Remarkable photo-induced anticancer activity of vitamin-S6 Schiff base copper(II) complexes of pyridyl bases

Vitamin-B6 (VB6) Schiff base (H2L) copper(II) complexes of pyridyl bases, viz. Cu(bpy)(L)] (1), Cu(phen)(L)] (2) and Cu(dppz)(L)] (3), where bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline and dppz is dipyrido3,2-a:2',3'c]phenazine are synthesized, characterized and their phto-induced anticancer activity studied. The non-electrolytic one electron paramagnetic complexes exhibit a d-d band near 700 nm in DMF. The dppz complex intercalatively binds to calf-thymus DNA with binding constant (K-b) values of similar to 10(6) M-1. This complex exhibits low chemical nuclease activity but excellent DNA photocleavage activity when irradiated with red light of 705 nm forming (OH)-O-center dot radical. It displays remarkable photocytotoxicity in human cervical cancer cells (HeLa) giving IC50 value of 0.9 mu M in visible light (400-700 nm) while being less toxic in darkness (IC50 : 23 mu M). The cellular uptake of the complexes seems to be via VB6 transporting membrane carrier mediated diffusion pathway. Photo-induced cell death follows apoptotic pathway involving photo-generated intracellular reactive oxygen species.

Interactions of methoxyamine with pyridoxal-5'-phosphate-Schiff's base at the active site of sheep liver serine hydroxymethyltransferase

The mechanism of interaction of methoxyamine with sheep liver serine hydroxymethyltransferase (EC 2.1.2.1) (SHMT) was established by measuring changes in enzyme activity, visible absorption spectra, circular dichroism and fluorescence, and by evaluating the rate constant by stopped-flow spectrophotometry. Methoxyamine can be considered as the smallest substituted aminooxy derivative of hydroxylamine. It was a reversible noncompetitive inhibitor (Ki = 25 microM) of SHMT similar to O-amino-D-serine. Like in the interaction of O-amino-D-serine and aminooxyacetic acid, the first step in the reaction was very fast. This was evident by the rapid disappearance of the enzyme-Schiff base absorbance at 425 nm with a rate constant of 1.3 x 10(3) M-1 sec-1 and CD intensity at 430 nm. Concomitantly, there was an increase in absorbance at 388 nm (intermediate I). The next step in the reaction was the unimolecular conversion (1.1 x 10(-3) sec-1) of this intermediate to the final oxime absorbing at 325 nm. The identity of the oxime was established by its characteristic fluorescence emission at 460 nm when excited at 360 nm and by high performance liquid chromatography. These results highlight the specificity in interactions of aminooxy compounds with sheep liver serine hydroxymethyltransferase and that the carboxyl group of the inhibitors enhances the rate of the initial interaction with the enzyme.

Peptide models for the bacteriorhodopsin chromophore. Retinylidene-lysine systems containing aspartic acid and serine residues

The retinylidene Schiff base derivative of seven lysine containing peptides have been prepared in order to investigate solvent and neighboring group effects, on the absorption maximum of the protonated Schiff base chromophore. The peptides studied are Boc-Aib-Lys-Aib-OMe (1), Boc-Ala-Aib-Lys-OMe (2), Boc-Ala-Aib-Lys-Aib-OMe (3), Boc-Aib-Asp-Aib-Aib-Lys-Aib-OMe (4), Boc-Aib-Asp-Aib-Ala-Aib-Lys-Aib-OMe (5), Boc-Lys-Val-Gly-Phe-OMe (6) and Boc-Ser-Ala-Lys-Val-Gly-Phe-OMe (7). In all cases protonation shifts the absorption maxima to the red by 3150–8450 cm-1. For peptides 1–3 the protonation shifts are significantly larger in nonhydrogen bonding solvents like CHCl3 or CH2Cl2 as compared to hydrogen bonding solvents like CH3OH. The presence of a proximal Asp residue in 4 and 5 results in pronounced blue shift of the absorption maximum of the protonated Schiff base in CHCl3, relative to peptides lacking this residue. Peptides 6 and 7 represent small segments of the bacteriorhodopsin sequence in the vicinity of Lys-216. The presence of Ser reduces the magnitude of the protonation shift.

