PubMed Health⌕ Search

Biomedical subjects

Mallayan Palaniandavar

Publications and source records attributed to Mallayan Palaniandavar.

16 recordsLinked to original sources
PubMed2006

Iron(III) complexes of certain meridionally coordinating tridentate ligands as models for non-heme iron enzymes: the role of carboxylate coordination.

The iron(III) complexes [Fe(pda)Cl(H(2)O)(2)] (1), [Fe(tpy)Cl(3)] (2), and [Fe(bbp)Cl(3)] (3), where H(2)pda is pyridine-2,6-dicarboxylic acid, tpy is 2,2':6,2''-terpyridine and bbp is 2,6-bis(benzimidazolyl)pyridine, have been isolated and studied as functional models for the intradiol-cleaving catechol dioxygenase enzymes. Mixed ligand complexes of H(2)pda with the bidentate ligands 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) have been also prepared and studied. All the complexes have been characterized using absorption spectral and electrochemical methods. The spectral changes in the catecholate adducts of the complexes generated in situ have been investigated. Upon interacting the complexes with catecholate anions a low energy catecholate to iron(III) charge transfer band appears, which is similar to that observed for enzyme-substrate complexes. All the complexes catalyze the oxidative intradiol cleavage of 3,5-di-tert-butylcatechol (H(2)dbc) in the presence of dioxygen. Interestingly, on replacing the pyridyl groups in 2 and the bulky benzimidazole groups in 3 by the carboxylate groups, the yields of the intradiol cleavage products of dioxygenation increases, 1 (50%)>2 (20%)>3 (10%). The higher intradiol yield for 1 has been ascribed to the meridional coordination of two carboxylate groups of pda(2-). In contrast to the trend in the intradiol cleavage yields, a tremendous decrease in the rate (200 times) is observed on replacing the two pyridyl moieties in 2 by two carboxylates as in 1 and a significant decrease in rate is observed on replacing the pyridyl moieties in 2 by strongly sigma-donating benzimidazole moieties as in 3. This is in conformity with the decrease in Lewis acidities of the iron(III) centers.

Carboxylic Acids↗
PubMed2006

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: the novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage.

The coordination geometry around copper(II) in [Cu(imda)(phen)(H2O)] (1) (H2imda = iminodiacetic acid, phen = 1,10-phenanthroline) is described as distorted octahedral while those in [Cu(imda)(5,6-dmp)] (2) (5,6-dmp = 5,6-dimethyl-1,10-phenanthroline) and [Cu(imda)(dpq)] (3) (dpq = dipyrido-[3,2-d:2',3'-f]-quinoxaline) as trigonal bipyramidal distorted square-based pyramidal with the imda anion facially coordinated to copper(II). Absorption spectral (Kb: 1, 0.60+/-0.04x10(3); 2, 3.9+/-0.3x10(3); 3, 1.7+/-0.5x10(4) M(-1)) and thermal denaturation studies (deltaTm: 1, 5.70+/-0.05; 2, 5.5+/-10; 3, 10.6+/-10 degrees C) and viscosity measurements indicate that 3 interacts with calf thymus DNA more strongly than 1 and 2. The relative viscosities of DNA bound to 1 and 3 increase while that of DNA bound to 2 decreases indicating formation of kinks or bends and/or conversion of B to A conformation as revealed by the decrease in intensity of the helicity band in the circular dichroism spectrum of DNA. While 1 and 3 are bound to DNA through partial intercalation, respectively, of phen ring and the extended planar ring of dpq with DNA base stack, the complex 2 is involved in groove binding. All the complexes show cleavage of pBR322 supercoiled DNA in the presence of ascorbic acid with the cleavage efficiency varying in the order 3 > 1 > 2. The highest oxidative DNA cleavage of dpq complex is ascribed to its highest Cu(II)/Cu(I) redox potential. Oxidative cleavage studies using distamycin reveal minor groove binding for the dpq complex but a major groove binding for the phen and 5,6-dmp complexes. Also, all the complexes show hydrolytic DNA cleavage activity in the absence of light or a reducing agent with cleavage efficiency varying in the order 1 > 3 > 2.

