Francisco Hueso-Ureña

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, structure and biological activity of a new and efficient Cd(II)–uracil derivative complex system for cleavage of DNA

The new complex formed by Cd(II) and the 1:2 Schiff-base-type ligand 2,6-bis[1-(4-amino-1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxopyrimidin-5-yl)imino]ethylpyridine (DAPDAAU) has been chemically and structurally characterized by X-ray diffraction: the ion Cd(II) is surrounded by six nitrogen atoms from two DAPDAAU ligands which coordinates each one in a tridentate fashion through the pyridine ring (N1) and both azomethine nitrogen atoms (N5). The interaction of the Cd(II) complex (compound I) with calf-thymus DNA as observed by circular dichroism spectroscopy suggests the initial unwinding of the DNA double helix strongly depends on increasing incubation times and metal-to-nucleic acid molar ratios. Electrophoretic experiments indicate that the cadmium complex induces cleavage of the plasmid pBR322 DNA to give ulterior nicking and shortening of this molecule, as a result of the complex binding to DNA, resulting in the conclusion that compound I behaves as a chemical nuclease. Cytotoxic activity of the Cd(II) complex against selected different human cancer cell lines is specific and increases with increasing concentration of the metal compound; this fact indicates the potential antitumor character of the complex. When the culture medium is supplemented with compound I, a remarkable inhibition of the growing cell is observed, important cell degeneration appears before 48xa0h and abundant precipitates are formed that correspond to cell residues and denatured proteins.

Transition metal complexes with monodeprotonated isoorotic and 2-thioisoorotic acids: Crystal structure, spectral and magnetic study, and antimicrobial activity

Abstract The reaction, in ethanol or water medium, of Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), Pd(II), and Pt(II) ions with isoorotic and 2-thioisoorotic acids (H 3 L) has allowed the isolation of complexes with the general formula M II (H 2 L) 2 ·2H 2 O. These were characterized by means of elemental analysis, spectral techniques (UV-Vis-NIR, IR, EPR, 13 C and 1 H NMR), magnetic moments, and conductivity measurements. The molar conductivities in dimethylsulphoxide indicate the non-ionic nature of isolated compounds. The most common coordination mode of uracil monoanions seems to be a O4-OCO bidentate scheme which leads to a six-membered chelate ring. Complexes of first row transition ions display an octahedral structure, whereas for Pd(II) and Pt(II) compounds a square-planar structure is suggested. The MO 6 octahedral structure has been corroborated from the single crystal x-ray study of bis-isoorotato-diaquazinc(II). This compound is monoclinic, space group P2 1 /c, with a = 5.067(5) A, b = 15.072(4) A, c = 11.239(8) A, β = 125.80(9)°, V = 696(1) A 3 , and Z = 2. The structure was solved by means of the heavy atom method from the zinc special position. Full matrix refinements based on F o were performed to R = 0.060 for 1884 data. The structure consists of discrete [Zn(H 2 CU) 2 (H 2 O) 2 ] units in which the Zn(II) ion is octahedrally MO 6 coordinated by two bidentate O4-OCO isoorotato ligands (Mue5f8O, 2.033 and 2.039 A) and two water molecules occupying the axial positions (Mue5f8O w , 2.170 A). Likewise, a previous study of biological activity of these complexes against several bacteria and yeasts was carried out. In general, complexes with the 2-thioisoorotato ligand possess greater antimicrobial activity than those with the isoorotate ligand, specially in the case of cobalt(II) complexes.

