Electrocatalytic Water Oxidation by Mononuclear Copper Complexes of Bis-amide Ligands with N4 Donor: Experimental and Theoretical Investigation.

The present work describes electrocatalytic water oxidation of three monomeric copper complexes [CuII(L1)] (1), [CuII(L2)(H2O)] (2), and [CuII(L3)] (3) with bis-amide tetradentate ligands: L1 = N,N'-(1,2-phenylene)dipicolinamide, L2 = N,N'-(4,5-dimethyl-1,2-phenylene)bis(pyrazine-2-carboxamide), L3 = N,N'-(1,2-phenylene)bis(pyrazine-2-carboxamide), for the production of molecular oxygen by the oxidation of water at pH 13.0. Ligands and all complexes have been synthesized and characterized by single crystal XRD, analytical, and spectroscopic techniques. X-ray crystallographic data show that the ligand coordinates to copper in a dianionic fashion through deprotonation of two -NH protons. Cyclic voltammetry study shows a reversible copper-centered redox couple with one ligand-based oxidation event. The electrocatalytic water oxidation occurs at an onset potential of 1.16 (overpotential, η ≈ 697 mV), 1.2 (η ≈ 737 mV), and 1.23 V (η ≈ 767 mV) for 1, 2, and 3 respectively. A systematic variation of the ligand scaffold has been found to display a profound effect on the rate of electrocatalytic oxygen evolution. The results of the theoretical (density functional theory) studies show the stepwise ligand-centered oxidation process and the formation of the O-O bond during water oxidation passes through the water nucleophilic attack for all the copper complexes. At pH = 13, the turnover frequencies have been experimentally obtained as 88, 1462, and 10 s-1 (peak current measurements) for complexes 1, 2, and 3, respectively. Production of oxygen gas during controlled potential electrolysis was detected by gas chromatography.

Electrocatalytic water oxidation by heteroleptic ruthenium complexes of 2,6-bis(benzimidazolyl)pyridine Scaffold: a mechanistic investigation.

Three monomeric ruthenium complexes with anionic ligands [RuII(L)(L1)(DMSO)][ClO4] (1), [RuII(L)(L2)(DMSO)] [PF6] (2), and [RuII(L)(L3)(DMSO)][PF6] (3) [L = pyrazine carboxylate, L1 = 2,6-bis(1H-benzo[d]imidazol-2-yl)pyridine, L2 = 4,5-dmbimpy = 2,6-bis(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)pyridine, L3 = 4-Fbimpy = 2,6-bis(5-fluoro-1H-benzo[d]imidazol-2-yl)pyridine, DMSO = dimethyl sulfoxide] as electrocatalysts for water oxidation are reported herein. The single crystal X-ray structure of the complexes reveals the presence of a DMSO molecule, which is supposed to be the labile group undergoing water exchange under the experimental condition of electrocatalysis. Linear sweep voltammetry (LSV) and cyclic voltammetry (CV) study shows the appearance of the catalytic wave for water oxidation at Ru(IV/V) oxidation. LSV, CV, and bulk electrolysis technique has been used to study the redox properties of the complexes and their electrocatalytic activity. A systematic variation on the ligand scaffold has been found to display a profound effect on the rate of electrocatalytic oxygen evolution. Electrochemical and theoretical (density functional theory) studies support the O-O bond formation during water oxidation passes through water nucleophilic attack (WNA) for all the ruthenium complexes. At pH 1, the maximum turnover frequency (TOFmax) has been experimentally obtained as 17556.25 s-1, 31648.41 s-1, and 39.69 s-1 for complexes 1, 2, and 3, respectively, from the foot of wave analysis (FOWA). The high value of TOFmax for complex 2 indicates its efficiency as an electrocatalyst for water oxidation in a homogeneous medium.

Cubane-like tetranuclear Cu(ii) complexes bearing a Cu4O4 core: crystal structure, magnetic properties, DFT calculations and phenoxazinone synthase like activity.