Binding, Competitive↗
PubMed2006

Interaction of rac-[Ru(5,6-dmp)3]2+ with DNA: enantiospecific DNA binding and ligand-promoted exciton coupling.

The X-ray crystal structure of the complex rac-[Ru(5,6-dmp)(3)]Cl(2) (5,6-dmp = 5,6-dimethyl-1,10-phenanthroline) reveals a distorted octahedral coordination geometry with the Ru-N bond distances shorter than in its phen analogue. Absorption spectral titrations with CT DNA reveal that rac-[Ru(5,6-dmp)(3)](2+) interacts (K(b), (8.0 +/- 0.2) x 10(4) M(-1)) much more strongly than its phen analogue. The emission intensity of the 5,6-dmp complex is dramatically enhanced on binding to DNA, which is higher than that of the phen analogue. Also, interestingly, time-resolved emission measurements on the DNA-bound complex shows biexponential decay of the excited states with the lifetimes of short- and long-lived components being higher than those for the phen analogue. The CD spectral studies of rac-[Ru(5,6-dmp)(3)](2+) bound to CT DNA provide a definite and elegant evidence for the enantiospecific interaction of the complex with B-form DNA. Competitive DNA binding studies using rac-[Ru(phen)(3)](2+) provide support for the strong binding of the complex with DNA. The Delta-enantiomer of rac-[Ru(5,6-dmp)(3)](2+) binds specifically to the right-handed B-form of poly d(GC)(12) at lower ionic strength (0.05 M NaCl), and the Lambda-enantiomer binds specifically to the left-handed Z-form of poly d(GC)(12) generated by treating the B-form with 5 M NaCl. The strong electronic coupling of the DNA-bound complex with the unbound complex facilitates the change in its enantiospecificity upon changing the conformation of DNA. The (1)H NMR spectra of rac-[Ru(5,6-dmp)(3)](2+) bound to poly d(GC)(12) reveal that the complex closely interacts most possibly in the major grooves of DNA. Electrochemical studies using ITO electrode show that the 5,6-dmp complex stabilizes CT DNA from electrocatalytic oxidation of its guanine base more than the phen analogue does.

Binding Sites↗
PubMed2005

Synthesis, characterization and DNA-binding properties of rac-[Ru(5,6-dmp)2(dppz)]2+--enantiopreferential DNA binding and co-ligand promoted exciton coupling.

The new mixed ligand complex [Ru(5,6-dmp)2(dppz)]Cl2 [5,6-dmp = 5,6-dimethyl-1,10-phenanthroline, dppz = dipyrido[3,2-a:2',3'-c]phenazine] has been isolated and its DNA-binding properties studied by employing UV-visible (UV-Vis), steady-state and time-resolved emission and circular dichroism spectral methods, viscometry, thermal denaturation and cyclic/differential pulse voltammetric techniques. The complex acts as a 'molecular light-switch' on binding to DNA, but the enhancement in emission intensity is only 75% of that of the parent complex [Ru(phen)2(dppz)]2+ (phen = 1,10-phenanthroline). The emission decay curves and quenching studies suggest two different DNA-binding modes both involving intercalation of the dppz ligand of [Ru(5,6-dmp)2(dppz)]Cl2. The characteristic red-shift of the induced CD signal, which is not observed for the phen analogue, arises from exciton coupling. The hydrophobicity and polarizability of 5,6-dmp co-ligand strongly favour the formation of a stable structural and electronic scaffold on the DNA surface for the unbound molecules to couple with the DNA-bound complexes facilitating spontaneous assembly of novel extended molecular aggregates using DNA as a helical nanotemplate. This observation is consistent with the shift in Ru(II)/Ru(III) redox potential to more positive values with a dramatic drop in peak current on binding of the 5,6-dmp complex to calf thymus (CT) DNA. Equilibrium dialysis experiments monitored by CD spectroscopy unambiguously reveal the preferential binding of the delta-enantiomer to the right-handed calf thymus (CT) DNA. The 5,6-dmp complex exhibits preferential binding to [d(AT)6]2 over [d(GC)6]2 and the complex aggregates formed consist of six [Ru(5,6-dmp)2(dppz)]2+ cations per base pair of [d(AT)6]2; however, only one [Ru(phen)2(dppz)]2+ cation per base pair is involved in DNA binding.

