Analysis of dynamics and mechanism of ligand binding to Artocarpus integrifolia agglutinin. A 13C and 19F NMR study

Binding of 13C-labeled N-acetylgalactosamine (13C-GalNAc) and N-trifluoroacetylgalactosamine (19F-GalNAc) to Artocarpus integrifolia agglutinin has been studied using 13C and 19F nuclear magnetic resonance spectroscopy, respectively. Binding of these saccharides resulted in broadening of the resonances, and no change in chemical shift was observed, suggesting that the alpha- and beta-anomers of 13C-GalNAc and 19F-GalNAc experience a magnetically equivalent environment in the lectin combining site. The alpha- and beta-anomers of 13C-GalNAc and 19F-GalNAc were found to be in slow exchange between free and protein bound states. Binding of 13C-GalNAc was studied as a function of temperature. From the temperature dependence of the line broadening, the thermodynamic and kinetic parameters were evaluated. The association rate constants obtained for the alpha-anomers of 13C-GalNAc and 19F-GalNAc (k+1 = 1.01 x 10(5) M-1.s-1 and 0.698 x 10(5) M-1.s-1, respectively) are in close agreement with those obtained for the corresponding beta-anomers (k+1 = 0.95 x 10(5) M-1.s-1 and 0.65 x 10(5) M-1.s-1, respectively), suggesting that the two anomers bind to the lectin by a similar mechanism. In addition these values are several orders of magnitude slower than those obtained for diffusion controlled processes. The dissociation rate constants obtained are 49.9, 56.9, 42, and 43 s-1, respectively, for the alpha- and beta-anomers of 13C-GalNAc and 19F-GalNAc. A two-step mechanism has been proposed for the interaction of 13C-GalNAc and 19F-GalNAc with A. integrifolia lectin in view of the slow association rates and high activation entropies. The thermodynamic parameters obtained for the association and dissociation reactions suggest that the binding process is entropically favored and that there is a small enthalpic contribution.

Photocytotoxic Lanthanum(III) and Gadolinium(III) Complexes of Phenanthroline Bases Showing Light-Induced DNA Cleavage Activity

Lanthanide complexes of formulation [La(B)(2)(NO3)(3)] (1-3) and [Gd(B)(2)(NO3)(3)] (4-6), where B is a N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1, 4),dipyrido[3,2-d2',3'-f]quinoxaline (dpq in 2,5) and dipyrido[3,2-a2',3'-c]phenazine (dppz in 3, 6), have been prepared, characterized from physicochemical data, and their photoinduced DNA and protein cleavage activity studied The photocytotoxicity of the dppz complexes 3 and 6 has been studied using HeLa cancer cells. The complexes exhibitligand centered bands in the UV region The dppz complexes show thelowest energy band at 380 nm in N,N-dimethylformamide (DMF) The La(III)complexes are diamagnetic. The Gd(III) complexes (4-6) have magneticmoments that correspond to seven unpaired electrons The complexes are1(.)1 electrolytic in aqueous DMF The dpq and dppz complexes in DMFshow ligand-based reductions. The complexes display moderate binding propensity to calf thymus DNA giving binding constant values in the range of 5.7 x 10(4)-5.8 x 10(5) M-1 with a relative order. 3, 6 (dppz)> 2, 5 (dpq) > 1, 4 (phen) The binding data suggest DNA surface and/or groove binding nature of the complexes. The complexes do not show any hydrolytic cleavage of plasmid supercoiled pUC19 DNA. The dpq and dppz complexes efficiently cleave SC DNA to its nicked circular form onexposure to UV-A light of 365 nm at nanomolar complex concentration. Mechanistic studies reveal the involvement of singlet oxygen (O-1(2)) and hydroxyl radical (HO center dot) as the cleavage active species.The complexes show binding propensity to bovine serum albumin (BSA)protein giving K-BSA values of similar to 10(5) M-1. The dppz complexes 3 and 6 show BSA protein cleavage activity in UV-A light of 365 nm The dppz complexes 3 and 6 exhibit significant photocytotoxicity in HeLa cells giving respective IC50 values of 341 nM and 573 nM in UV-A light of 365 nm for an exposure time of 15 min (IC50 > 100 mu M in dark for both the complexes) Control experiments show significant dark and phototoxicity of the dppz base alone (IC50 = 413 nM in light with 4 h incubation in dark and 116 mu M in dark with 24 h incubation). A significant decrease in the dark toxicity of the dppz base is observedon binding to the lanthanide ions while retaining similar phototoxicity.