Synthesis and structural studies on metal nitrate complexes with 1,3-dimethyllumazine and 1,3,6,7-tetramethyllumazine: crystal structure of two new cobalt(II) and copper(II) three-dimensionally hydrogen-bonded complexes and a cadmium(II) complex with unusual geometry

Abstract In absolute methanol medium, M II (NO 3 ) 2 (M = Co,Ni,Cu,Zn and Cd) react with 1,3-dimethyllumazine (DLM) and 1,3,6,7-tetramethyllumazine (DLMD) (lumazine = (1 H ,3 H )-pteridin-2,4-dione) to give complexes with general formula M II (NO 3 ) 2 (pteridine) 2 · n H 2 O. These compounds have been characterized by means of the analytical techniques (elemental analysis and thermogravimetry), spectral methods (IR, 13 C and 1 H NMR, UV-Vis-NIR, EPR) and magnetic measurements (77–290 K). Single-crystal X-ray diffraction studies have been made on the complexes [Co(DLM) 2 (H 2 O) 2 ](NO 3 ) 2 ·2H 2 O, [Cu(DLMD) 2 (H 2 O) 2 ](NO 3 ) 2 ·2H 2 O and [Cd(NO 3 ) 2 (DLMD) 2 ]. Cobalt and copper complexes crystallize in the monoclinic system (space group P 2 1 / n , Z = 2) with a = 8.746(1), b = 13.584(2), c = 10.997(1) A , β = 94.89(1)°, V = 1301.8(3) A 1 , and R = 0.057 for 3787 independent reflections with l >2 σ (1) and 202 parameters (Co/DLM complex) and a = 8.9929(7), b = 1.0574(9), c = 11.9242(7) A , β = 98.124(5)°, V = 1492.3(2) A 1 , and R = 0.039 for 2612 independent reflections with l >2 σ ( l ) and 230 parameters (Cu/DLMD complex). In both complexes, the metal ion occupies an inversion center and exhibits an octahedral coordination. The Co(II) coordination octahedron is tetragonally flattened, but the Cu(II) coordination is rhombically distorted. The equatorial plane consists of two N(5) and two O(4) atoms of pteridine ligands and the two axial sites are occupied by two oxygen atoms from the coordinated water molecules. The monomeric units together with non-coordinated water molecules and nitrate anions are involved in a complex three-dimensional H-bond network. The cadmium complex crystallizes in the monoclinic system (space group P 2 1 / c , Z = 2) with a = 8.5689(4), b = 18.5279(9), c = 8.6209(3) A , β = 106.894(3)°, V = 1309.6(1) A 3 , and R = 0.030 for 1260 independent reflections with l >2 σ ( l ) and 192 parameters. The structure consists of monomeric centrosymmetric units in which the cadmium atom is eight-coordinated by four nitrate oxygen atoms of two bidentate nitrate anions and two N(5)-O(4) lumazine bidentate ligands. The geometry of the coordination polyhedron could be described as an octahedron whose equatorial plane is formed by two bidentate N(5)-O(4) pteridine ligands and whose apical positions each seem to be split into two coordination positions occupied by bidentate nitrate ligands.

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.

Palladium, platinum, cadmium, and mercury complexes with neutral isoorotic and 2-thioisoorotic acids: IR and NMR spectroscopies, thermal behavior and biological properties

Seven complexes containing neutral isoorotic and 2-thioisoorotic acids, as well as thiocyanate and chloride anions as lignands, have been synthesized and characterized by means of both spectral (IR, 1H, and 13C NMR) and thermal (TG and DSC) methods, as well as conductivity measurements. Spectral data suggest that any binding metal-ligand mode for uracil derivatives is not easy to propose. Therefore, isoorotic ligands must link through some oxygen atom. Likewise, 2-thioisoorotic acid seems to be [N,S] bonded in Pd(II) and Pt(IV) complexes, whereas for Hg(II) complex a distorted tetrahedral HgCl2S2 structure has been proposed. In the cadmium complex, the metal ion exhibits a CdCl2O2 coordination sphere. Antimicrobial activities of the complexes against Pseudomonas sp, E. coli, Proteus sp, Salmonella sp, Micrococcus sp, Staphylococcus sp, Bacillus sp and Candida sp were performed as a previous step in the study of their biological activity.