1-D hydrogen-bonded organization of hexanuclear {3d-4f-5d} complexes: evidence for slow relaxation of the magnetization for [{LMe2Ni(H2O)Ln(H2O)4.5}2{W(CN)8}2] with Ln = Tb and Dy

Heterometallic {3d-4f-5d} aggregates with formula [{LMe2Ni(H2O)Ln(H2O)4.5}2{W(CN)8}2]·15H2O, (LMe2 stands for N,N-2,2-dimethylpropylenedi(3-methoxysalicylideneiminato) Schiff-base ligand) with Ln = Gd, Tb, Dy, have been obtained by reacting bimetallic [LMe2Ni(H2O)2Ln(NO3)3] and Cs3{W(CN)8} in H2O. The hexanuclear complexes are organized in 1-D arrays by means of hydrogen bonds established between the solvent molecules coordinated to Ln and the CN ligands of an octacyanometallate moiety. The X-ray structure was solved for the Tb derivative. Magnetic behavior indicates ferromagnetic {W–Ni} and {Ni–Ln} interactions (JNiW = 18.5 cm-1, JNiGd = 1.85 cm-1) as well as ferromagnetic intermolecular interactions mediated by the H-bonds. Dynamic magnetic susceptibility studies reveal slow magnetic relaxation processes for the Tb and Dy derivatives, suggesting SMM type behavior for these compounds.

Stabilisation and characterisation of N,N′-dibenzylidene-o-phenylenediamine as a copper(I) perchlorate complex

QUITE OFTEN, metal ions profoundly affect the condensation of carbonyl compounds with primary amines to form Schiff bases as well as their subsequent reactions[I-4]. Condensation of benzaldehyde with o-phenylenediamine (opd) in glacial acetic acid[5] or in absolute alcohol[6] gives benzimidazole derivative, 1-benzyl-2-phenylbenzimidazole (bpbi). In this reaction, the Schiff base N,N'-dibenzylidene-o-phenylenedianfme (dbpd) has been postulated as an intermediate, which cyclises to give bpbi. It was found that the reaction of opd in presence of copperO1) perchlorate with benzaldehyde gave dbpd complex of copper(l) perchlorate instead of bpbi.

Synthesis, spectral and structural studies on metal complexes of Schiff bases involving vitamin B6 and histamine

Six metal complexes of Schiff bases involving Vitamin B6 and the decarboxylated amino acid histamine have been synthesised and characterized. Crystal structures have been determined for [CuL1(H2O)Br]-NO31(L1= pyridoxylidenehistamine) and [Cu2L22(NO3)2]·6H2O 2(L2= 5′-phosphopyridoxylidenehistaminate). The crystal structure of complex 1[space group P[1 with combining macron], a= 8.161(2), b= 10.368(2), c= 11.110(2)Å, α= 105.18(1), β= 102.12(1), γ= 72.10(1)° and Z= 2; R= 0.072, R′= 0.083] consists of square-pyramidally co-ordinated copper with the tridentate Schiff base in the zwitterionic form, whereas in 2[space group P[1 with combining macron], a= 8.727(1), b= 10.308(1), c= 12.845(2)Å, α= 110.00(1), β= 78.94(1), γ= 114.35(1)° and Z= 1; R= 0.035, R′= 0.034] the copper has the same co-ordination geometry but the tetradentate Schiff-base ligand exists as a monoanion. The conformational parameters deduced from such structures are important for understanding the stereochemical aspects of Vitamin B6-catalysed model reactions involving histidine.

