Mallayan Palaniandavar

Spectroscopic and voltammetric studies of copper(II) complexes of bis(pyrid-2-yl)-di/trithia ligands bound to calf thymus DNA

Abstract Absorption and circular dichroic (CD) spectral, viscometric and electrochemical studies have been carried out on the interaction of [Cu(pdto)(ClO 4 )] (ClO 4 ) (pdto = bis(pyrid-2-yl-3,6-dithiaoctane), [Cu(pttu)] (ClO 4 ) 2 (pttu = bis(pyrid-2-yl-3,6,9-trithiaundecane) and [Cu(pttn)] (ClO 4 ) 2 (pttn = bis(pyrid-2,yl)-3,6,9-trithianonane) with calf thymus DNA. The intense S( σ ) → Cu(II) charge transfer band of almost all these complexes exhibits a large hypochromism in the presence of DNA suggesting that all the complexes undergo ligand displacement in the presence of DNA leading to stabilisation of the Cu 2+ -DNA interaction. Spectral, viscosity and electrochemical studies suggest that the [Cu(pdto)] 2+ complex binds to DNA presaturated with copper(II) perchlorate (Cu 2+ -DNA, [NP]/[Cu(ClO 4 ) 2 ] ∼-2.2). via partial intercalation of the pyridine ring of the ligand. On the other hand, [Cu(pttu)] 2+ and [Cu(pttn)] 2+ engage in relatively weak binding with Cu 2+ -DNA via simple surface contact. CD spectral studies suggest negligible transconformational changes for Cu 2 -DNA from a more B-like to a more C-like structure on binding to all the complexes. The diaza analogue of [Cu(pdto)] 2+ is stable in the presence of DNA due to the hydrogen bonding interaction of the coordinated NH with DNA. The residual charge on Cu(II), the coordination geometry and the ligand donor atom type play a key role in deciding the mode and extent of binding of complexes to DNA.

Spectral, viscometric and electrochemical studies on mixed ligand cobalt(III) complexes of certain diimine ligands bound to calf thymus DNA

Abstract The complex [Co(5,6-dmp)3]Cl3 (1) and the mixed ligand complexes [Co(bipy)2(5,6-dmp)]Cl3 (2), [Co(bipy)2(phen)]Cl3 (3), [Co(phen)2(bipy)]Cl3 (4), [Co(bipy)2(imp)]Cl3 (5) and [Co(phen)2(imp)]Cl3 (6) where bipy=2,2′-bipyridine, phen=1,10-phenanthroline, 5,6-dmp=5,6-dimethyl-1,10-phenanthroline and imp=imidazo[4,5-f][1,10]-phenanthroline, have been isolated and characterised by elemental analysis. The interaction of these complexes with calf thymus DNA has been explored by using absorption, emission and circular dichroic spectral and electrochemical studies and viscosity measurements. Absorption spectral studies and viscosity measurements reveal that the complexes 1 and 2 interact with DNA primarily by groove binding while 3 and 4 may possibly bind by two modes. The complexes 5 and 6 associate with DNA involving the non-classical intercalation of the imp ligand with DNA base pairs. Circular dichroic spectral studies reveal that calf thymus B-DNA becomes more A-like in structure on interaction with all the complexes except 5. The complex 5, in contrast, exhibit a spectral band shift of about 10 nm to longer wavelength, which is characteristic of A conformation of DNA. Electrochemical studies reveal that the phen complexes facilitate the electrostatic interaction of cobalt(III) complexes, preferentially in the higher oxidation state of cobalt. On the other hand, the presence of 5,6-dimethyl groups on phen favour DNA groove binding of complexes. The presence of hydrophobic imp ligand facilitates its intercalative interaction with the hydrophobic interior of the nucleic acid bases, interestingly, in the lower oxidation state of cobalt.

