Maria Assunta Girasolo

Spectroscopic characterization and biological activity of L-methionyl-L histidinato complexes of R2Sn(IV) ions (R = Me, nBu, Ph) and X-ray structure of Me2SnMetHis ˙ 0.5MeOH

Complexes of L-methionyl-L-histidine (H2MetHis) with R2Sn(IV) ions (R = Me, nBu, Ph) have been synthesized. The crystal and molecular structures of Me2SnMetHis·0.5MeOH have been determined by X-ray diffraction. The title compound contains two crystallographically independent molecular units possessing the same trigonal-bipyramidal geometry at tin, each dimethyltin(IV) moiety being coordinated by the terminal amino nitrogen, deprotonated peptide nitrogen and terminal carboxylate group, neither the imidazole nor thioether groups being involved in bonding. IR spectroscopy was used to probe the structure of the complexes in the solid state, and the structure in solution (CD3OD) was assessed by 1H and 13C NMR. Me2Sn(IV)dipeptide complexes appear to be undissociated and to retain a pentacoordinated structure. Rotamer population of C-terminal histidine was determined by analysis of vicinal coupling constants and side-chain orientations have been interpreted with a view to potential applications of the compounds as recognition agents. Biological activity was tested on Ascidian embryos of Ciona intestinalis at different stages of development. Copyright

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.

Crystal and molecular structure of dimethyl(L-tryptophyl-L-alaninato)tin(IV)–methanol (1/1) and Mössbauer spectroscopy studies of lattice dynamics of diorganotin(IV) dipeptide complexes

The crystal and molecular structure of dimethyl(L-tryptophyl-L-alaninato)tin(IV)–methanol (1/1) has been determined by X-ray crystallography. The tin atom, bonding to two methyl carbons [Sn–C(1) 2.107(6), Sn–C(2) 2.121(8)A; C(1)–Sn–C(2) 123.8(3)°], terminal amino nitrogen [Sn–Namino 2.272(5)A], deprotonated peptide nitrogen [Sn–Npeptide 2.064(5)A] and terminal carboxylate [Sn–Ocarboxylate 2.174(5)A], has a five-co-ordinated trigonal-bipyramidal environment. An extended hydrogen-bond network gives rise to one-dimensional polymeric chains. The molecular dynamics of three tryptophan-containing dipeptide complexes with R2SnIV(dipeptide dianion = Trp-AlaO, R = Me or Ph; dipeptide dianion = TrpTyrO, R = Me) have been investigated by variable-temperature 119Sn Mossbauer spectroscopy. The complexes behaved as Debye solid and, in particular, the calculated mean-square displacements of the tin atom confirm the occurrence of monomeric structures in such complexes interconnected through hydrogen bonds, which appear to be much stronger in SnMe2(Trp-AlaO) and SnMe2(Trp-TyrO) than in SnPh2(Trp-AlaO).

ORGANOMERCURY(II) DERIVATIVES OF 2-THIOURACIL. AN INFRARED AND PROTON MAGNETIC RESONANCE STUDY OF STRUCTURES

Abstract The novel complexes RHg(s2UraH−1) (R = Me, Ph) where s2UraH−1 is the monoanion of 2-thiouracil, have been synthesized. Comparison of the infrared spectra of the solid complexes and of 1H nuclear magnetic resonance spectra of the complexes in dimethyl-d6 sulfoxide with spectra of s2 Ura and Na[s2UraH−1] allows the recognition of the existence of isomers in the solid, with bonding to exocyclic sulfur and to pyrimidine nitrogens. In solution, a simpler pattern is observed, with 2J(1H199Hg) indicating bonding to sulfur only.

Organotin(IV) derivatives of the ambidentate ligand 2-thiouracil. Infrared, Mössbauer, 1H and 13C NMR studies

Abstract Complexes Bu 2 n Sn(s 2 UraH −2 and [Me 2 SnOH] 2 (s 2 UraH −2 have been synthesized. Comparison of infrared spectra of the solid complexes with spectra of s 2 Ura and (PhHg) 2 (s 2 UraH −2 complex and point charge calculations (Mossbauer spectra) allow assignment of structures for the complexes of this ambivalent ligand. Polymeric structures are proposed for the complexes in the solid state, where the organometallic moieties are bonded to exocyclic S and N(3) atoms of the dianionic base, with formation of a four-membered chelate ring for Bu 2 n Sn(s 2 UraH −2 ). For [Me 2 SnOH] 2 (s 2 UraH −2 , 1 H and 13 C NMR data suggest retention of penta-coordination in trifluoacetic acid solution and indicate rapid exchange of Me 2 SnOH + between the binding sites.

The dynamics of 57Fe nuclei in FeIII–DNA condensates

Abstract The dynamics of iron nuclei in the condensates obtained by interaction of Fe III with DNA, Fe III (DNA monomer) 2 , have been investigated by variable temperature 57 Fe Mossbauer spectroscopy. Studies were effected on gel and freeze-dried samples, obtaining nearly coincident values of the parameters isomer shift and nuclear quadrupole splitting in T ranges 20–260 K. Functions ln( A T / A 77.3 ) vs. T , here employed to investigate the dynamics of Fe nuclei, showed linear trends in the T ranges 20–150 and 150–260 K, respectively, the latter with larger slopes. Data coincided for gelled and freeze-dried specimens. No variation of δ or Δ E parameters occurred at the two T intervals, which suggests constancy of structure and bonding with the temperature changes. Functions 〈 x 2 〉( T ) showed trends analogous to the corresponding functions determined for iron proteins, which were attributed to the occurrence of ‘conformational substates’.

