Nuria A. Illán-Cabeza

Synthesis and spectroscopic studies on the new Schiff base derived from the 1:2 condensation of 2,6-diformyl-4-methylphenol with 5-aminouracil (BDF5AU) and its transition metal complexes: Influence on biologically active peptides-regulating aminopeptidases

The synthesis, spectroscopic (IR, 1H and 13C NMR, UV-Vis-NIR, EPR), magnetic measurements and biological studies of a number of complexes of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Au(III) and Hg(II) of the Schiff base derived from the 1:2 condensation of 2,6-diformyl-4-methylphenol and 5-aminouracil, ((5-[[(3-[[(2,4-dioxopyrimidin-5(1H,3H)-yl)imino]methyl]-2-hydroxy-5-methylphenyl)methylene]amino]pyrimidine-2,4(1H,3H)-dione, hereafter denoted as BDF5AU) are reported. In all cases, the complexes appear to be monomeric. The deprotonated ligand in the phenolic oxygen atom shows a tridentate coordination mode through the two azomethine nitrogen atoms and the phenolic oxygen atom. The coordination of the neutral ligand takes place through the phenolic oxygen atom and one azomethine nitrogen atom and the carbonylic oxygen atom in fourth position of one uracil ring. The biological properties of some perchlorate complexes on the activity of some neutral, acid, basic and omega aminopeptidases (AP) are assayed, demonstrating a general inhibitory effect. Neutral and basic AP are mainly inhibited by Cu(II), Ni(II) and Cd(II) complexes, although tyrosyl-AP is activated by Zn(II) complex. Glutamyl-AP but not aspartyl-AP is inhibited by all the complexes assayed excepting Zn(II) complex. Finally, omega AP is inhibited by Ni(II) and Cd(II) complexes.

Chloro-fac-tricarbonylrhenium(I) complexes of asymmetric azines derived from 6-acetyl-1,3,7-trimethylpteridine-2,4(1H,3H)-dione with hydrazine and aromatic aldehydes: preparation, structural characterization and biological activity against several human tumor cell lines.

A number of new asymmetric azines derived from hydrazine and 6-acetyl-1,3,7-trimethyllumazine (lumazine=pteridine-2,4(1H,3H)-dione) and its derivatives with several aromatic aldehydes have been prepared and characterized by usual procedures (XRD, IR, (1)H and (13)C NMR). These were reacted with [ReCl(CO)(5)] to give the corresponding mononuclear chloro-fac-tricarbonylrhenium(I) [ReCl(CO)(3)L] compounds. The complexes were characterized by elemental analysis, thermogravimetry (TG) and differential scanning calorimetry (DSC), IR, (1)H and (13)C NMR. Furthermore, single-crystal X-ray diffraction studies have also allowed to report two different coordination modes of the ligands, which are strongly influenced by the basicity of the heteroatoms on the aromatic aldehyde; thus, the hydrazones derived from hydrazine and hydroxyaldehydes are linked to Re(I) through N5 atom from the pyrazine ring and the N61 one from the hydrazino group, whereas with the ligand derived from pyridin-2-carbaldehyde, the N62 atom of the hydrazino group and the N1 from the pyridine moiety are preferred ligand-to-metal binding sites. The study of the effects of the compounds on the growth of four human tumor cell lines (neuroblastoma NB69, glioma U373, and breast cancer MCF-7 and EVSA-T) suggests a modulator behaviour, according to the concentration, of cell growth due to their estrogen-like characteristics.

Synthesis and characterization of new complexes formed between 1-methyllumazine and 1,6,7-trimethyllumazine ligand with transition metal(II) nitrate. Crystal structure of cobalt(II), copper(II) and cadmium(II) complexes

Abstract The structures and spectroscopic properties of Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) nitrate complexes of 1-methyllumazine (MLM) and 1,6,7-trimethyllumazine (MLMD) with general formula M(II)(NO 3 ) 2 L 2 · n H 2 O are reported. In all the complexes, the lumazine-derived ligands seem to be coordinated in bidentate form through the N5 and O4 atoms. The crystal structures of [Cu(MLM) 2 (H 2 O) 2 ](NO 3 ) 2 ( 1 ), [Co(MLMD) 2 (H 2 O) 2 ](NO 3 ) 2 ( 2 ) and [Cd(MLMD) 2 (NO 3 ) 2 ] ( 3 ) have been determined by X-ray crystallographic methods. In compounds 1 and 2 the nitrate anions are uncoordinated, and the metal ions are surrounded in an octahedral geometry by two bidentate lumazine ligands and two coordinated water molecules. The absolute configuration of the complex 1 can be described as the 4M stereoisomer, following Bailars nomenclature, with the two lumazine in a cis arrangement and the complex 2 exhibits the 2L stereoisomer as is usually in this kind of complexes. Compound 3 consists of neutral mononuclear units, the Cd(II) environment being a bicapped octahedral close to the trigonal antiprism due to the two nitrate anions coordinating in a very unsymmetrical bidentate mode.