In the present work, two new copper complexes 3a and 3b with a Cu4O4 cubane core are reported. Both complexes are obtained by means of the in situ conversion of the imine functionality of Schiff's base ligands 1a [(E)-4-chloro-2-((thiazol-2-ylimino)methyl)phenol] and 1b [(E)-4-bromo-2-((thiazol-2-ylimino)methyl)phenol] into amino alcohols 2a (4-chloro-2-(hydroxy(thiazol-2-ylamino)methyl)phenol) and 2b (4-bromo-2-(hydroxy(thiazol-2-ylamino)methyl)phenol), respectively. The ligand transformation may be metal assisted and the generated ligands show an interesting mode of coordination in which the alkoxo-O atom binds in a µ3-manner connecting simultaneously three copper centers and forming a Cu4O4 cubane core. The first analysis of single crystal X-ray diffraction studies reveals that both molecules possess a [4 + 2] cubane-type core, and low temperature magnetic measurements show antiferromagnetic behaviour, in agreement with DFT calculations. However, the best fit and DFT calculations point out three pairs of coupling constants, more coherent with a [2 + 2 + 2] situation, in accordance with the fine analysis of structural data. Finally, phenoxazinone synthase activity has been measured for both molecules, finding kcat = 86.3 h-1 for the chloride derivative copper(ii) complex in methanol, whereas the bromide derivative copper(ii) complex displays kcat = 3.4026 × 102 h-1 and 10.289 × 102 h-1 in methanol and DMSO, respectively.

Cytotoxic activity and apoptosis-inducing potential of di-spiropyrrolidino and di-spiropyrrolizidino oxindole andrographolide derivatives.

Anticancer role of andrographolide is well documented. To find novel potent derivatives with improved cytotoxicity than andrographolide on cancer cells, two series of di-spiropyrrolidino- and di-spiropyrrolizidino oxindole andrographolide derivatives prepared by cyclo-addition of azomethine ylide along with sarcosine or proline (viz. sarcosine and proline series respectively) and substitution of different functional groups (-CH3, -OCH3 and halogens) were examined for their cytotoxic effect on a panel of six human cancer cell lines (colorectal carcinoma HCT116 cells, pancreatic carcinoma MiaPaCa-2 cells, hepatocarcinoma HepG2 cells, cervical carcinoma HeLa cells, lung carcinoma A549 and melanoma A375 cells). Except halogen substituted derivatives of proline series (viz. CY2, CY14 and CY15 for Br, Cl and I substitution respectively), none of the other derivatives showed improved cytotoxicity than andrographolide in the cancer cell lines examined. Order of cytotoxicity of the potent compounds is CY2>CY14>CY15>andrographolide. Higher toxicity was observed in HCT116, MiaPaCa-2 and HepG2 cells. CY2, induced death of HCT116 (GI50 10.5), MiaPaCa-2 (GI50 11.2) and HepG2 (GI50 16.6) cells were associated with cell rounding, nuclear fragmentation and increased percentage of apoptotic cells, cell cycle arrest at G1 phase, ROS generation, and involvement of mitochondrial pathway. Upregulation of Bax, Bad, p53, caspases-3,-9 and cleaved PARP; downregulation of Bcl-2, cytosolic NF-κB p65, PI3K and p-Akt; translocation of P53/P21, NF-κB p65 were seen in CY2 treated HCT116 cells. Thus, three halogenated di-spiropyrrolizidino oxindole derivatives of andrographolide are found to be more cytotoxic than andrographolide in some cancer cells. The most potent derivative, CY2 induced death of the cancer cells involves ROS dependent mitochondrial pathway like andrographolide.

Electron density of two bioactive oligocyclic indole and oxindole derivatives obtained from low-order X-ray data and invariom application.

For two indole and oxindole bioactive molecules, low-order room-temperature X-ray data were used to generate aspherical electron density (ED) distributions by application of the invariom formalism. An analysis of the ED using the quantum theory of atoms in molecules (QTAIM) was carried out, which allowed for quantitatively examining bond orders and charge separations in various parts of the molecules. The inspection of electrostatic potentials (ESPs) and Hirshfeld surfaces provided additional information on the intermolecular interactions. Thus, reactive regions of the molecules could be identified, covalent and electrostatic contributions to interactions could be visualized, and the forces causing the crystal packing scheme could be rationalized. As the used invariom formalism needs no extra experimental effort compared to routine X-ray analysis, its wide application is recommended because it delivers information far beyond the normally obtained steric properties. In this way, complementary contributions to drug design can be given as is demonstrated for indoles in this study, which are involved in the metabolism of plants and animals as well as in cancer therapy.

Amberlite-IRA-402 (OH) ion exchange resin mediated synthesis of indolizines, pyrrolo [1,2-a] quinolines and isoquinolines: antibacterial and antifungal evaluation of the products.