Circular Dichroism↗
PubMed2005

Synthesis, structure and spectral and redox properties of new mixed ligand monomeric and dimeric Ru(II) complexes: predominant formation of the "cis-alpha" diastereoisomer and unusual 3MC emission by dimeric complexes.

The tetradentate ligands 1,8-bis(pyrid-2-yl)-3,6-dithiaoctane (pdto) and 1,8-bis(benzimidazol-2-yl)-3,6-dithiaoctane (bbdo) form the complexes [Ru(pdto)(mu-Cl)](2)(ClO(4))(2) 1 and [Ru(bbdo)(mu-Cl)](2)(ClO(4))(2) 2 respectively. The new di-mu-chloro dimers 1 and 2 undergo facile symmetrical bridge cleavage reactions with the diimine ligands 2,2'-bipyridine (bpy) and dipyridylamine (dpa) to form the six-coordinate complexes [Ru(pdto)(bpy)](ClO(4))(2) 3, [Ru(bbdo)(bpy)](ClO(4))(2) 4, [Ru(pdto)(dpa)](ClO(4))(2) 5 and [Ru(bbdo)(dpa)](ClO(4))(2) 6 and with the triimine ligand 2,2':6,2''-terpyridine (terpy) to form the unusual seven-coordinate complexes [Ru(pdto)(terpy)](ClO(4))(2) 7 and [Ru(bbdo)(terpy)](ClO(4))(2) 8. In 1 the dimeric cation [Ru(pdto)(mu-Cl)](2)(2+) is made up of two approximately octahedrally coordinated Ru(II) centers bridged by two chloride ions, which constitute a common edge between the two Ru(II) octahedra. Each ruthenium is coordinated also to two pyridine nitrogen and two thioether sulfur atoms of the tetradentate ligand. The ligand pdto is folded around Ru(II) as a result of the cis-dichloro coordination, which corresponds to a "cis-alpha" configuration [DeltaDelta/LambdaLambda(rac) diastereoisomer] supporting the possibility of some attractive pi-stacking interactions between the parallel py rings at each ruthenium atom. The ruthenium atom in the complex cations 3a and 4 exhibit a distorted octahedral coordination geometry composed of two nitrogen atoms of the bpy and the two thioether sulfur and two py/bzim nitrogen atoms of the pdto/bbdo ligand, which is actually folded around Ru(II) to give a "cis-alpha" isomer. The molecule of complex 5 contains a six-coordinated ruthenium atom chelated by pdto and dpa ligands in the expected distorted octahedral fashion. The (1)H and (13)C NMR spectral data of the complexes throw light on the nature of metal-ligand bonding and the conformations of the chelate rings, which indicates that the dithioether ligands maintain their tendency to fold themselves even in solution. The bis-mu-chloro dimers 1 and 2 show a spin-allowed but Laporte-forbidden t(2g)(6)((1)A(1g))--> t(2g)(5) e(g)(1)((1)T(1g), (1)T(2g)) d-d transition. They also display an intense Ru(II) dpi--> py/bzim (pi*) metal-to-ligand charge transfer (MLCT) transition. The mononuclear complexes 3-8 exhibit dpi-->pi* MLCT transitions in the range 340-450 nm. The binuclear complexes 1 and 2 exhibit a ligand field ((3)MC) luminescence even at room temperature, whereas the mononuclear complexes 3 and 4 show a ligand based radical anion ((3)MLCT) luminescence. The binuclear complexes 1 and 2 undergo two successive oxidation processes corresponding to successive Ru(II)/Ru(III) couples, affording a stable mixed-valence Ru(II)Ru(III) state (K(c): 1, 3.97 x 10(6); 2, 1.10 x 10(6)). The mononuclear complexes 3-7 exhibit only one while 8 shows two quasi-reversible metal-based oxidative processes. The coordinated 'soft' thioether raises the redox potentials significantly by stabilising the 'soft' Ru(II) oxidation state. One or two ligand-based reduction processes were also observed for the mononuclear complexes.

Journal Article↗
PubMed2005

Synthesis, structure and DNA interaction of cobalt(III) bis-complexes of 1,3-bis(2-pyridylimino)isoindoline and 1,4,7-triazacyclononane.