Structural characterization of a novel tetranuclear palladium(II) complex containing the Pd4S4 core, with the N,N,S-tridentate 6-amino-5-formyl-1,3-dimethyluracil-thiosemicarbazonate ligand

Abstract The recrystallization in DMF/H2O medium of the complexes Pd(H2TSDO)Cl2 and Pd(HTSDO)Cl (H2TSDO=6-amino-5-formyl-1,3-dimethyluracil-thiosemicarbazone) leads to single crystals of the tetranuclear [Pd4(TSDO)4]·4H2O·2DMF compound. The structural characterization of this compound has been achieved by IR, Raman, 13C and 1H NMR and XRD methods.

Synthesis and characterization of several lumazine derivative complexes of Co(II), Ni(II), Cu(II), Cd(II), Pd(II) and Pt(II). X-ray structures of a mononuclear copper complex and a dinuclear cadmium complex

The synthesis of the new Co(II), Ni(II), Cu(II), Cd(II), Pd(II) and Pt(II) complexes with 1-methyllumazine (1-methylpteridine-2,4(1 H ,3 H )-dione, MLM) and 1,6,7-trymethyllumazine (1,6,7-trimethylpteridine-2,4(1 H ,3 H )-dione, MLMD) is described. The coordination chemistry of these ligands have been investigated and an usual bidentate bonding mode through the N5 and O4 atoms is observed. These complexes present the form M II Cl 2 L and were characterized by elemental analyses, TG and DSC, as well as by IR, UV–Vis, EPR spectroscopy and magnetic measurements. The crystal structures of [CuCl 2 (MLMD)(H 2 O)] and [CdCl 2 (MLM)(H 2 O)] 2 have been determined by X-ray diffraction methods. The copper(II) compound exists in the monomeric form with an environment around the metal ion as a distorted square-based pyramidal geometry whereas the cadmium complex was observed as dimers with an edge-sharing distorted octahedral coordination sphere around each cadmium center.

Spectral and XRD studies on perchlorate salts of several Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) complexes from 1-methyllumazine and 1,6,7-trimethyllumazine

Abstract A number of complexes with general formula ML2(ClO4)2·nH2O·mCH3CN [M=Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)] have been synthesized by reaction of 1-methyllumazine (MLM) and 1,6,7-trimethyllumazine (MLMD) and perchlorate salts in acetonitrile. The complexes have been characterized by elemental analysis, TG and DSC, as well as by IR, UV–Vis, EPR spectroscopies and magnetic measurements. The crystal structures of [Cu(MLM)2(H2O)2](ClO4)2, [Zn(MLM)2(H2O)2](ClO4)2 and [Cu(MLM)(MLMD)(H2O)(CH3CN)](ClO4)2 have been determined by X-ray diffraction methods. In the complexes Cu/MLM and Zn/MLM, the metal ions involve an octahedral geometry with two water molecules and two lumazine ligands coordinated through O4 and N5 atoms. The compound Cu/MLM/MLMD consists of monomeric units in which the Cu(II) atom is linked by two different lumazine derivatives (MLM and MLMD), a water and an acetonitrile molecules bonding directly to the metal ion. The environment around metal ion exhibits a geometry between a square-based pyramidal and an elongated tetragonal octahedral due to the different distances CuO4 in the apical positions.

Synthesis and structural studies on new MIIX2L2 dihalocomplexes of 1-methyllumazine and 1,6,7-trimethyllumazine.: Crystal structure of copper(II) and palladium(II) complexes

In order to continue our studies in coordination chemistry with pteridine derivatives, four new complexes with general formula M II X2(pteridine)2/n H2O/m CH3CN (M � /Cu, Pd, Pt) have been synthesized by reaction of 1-methyllumazine (MLM) and 1,6,7trimethyllumazine (MLMD) and different halide salts in acetonitrile solutions. These compounds have been characterized by means of analytical techniques (elemental analysis and TG), spectral methods (IR, 13 C and 1 H NMR, UV � /Vis � /NIR, EPR) and magnetics measurements. Single-crystal X-ray diffraction studies have been developed on the [CuCl2(MLM)2] and [PdBr2(MLM)2] complexes. In the complex Cu/MLM, a six-coordinated environment around metal ion is shown, with two pteridine ligands behaving in a bidentante manner through N5/O4 atoms being the other positions occupied by two chlorine atoms. The molecular unit of the compound Pd/MLM shows an ion Pd(II) linking to two bromide ions placed in a trans position, and two N5 atoms of two organic ligands, exhibiting a square-planar geometry as it is usual in complexes with d 8 -configuration ions.

