Eduardo E. Castellano

Diorganotin(IV) derivatives of salicylaldehydethiosemicarbazone. The crystal structure of dimethyl- and diphenyl- (salicylaldehydethiosemicarbazonato)tin(IV)

Abstract The title compounds have been prepared by reacting the corresponding diorganotin(IV) oxide with salicylaldehyde thiosemicarbazone (H2L). [SnMe2(L)] crystallizes in the monoclinic space group P21/n with a=9.480(3), b=13.532(7), c=10.541(3) A, β=100.33(2)° and Z=4 (R=0.0230, R′=0.0258). [SnPh2(L)] crystallizes in the space group P21/a with a=13.483(8), b=10.078(1), c=15.622(4) A, β=113.66(4)° and Z=4 (R=0.030, R′=0.031). Both complexes consist of molecules in which the bisdeprotonated ligand is O,N,S-bonded and the tin atom exhibits distorted pentacoordination, with small differences between the methyl and phenyl derivatives in bond distances, bond angles and intermolecular hydrogen bonds. The spectral properties of the complexes (IR, Mossbauer and 1H, 13C and 119Sn NMR spectra) are discussed in the light of this structural information.

Antimycobacterial and antitumor activities of palladium(II) complexes containing isonicotinamide (isn): X-ray structure of trans-[Pd(N3)2(isn)(2)].

Complexes of the type trans-[PdX(2)(isn)(2)] {X = Cl (1), N(3) (2), SCN (3), NCO (4); isn = isonicotinamide} were synthesized and evaluated for in vitro antimycobacterial and antitumor activities. The coordination mode of the isonicotinamide and the pseudohalide ligands was inferred by IR spectroscopy. Single crystal X-ray diffraction determination on 2 showed that coordination geometry around Pd(II) is nearly square planar, with the ligands in a trans configuration. All the compounds demonstrated better in vitro activity against Mycobacterium tuberculosis than isonicotinamide and pyrazinamide. Among the complexes, compound 2 was found to be the most active with MIC of 35.89 μM. Complexes 1-4 were also screened for their in vitro antitumor activity towards LM3 and LP07 murine cancer cell lines.

1,2,5-Oxadiazole N-oxide derivatives as potential anti-cancer agents: synthesis and biological evaluation. Part IV

Several new 1,2,5-oxadiazole N-oxide derivatives and some deoxygenated analogues were synthesized to be tested as potential selective hypoxic cell cytotoxins. Compounds prepared were designed in order to gain insight into the mechanism of action of this kind of cytotoxin. Compounds were tested in oxia and hypoxia and they proved to be non-selective. 3-Cyano-N(2)-oxide-4-phenyl-1,2,5-oxadiazole showed the best cytotoxic activity in oxia. The cytotoxicity observed for these derivatives could be explained in terms of the electronic characteristics of the 1,2,5-oxadiazole substituents. Electrochemical and ESR studies were performed on the more cytotoxic derivative.

Copper(I) complexes with 4,6-dimethylpyrimidine-2-thione (Hdmpymt); the crystal and molecular structure of [Cu6(dmpymt)6]

The complex [Cu6(dmpymt)6]·H2O was synthesised by electrochemical oxidation of copper in an acetonitrile solution of the neutral ligand 4,6-dimethylpyrimidine-2-thione (Hdmpymt). The reaction of [Cu6(dmpymt)6] with 1,2-bis(diphenylphosphino)methane (dppm) and 1,2-bis(diphenylphosphino)ethane (dppe) yielded compounds of general formulae [Cu(dmpymt)(dppm)] and [Cu2(dmpymt)2(dppe)3]. The molecular structure of [Cu6(dmpymt)6] was determined: the crystals are triclinic, space group P1, a= 11.432(3), b= 13.395(2), c= 15.694(4)A, α= 80.28(2), β= 87.75(2), γ= 73.87(2)° and Z= 2. The six copper atoms are arranged with distorted-octahedral geometry, each copper atom being trigonally co-ordinated to one nitrogen and two sulfur atoms of three different ligands. Infrared, 1H, 13C and 31P NMR spectral data are presented for all the compounds.

Synthesis and characterization of three new Cu(II)-dipeptide complexes

Three new copper(II) complexes of stoichiometry [Cu(L-dipeptide)].nH(2)O, containing as ligands the dipeptides L-alanine-L-isoleucine, L-alanine-L-threonine and L-alanine-L-tyrosine were prepared. They were characterized by single crystal X-ray diffractometry, and electronic and infrared spectroscopy. In all cases, the Cu(II) cation has essentially the same elongated square pyramidal coordination, being equatorially cis coordinated by a N(2)O(2) arrangement of ligand atoms and axially by a carbonyl oxygen atom. The compounds show rather similar polymeric structures which resemble those recently reported for the [Cu(ala-val)] and [Cu(ala-phe)] complexes. The electronic and infrared spectra are briefly discussed on the basis of the structural peculiarities of the complexes. Superoxide dismutase (SOD)-like activity was also tested for the compounds.