Mixed-ligand copper(II) complexes of dipicolylamine and 1,10-phenanthrolines: The role of diimines in the interaction of the complexes with DNA

Mixed-ligand copper(II) complexes of the type [Cu(dipica)(diimine)](ClO4)2, where dipica is di(2-picolyl)amine and diimine is 1,10-phenanthroline (phen), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp), 2,9-dimethyl-1,10-phenanthroline (2,9-dmp) or dipyridoquinoxaline (dpq), have been isolated and characterized by analytical and spectral methods. The copper(II) complexes exhibit a broad band in the visible region around 675 nm and axial EPR spectra in acetonitrile glass (77 K) with g∥ and A∥ values of ∼2·22 and 185 × 10−4 cm−1 respectively, suggesting the presence of a square-based coordination geometry for the CuN5 chromophore involving strong axial interaction. The interaction of the complexes with CT DNA has been studied using absorption, emission and circular dichroic spectral methods and viscosity measurements. Absorption spectral titrations reveal that the intrinsic DNA binding affinities are dependent upon the nature of the diimine ligand: dpq > 5,6-dmp > phen > 2,9-dmp. This suggests the involvement of the diimine rather than the dipica ‘face’ of the complexes in DNA binding. An intercalative mode of DNA interaction, which involves the insertion of dpq and to a lesser extent the phen ring of the complexes in between the DNA base pairs, is proposed. However, interestingly, the 5,6-dmp complex is involved in hydrophobic interaction of the 5,6-dmp ring in the grooves of DNA. The large enhancement in the relative viscosity of DNA on binding to the dpq and 5,6-dmp complexes supports the proposed DNA binding modes. Further, remarkably, the 5,6-dmp complex is selective in exhibiting a positive-induced CD band on binding to DNA suggesting the transition of the B form of CT DNA to A-like conformation. The variation in relative emission intensities of DNA-bound ethidium bromide observed upon treatment with the complexes parallels the trend in DNA binding affinities.

Copper(II) Complexes with Unusual Axial Phenolate Coordination as Structural Models for the Active Site in Galactose Oxidase: X-ray Crystal Structures and Spectral and Redox Properties of [Cu(bpnp)X] Complexes.

The crystal structures of [Cu(bpnp)(SCN)].NH(4)SCN (1), [Cu(bpnp)(CH(3)COO)].CH(3)OH.C(8)H(10) (2), and [Cu(bpnp)ClO(4)] (3) [Hbpnp = 2-(bis(pyrid-2-ylmethyl)aminomethyl)-4-nitrophenol] reveal a distorted square pyramidal geometry around Cu(II) with an unusual axial coordination of phenolate. The mononuclear complex [Cu(bpnp)(SCN)].NH(4)SCN crystallizes in the triclinic space group P&onemacr; with a = 10.796(2) Å, b = 10.804(2) Å, c = 12.559(2) Å, alpha = 71.38(1) degrees, beta = 72.68(1) degrees, gamma = 61.69(1) degrees, and Z = 2. The mononuclear acetate [Cu(bpnp)(CH(3)COO)].CH(3)OH.C(8)H(10) crystallizes in the triclinic space group P&onemacr; with a = 10.480(6) Å, b = 12.116(4) Å, c = 12.547(3) Å, alpha = 98.77(3) degrees, beta = 113.37(3) degrees, gamma = 100.78(3) degrees, and Z = 2. The binuclear perchlorate complex crystallizes in the monoclinic space group C2/c with a = 13.417(3) Å, b = 20.095(2) Å, c= 16.401(2) Å, alpha = 102.21(2) degrees, and Z = 8. The coordination plane in all these complexes is comprised of the tertiary amine and two pyridine nitrogens. The fourth equatorial position is occupied by SCN(-)/CH(3)COO(-) in the mononuclear complexes but by the coordinated phenolate ion from the adjacent molecule in the perchlorate complex, resulting in its dimerization. The unusual occupation of phenolate ion in the axial site is possibly due to the steric constraint at copper imposed by the 5,5,6-chelate ring sequence. The thiocyanate/acetate coordination geometry is reminiscent of the active site of the radical copper enzyme galactose oxidase (GOase) with an axial phenolate and equatorial SCN(-)/CH(3)COO(-) ligands. Further, the present complexes exhibit several spectral features also similar to this enzyme. The addition of chloride or thiocyanate or acetate ions dissociates the dimeric structure of the perchlorate complex to produce the corresponding monomeric derivatives. The study of the interaction of the acetate complex with N(3)(-) and CN(-) ions provide insight into the anion binding properties of the enzyme. The sensitivity of the acetate complex to protons suggests the facile dissociation of the axial phenolate which then acts as a base to bind to protons. The implication of this reaction to the GOase mechanism is discussed.

Mixed ligand copper(II) complexes of 1,10-phenanthroline with tridentate phenolate/pyridyl/(benz)imidazolyl Schiff base ligands: covalent vs non-covalent DNA binding, DNA cleavage and cytotoxicity.