The complex [CoL(2)](ClO(4)).MeOH (1), where HL is the tridentate 3N ligand 1,3-bis(2-pyridylimino)isoindoline, has been isolated and its X-ray crystal structure successfully determined. It possesses a distorted octahedral structure in which both the ligands are coordinated meridionally to cobalt(III) via one deprotonated isoindoline (L(-)) and two pyridine nitrogen atoms. Interestingly, the average dihedral angle between pyridine and isoindoline rings is 25.9 degrees , indicating that the ligand is twisted upon coordination to cobalt(III). The interaction of the complex with calf-thymus DNA has been studied using various spectral methods and viscosity and electrochemical measurements. For comparison, the DNA interaction of [Co(tacn)(2)]Cl(3) (2), where tacn is facially coordinating 1,4,7-triazacyclononane, has been also studied. The ligand-based electronic spectral band of 1 and the N(sigma)-->Co(III) charge transfer band of 2 exhibit moderate hypochromism with small or no blue shift on interaction with DNA. The intrinsic binding constants calculated reveal that the monopositive complex ion [CoL(2)](+) exhibits a DNA-binding affinity lower than the tripositive complex ion [Co(tacn)(2)](3+). The steric clashes with DNA exterior caused by the second L(-) ligand bound to cobalt(III), apart from the lower overall positive charge on the [CoL(2)](+) complex, dictates its DNA-binding mode to be surface binding rather than partial intercalative interaction expected of the extended aromatic chromophore of deprotonated isoindoline anion. An enhancement in relative viscosity of CT DNA on binding to 1 is consistent with its DNA surface binding. On the other hand, a slight decrease in viscosity of CT DNA was observed on binding to 2 revealing that the smaller cation leads to bending (kinking) and hence shortening of DNA chain length. The electrochemical studies indicate that the DNA-bound complexes are stabilised in the higher Co(III) rather than the lower Co(II) oxidation state, suggesting the importance of electrostatic forces of DNA interaction.

Cobalt↗
PubMed2005

Functional models for catechol dioxygenases: iron(III) complexes of cis-facially coordinating linear 3N ligands.

A series of 1:1 iron(III) complexes of simple and sterically hindered tridentate 3N donor ligands have been synthesized and studied as functional models for catechol dioxygenases. All of them are of the type [FeLCl3], where L is bis(pyrid-2-yl-methyl)amine (L1), N,N-bis(benzimidazol-2-ylmethyl)amine (L2), N-methyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L3), N,N-dimethyl-N'-(pyrid-2-ylmethyl)-ethylenediamine (L4) and N-phenyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L5). They have been characterised by spectral and electrochemical methods. The X-ray crystal structure of the complex [Fe(L4)Cl3] has been successfully determined. The complex crystallizes in the triclinic space group P1 with a = 7.250(6), b = 8.284(3), c = 12.409(4) angstroms, alpha = 80.84(3) degrees, beta = 86.76(6) degrees, gamma = 72.09(7) degrees and Z = 2. It possesses a distorted octahedral geometry in which the L4 ligand is cis-facially coordinated to iron(III) and the chloride ions occupy the remaining coordination sites. The systematic variation in the ligand donor atom type significantly influences the Lewis acidity of the iron(III) center and hence the binding interaction of the complexes with simple and substituted catechols. The spectroscopic and electrochemical properties of the catecholate complexes generated in situ have been investigated. All the complexes catalyze mainly the oxidative intradiol cleavage of 3,5-di-tert-butylcatechol (H2DBC) in the presence of dioxygen, which is unexpected of the cis-facial coordination of the ligands. The rate of intradiol catechol cleavage reaction depends upon the Lewis acidity of iron(III) center and steric demand and hydrogen-bonding functionalities of the ligands. Interestingly, the electron-sink property of N-phenyl substituent in [Fe(L5)Cl3] complex leads to enhancement in rate of cleavage. All these observations provide support to the substrate activation mechanism proposed for intradiol-cleaving enzymes.

Catechol 1,2-Dioxygenase↗
PubMed2005

Copper(II) complexes of 1,10-phenanthroline-derived ligands: studies on DNA binding properties and nuclease activity.