Cadmium coordination chemistry related to chelate therapy

Abstract Various aspects of the coordination chemistry of cadmium in its dithiocarbamate complexes, which are known to affect the in vivo distribution of this toxic metal ion have been examined. Under appropriate conditions, solid complexes of the composition Cd(DTC)2 have been obtained as reaction products with seven dithiocarbamates. The general properties, octanol/water partition coefficients, mass spectra, 1H, 13C and 113Cd NMR spectra and infrared spectra have been obtained. The molecular structure of the Cd{S2CN(n-C4H9)2}2 complex has been determined. This compound forms monoclinic crystals C2/c a= 23.577(7), b=16.877(8), c=16.209(9) A, β= 126.93(3)o, V=5156(8) A3, Z=8, density=1.343 g cm−3. For the structure determination: λ(Mo Kα)= 0.71073 A, μ=1.076 mm−1, F(000)=2160, T= 296 K and R=0.064 for 1330 observed reflections. The Cd ion is coordinated to four S atoms at distances ranging from 2.513(5) to 2.601(7) A and to a fifth one at the much longer distance of 2.888(5) A. Two of the short metal-sulphur distances are realized by the S atoms of one of the chelate moieties whilst the S atoms of the other moiety realize one short and the longest [2.888(5) A] metal sulphur distance. The other short bond is subtended to a sulphur atom of an asymmetry-related ligand. The coordination polyhedron can be described as either a very distorted tetragonal pyramid or a very distorted trigonal bi-pyramid. The shortest CdCd distance is 3.772(6) A.

Pt(II) and Ag(I) complexes with acesulfame: Crystal structure and a study of their antitumoral, antimicrobial and antiviral activities

Two new complexes of platinum(II) and silver(I) with acesulfame were synthesized. Acesulfame is in the anionic form acesulfamate (ace). The structures of both complexes were determined by X-ray crystallography. For K(2)[PtCl(2)(ace)(2)] the platinum atom is coordinated to two Cl(-) and two N-acesulfamate atoms forming a trans-square planar geometry. Each K(+) ion interacts with two oxygen atoms of the S(O)(2) group of each acesulfamate. For the polymeric complex [Ag(ace)](n) the water molecule bridges between two crystallographic equivalent Ag1 atoms which are related each other by a twofold symmetry axis. Two Ag1 atoms, related to each other by a symmetry centre, make bond contact with two equivalent oxygen atoms. These bonds give rise to infinite chains along the unit cell diagonal in the ac plane. The in vitro cytotoxic analyses for the platinum complex using HeLa (human cervix cancer) cells show its low activity when compared to the vehicle-treated cells. The Ag(I) complex submitted to in vitro antimycobacterial tests, using the Microplate Alamar Blue (MABA) method, showed a good activity against Mycobacterium tuberculosis, responsible for tuberculosis, with a minimal inhibitory concentration (MIC) value of 11.6microM. The Ag(I) complex also presented a promising activity against Gram negative (Escherichia coli and Pseudomonas aeruginosa) and Gram positive (Enterococcus faecalis) microorganisms. The complex K(2)[PtCl(2)(ace)(2)] was also evaluated for antiviral properties against dengue virus type 2 (New Guinea C strain) in Vero cells and showed a good inhibition of dengue virus type 2 (New Guinea C strain) replication at 200microM, when compared to vehicle-treated cells.

CRYSTAL STRUCTURE OF TRIPHENYL(5-MERCAPTO-1-PHENYL-1,2,3,4-TETRAZOLATO)TIN(IV)

Abstract The title compound was prepared from 1-phenyl-5-thione-1,2,3,4-tetrazole and triphenyltin(IV) hydroxide and its crystal structure was determined by X-ray diffraction. The lattice is formed by discrete molecules that contain the tin atom coordinated to three phenyl groups and to the tetrazole via the deprotonated -SH group in a distorted tetrahedral coordination polyhedron. There is evidence of a very weak intramolecular interaction between N(4) of the tetrazole and the Sn atom. 13C and 15N NMR studies (CDCl3) suggest that in solution the tetrazole is also in the deprotonated thiol form, and binds to the tin via its S atom.

Analgesic and Anti-Inflammatory Activities of Salicylaldehyde 2-Chlorobenzoyl Hydrazone (H2LASSBio-466), Salicylaldehyde 4-Chlorobenzoyl Hydrazone (H2LASSBio-1064) and Their Zinc(II) Complexes

Salicylaldehyde 2-chlorobenzoyl hydrazone (H2LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H2LASSBio-1064) and their complexes [Zn(LASSBio-466)H2O]2 (1) and [Zn(HLASSBio-1064)Cl]2 (2) were evaluated in animal models of peripheral and central nociception, and acute inflammation. All studied compounds significantly inhibited acetic acid-induced writhing response. Upon coordination the anti-nociceptive activity was favored in the complex 1. H2LASSBio-466 inhibited only the first phase of the formalin test, while 1 was active in the second phase, like indomethacin, indicating its ability to inhibit nociception associated with the inflammatory response. Hence coordination to zinc(II) altered the pharmacological profile of H2LASSBio-466. H2LASSBio-1064 inhibited both phases but this effect was not improved by coordination. The studied compounds did not increase the latency of response in the hot plate model, indicating their lack of central anti-nociceptive activity. All compounds showed levels of inhibition of zymosan-induced peritonitis comparable or superior to indomethacin, indicating an expressive anti-inflammatory profile.

Structural and spectroscopic characterization of two new Cd(II) complexes: bis(thiosaccharinato)bis(imidazole) cadmium(II) and tris(thiosaccharinato)aquacadmate(II)

Abstract The crystal structures of [Cd(tsac)2(im)2] (1) (tsac=anion of thiosaccharine; im=imidazole) and of (Him)[Cd(tsac)3(H2O)] (2) (Him=imidazolium cation) have been determined at 120 K by single crystal X-ray diffractometry. Complex 1 crystallises in the monoclinic space group P21/a with Z=4 whereas compound 2 is triclinic, space group P(−1) and Z=2. In both compounds, Cd(II) is in a distorted tetrahedral environment. In the neutral complex 1 the metal is coordinated to the S-atom of the two thiosaccharinato ligands and to the N-atom of the imidazole molecules. In the anionic complex 2, Cd(II) is coordinated to three thiosaccharinato S-atoms and to the O-atom of the water molecule. The FTIR spectra of both compounds were also recorded and briefly discussed.