A number of indolizines and pyrrolo[1,2-a]quinolines/isoquinolines were prepared from phenacyl pyridinium, quinolinium and isoquinolinium salts derived from the reaction of the heterocycles with 2-bromo acetophenone with alkynes and alkenes using amberlite-IRA-402 (OH) ion exchange resin as the base. Antibacterial and antifungal studies were carried out against thirteen bacterial and four fungal strains, which revealed that three derivatives (4a, 4b, 7a) out of fifteen are effective against all the thirteen strains and one derivative, 10, showed dual antibactericidal and antifungal efficacy.

Efficient synthesis of 3,3-diheteroaromatic oxindole analogues and their in vitro evaluation for spermicidal potential.

Syntheses of 3,3-diheteroaromatic oxindole derivatives has been achieved by coupling indole-2,3-dione (isatin) with differently substituted indoles and pyrrole in presence of I(2) in i-PrOH. The in vitro spermicidal potentials and the mode of spermicidal action of the synthesized analogues were evaluated and the derivative, 3,3-bis (5-methoxy-1H-indol-3-yl) indolin-2-one (3d) exhibited most significant activity.

Versatility of 2,6-diacetylpyridine (dap) hydrazones in generating varied molecular architectures: synthesis and structural characterization of a binuclear double helical Zn(II) complex and a Mn(II) coordination polymer.

A binuclear complex of Zn(ii) with formula [Zn(dap(A)(2))](2).2.25DMF (.2.25DMF) and a Mn(ii) coordination polymer with formula [Mn(3)(dap(In)(2))(3)(H(2)O)(2).2DMSO](n) (.2DMSO)(n) have been prepared and structurally characterized [dap(A)(2) = dideprotonated form of 2,6-diacetylpyridine bis(anthraniloyl hydrazone); dap(In)(2) = doubly deprotonated form of 2,6-diacetylpyridine bis(isonicotinoyl hydrazone)]. In the Zn(ii) complex the molecular units are double helical, with the Zn(ii) ions in a square pyramidal environment. The Mn(ii) complex on the other hand is a coordination polymer containing two different types of hepta-coordinated Mn(ii) ions, which differ in their axial ligands. The magnetic properties of the Mn(ii) complex, along with those of a double helical pyridine bridged binuclear Ni(ii) complex, earlier synthesized by us, are also reported. The ability of the 2,6-diacetylpyridine bis(aroyl hydrazone) ligands to form double helical complexes is analyzed in terms of the conformational flexibility of the ligands. The differences in the magnetic properties of the micro-N bridged binuclear complexes formed by 1,1 azido N-bridging ligands, and pyridine N-bridging ligands, is analyzed with the help of EHMO calculations.

Versatility of 2,6-diacetylpyridine (dap) hydrazones in stabilizing uncommon coordination geometries of Mn(II): synthesis, spectroscopic, magnetic and structural characterization.

Five seven- or eight-coordinate manganese complexes of hydrazone ligands have been prepared. Three seven-coordinate neutral Mn(II) complexes: [Mn(dapA2)]n (1), [Mn(dapB2)(H2O)2] (2), [Mn(dapS2)(H2O)2] (3) have been synthesized from the bis-Schiff bases of 2,6-diacetylpyridine: dap(AH)2, dap(BH)2 and dap(SH)2 (AH = anthraniloyl hydrazide, BH = benzoyl hydrazide, SH = salicyloyl hydrazide), respectively. Two eight-coordinate Mn(II) complexes: [Mn(dapS)2] (4) and [Mn(dapB)2].3H2O (5) have been synthesized from the mono-Schiff bases dapBH and dapSH, respectively. The complexes have been characterized by elemental analyses and by IR, UV-Vis., FAB mass, EI mass and EPR spectroscopy. The molecular structures of 1, 3.DMF and 4.DMF have been determined by single-crystal X-ray diffraction. The mono-Schiff bases are monoanionic and the bis-Schiff bases are dianionic. The octa-coordinated mono-Schiff base complex 4 adopts a dodecahedral geometry, while the hepta-coordinated bis-Schiff base complex 1 forms a one-dimensional linear polymeric chain. A weak antiferromagnetic exchange interaction (J=-0.15 cm(-1)) between the Mn(II) ions in is attributed to weak Mn...Mn interaction through the PhNH(2) moiety of the ligand, as indicated by extended-Hückel molecular orbital calculations. A good simulation of the EPR spectrum of a frozen solution (DMSO at 4 K) of compound 1 was obtained with g=2.0, D=0.1 cm(-1), E=0.01 cm(-1). The EPR spectrum of a powdered sample of compound 1 shows a large broadening of the signal, due in part, to the important zero-field splitting of the hepta-coordinated Mn(II) ion.