Miguel N. Moreno-Carretero

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.

Metal complexes with the ligand derived from 6-acetyl-1,3,7-trimethyllumazine and benzohydrazide. Molecular structures of two new Co(II) and Rh(III) complexes and analysis of in vitro antitumor activity.

The structures and spectroscopic properties of new Mn(II), Co(II), Cd(II), Hg(II), Ag(I), Rh(III), and Ir(I) complexes with the ligand BZLMH derived from 6-acetyl-1,3,7-trimethyllumazine (lumazine=pteridine-2,4(1H,3H)-dione) and benzohydrazide are reported. Complexes have been characterized by elemental analyses, spectroscopic studies (IR, UV-vis, (1)H, (13)C and (15)N NMR) and magnetic measurements. In all the complexes, the lumazine-derived ligand appears to be coordinated in either tridentate (N5, N61 and O63) or tetradentate forms (O4, N5, N61 and O63). The molecular structures of the [Co(BZLMH)(H(2)O)(CH(3)CN)(2)](ClO(4))(2) x CH(3)CN and [RhCl(2)(BZLM)(CH(3)CN)] x CH(3)CN complexes, determined by single crystal X-ray diffraction, have allowed to corroborate both coordination behaviours. The cytotoxic activity of the free ligand and complexes against human neuroblastoma NB69 cell line is also described. The differential analysis of the initial cytotoxic screening data has shown good activity only for the [RhCl(2)(BZLM)(CH(3)CN)] x CH(3)CN compound at concentrations at around 2 microM; for the other complexes, a modulation of the cell growth was not found upon complexation, this non-specific effect strongly suggesting an apoptotic behaviour.

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.

Rhenium(I) coordinated lumazine and pterin derivatives: structure and spectroelectrochemistry of reversibly reducible (6-ATML)Re(CO)3Cl (6-ATML=6-acetyl-1,3,7-trimethyllumazine)

Abstract A number of complexes between substituted lumazines (2,4-dioxo-(1H,3H)pteridines) or pterins (2-amino-4-oxo-(3H)pteridines) and Re(CO)3Cl have been synthesized and characterized electrochemically and spectroscopically. The structure of the (6-ATML)Re(CO)3Cl derivative (6-ATML=6-acetyl-1,3,7-trimethyllumazine) could be determined in [fac-(6-ATML)Re(CO)3Cl]·3C6H6. The rhenium(I) center coordinates in a rather symmetrical fashion through the O4–N5 α-carbonylimino chelate site of 6-ATML; the potentially available acetyl function is not involved in the metal coordination. The acetyl acceptor substituent facilitates the reversible one-electron reduction of this compound to a persistent anion radical complex [(6-ATML)Re(CO)3Cl] −, which is accompanied by variable low-frequency shifts of the six carbonyl stretching bands and by the appearance of a broad EPR signal.

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 (MO, 2.033 and 2.039 A) and two water molecules occupying the axial positions (MO 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.

Crystal structure, raman and 57Fe mo¨ssbauer spectra of the FeII complex of iso-orotic acid

Abstract The crystal structure of [Fe(H 2 isoor) 2 (H 2 O) 2 ]·2H 2 O has been solved by single-crystal X-ray diffractometry. Thermogravimetric analysis shows simultaneous loss of all water molecules between 120 and 266°C, followed immediately by a rapid degradation of the compound. A comparative analysis of the Raman spectra of the complex with that of free-iso-orotic acid allowed a straightforward assignment of the vibrations of the ligand groups involved in coordination. The 57 Fe Mo¨ssbauer spectrum of the complex confirms the presence of a high-spin Fe II ion and the distortion of the octahedral Fe II environment.

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.

A new three-dimensional, hydrogen-bonded metal-pteridine complex: synthesis, characterization and crystal structure of diaqua bis(1,3-dimethylpteridine-2,4(1H,3H)-dione-O4,N5) copper(II) nitrate dihydrate

Abstract In absolute methanol, copper(II) nitrate reacted with 1,3-dimethyl-(1H, 3H)-pteridin-2,4-dione (1,3-dimethyllumazine, DMLM) giving a complex with formula [Cu(DMLM)2(H2O)2] (NO3)2 · 2H2O. 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 copper(II) ion occupies an inversion centre and exhibits an elongated octahedral coordination. The equatorial plane consists of two N(5) atoms of the pteridine ligands and two oxygen atoms from water molecules, and the two axial sites are occupied by two O(4) atoms of the ligands. The non-coordinated water molecules and nitrate anions, as well as the pteridine ligands are involved in a two-dimensional H-bond network, the metal-pteridine moieties being linked to the non-coordinated water molecules and nitrate anions of neighbouring molecules through the O(2) atom of the pteridine ligands. The molecules are packed in planes parallel to the b-axis, these planes being stacked at a mean distance of 3.297A˚to each other. A three-dimensional arrangement is defined by the involvement of the coordinated water molecules in a hydrogen bond with one oxygen atom from the uncoordinated water and another oxygen from the nitrate group of the adjacent layers.