Antiproliferative effects of palladium(II) complexes of 5-nitrosopyrimidines and interactions with the proteolytic regulatory enzymes of the renin–angiotensin system in tumoral brain cells

Please cite this article as: Nuria A. Illán-Cabeza, Antonio R. Garćıa-Garćıa, José M. Mart́ınez-Martos, Maŕıa J. Ramı́rez-Expósito, Miguel N. Moreno-Carretero, Antiproliferative effects of palladium(II) complexes of 5-nitrosopyrimidines and interactions with the proteolytic regulatory enzymes of the renin-angiotensin system in tumoral brain cells, Journal of Inorganic Biochemistry (2013), doi: 10.1016/j.jinorgbio.2013.06.005Seventeen new palladium(II) complexes of general formulaes PdCl2L, PdCl(LH-1)(solvent) and PdCl2(PPh3)2L containing pyrimidine ligands derived from 6-amino-5-nitrosouracil and violuric acid have been prepared and characterized by elemental analysis, IR and NMR ((1)H and (13)C) methods and, two of them, PdCl(DANUH-1)(CH3CN)]·½H2O and [PdCl(2MeOANUH-1)(CH3CN)] by X-ray single-crystal diffraction (DANU: 6-amino-1,3-dimethyl-5-nitrosouracil; 2MeOANU: 6-amino-2-methoxy-5-nitroso-3H-pyrimidin-4-one). The coordination environment around palladium is nearly square planar in the two compounds with different supramolecular arrangements. Crystallographic and spectral data are consistent with a bidentate coordination mode through N5 and O4 atoms when the ligands act in neutral form and N5 and N6 atoms in the monodeprotonated ones. The cytotoxicity of the complexes against human neuroblastoma (NB69) and human glioma (U373-MG) cell lines has been tested showing a considerable antiproliferative activity. Also, the study of the effects of palladium(II) complexes on the renin-angiotensin system (RAS) regulating proteolytic regulatory enzymes aminopeptidase A (APA), aminopeptidase N (APN) and insulin-regulated aminopeptidase (IRAP) shows a strong dependence on the compound tested and the tumoral cell type, also affecting different catalytic routes; the compounds affect in a different way the activities of enzymes of the RAS system, changing their functional roles as initiators of cell proliferation in tumors as autocrine/paracrine mediators.

A potential antitumor agent, (6-amino-1-methyl-5-nitrosouracilato- N3)-triphenylphosphine-gold(I): Structural studies and in vivo biological effects against experimental glioma

The synthesis and molecular and supramolecular structures of the compound (6-amino-1-methyl-5-nitrosouracilato-N3)-triphenylphosphine-gold(I) with interesting abilities to inhibit tumor growth in an animal model of experimental glioma are reported. Thus, its antitumor properties, effects on both enzyme and non-enzyme antioxidant defense systems and the response of several biochemical biomarkers have been analyzed. After seven days of treatment, the gold compound decreased the tumor growth to ca. one-tenth and reduced oxidative stress biomarkers (thiobarbituric acid-reactive substances (TBARS) and protein oxidation levels) compared to animals treated with the vehicle. Also, gold compound maintained non-enzyme antioxidant defense systems as in non-tumor animals and increased enzyme antioxidant defenses, such as superoxide dismutase and glutathione peroxidase activities, and decreased catalase activity. Analysis of serum levels of electrolytes, nitrogenous compounds, glucose, lipids, total protein, albumin, transaminases and alkaline phosphatase indicated that gold compound treatment showed few adverse effects, while effectively inhibiting tumor growth through mechanisms that involved endogenous antioxidant defenses.

Ni(II) and Cu(II) complexes with the dianionic N,N,O-tridentate Schiff base 6-amino-5-formyl-1,3-dimethyluracil-benzoylhydrazone: Crystal structure of the monodimensionally hydrogen-bonded aqua-(6-amino-1,3-dimethyl-uracilato-benzoylhydrazone(2-)-N6,N51,O52]-copper(II) hydrate

Abstract From the reaction between Cu(II) and Ni(II) salts and the Schiff base 6-amino-5-formyl-1,3-dimethyluracil-benzoylhydrazone (H 2 BEZDO), in dimethylformamide (DMF)–water and ammonia media, the complexes Ni(BEZDO)·H 2 O·NH 3 , Cu(BEZDO)·H 2 O·NH 3 and [Cu(BEZDO)(H 2 O)]·H 2 O containing the dianionic organic ligand have been obtained. These compounds have been studied by IR, electronic and EPR spectroscopy and magnetic measurements. The structure of [Cu(BEZDO)(H 2 O)]·H 2 O has been solved by means of X-ray diffraction methods. The coordination environment around the Cu(II) may be described as a square-plane structure in which the Schiff base acts as tridentate ligand through the N(6), N(51) and O(52) atoms, making two five- and six-membered chelate rings. The coordination sphere is completed with the oxygen atom of a water molecule; any additional interactions with potential donor atoms in the axial direction have not been found. The crystal structure is formed by infinite hydrogen-bonded monodimensional chains, in which the nearest metal centres are at distances of 4.511 and 3.585 A.