Ligand series from V = O stretching frequency of oxovanadium(IV) complexes*1

A ligand series obtained from V = O stretching frequencies for different monomeric complexes of oxovanadium(IV) is shown to parallel the nephelauxetic series. The ligand series obtained from streching frequencies of other systems are also shown to compare well with the nephelauxetic series rather than the spectrochemical series.

Studies on some metal monothiobenzoates

Monothiobenzoate (MTB) (Chemical Equation Presented) complexes with the molecular formulas Cr(MTB)3, [Ni(MTB)2]n, [Zn(MTB)2]n, [Cd(MTB)2]n, [Hg(MTB)2]n, [Cu(MTB)]n, and [Ag(MTB)]n have been prepared and studied. All the complexes are nonionic in acetonitrile. Only the chromium complex is soluble in nitrobenzene and found to be monomeric cryoscopically. The thiobenzoate ligand appears to be asymmetrically chelated in Cr(III) and Cd(II) complexes, with stronger oxygen and sulfur coordination, respectively, while practically symmetrically coordinated in Ni(II) and Zn(II) complexes. These four complexes are assigned distorted octahedral structures around the metal ion. The coordination in Hg(II), Cu(I), and Ag(I) complexes is mainly through sulfur indicating the monodentate nature of the thiobenzoate ligand in these complexes. The coordination of monothiobenzoate ion in the complexes has been rationalized in terms of "hard" and "soft" acid-base concept.

Role of the leaving group in the base-catalysed hydrolysis of pseudo-esters

The relative insensitivity of the rate of hydrolysis of γ-pseudo-esters to the leaving group compared to that of the normal esters emphasises that the conjugative ability is an important factor in determining the rate of hydrolysis of esters

Generation of Cationic Two-Coordinate Group-13 Ligand Systems by Spontaneous Halide Ejection: Remarkably Nucleophile-Resistant (Dimethylamino)borylene Complexes

Spontaneous ejection of chloride from a three-coordinate boron Lewis acid can be effected by employing very electron rich metal substituents and leads to the formation of a sterically unprotected terminal (dimethylamino)borylene complex that has a short metal-boron bond and remarkable resistance to attack by nucleophilic and protic reagents.

Surface Ligand Population Controlled Oriented Attachment: A Case of CdS Nanowires

using two types of organic ligands having similar chemical structure but different physical properties and varying their dynamic population at the surface of zinc blende seed nanocrystals, self-assembled zinc blende semicircular-shaped bent nanowires of CdS are synthesized via a colloidal synthetic approach. It is found that the hydrophobic tail interaction of long-chain ligands puts strain on these thin nanowires (< 2 nm diameter) and bend them to some extent, forming strained nanowires.

Photocatalytic degradation of phenol by base metal-substituted orthovanadates

Base metal (Cr, Mn, Fe, Ni, Cu) substituted CeVO4 compounds were synthesized by the solution combustion technique. These compounds were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, UV-vis spectroscopy, transmission electron microscopy and BET surface area analyzer. The characterization indicated that the base metals were substituted in the ionic state in all the compounds. These compounds were used for the photocatalytic degradation of phenol and the degradation rates obtained in the presence of these compounds werecompared against that obtained with the commercial Degussa P-25 TiO2 catalyst. Fe and Cr substituted CeVO4 showed photocatalytic activity that was comparable with that of Degussa P-25 TiO2. The concentration of toxic intermediates was high when the reaction was carried out in presence of Degussa P-25 TiO2 but it was found to be insignificant when the reaction was carried out in presence of base metal-substituted CeVO4. The effect of % Fe-substitution (varied from 1 to 5 at%) in CeVO4 on the photocatalytic activity was also investigated and it was observed that 1 at% Fe-substituted compound showed the highest activity. A mathematical model describing the kinetics of the photocatalytic degradation of phenol was developed on the basis of the catalyst structure and taking into account the formation of all the possible intermediates. The variation of the concentration of phenol and the intermediates was described by the model and the reaction rateconstants were determined. (C) 2010 Elsevier B.V. All rights reserved.

Observation of a large coupling of a bound dihydrogen ligand to phosphorus ligands in trans-[(dppe)(2)Ru(eta(2)-H-2) (PF(OMe)(2))][BF4](2) complex

A new dicationic dihydrogen complex of the type trans-[(dppe)(2)Ru(eta (2)-H-2)(PF(OMe)(2))]BF4](2) has been prepared and characterized. A large coupling of about 50 Hz between the H-2 and trans-phosphorus ligand in this complex has been observed.