A series of copper(II) complexes of the type [Cu(L)]2+, where L = N,N'-dialkyl-1,10-phenanthroline-2,9-dimethanamine and R = methyl (L1), n-propyl (L2), isopropyl (L3), sec-butyl (L4), or tert-butyl (L5) group, have been synthesized. The interaction of the complexes with DNA has been studied by DNA fiber electron paramagnetic resonance (EPR) spectroscopy, emission, viscosity and electrochemical measurements and agarose gel electrophoresis. In the X-ray crystal structure of [Cu(HL2)Cl2]NO3, copper(II) is coordinated to two ring nitrogens and one of the two secondary amine nitrogens of the side chains and two chloride ions as well and the coordination geometry is best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). Electronic and EPR spectral studies reveal that all the complexes in aqueous solution around pH 7 possess CuN3O2 rather than CuN4O chromophore with one of the alkylamino side chain not involved in coordination. The structures of the complexes in aqueous solution around pH 7 change from distorted tetragonal to trigonal bipyramidal as the size of the alkyl group is increased. The observed changes in the physicochemical features of the complexes on binding to DNA suggest that the complexes, except [Cu(L5)]2+, bind to DNA with partial intercalation of the derivatised phen ring in between the DNA base pairs. Electrochemical studies reveal that the complexes prefer to bind to DNA in Cu(II) rather than Cu(I) oxidation state. Interestingly, [Cu(L5)]2+ shows the highest DNA cleavage activity among all the present copper(II) complexes suggesting that the bulky N-tert-butyl group plays an important role in modifying the coordination environment around the copper(II) center, the Cu(II)/Cu(I) redox potential and hence the formation of activated oxidant responsible for the cleavage. These results were compared with those for bis(1,10-phenanthroline)copper(II), [Cu(phen)2]2+.

Chelating Agents↗
PubMed2005

Copper(II) complexes of tridentate pyridylmethylethylenediamines: role of ligand steric hindrance on DNA binding and cleavage.

Copper(II) complexes of three linear unsymmetrical tridentate ligands viz. N-methyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L1), N,N-dimethyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L2) and N,N-dimethyl-N'-((6-methyl)pyrid-2-ylmethyl)ethylenediamine (L3) have been isolated and characterized by elemental analysis, electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes [Cu(L2)Cl2] and [Cu(L3)Cl2] have been structurally characterized by X-ray crystallography. The [Cu(L2)Cl2] complex crystallizes in the monoclinic space group P2(1)/n with a=11.566(2) A, b=7.369(1) A, c=15.703(3) A, alpha=90 degrees , beta=109.68(8) degrees , gamma=90 degrees and Z=4 while [Cu(L3)Cl2] crystallizes in the triclinic space group P1 with a=9.191(2) A, b=12.359(3) A, c=14.880(3) A, alpha=79.61(13) degrees , beta=86.64(13) degrees , gamma=87.28(8) degrees and Z=2. The coordination geometries around copper (II) in these two complexes are best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). The distorted CuN3Cl basal plane in them is comprised of three nitrogen atoms of the meridionally coordinated ligand and a chloride ion and the axial position is occupied by the other chloride ion. The interaction of these complexes with Calf Thymus DNA (CT DNA) has been studied by using absorption, emission and circular dichroic spectral methods, thermal denaturation studies, viscometry and cyclic and differential pulse voltammetry. A strong blueshift in the ligand field band and a redshift in the ligand based bands of the copper(II) complexes on binding to DNA imply a covalent mode of DNA binding of the complexes, which involves coordination of most possibly guanine N7 nitrogen of DNA to form a CuN4 chromophore. This is supported by studying the interaction of the complexes with N-methylimidazole (N-meim), guanosine monophosphate (GMP), adenosine monophosphate (AMP) and cytidine (cytd) by ligand field and EPR spectral methods, which indicate the formation of a CuN4 chromophore only in the case of the more basic N-meim and GMP. The DNA melting curves obtained in the presence of copper(II) complexes reveal a monophasic and irreversible melting of the DNA strands and the high positive DeltaTm values (12-21 degrees C) also support the formation of strong Cu-N bonds by the complexes with DNA, leading to intra- and/or interstrand crosslinking of DNA. Competitive ethidium bromide (EthBr) binding studies show that the L2 and L3 complexes are less efficient than the L1 complex in quenching EthBr emission, which is consistent with their forming DNA crosslinking preventing the displacement of the DNA-bound EthBr. A very slight decrease in relative viscosity of DNA is observed on treating the L1 and L2 complexes with CT DNA; however, a relatively significant decrease is observed for the L3 complex suggesting that the length of the DNA fiber is shortened. DNA cleavage experiments show that all the complexes induce the cleavage of pBR322 plasmid DNA, the complex of L1 being more efficient than those of sterically hindered L2 and L3 ligands.