First hyperpolarizability of bacteriorhodopsin, retinal and related molecules revisited

The previously reported beta values of BR and retinal based chromophores were very high but subsequent measurements found them to be much less. We have found that the beta values of these compounds do not vary so much with experimental conditions as with the method of analysis. Hyper-Rayleigh scattering measurements at 1543 and 1907 nm produce more realistic beta values close to the intrinsic (static) hyperpolarizability, beta(0) which for BR is still very high (275 x 10 (30) esu). The optical nonlinearity of BR arises entirely due to the protonated retinal Schiff Base (PRSB) which in its isolated form has the same intrinsic hyperpolarizability as that of the rotein.

Complexes of lanthanide perchlorates with two new O,N,O ligands derived from antipyraldehyde and acetic and benzoic acid hydrazides

Antipyrine is a well known ligand for lanthanides (I). A forage through the organic literature of pyrazolones reveals that the 4-position of antipyrine is amenable to a wide variety of organic reactions. It should thus be possible to introduce suitable functional groups at this position and design new multidentate ligands for metal ions. It is also found that the coordination chemistry of lanthanides is much less well developed and far fewer ligands have been used for complexation with lanthanide ions compared to that of the d-transition metal ions. Keeping these points in view we have reported earlier, complexes of lanthanides with a bidentate ligand N,N-diethyl-antipyrine-4-carboxamide (2). In this communication we report the synthesis of two new ligands from Schiff base condensation of antipyraldehyde and the hydrazides of acetic and benzoic acids and the complexes formed by these hydrazones with lanthanide perchlorates.

Crystal structure of 3-acetylcoumarin-o-aminobenzoylhydrazone and synthesis, spectral and thermal studies of its transition metal complexes

Transition metal [Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II)] complexes of a new Schiff base, 3-acetylcoumarin-o-aminobenzoylhydrazone were synthesized and characterized by elemental analyses, magnetic moments, conductivity measurements, spectral [Electronic, IR, H-1 and C-13 NMR, EPR] and thermal studies. The ligand crystallizes in the monoclinic system, space group P2(1)/n with a = 9.201(5), b = 16.596( 9), c = 11.517(6) angstrom, beta= 101.388(9)degrees, V = 1724.2 (17) angstrom(3) and Z = 4. Conductivity measurements indicated Mn(II) and Co(II) complexes to be 1 : 1 electrolytes whereas Ni(II), Cu(II), Zn(II) and Cd(II) complexes are non-electrolytes. Electronic spectra reveal that all the complexes possess four-coordinate geometry around the metal.

Synthesis, spectral characterization, in-vitro microbiological evaluation and cytotoxic activities of novel macrocyclic bis hydrazone

A macrocyclic hydrazone Schiff base was synthesized by reacting 1,4-dicarbonyl phenyl dihydrazide with 2,6-diformyl-4-methyl phenol and a series of metal complexes with this new Schiff base were synthesized by reaction with Co(II), Ni(II) and Cu(II) metal salts. The Schiff base and its complexes have been characterized by elemental analyses, IR, H-1 NMR, UV-vis, FAB mass, ESR spectra, fluorescence, thermal, magnetic and molar conductance data. The analytical data reveal that the Co(II), Ni(II) and Cu(II) complexes possess 2:1 metal-ligand ratios. All the complexes are non-electrolytes in DMF and DMSO due to their low molar conductance values. Infrared spectral data suggest that the hydrazone Schiff base behaves as a hexadentate ligand with NON NON donor sequence towards the metal ions. The ESR spectral data shows that the metal-ligand bond has considerable covalent character. The electrochemical behavior of the copper(II) complex was investigated by cyclic voltammetry. The Schiff base and its complexes have also been screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Shigella dysentery, Micrococcus, Bacillus subtilis, Bacillus cereus and Pseudomonas aeruginosa) and antifungal activities (Aspergillus niger, Penicillium and Candida albicans) by MIC method. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties. (C) 2009 Elsevier Masson SAS. All rights reserved.