A series of copper(II) complexes of the types [Cu(L)(phen)](ClO4) 1-2, where HL is a tridentate ligand with two nitrogen and one oxygen donor atoms (2NO) such as 2-(2-(1H-benzimidazol-2-yl)ethyliminomethyl)phenol (HL1) and 2-(2-(1H-benzimidazol-2-yl)ethyl-imino)methyl)-4-methylphenol (HL2), phen is 1,10-phenanthroline and [Cu(L)(phen)](ClO4)23-6, where L is a tridentate ligand with three nitrogen donor atoms (3N) such as (2-pyridin-2-ylethyl)pyridin-2-ylmethyleneamine (L3), 2-(1H-benzimidazol-2-yl)ethyl)-pyridin-2-yl-methyleneamine (L4), 2-(1H-benzimidazol-2-yl)ethyl)(1H-imidazol-2-ylmethylene)-amine (L5) and 2-(1H-benzimidazol-2-yl)ethyl)(4,4a-dihydroquinolin-2-ylmethylene)amine (L6), has been isolated and characterized by different spectral techniques. In single crystal X-ray structures, 1 possesses square pyramidal distorted trigonal bipyramidal (SPDTBP), geometry whereas 3 and 4 possess trigonal bipyramidal distorted square pyramidal (TBDSP) geometry. UV-Vis and fluorescence spectral studies reveal that the complexes 1-6 bind non-covalently to calf thymus DNA more strongly than the corresponding covalently bound chlorido complexes [Cu(2NO)Cl] 1a-2a and [Cu(3N)Cl2] 3a-6a. On prolonged incubation, all the complexes 1-6 exhibit double strand cleavage of supercoiled (SC) plasmid DNA in the absence of an activator. Also, they exhibit cytotoxicity against human breast cancer cell lines (HBL-100) more potent than their corresponding chlorido complexes 1a-6a, and have the potential to act as efficient cytotoxic drugs.

Mechanistic Insight into the Reactivity of Oxotransferases by Novel Asymmetric Dioxomolybdenum(VI) Model Complexes

The asymmetric molybdenum(VI) dioxo complexes of the bis(phenolate) ligands 1,4-bis(2-hydroxybenzyl)-1,4-diazepane, 1,4-bis(2-hydroxy-4-methylbenzyl)-1,4-diazepane, 1,4-bis(2-hydroxy-3,5-dimethylbenzyl)-1,4-diazepane, 1,4-bis(2-hydroxy-3,5-di-tert-butylbenzyl)-1,4-diazepane, 1,4-bis(2-hydroxy-4-flurobenzyl)-1,4-diazepane, and 1,4-bis(2-hydroxy-4-chlorobenzyl)-1,4-diazepane (H(2)(L1)-H(2)(L6), respectively) have been isolated and studied as functional models for molybdenum oxotransferase enzymes. These complexes have been characterized as asymmetric complexes of type [MoO(2)(L)] 1-6 by using NMR spectroscopy, mass spectrometry, elemental analysis, and electrochemical methods. The molecular structures of [MoO(2)(L)] 1-4 have been successfully determined by single-crystal X-ray diffraction analyses, which show them to exhibit a distorted octahedral coordination geometry around molybdenum(VI) in an asymmetrical cis-β configuration. The Mo-O(oxo) bond lengths differ only by ≈0.01 Å. Complexes 1, 2, 5, and 6 exhibit two successive Mo(VI)/Mo(V) (E(1/2), -1.141 to -1.848 V) and Mo(V)/Mo(IV) (E(1/2), -1.531 to -2.114 V) redox processes. However, only the Mo(VI)/Mo(V) redox couple was observed for 3 and 4, suggesting that the subsequent reduction of the molybdenum(V) species is difficult. Complexes 1, 2, 5, and 6 elicit efficient catalytic oxygen-atom transfer (OAT) from dimethylsulfoxide (DMSO) to PMe(3) at 65 °C at a significantly faster rate than the symmetric molybdenum(VI) complexes of the analogous linear bis(phenolate) ligands known so far to exhibit OAT reactions at a higher temperature (130 °C). However, complexes 3 and 4 fail to perform the OAT reaction from DMSO to PMe(3) at 65 °C. DFT/B3LYP calculations on the OAT mechanism reveal a strong trans effect.