Animals↗
PubMed2004

Iron(III) complexes of sterically hindered tetradentate monophenolate ligands as functional models for catechol 1,2-dioxygenases: the role of ligand stereoelectronic properties.

The iron(III) complexes of the monophenolate ligands 2-(bis(pyrid-2-ylmethyl)aminomethyl)-4-nitrophenol [H(L1)], N,N-dimethyl-N'-(pyrid-2-ylmethyl)-N'-(2-hydroxy-4-nitrobenzyl)ethylenediamine [H(L2)], N,N-dimethyl-N'-(6-methyl-pyrid-2-ylmethyl)-N'-(2-hydroxy-4-nitrobenzyl)ethylenediamine [H(L3)], and N,N-dimethyl-N'-(1-methylimidazole-2-ylmethyl)-N'-(2-hydroxy-4-nitrobenzyl)ethylenediamine [H(L4)] have been obtained and studied as structural and functional models for the intradiol-cleaving catechol dioxygenase enzymes. The complexes [Fe(L1)Cl(2)].CH(3)CN (1), [Fe(L2)Cl(2)] (2), [Fe(L3)Cl(2)] (3), and [Fe(L4)Cl(2)] (4) have been characterized using absorption spectral and electrochemical methods. The single crystal X-ray crystal structures of 1 and 2 have been successfully determined. Both the complexes possess a rhombically distorted octahedral coordination geometry for the FeN(3)OCl(2) chromophore. In 2, the phenolate oxygen, the pyridine nitrogen, an amine nitrogen, and a chloride ion are located on the corners of a square plane with the nitrogen atom of a -NMe(2) group and the other chloride ion occupying the axial positions. In 1, also the equatorial plane is constituted by the phenolate oxygen, the pyridine nitrogen, an amine nitrogen atom, and a chloride ion; however, the axial positions are occupied by the second pyridine nitrogen and the second chloride ion. Interestingly, the Fe-O-C angle of 136.1 degrees observed for 2 is higher than that (128.5 degrees ) in 1; however, the Fe-O(phenolate) bond distances in both the complexes are the same (1.929 A). This illustrates the importance of the nearby sterically demanding coordinated -NMe(2) group and implies similar stereochemical constraints from the other ligated amino acid moieties in the 3,4-PCD enzymes, the enzyme activity of which is traced to the difference in the equatorial and axial Fe-O(tyrosinate) bonds (Fe-O-C, 133 degrees, 148 degrees ). The nature of heterocyclic rings of the ligands and the methyl substituents on them regulates the electronic spectral features, Fe(III)/Fe(II) redox potentials, and catechol cleavage activity of the complexes. Upon interacting the complexes with catecholate anions, two catecholate to iron(III) charge transfer bands appear, and the low energy band is similar to that of catechol dioxygenase-substrate complex. Complexes 1 and 3 fail to catalyze the oxidative intradiol cleavage of 3,5-di-tert-butylcatechol (H(2)DBC). However, interestingly, the replacement of pyridine pendant in 1 by the -NMe(2) group to obtain 2 restores the dioxygenase activity, which is consistent with its higher Fe-O-C bond angle. Remarkably, the more basic N-methylimidazole ring in 4 facilitates the rate-determining product releasing phase of the catalytic reaction, leading to enhancement in reaction rate and efficient conversion (77.1%) of the substrate to intradiol cleavage products as well. All these observations provide support to the novel substrate activation mechanism proposed for the intradiol-cleavage pathway.