M.tuberculosis Pantothenate Kinase: Dual Substrate Specificity and Unusual Changes in Ligand Locations

Kinetic measurements of enzyme activity indicate that type I pantothenate kinase from Mycobacterium tuberculosis has dual substrate specificity for ATP and GTP, unlike the enzyme from Escherichia coli, which shows a higher specificity for ATP. A molecular explanation for the difference in the specificities of the two homologous enzymes is provided by the crystal structures of the complexes of the M. tuberculosis enzyme with (1) GMPPCP and pantothenate, (2) GDP and phosphopantothenate, (3) GDP, (4) GDP and pantothenate, (5) AMPPCP, and (6) GMPPCP, reported here, and the structures of the complexes of the two enzymes involving coenzyme A and different adenyl nucleotides reported earlier. The explanation is substantially based on two critical substitutions in the amino acid sequence and the local conformational change resulting from them. The structures also provide a rationale for the movement of ligands during the action of the mycobacterial enzyme. Dual specificity of the type exhibited by this enzyme is rare. The change in locations of ligands during action,observed in the case of the M. tuberculosis enzyme, is unusual, so is the striking difference between two homologous enzymes in the geometryof the binding site, locations of ligands, and specificity. Furthermore, the dual specificity of the mycobacterial enzyme appears to have been caused by a biological necessity. (C) 2010 Elsevier Ltd.All rights reserved.

X-Ray structure of a ternary complex, copper(II)–lnosine 5-monophosphate–benzimidazole. The first example for the absence of direct metal–nucleotide interaction

The unprecedented absence of direct metal–nucleotide interaction has been observed in the X-ray structure of the ternary metal nucleotide system [Cu(bzim)(H2O)5]2+[IMP]2–·3H2O [IMP = inosine 5-monophosphate(2–), bzim = benzimidazole). The complex crystallizes in the space group P21 with a= 7.013(2), b= 13.179(9), c= 14.565(9)Å, = 94.82(4)°, and Z= 2. The structure was solved by the heavy-atom method and refined by full-matrix least squares on the basis of 1 761 observed (I? 3i) reflections to final R and R values of 0.034 and 0.036 respectively. The CuII has a distorted octahedral co-ordination with a nitrogen of the bzim ligand [Cu–N 1.947(5)Å] and three oxygens of water molecules in the basal plane [mean Cu–O 2.017(3)Å] and two more water oxygens at axial positions [Cu–O 2.194(6) and 2.732(5)Å]. The nucleotide base stacks with the bzim ligand at an average distance of 3.5 Å and an angle of 22°. In the lattice, N(7) of the base is linked to a lattice water through a hydrogen bond, while all the phosphate oxygens are involved in hydrogen bonds with co-ordinated as well as lattice water molecules. The co-ordination behaviour of IMP to CuII is compared in structures containing different -aromatic amines in order to assess the influence of the ternary ligand in complex formation. The present results indicate that, apart from the commonly observed phosphate binding, other modes of co-ordination are possible, these being influenced mainly by the -accepting properties of the ternary ligand.

Symmetrical Bisbenzimidazoles with Benzenediyl Spacer: The Role of the Shape of the Ligand on the Stabilization and Structural Alterations in Telomeric G-Quadruplex DNA and Telomerase Inhibition

The extremities of chromosomes end in a G-rich single-stranded overhang that has been implicated in the onset of the replicate senescence. The repeated sequence forming a G-overhang is able to adopt a four-stranded DNA structure called G-quadruplex, which is a poor substrate for the enzyme telomerase. Small molecule based ligands that selectively stabilize the telomeric G-quadruplex DNA, induce telomere shortening eventually leading to cell death. Herein, we have investigated the G-quadruplex DNA interaction with two isomeric bisbenzimidazole-based compounds that differ in terms of shape (V-shaped angular vs linear).While the linear isomer induced some stabilization of the intramolecular G-quadruplex structure generated in the presence of Na+ the other, having V-shaped central planar core, caused a dramatic structural alteration of the latter, above a threshold concentration. This transition was evident from the pronounced changes observed in the circular dichroism spectra and from the get mobility shift assa involving the G-quadruples DNA. Notably, this angular isomer could also induce the G-quadruplex formation in the absence of any added cation. The ligand-quadruples complexes were investigated by computational molecular modeling, providing further information on structure-activity relationships. Finally, TRAP (telomerase repeat amplification protocol) experiments demonstrated that the angular isomer is selective toward the inhibition of telomerase activity.