From the {Cu(μ2-S)N}4 butterfly architecture to the {Cu(μ3-S)N}12 double wheel

Copper(I) complexes with {Cu(μ2-S)N}4 and {Cu(μ3-S)N}12 core portions of butterfly-shaped or double wheel architectures have been isolated in the reaction of Cu(I) with the Schiff base ligand C6H4(CHNC6H4S)2, aiso-abtâ, under different conditions. View the MathML source containing the tetranuclear electroneutral complex View the MathML source is formed by the reaction of CuI in acetonitrilic solution and recrystallization from DMF, whereas View the MathML source containing dodecanuclear View the MathML source wheels is accessible starting from CuBF4. Complexes 2 and 4 represent the first examples of cyclic complexes with the same overall stoichiometry but different ring sizes. The ligand induces two different coordination environments around copper(I) by switching between μ2- and μ3-sulfur bridging modes.

Metal-ion-ligand interactions in thermotropic liquid crystals

The interactions of lithium perchlorate with ligands such as dimethyl sulphoxide, acetonitrile, pyridine and the Schiff base liquid crystals are investigated. The experiments open a new field for the study of metal-ion-ligand interactions in thermotropic liquid crystals.

Chemical Aspects of the Synergistic Hypergolic Ignition in Hybrid Systems with N2O4 as Oxidizer

Synergistic hypergolic ignition with nitrogen tetroxide ( N2O4) as oxidizer has been observed in hybrid systems comprising of a mixture of magnesium and Schiff bases as fuels. The ignition delays (IDs) measured using a modified device, have been compared with those of magnesium-Schiff base-WFNA systems under identical conditions. The ID has been found to vary with the nature of the substitution in both the benzene rings. A linear relationship emerges when the ignition delays are plotted against the Hammett substitution constants (σ). The preignition products of the reaction of N2O4 with magnesium and benzylidineaniline have been analysed to be Mg(NO3)2, benzenediazonium salt and benzaldehyde. Based on the preignition products isolated, a probable reaction mechanism has been proposed. The previously proposed preignition mechanism for the Schiff base-magnesium-WFNA system has been further supported from the present ignition delay data.

Mechanism of interaction of O-amino-D-serine with sheep liver serine hydroxymethyltransferase

The mechanism of interaction of 0-amino-D-serine (OADS) with sheep liver serine hydroxymethyltransferase (EC 2.1.2.1) (SHMT) was established by measuring changes in the enzyme activity,absorption spectra, circular dichroism (CD) spectra, and stopped-flow spectrophotometry. OADS was a reversible noncompetitive inhibitor (Ki = 1.8 pM) when serine was the varied substrate. The first step in the interaction of OADS with the enzyme was the disruption of enzyme-Schiff base, characterized by the rapid disappearance of absorbance at 425 nm (6.5 X lo3 M-' s-') and CD intensity at 430 nm. Concomitantly,there was a rapid increase in absorbance and CD intensity at 390 nm. The spectral properties of this intermediate enabled its identification as pyridoxal 5'-phosphate (PLP). These changes were followed by a slow unimolecular step (2 X s-') leading to the formation of PLP-OADS oxime, which was confirmed by its absorbance and fluorescence spectra and retention time on high-performance liquid chromatography. The PLP-OADS oxime was displaced from the enzyme by the addition of PLP as evidenced by the restoration of complete enzyme activity as well as by the spectral properties. The unique feature of the mechanism proposed for the interaction of OADS with sheep liver SHMT was the formation of PLP as an intermediate.

Physicochemical studies of (o-vanillin thiosemicarbazonato)-nickel(Ii) chelate

Five- and six-membered rings result from the chelation of nickel(II) by the dibasic tridentate Schiff base ligand, o-vanillin thiosemicarbazone(o-VTSC), a new chelate prepared and characterized. The structural results are discussed in the light of spectroscopic and other data.