Catalysis↗
PubMed2003

Novel iron(III) complexes of tripodal and linear tetradentate bis(phenolate) ligands: close relevance to intradiol-cleaving catechol dioxygenases.

Four new iron(III) complexes of the bis(phenolate) ligands N,N-dimethyl-N',N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine [H2(L1)], N,N-dimethyl-N',N'-bis(2-hydroxy-4-nitrobenzyl)ethylenediamine [H2(L2)], N,N'-dimethyl-N,N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine [H2(L3)], and N,N'-dimethyl-N,N'-bis(2-hydroxy-4-nitrobenzyl)ethylenediamine [H2(L4)] have been isolated and studied as structural and functional models for the intradiol-cleaving catechol 1,2-dioxygenases (CTD). The complexes [Fe(L1)Cl] (1), [Fe(L2)(H2O)Cl] (2), [Fe(L3)Cl] (3), and [Fe(L4)(H2O)Cl] (4) have been characterized using absorption spectral and electrochemical techniques. The single-crystal X-ray structures of the ligand H2(L1) and the complexes 1 and 2 have been successfully determined. The tripodal ligand H2(L1) containing a N2O2 donor set represents the metal-binding region of the iron proteins. Complex 1 contains an FeN2O2Cl chromophore with a novel trigonal bipyramidal coordination geometry. While two phenolate oxygens and an amine nitrogen constitute the trigonal plane, the other amine nitrogen and chloride ion are located in the axial positions. In contrast, 2 exhibits a rhombically distorted octahedral coordination geometry for the FeN2O3Cl chromophore. Two phenolate oxygen atoms, an amine nitrogen atom, and a water molecule are located on the corners of a square plane with the axial positions being occupied by the other nitrogen atom and chloride ion. The interaction of the complexes with a few monodentate bases and phenolates and differently substituted catechols have been investigated using absorption spectral and electrochemical methods. The effect of substituents on the phenolate rings on the electronic spectral features and FeIII/FeII redox potentials of the complexes are discussed. The interaction of the complexes with catecholate anions reveals changes in the phenolate to iron(III) charge-transfer band and also the appearance of a low-energy catecholate to iron(III) charge-transfer band similar to catechol dioxygenase-substrate complexes. The redox behavior of the 1:1 adducts of the complexes with 3,5-di-tert-butylcatechol (H2DBC) has been also studied. The reactivities of the present complexes with H2DBC have been studied and illustrated. Interestingly, only 2 and 4 catalyze the intradiol-cleavage of H2DBC, the rate of oxygenation being much faster for 4. Also 2, but not 4, yields an extradiol cleavage product. The reactivity of the complexes could be illustrated not on the basis of the Lewis acidity of the complexes alone but by assuming that the product release is the rate-determining phase of the catalytic reaction.

Catechol 1,2-Dioxygenase↗
PubMed2002

DNA-fiber EPR study of the orientation of Cu(II) complexes of 1,10-phenanthroline and its derivatives bound to DNA: mono(phenanthroline)-copper(II) and its ternary complexes with amino acids.

The orientation of mono(1,10-phenanthroline)copper(II), [Cu(phen)]2+, and the ternary complexes with amino acids, [Cu(phen)X(aa)]n+, where X(aa) stands for an alpha-amino acid, has been investigated by electron paramagnetic resonance (EPR) spectra of the complexes on DNA fibers. It has been revealed that these complexes bind to DNA with several different binding modes. The observation of a species whose g axis is almost parallel to the DNA double helical axis has suggested that the phenanthroline moiety intercalates to DNA. An absence of the intercalated species for the corresponding 2,2'-bipyridine complex has shown that the three-fused aromatic rings in phenanthroline are critical for the intercalative binding of the complexes. The intercalative binding was promoted by 5,6-dimethyl groups on the phenanthroline ring, whereas it was disturbed by 2,9-dimethyl groups, indicating that the planarity of the coordination sphere is important for the intercalative binding. In all cases, the amount of the non-intercalated species was larger than that of the intercalated one. The amino acids in the ternary complexes of glycine, leucine, serine, threonine, cysteine, methionine, and asparagine were partly substituted with some coordinating groups in DNA, whereas the ternary complexes of lysine, arginine, and glutamine remained intact on DNA.

