Benigno Macías

Toward the development of metal-based synthetic nucleases: DNA binding and oxidative DNA cleavage of a mixed copper(II) complex with N-(9H-purin-6-yl)benzenesulfonamide and 1,10-phenantroline. Antitumor activity in human Caco-2 cells and Jurkat T lymphocytes. Evaluation of p53 and Bcl-2 proteins in the apoptotic mechanism.

The complex [Cu(N9-ABS)(phen)2].3.6H2O, H2N9-ABS = N-(9H-purin-6-yl)benzenesulfonamide and phen = 1,10-phenanthroline, has been synthesized and then characterized with the aid of X-ray diffraction, analytical, and spectroscopic techniques. The geometry of Cu(II) is distorted square pyramidal with the equatorial positions occupied by three N atoms from two phenantroline molecules and one N atom from the adenine ring of the sulfonamide ligand. The interaction of the complex with DNA was studied by means of viscosity measurements and fluorescence spectroscopy. The results pointed to a classic intercalation of the complex between the DNA base pairs. The complex was found to be a very efficient agent of plasmid DNA cleavage in the presence of ascorbate. Both the kinetics and the mechanism of the cleavage reaction were studied. In addition, the cytotoxic properties of the complex were evaluated in human Jurkat T and Caco-2 cell lines. The cytotoxicity of the compound was higher than that of the reference ([Cu(phen)2]2+). The mechanism and type of cell death induced by the compound was determined by flow cytometry and Hoechst dye staining. The compound demonstrated a significant ability to induce cell death by apoptosis. The apoptosis induced by [Cu(N9-ABS)(phen)2].3.6H2O was associated with an increase in p53 protein levels while those of Bcl-2 were reduced.

Complexes of Ni(II) and Cu(II) with ofloxacin. Crystal structure of a new Cu(II) ofloxacin complex.

Several coordination compounds formed between Ni(II) or Cu(II) with ofloxacin have been synthesised and characterised. According to elemental chemical analysis and FT-IR spectroscopy data, direct reaction of Ni(II) and Cu(II) salts with ofloxacin leads to formation of precipitates for which mass spectrometry demonstrates their polymeric nature. However, crystalline [Cu(oflo)2(H2O)].2H2O is formed if the reaction is carried out in the presence of ammonia. This complex crystallises in the triclinic system, space group P-1 with a=9.2887(12), b=11.2376(14), c=17.874(2) A, alpha=92.12(3), beta=95.39(3), gamma=91.71(3) degrees and Z=2. The local geometry around the Cu(II) ion is a slightly distorted square base pyramid. Electronic spectra, magnetic susceptibility measurements and EPR spectra of the synthesised complexes indicate a tetragonal environment.

Chemistry of dithiocarbamate derivatives of amino acids. I: Study of some dithiocarbamate derivatives of linear α-amino acids and their nickel(II) complexes

Abstract The barium dithiocarbamate derivates of the α-amino acids glycine, DL-alanine, DL-2-amino- butyric acid, DL-norvaline and DL-norleucine have been synthesized. The crystal structure of the glycine derivative was determined. The anions were used to obtain the corresponding nickel(II) complexes in acid form. The complexes are diamagnetic, and coordination takes place in a near-square planar geometry around the Ni(II) ion through the sulphur atoms of the dithiocarbamate moiety, the structure having been confirmed by IR, 1 H NMR, UV-Vis spectroscopies and chemical analysis.

Oxidative DNA damage of mixed copper(II) complexes with sulfonamides and 1,10-phenanthroline: Crystal structure of [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)2(1,10-phenanthroline)]

Mixed coordination compounds of Cu(II) with sulfonamides and 1,10-phenanthroline as ligands have been prepared and characterised. Single crystal structural determination of the complex [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)(2)(phen)] shows Cu(II) ions are located in a highly distorted octahedral environment, probably as a consequence of the Jahn-Teller effect. The FT-IR and electronic paramagnetic resonance (EPR) spectra are also discussed. The mixed complexes prepared undergo an extensive DNA cleavage in the presence of ascorbate and hydrogen peroxide. Two of the complexes have higher nucleolytic efficiency than the bis(o-phenanthroline)copper(II) complex.

Au(III) complexes of tris-dithiocarbamate derivatives of α-amino acids: spectroscopic studies, thermal behaviour and antibacterial activity

Abstract The synthesis and characterization of new coordination compounds of Au(III), with dithiocarbamates derived from α-amino acids (DL-alanine, DL-valine, L-valine and DL-leucine) is reported. As single crystals were not synthesized, a large number of experimental techniques was used to accomplish a definitive characterization and determination of the structures of these compounds. The compounds are hexacoordinated, but diamagnetic, the structure thus corresponding to a distorted trigonal prism. Only one XPS S(2p) signal is recorded, indicating a symmetric dithiocarbamate moiety surrounding the metallic cation; two Au(4f) signals are recorded in all cases, due to Au(III) and Au(I), through reduction of the former in the spectrometer chamber. Results obtained by applying other techniques (FT-IR, Vis-UV, NMR, MS) support the above conclusions. Antibacterial activity against nine Gram+ and Gram− species has been studied for the gold salt, the ligands, the complexes and control antimicrobial agents. Only the gold complexes exhibit a larger activity than the reference compounds, against Streptococcus pneumoniae.

