Juan M. Salas

Metal complexes of [1,2,4]triazolo-[1,5-a]pyrimidine derivatives

Abstract This article covers all the research work published until September 1998 about the coordination chemistry of 1,2,4-triazolo-[1,5-a]pyrimidine derivatives. The revision is mainly focused in the structural features of the compounds, obtained from single crystal X-ray diffraction. The references are classified according to the present metal atoms. These kind of ligands display a broad versatility when binding metal ions, monodentate binding through the endocyclic nitrogen atom at position 3 being however their main coordinating behaviour. Dimeric and polymeric structures are observed when a bidentate binding through N3–N4 or N3–N1, respectively, takes place. N1–O7 chelating binding mode has also been observed in a few cases. In some cases, dimers or polymers are also generated when the present auxiliary ligands are the ones that bridge the metal centres.

Polymorphic coordination networks responsive to CO2, moisture, and thermal stimuli: porous cobalt(II) and zinc(II) fluoropyrimidinolates.

The novel porous [{M(F-pymo)(2)}(n)]2.5n H(2)O coordination networks (M=Co, Zn; F-pymo=5-fluoropyrimidin-2-olate), possessing sodalitic topology, have been synthesised and structurally characterised by means of powder diffraction methods. Thermodiffractometry demonstrated their plasticity: when heated up to 363 K, they reversibly transform into three-dimensional dehydrated [{M(F-pymo)(2)}(n)] species, with significantly different lattice parameters. Further heating induces irreversible polymorphic transformations into layered phases, in which the original MN(4) coordination sphere changes into an MN(3)O one. A mixed-metal phase, [{Co(x)Zn(1-x)(F-pymo)(2)}(n)]2.5n H(2)O, was also prepared, showing that zinc is preferentially inserted, when starting from a Co/Zn reagent ratio of 1:1. The solid-gas adsorption properties of the anhydrous 3D frameworks have been explored towards N(2), H(2) (77 K) and CH(4), CO(2) (273 K). These results show that these materials permit the diffusion of CO(2) molecules only. Remarkably, the CO(2) adsorption process for the [{Co(F-pymo)(2)}(n)] network proceeds in two steps: the first step takes place at low pressures (<600 kPa) and the second one above a threshold pressure of 600 kPa. By contrast, the [{Zn(F-pymo)(2)}(n)] network only permits CO(2) diffusion by applying pressures above 900 kPa. This type of behaviour is typical of porous networks with gated channels. The high CO(2) selectivity of these systems over the rest of the essayed probe gases is explained in terms of flexibility and polarity of the porous network. Finally, the magnetic studies on the Co(II) systems reveal that the as synthesised [{Co(F-pymo)(2)}(n)]2.5n H(2)O material behaves as an antiferromagnet with a T(N) of about 29 K. At variance, the [{Co(F-pymo)(2)}(n)] layered phase shows an unusually weak ferromagnetic ordering below 17 K, arising from a spin-canting phenomenon.

Study of the biological effects and DNA damage exerted by a new dipalladium-Hmtpo complex on human cancer cells

The new dipalladium complex [Pd(2)(mu-mtpo-N(3),N(4))(2)(phen)(2)](NO(3))(2) (where phen=1,10-phenantroline; Hmtpo=5,7-dihydro-7-oxo-5-methyl[1,2,4]triazolopyrimidine), (Pd(2)-Hmtpo, or complex I), interacts effectively with DNA plasmid (pBS), as studied by circular dichroism spectroscopy (CD), causing large helix distortions, altering the direction of the main DNA helix axis and producing unwinding of the DNA double helix. DNA damage induced by complex I was highly significant at 2.81 microM (ovarian carcinoma TG cell line), as assessed by comet assay, a dose at which all treated nuclei showed more than 30% DNA migration to the comet tail. DNA damage effect is a consequence of genotoxicity and not a false positive response caused by cytotoxicity. In vitro cytotoxic assay on the two human tumor cell lines TG and BT-20 (breast carcinoma), shows that doses of 0.47, 1.41 and 2.81 microM produce significant antiproliferative effects after 4 days of treatment compared with control. Complex I was highly cytotoxic at 2.81 microM causing an inhibition of viable cells of 65.5%. Cisplatin (cis-DDP) exhibits lower cytotoxic activity in TG cells than dipalladium complex (a cisplatin dose of 6.67 microM inhibits 30.3%) and does not cause migration of DNA to comet tail.

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.

In vitro and in vivo antiparasital activity against Trypanosoma cruzi of three novel 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one-based complexes.

Conventional reactions of the versatile multidentate ligand 5-methyl-1,2,4-triazolo[1,5-a] pyrimidin-7(4H)-one (HmtpO) with metallic(II) perchlorate salts lead to three novel multidimensional complexes [Cu(HmtpO)(2)(H(2)O)(3)](ClO(4))(2)·H(2)O (1), {[Cu(HmtpO)(2)(H(2)O)(2)](ClO(4))(2) ·2HmtpO}(n) (2) and {[Co(HmtpO)(H(2)O)(3)](ClO(4))(2)·2H(2)O}(n) (3). We have tested the antiparasital activity in vitro and in vivo of the three new complexes against Trypanosoma cruzi showing very promising results and overcoming clearly the reference drug commonly used for the Chagas disease treatment, benznidazole.