Novel Iron(III) Complexes of Sterically Hindered 4N Ligands: Regioselectivity in Biomimetic Extradiol Cleavage of Catechols

The iron(III) complexes of the 4N ligands 1,4-bis(2-pyridylmethyl)-1,4-diazepane (L1), 1,4-bis(6-methyl-2-pyridylmethyl)-1,4-diazepane (L2), and 1,4-bis(2-quinolylmethyl)-1,4-diazepane (L3) have been generated in situ in CH 3CN solution, characterized as [Fe(L1)Cl 2] (+) 1, [Fe(L2)Cl 2] (+) 2, and [Fe(L3)Cl 2] (+) 3 by using ESI-MS, absorption and EPR spectral and electrochemical methods and studied as functional models for the extradiol cleaving catechol dioxygenase enzymes. The tetrachlorocatecholate (TCC (2-)) adducts [Fe(L1)(TCC)](ClO 4) 1a, [Fe(L2)(TCC)](ClO 4) 2a, and [Fe(L3)(TCC)](ClO 4) 3a have been isolated and characterized by elemental analysis, absorption spectral and electrochemical methods. The molecular structure of [Fe(L1)(TCC)](ClO 4) 1a has been successfully determined by single crystal X-ray diffraction. The complex 1a possesses a distorted octahedral coordination geometry around iron(III). The two tertiary amine (Fe-N amine, 2.245, 2.145 A) and two pyridyl nitrogen (Fe-N py, 2.104, 2.249 A) atoms of the tetradentate 4N ligand are coordinated to iron(III) in a cis-beta configuration, and the two catecholate oxygen atoms of TCC (2-) occupy the remaining cis positions. The Fe-O cat bond lengths (1.940, 1.967 A) are slightly asymmetric and differ by 0.027 A only. On adding catecholate anion to all the [Fe(L)Cl 2] (+) complexes the linear tetradentate ligand rearranges itself to provide cis-coordination positions for bidentate coordination of the catechol. Upon adding 3,5-di- tert-butylcatechol (H 2DBC) pretreated with 1 equiv of Et 3N to 1- 3, only one catecholate-to-iron(III) LMCT band (648-800 nm) is observed revealing the formation of [Fe(L)(HDBC)] (2+) involving bidentate coordination of the monoanion HDBC (-). On the other hand, when H 2DBC pretreated with 2 equiv of Et 3N or 1 or 2 equiv of piperidine is added to 1- 3, two intense catecholate-to-iron(III) LMCT bands appear suggesting the formation of [Fe(L)(DBC)] (+) with bidentate coordination of DBC (2-). The appearance of the DBSQ/H 2DBC couple for [Fe(L)Cl 2] (+) at positive potentials (-0.079 to 0.165 V) upon treatment with DBC (2-) reveals that chelated DBC (2-) in the former is stabilized toward oxidation more than the uncoordinated H 2DBC. It is remarkable that the [Fe(L)(HDBC)] (2+) complexes elicit fast regioselective extradiol cleavage (34.6-85.5%) in the presence of O 2 unlike the iron(III) complexes of the analogous linear 4N ligands known so far to yield intradiol cleavage products exclusively. Also, the adduct [Fe(L2)(HDBC)] (2+) shows a higher extradiol to intradiol cleavage product selectivity ( E/ I, 181:1) than the other adducts [Fe(L3)(HDBC)] (2+) ( E/ I, 57:1) and [Fe(L1)(HDBC)] (2+) ( E/ I, 9:1). It is proposed that the coordinated pyridyl nitrogen abstracts the proton from chelated HDBC (-) in the substrate-bound complex and then gets displaced to facilitate O 2 attack on the iron(III) center to yield the extradiol cleavage product. In contrast, when the cleavage reaction is performed in the presence of a stronger base like piperidine or 2 equiv of Et 3N a faster intradiol cleavage is favored over extradiol cleavage suggesting the importance of bidentate coordination of DBC (2-) in facilitating intradiol cleavage.