Novel chelates of Pd(II) dithiocarbamates. Spectroscopic studies and thermal behaviour

Abstract Complexes of Pd(II) with dithiocarbamate derived from α-amino acid (glycine, DL -alanine, DL -valine, L -valine and DL -leucine) have been synthesized. The complexes have been characterized by chemical analysis, infrared, electronic, 1 H and 13 C NMR and X-ray photoelectron spectroscopies, magnetic susceptibilities measurements, mass spectrometry and TG and DSC analysis. The stoichiometry of these complexes is Pd:L = 1:2 and coordination around the metallic cation seems to be distorted square planar, close to D 2 h . Coordination takes place through the sulphur atoms of the ligands and the carboxylic group is in a free, acidic form. Both sulphur atoms are chemically equivalent, according to the XPS results. 1 H and 13 C NMR spectra for the DL - and L -valine derivatives indicate that different complexes DD , DL and DL do not have any spectroscopic difference due to the large distance between the chiral centers. Thermal decomposition of the complexes takes place through a multi-step process, the first step being a decarboxylation, followed by a complex pyrolysis that leads to palladium oxide. The thermal stability of these complexes decreases in the order Pd(dtc- DL - val) 2 > Pd(dtc- DL -ala) 2 > Pd(dtc-gly) 2 > Pd(dtc- DL - leu) 2 . The mass spectrometric data indicate that the [S 2 CNHCH 2 COO] + ion is formed in all cases, with the final formation of [S 2 C] + for the ligands. For the complexes, however, the species [S-C-ala] + , [S-C-val] + and [S-C-leu] + are formed.

Crystal structure of [Cu(N-quinolin-8-yl-p-toluenesulfonamidate)2]: study of its interaction with DNA and hydrogen peroxide

A new copper complex with N-quinolin-8-yl-p-toulenesulfonamide has been prepared and characterised. The compound crystallises in the triclinic system, space group P1, with a=13.457(3), b=15.067(5), c=18.589(3) A; alpha=112.05(2), beta=93.92(2), gamma=108.30(2) degrees and Z=4. The geometry of the Cu(II) ion is distorted square planar. The N-quinolin-8-yl-p-toulenesulfonamidate anion behaves as a bidentate ligand through the N(sulfonamidate)and N(quinoline) atoms. The complex does not cleave DNA in the presence of hydrogen peroxide.

New PtS4 chromophores of dithiocarbamates derived from α-amino acids: synthesis, characterization and thermal behaviour

Abstract Complexes of Pt(II) with dithiocarbamates derived from α-amino acid (glycine, DL-alanine, DL-valine and DL -leucine) have been synthesized. The complexes have been characterized by chemical analysis, infrared, electronic, 1 H and 13 C NMR and X-ray photoelectron spectroscopies, magnetic susceptibilities measurements and TG and DSC analysis. The stoichiometry of these complexes is Pt:L= 1:2 and coordination around the metallic cation seems to be a distorted square-planar, dose to D 2 h . Coordination takes place through the sulphur atoms of the ligands and the carboxylic group is in a free, acidic form. 13 C NMR spectra indicate that all complexes are optically inactive due to the close vicinity of the chiral centers. Thermal decomposition of the complexes takes place through a multi-step process, the first step being a decarboxylation, followed by a complex pyrolysis that leads to metallic platinum. The thermal stability of these complexes decreases in the order Pt(gly dtc) 2 > Pt( DL -ala dtc) 2 > Pt( DL - val dtc) 2 > Pt( DL -leu dtc) 2 .

Nuclease activity of [Cu(sulfathiazolato)2(benzimidazole)2]2MeOH. Synthesis, properties and crystal structure

The [Cu(sulfathiazolato)(2)(benzimidazole)(2)]2MeOH complex has been synthesised and characterised. It crystallises in the monoclinic system, space group C1c1, with unit cell dimensions a=18.829(7) A, b=12.206(3) A, c=17.233(5) A, alpha=90.06(2) degrees, beta=97.28(3) degrees, gamma=90.21(3) degrees and Z=4. The geometry around the copper(II) ion is intermediate between tetrahedral and square planar. The complex produces cleavage of plasmid pUC18 in presence of reducing agents. The efficiency of cleavage reaction of the title compound with pUC18 and with different reducing agents follows the order ascorbate-H(2)O(2)>ascorbate>MPA>dithiothreitol>H(2)O(2).

Copper complexes with dithiocarbamates derived from natural occurring amino acids. Crystal and molecular structure of [Cu(en)(EtOH)(H2O)3][Cu(dtc-pro)2]

Abstract Reaction of Cu(II) salts with dithiocarbamates derived from the amino acids asparagine, glutamine, serine, threonine and tyrosine leads to reduction of the metallic cation and formation of Cu(I) complexes, whereas reaction with proline dithiocarbamate takes place without reduction, leading to formation of a Cu(II) coordination compound. Simultaneous reaction of proline dithiocarbamate and ethylenediamine with Cu(II) leads to the formation of the mixed complex [Cu(en)(EtOH)(H2O)3][Cu(dtc-pro)2]. In the anion, the Cu(II) centre possesses a D2h local symmetry, coordinated by two bidentate dithiocarbamate ligands, while the Cu(II) centre is in a distorted octahedral coordination in the cationic unit. The spectroscopic and magnetic properties of the complexes synthesised are also investigated.