Borderline microporous-ultramicroporous palladium(II) coordination polymer networks. Effect of pore functionalisation on gas adsorption properties

PdII coordination polymer networks of the type [Pd(μ-X-pymo-N1,N3)2·(H2O)m]n (X = H, 2HHH; F, 2FFF; Br, 2BrBrBr; I, 2III), containing the X-pymo (X-Hpymo = 5-X-2-hydroxypyrimidine) ligands, have been obtained by refluxing aqueous suspensions of the monomeric trans-[Pd(X-Hpymo-N1)2Cl2] (1HH-1II) precursors with NaOH in a 1 : 1 ratio. While 2BrBrBr and 2III have been recovered as amorphous materials, the microcrystalline species 2HHH and 2FFF, in their hydrated and anhydrous forms, have been structurally characterised by ab initio XRPD methods: square planar PdII ions, symmetrically connected by exobidentate N1,N3-X-pymo bridges, give rise to neutral sodalite zeotypic frameworks (with H2O guest molecules eventually included in the pores). The thermal properties and porosity have been determined for all of the 2XXX systems. The H2, N2 and CO2 adsorption isotherms showed that the 2HHH and 2FFF materials possess permanent porosity, as opposed to the 2BrBrBr and 2III ones. Moreover, the isomorphic incorporation of fluorine in the framework causes important modifications in the gas-adsorption isotherms; stronger interactions at very low pressures (Henrys law region) appear in all of the probes studied (N2, CO2 and H2). Compounds 2HHH and 2FFF possess high H2 adsorption capacities at 77 K with respective values of 1.3 and 1.15 weight percentage, and storage densities of about 0.018 kg H2 L−1, which are combined with large isosteric adsorption heats (8–9 kJ mol−1).

Synthesis, Spectroscopic and X-ray Structural Study of cis-diazidobis- (ethylenediamine)Cobalt(III) Thiocyanate

Reaction of cis-diazidobis(ethylenediamine)cobalt(III)nitrate with ammonium thiocyanate in a 1 : 2 molar ratio in aqueous medium gave the title cobalt(III) compound, cis-[Co(en)2(N3)2]SCN, as reddish brown crystals in almost quantitative yield. The complex salt was characterized by elemental analysis, IR, electronic, 1H and 13C NMR spectroscopic studies. An X-ray structure determination revealed an ionic structure with the monoclinic space group P21/c, having cell dimensions a = 12.1950(6), b = 9.0317(5), c = 12.6017(7) Å; β = 113.419(1)°, V = 1273.63(12) Å3 and Z = 4. The structure was refined by a full-matrix least-square procedures to R 1 = 0.0297 and wR 2 = 0.0697.

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.

Biological activity of three novel complexes with the ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one against Leishmania spp.

OBJECTIVES We report on new 1,2,4-triazolo[1,5-a]pyrimidine complexes that have been developed and examined for both antiproliferative in vitro activity against Leishmania infantum and Leishmania braziliensis, and report their possible mechanism of action on L. infantum and L. braziliensis. RESULTS Antileishmanial effects are described for newly synthesized Cu(II) and Co(II) complexes containing 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) as a ligand. These complexes display a wide structural diversity: (i) mononuclear unit, [Cu(HmtpO)2(H2O)3](ClO4)2·H2O (1); (ii) two-dimensional framework, {[Cu(HmtpO)2(H2O)2](ClO4)(2)·2HmtpO}n (2); and (iii) chains, {[Co(HmtpO)(H2O)3](ClO4)(2)·2H2O}n (3). Compounds 1 and 2 appeared to be the most active against L. infantum (IC50 20.0 and 24.4 μM, respectively), and compounds 1 and 3 the most active against L. braziliensis (IC50 22.1 and 23.5 μM, respectively), with IC50s similar to those of the reference drug, glucantime (18.0 μM for L. infantum and 25.6 μM for L. braziliensis). These compounds were not toxic towards J774.2 macrophages. IC25 decreased infection capacity and severely reduced the multiplication of intracellular amastigotes, following the trend 1>3>2 for L. infantum and 3>1>2 for L. braziliensis. These complexes had an effect on the energy metabolism of the parasites at the level of the NAD+/NADH balance and the organelle membranes, causing their degradation and cell death. CONCLUSIONS Cellular proliferation, metabolic and ultrastructural studies showed that the compounds 2>1>3 were highly active against L. infantum and L. braziliensis.

Influence of pseudohalide ligands on the structural versatility and properties of novel ternary metal complexes with 1,2,4-triazolo(1,5-a)pyrimidine†

Eight new multidimensional metal(II) complexes [Zn(tp)2(NCS)2] (1), [Ni(tp)2(H2O)2(µ-tp)2Ni(NCS)4]n (2), [Co(tp)2(H2O)2(µ-tp)2Co(NCS)4]n (3), [Cd(tp)2(NCS)2]n (4), [Mn(tp)2(NCS)2(H2O)2] (5), [Zn(tp)2(NCO)2] (6), [Cd(tp)(NCO)2]n (7) and [Cd(tp)(N3)2]n (8) have been synthesized by conventional reactions of the 1,2,4-triazolo[1,5-a]pyrimidine with metallic(II) salts in the presence of thiocyanate, cyanate and azide as auxiliary ligands. X-Ray diffraction studies on these compounds show that species 1, 5 and 6 are mononuclear units in which zinc and manganese have tetrahedral and octahedral coordination geometry, respectively. Complexes 2 and 3 are isostructural and consist of neutral chains with triazolopyrimidine bridging ligands through N1, N3 nitrogen atoms. Compound 4 exhibits a 2D rectangular-grid-like structure and complexes 7 and 8 are cyanate-bridged chains formed by defective cubanes. Magnetic and luminescent properties of these materials have also been studied.