Mixed complexes of 5-nitrosouracil derivatives: Synthesis and structural study of 6-amino-1,3-dimethyl-5-nitrosouracilato (N5,N6)-aqua-2,2′-bipyridine (N,N′)-copper(II) perchlorate hydrate and 2,2′-bipyridine (N,N′)-chloro-1,3-dimethylviolurato (N5,O6)-copper(II) hemihydrate

Abstract The mixed [Cu(DANU)(bipy)(H2O)]ClO4·H2O (1) and [Cu(DMV)(ipyl)Cl]·1/2H2O (2) complexes have been isolated from the reaction, in water/EtOH medium, of copper(II) perchlorate and chloride with 6-amino-1,3-dimethyl-5-nitrosouracil (HDANU) and 2,2′-bipyridine (bipy). It is noteworthy that, in the second complex, the uracil ligand is the 1,3-dimethyl-violurato monoanion (DMV), appeared from the hydrolysis of HDANU. In addition to X-ray diffraction studies, these compounds have been characterized from IR and EPR spectra and magnetic measurements (77–290 K). The crystal lattice of 1 is made up of discrete square pyramidal [Cu(DANU)(bipy)(H2O)]+ cations, a disordered perchlorate group and a water molecule. The coordination geometry about the metal centre is square pyramidal (N4+O). The basal positions are occupied by a bidentate DANU ligand, coordinated through the N15 and N16 donor positions, and a bipyridine ligand. A water molecule (Cuue5f8O1W 2.193(3) A) occupies the apical site. The compound 2 presents a similar molecular structure to that of 1 with the copper centre lying in a N3O+Cl environment. In this case, the basal positions are occupied by a bipy ligand and a DMV ligand coordinated through the N15 and O16 donor positions, instead of the DANU ligand found in the previous compound. The apical position is occupied in this case by a chlorine atom (Culue5f8Cll 2.413(2) and Cu2ue5f8C12 2.389(2) A).

Mixed complexes of 6-aminouracil derivatives: Synthesis, spectral properties and crystal structure of 6-amino-1,3-dimethyl-5-nitrosouracilato (N5,N6)-2,2′-bipyridine(N,N′)-ethanol (O)-copper(II) nitrate

Abstract In absolute ethanol medium, copper(II) nitrate reacts with 6-amino-1,3-dimethyl-5-nitrosouracil (HDANU) and 2,2′-bipyridine to give a mixed complex with the formula [Cu(DANU)(bipy)(EtOH)](NO 3 ). This compound has been characterized by means of analytical techniques (elemental analysis and TG), spectral methods (IR, UV-VIS-NIR, EPR), magnetic measurements (77–290 K) and single-crystal X-ray diffraction. The structure consists of monomeric CuN 4 O units in which the copper ion displays a 4 +1 square-pyramidal coordination. The base of the polyhedron is occupied by four nitrogen atoms (Cu-N ca 2 , two from bipy and the other two from 5-nitroso and 6-amino groups of the uracil derivative in the N 6 -mono-deprotonated form, leaving two five-membered chelate rings. In the apical position of the pyramid, an O-coordinated ethanol molecule with a long Cu-O distance (2.248 ) is located, the metallic centre being 0.144above the base of the polyhedron. The nitrate group is out of the coordination sphere, stabilizing the complex by hydrogen bonds formed between the hydrogen atom attached to the ethanolic oxygen and an oxygen atom from the nitrate group. The molecules are stacked as planes perpendicular to the a axis. Copyright

Thermal, spectral and biological studies or metal complexes of isoorotic and 2-thioisoorotic acids

Abstract From reaction, in aqueous medium, of isoorotic (H2 CU) and 2-thioisoorotic (H2 CTU) acids with several first row transition metal ions, complexes of general formula M(HL)2 . 2H2O have been obtained. These were studied by thermal (TG, DTG and DSC) and spectral methods (IR). Likewise, the antibacterial activity of these compounds is reported.