Cis-facial coordination of bis(pyrid-2-ylmethyl)amine (bpma). Synthesis, structure and spectral behaviour of [Ni(bpma) 2 ] 2+

Abstract Nickel(II) bis-complexes of bis(pyrid-2-ylmethyl)amine (bpma) and bis(benzimidazol-2-ylmethyl)amine (bbma) have been isolated. The complexes have been characterised using IR,UV-VIS and 1H NMR spectral techniques. The pink complex [Ni(bpma)2](ClO4)2 crystallises in the orthorhombic space group Fdd2, with a = 22.12(2), b = 28.087(2), c = 8.857(3) A , α = β = gg = 90° and z = 8 . The nickel(II) atom hasa slightly distorted octahedral structure in which the ligands are cis-facially coordinated. The MNpy bond length in [M(bpma)2]2+ [M=Mn(II), Fe(II), Ni(II), Cu(II), Zn(II)] complexes decrease and then increase with increase in d-orbital population. The ligand field parameters of the new complexes are compared with those of other complexes with NiN6 chromophore.

Synthesis, spectra and electrochemical behaviour of biomimetic copper(II) complexes with CuN5 and CuN6 chromophores

The Cu(ClO4)2 complexes of the two pentadentate ligands, N-(2-hydroxyethyl)-N,N′,N′-tris(benzimidazol-2′-ylmethyl)-1,2- ethanediamine and its 6′-methyl derivative and four sexadentate ligands, N,N,N′,N′-tetrakis(benzimidazol-2′-ylmethyl)-1,2- ethanediamine, N,N,N′,N′-tetrakis(benzimidazol-2′-ylmethyl)-1,2-cyclohexanediamine and their 6′-methyl derivatives have been isolated and studied. They are of the type CuL(ClO4)2·nH2O where n = 0, 1. All the complexes exhibit two ligand field bands and the νmax and ϵ values are lower and higher, respectively, than the range known for CuN4 chromophores. Compared to the latter they also have high g∥, low A∥ and high g∥/A∥ values. These spectral data are consistent with an appreciable displacement and/or tetrahedral twist of copper from the N4 square plane of the complexes. The anchoring of a bulky benzimidazole moiety to N,N′-bis(benzimidazol-2-ylmethyl)-1,2-ethanediamine to incorporate a N-donor axial to the planar CuN4 chromophore decreases CFSE and enhances the CuIICuI redox potential. However, addition of two benzimidazole nitrogens to the N4 ligand to obtain a CuN6 chromophore, depresses the redox potential. Further, the fusion of a cyclohexyl ring into the above CuN6 chromophore dramatically leads to elevation in E12 with increase in reversibility. The introduction of a methyl group in the aromatic ring, far away from the redox centre, depresses E12.

X-ray crystal structure of tetrakis(1-methylcytosine)copper(II) perchlorate dihydrate: effect of 1-methyl substitution on cytosine on the spectral and redox behaviour

Abstract Copper(II) tetrakis-complexes of cytosine (cyt), 1-methylcytosine (1-mcyt) and cytidine (cyd) have been isolated and their spectral and electrochemical properties investigated. The X-ray crystal structure of tetrakis(1-mcyt)copper(II) perchlorate dihydrate has been successfully determined. The co-ordination geometry around copper in the complex corresponds to square-based 4+4′ co-ordination. In addition to the preferential CuN3 bonds, there is significant interaction between copper(II) and the exocyclic O2 of 1-mcyt rings. The mutually cis 1-mcyt rings are present in a head-tail-head-tail arrangement, which is stabilised by a network of bifurcated hydrogen-bonding between the exocyclic amine hydrogen atoms and the oxygen atoms of the adjacent carbonyl groups. The aqueous solution spectra of the complexes are slightly different from solid state spectra revealing that the solid state structures undergo slight changes on dissolution in water. The electronic and EPR spectral and electrochemical results are consistent with the retention of the solid state structure even in solution. The EPR spectra exhibit N-superhyperfine lines corresponding to the coordination of four N3 atoms of cytosines. The higher g‖ values indicate decreased covalency in the metalligand bond and the range of g‖/A‖ quotient (119–121 cm) confirms the presence of CuN4 square-planar co-ordination geometry even in solution. The plot of ipc and E1/2 values versus 1-mcyt concentration for the electrochemical titration of Cu(ClO4)2 with 1-mcyt reveals an inflection point indicating the formation of 1:4 species in solution. The trend in E1/2 values of the complexes shows that the incorporation of electron releasing methyl group/ribose moiety at N1 position of cytosine ring enhances the stabilisation of Cu(II), in spite of the steric demand from OC2.