Amino Acids↗
PubMed1998

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.

Journal Article↗
PubMed1998

Spectral and Electrochemical Behavior of Copper(II)-Phenanthrolines Bound to Calf Thymus DNA. [(5,6-dimethyl-OP)(2)Cu](2+) (5,6-dimethyl-OP = 5,6-Dimethyl-1,10-phenanthroline) Induces a Conformational Transition from B to Z DNA.

The interaction of 1:2 copper(II) complexes of 1,10-phenanthroline (OP) and variously methyl-substituted phenanthrolines with calf thymus DNA has been investigated by viscometry and spectral and electrochemical techniques. Viscometry and competitive ethidium bromide (EthBr) emission studies reveal that substitutions at 4- and 4,7-positions confer the complex a reduced affinity for DNA via partial intercalative interaction of the middle ring of OP between the base pairs of DNA, while substitutions at 5- and 5,6-positions confer a weak affinity toward DNA. The tetramethyl substitution at 3,4,7,8-positions lead to an intermediate behavior for the complex. Circular dichroism spectral studies of the interaction disclose for the first time that, of all the complexes, the 5,6-dimethyl-OP complex is a unique and remarkable reagent in that it reversibly binds to DNA and effects the important conversion of right-handed B DNA to left-handed Z DNA even in the presence of EthBr, an allosteric effector of the B conformation of DNA. This novel conformational transition is unexpected of the low GC content of natural DNA. The ratios of the binding constants (K(+)/K(2+)) for DNA binding of the Cu(I) and Cu(II) forms of the redox active OP complexes rather than the Cu(II)/Cu(I) redox potentials (0.023 to -0.098 V vs SCE) are good measures of the substituent dependent DNA cleavage efficiency and rate. They also reveal that the Cu(I) form of OP and 4-methyl- and 5,6-dimethyl-substituted OP complexes displays enhanced affinity to bind but noncovalently to the minor groove of DNA. Attempts have been made to illustrate the cleavage rate and efficiency of nucleolytic reactions in the light of the relative binding constants of Cu(I) and Cu(II) forms of the OP complexes.

Journal Article↗
PubMed1996

Dipicolylamine Complexes of Copper(II): Two Different Coordination Geometries in the Same Unit Cell of Cu(Dipica)(2)(BF(4))(2).

Bright blue Cu(Dipica)(2)(BF(4))(2) crystallizes in the monoclinic space group P2(1)/n, with unit cell parameters a = 23.406(6) Å, b = 9.338(2) Å, c = 25.573(7) Å, beta = 95.39(2) degrees, and Z = 8. The structure was solved by conventional Patterson and Fourier methods. The R and R(w) values for 5282 observed reflections were 7.06% and 9.10% respectively. Two structurally different complex cations are present in the same unit cell, one hexacoordinate and the other pentacoordinate. In the hexacoordinate cation, the two tridentate bis(2'-picolyl)amine ligands are trans-facially coordinated with two pyridine nitrogens and the two secondary amine nitrogens situated on four positions in a plane [Cu-N(pyr) = 2.189(6), 2.146(6) Å; Cu-N(sat) = 2.207(6), 2.201(5) Å]. The remaining two pyridine nitrogens constitute the axis [Cu-N(pyr) = 2.035(5), 2.038(5) Å] in an equatorially expanded pseudooctahedral geometry. The pentacoordinate cation possesses a square-pyramidal configuration, the two secondary nitrogens being mutually cis, with one Dipica equatorially tridentate [Cu-N(pyr) = 2.044(5), 2.027(5) Å, Cu-N(sat) = 1.995(5) Å]. The other Dipica functions as a bidentate ligand, with one of the pyridine nitrogens occupying the equator [Cu-N(pyr) = 1.986(5) Å] and the aliphatic nitrogen defining the axial copper position [Cu-N(sat) = 2.344(5) Å]. Its second pyridine is uncoordinated but hydrogen-bonded to the coordinated NH of the other ligand. Solution properties offer no clear distinction between the two cation stereochemistries. The ternary chelates [Cu(Dipica)(Acac)]ClO(4) and [Cu(Dipica)(Bipy)](ClO(4))(2) are also described.

Journal Article↗