Synthesis of platinum complexes with 2-(5-perfluoroalkyl-1,2,4-oxadiazol-3yl)-pyridine and 2-(3-perfluoroalkyl-1-methyl-1,2,4-triazole-5yl)-pyridine ligands and their in vitro antitumor activity.

Five new mononuclear Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1,2,4-triazolyl-pyridine ligands are reported. The ligands 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(5-perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp) and their complexes [PtCl2(pfhop)2]·1.5 DMSO (2a), [PtCl2(pfpop)2]·1.5 DMSO (3a), [PtCl2(pfhtp)2]·1.5 DMSO (4a), PtCl2(pfhtp) (4b), [PtCl2(pfptp)2]·1.5 DMSO (5a) have been synthesized and structurally characterized. The complexes 2a, 3a, 4a and 5a have the same chemical environment of Pt(II) where PtCl2 moieties coordinate two molecules of ligand via N1 atom of pyridine in the case of pfhop and pfpop, and N2 atom of 1,2,4-triazole in the case of pfhtp and pfptp. For 4b, pfhtp behaves as bidentate ligand, coordinating Pt(II) ion via N4 atom of triazole and N1 atom of pyridine. All complexes have been tested in vitro by 3-(4,5-dimethyl-2-thiazolyl)bromide-2,5-diphenyl-2H-tetrazolium (MTT) test on four tumor cell lines MCF-7 (human breast cancer), HepG2 (human hepatocellular carcinoma), HCT116 (human colorectal carcinoma). Compounds 2a and 4b showed a dose-dependent anti-proliferative effect against the three tumor cell lines whereas did not affect viability of intestinal normal-like differentiated Caco-2 cells. The cell death of HepG2, MCF-7 and HCT116 induced by the compounds, was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observing the typical apoptotic morphological change by acridine orange (AO)/ethidium bromide (EB) staining.

THE STRUCTURE AND DYNAMICS OF CL-SUBSTITUTED TETRAPHENYL- AND TETRABENZYL-TIN(IV)

Abstract The crystal and molecular structure of (o-ClC6H4CH2)4Sn has been determined by X-ray crystallography. Tin is in a slightly distorted environment. The molecular dynamics of (p-ClC6H4)4Sn, (o-ClC6H4)4Sn and (o-ClC6H4CH2)4Sn have been investigated by variable temperature 119Sn Mossbauer spectroscopy (VTMS). A Debye-solid behaviour has been detected for (p-ClC6H4)4Sn, where, on the other hand, no influence by hydrogen–chlorine interaction on the magnitude of the dynamics data and functions seems to occur. For the o-Cl-substituted derivatives, a non-Debye-solid character could be advanced.

The dynamics of 57Fe nuclei in FeII-DNA and [FeII (1-methyl-2-mercaptoimidazole)2]-DNA condensates

Alcoholic solutions of FeCl(2) and Fe(II)(Hmmi)(2)Cl(2) (Hmmi=1-methyl-2-mercaptoimidazole) induce calf thymus DNA condensation from aqueous solutions buffered at pH 7.4. A 1:1 Fe(II)-(DNA monomer) stoichiometry is assumed. The (57)Fe Mössbauer hyperfine parameters suggest an octahedral coordination environment, severely distorted, in both Fe(II)-(DNA monomer) and [Fe(II)(Hmmi)(2)]-(DNA monomer) condensates. The dynamic properties of iron nuclei in freeze-dried samples were investigated by means of variable temperature (57)Fe Mössbauer spectroscopy. Mean square displacements, (T), were calculated, such as the effective vibrating mass and the Mössbauer lattice temperature of the solids. increases linearly with the temperature in the whole temperature range explored; the absolute values are typical for lattice or solid-state vibrations. Very similar values for the effective vibrating masses were extracted, suggesting comparable covalency of the bonding interaction between the metal atom and its ligands, while the Mössbauer lattice temperatures show a softening of the lattice for [Fe(II)(Hmmi)(2)]-(DNA monomer) with respect to Fe(II)-(DNA monomer) condensate.

Anti-cancer activity of di- and tri-organotin(IV) compounds with D-(+)-Galacturonic acid on human tumor cells

We have compared the anti-proliferative activity in vitro, of R2SnGala (1-3) [R = Me, n-Bu, Ph] and novel R3SnGala (4, 5) [R = Me, n-Bu] with D-(+)-Galacturonic acid [HGala; Galaq-, q = (2) and (1) for R2SnGala and R3SnGala, respectively] compounds, towards human tumor cell lines of intestinal carcinoma (HCT-116) and breast adenocarcinoma (MCF-7). The new synthesized 4 and 5 compounds were characterized, in solution, by 1H, 13C and 119Sn NMR, that showed that HGala acts as monoanionic moiety and evidenced the dynamic behavior of the compounds, due to inter-conversions involving the anomeric carbon atom of the ligand. Cell viability, apoptosis induction and cell cycle distribution were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and flow cytometry, respectively. The cytotoxicity of the compounds, in the micro-submicromolar range, changed in the order of the organotin(IV) moieties, according to 5 > 3 > 2, while 1 and 4, containing MenSn(IV) (n = 2,3) moieties, were ineffective. Compound 5 showed peculiar cytotoxic effects. It did not cause time dependent inhibition of cell growth nor accumulated into the cells. Cell death induced by the active 2, 3, and 5, was shown to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and the loss of mitochondrial potential. All the cytotoxic compounds induced an accumulation of cells in the subG0/G1phase, while only 2 and 3 perturbed the cell cycle confining viable cells in G0/G1phase. Finally, none of the compounds investigated affected the viability of normal intestinal or liver cells, indicating selectivity towards tumor cells.