiazolin-kappaN-2-yl)thiazolidine]zinc(II) (1) and dichloro[2-(3,4-dichlorophenyl)imino-kappaN-(4H-5,6-dihydro-1,3-thiazin-kappaN-2-yl)tetrahydrothiazine]zinc(II) (2) have been isolated and characterized in the solid state by X-ray diffraction, elemental analysis and IR spectra. In both complexes, the environment around the zinc(II) ion may be described as a distorted tetrahedral geometry, with the metallic atom coordinated to two chlorine atoms [Zn-Cl(1)=2.218(1)A; Zn-Cl(2)=2.221(1)A], one imino nitrogen [Zn-N(3)=2.042(2)A] and one thiazoline nitrogen [Zn-N(1)=2.022(2)A] in complex 1 and to two chlorine atoms [Zn-Cl(1)=2.216(1)A; Zn-Cl(2)=2.192(1)A], one imino nitrogen [Zn-N(3)=2.045(2)A] and one thiazine nitrogen [Zn-N(1)=2.039(2)A] in complex 2. In addition, we also report in this study the crystal structure of the 2-(3,4-dichlorophenyl)imino-N-(2-thiazolin-2-yl)thiazolidine (TdTn) ligand as well as the synthesis and characterization by X-ray diffraction, (1)H and (13)C NMR spectra, elemental analysis, IR and electronic spectra of the 2-(3,4-dichlorophenyl)imino-N-(4H-5,6-dihydro-1,3-thiazin-2-yl)tetrahydrothiazine (TzTz) ligand. Besides, we study the phagocytic function in humans neutrophils treated with each complex and ligand aforementioned.     

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.     

Model investigations for vanadium-protein interactions: vanadium(III) compounds with dipeptides and their oxovanadium(IV) analogues

The reaction of VCl(3) with 1,10-phenanthroline and a series of dipeptides (H(2)dip), having aliphatic as well as aromatic side chains, in methyl alcohol and in the presence of triethylamine affords vanadium(III) compounds of the general formula [V(III)(dip)(MeOH)(phen)]Cl. Aerial oxidation/hydrolysis of the vanadium(III) species gives their oxovanadium(IV) analogues of the general formula [V(IV)O(dip)(phen)]. X-ray crystallographic characterization of the [V(IV)O(dip)(phen)] compounds (where dip(2-)=Gly- L-Ala, Gly- L-Val and Gly- L-Phe) revealed that the vanadium atom possesses a severely distorted octahedral coordination and is ligated to a tridentate dip(2-) ligand at the N(amine) atom, the deprotonated N(peptide) atom and one of the O(carboxylate) atoms, as well as an oxo group and two phenanthroline nitrogen atoms. Circular dichroism characterization of the V(III)/V(IV)O(2+)-dipeptide compounds revealed a strong signal for the V(IV)O(2+) species in the visible range of the spectrum, with a characteristic pattern which may be exploited to identify the N(am), N(pep) and O(car) ligation of a peptide or a protein to V(IV)O(2+) center, and a weak Cotton effect of opposite sign to their vanadium(III) analogues. The visible spectra of the V(III)-dipeptide compounds revealed two d-d bands with high intensity, thus indicating that the covalency of the metal-donor atoms is significant, i.e. the vanadium d orbitals are significantly mixed with the ligand orbitals, and this is confirmed by the low values of their Racah B parameters. The high-intensity band of the V(IV)O(2+)-dipeptide compounds at approximately 460 nm implies also a strong covalency of the metal with the equatorial donor atoms and this was supported by the EPR spectra of these compounds. Moreover, the V(III)/V(IV)O(2+)-dipeptide complexes were characterized by EPR and IR spectroscopies as well as conductivity and magnetic susceptibility measurements.     

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.