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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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The interaction of native calf thymus DNA with the Zn(II) and Cu(II) complexes of 5-triethyl ammonium methyl salicylidene orto-phenylendiimine (ZnL(2+) and CuL(2+)), in 1 mM Tris-HCl aqueous solutions at neutral pH, has been monitored as a function of the metal complex-DNA molar ratio by UV absorption spectrophotometry, circular dichroism (CD) and fluorescence spectroscopy. The results support for an intercalative interaction of both ZnL(2+) and CuL(2+) with DNA, showing CuL(2+) an affinity of approximately 10 times higher than ZnL(2+). In particular, the values of the binding constant, determined by UV spectrophotometric titration, equal to 7.3x10(4) and 1.3x10(6)M(-1), for ZnL(2+) and CuL(2+), respectively, indicate the occurrence of a marked interaction with a binding size of about 0.7 in base pairs. The temperature dependence of the absorbance at 258 nm suggests that both complexes strongly increase the DNA melting temperature (Tm) already at metal complex-DNA molar ratios equal to 0.1. As evidenced by the quenching of the fluorescence of ethidium bromide-DNA solutions in the presence of increasing amounts of metal complex, ZnL(2+) and CuL(2+) are able to displace the ethidium cation intercalated into DNA. A tight ZnL(2+)-DNA and CuL(2+)-DNA binding has been also proven by the appearance, in both metal complex-DNA solutions, of a broad induced CD band in the range 350-450 nm. In the case of the CuL(2+)-DNA system, the shape of the CD spectrum, at high CuL(2+) content, is similar to that observed for psi-DNA solutions. Such result allowed us to hypothesize that CuL(2+) induces the formation of supramolecular aggregates of DNA in aqueous solutions.

The interaction between native calf thymus deoxyribonucleic acid (DNA) and Fe(III)- N ,N'-ethylene-bis (salicylideneiminato)-chloride, Fe(Salen)Cl, was investigated in aqueous solutions by UV-visible (UV-vis) absorption, circular dichroism (CD), thermal denaturation and viscosity measurements. The results obtained from CD, UV-vis and viscosity measurements exclude DNA intercalation and can be interpreted in terms of an electrostatic binding between the Fe(Salen)(+) cation and the phosphate groups of DNA. The trend of the UV-vis absorption band of the Fe(Salen)Cl complex at different ratios [DNA(phosphate)]/[Fe(Salen)Cl] and the large increase of the melting temperature of DNA in the presence of Fe(Salen)Cl, support the hypothesis of an external electrostatic interaction between the negatively charged DNA double helix and the axially stacked positively charged Fe(Salen)(+) moieties, analogously to what reported for a number of porphyrazines and metal-porphyrazine complexes interacting with DNA.

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.

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 Mössbauer 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 delta or Delta E parameters occurred at the two T intervals, which suggests constancy of structure and bonding with the temperature changes. Functions (T) showed trends analogous to the corresponding functions determined for iron proteins, which were attributed to the occurrence of 'conformational substates'.

Bis(adeninato-N9)diphenyltin(IV) has been selected as a tumor panel compound by the U.S. National Cancer Institute and tested against a number of tumors according to standard protocols. The activity criteria were not passed. The solid state structure of the environment of tin in the complex has been definitely established to be of the tetrahedral type by means of 119Sn Mössbauer-Zeeman spectroscopy; this configuration has been assumed to be maintained also in aqueous suspensions of the drug, in conditions corresponding to the administration to mice. The occurrence of strong Sn-N bonds, consistently resistant to hydrolytic processes, has been assumed, and correlated to the observed low toxicity of the drug. The extent of the antitumor action corresponds to the standard response to Ph2SnIV moieties.

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.