NOPR Collection:

Molecular structure-activity relationship study of some non-steroidal antiinflammatory agents using electrostatic potential mapping

Tue, 01 Aug 2000 00:00:00 GMT

Title: Molecular structure-activity relationship study of some non-steroidal antiinflammatory agents using electrostatic potential mapping Authors: Mohan, C Gopi; Mishra, PC Abstract: A series of 6, 11 -dihydro-11-oxodibenz[b,e]oxepin-2-acetic acids (DOAA) which are known to be anti-inflammatory agents were studied. The geometries of some of the molecules obtained from X-ray crystallography were used in the calculations as such while the geometries of their derivatives were obtained by local, partial geometry optimization around the sites of substitution employing the AM1 method, keeping the remaining parts of the geometries the same as those in the parent molecules. Molecular electrostatic potential (MEP) mapping was performed for the molecules using optimized hybridization displacement charges (HDC) combined with Lowdin charges, as this charge distribution has been shown earlier to yield near ab initio quality results. A good correlation has been found between the MEP values near the oxygen atoms of the hydroxyl groups of the carboxy groups of the molecules and their anti-inflammatory activities. The result is broadly in agreement with the model proposed earlier by other authors regarding the structure-activity relationship for other similar molecules. Page(s): 268-272

Metal ion mediated inhibition of firefly bioluminescence: A possibility via a quaternary complex

Tue, 01 Aug 2000 00:00:00 GMT

Title: Metal ion mediated inhibition of firefly bioluminescence: A possibility via a quaternary complex Authors: Sudhaharan, T; Reddy, A Ram Abstract: D(-) Luciferin, interacts with different metal ions to produce colourless soluble salts with absorption spectra broader, intense and red shifted as compared to those of the parent compound. The equilibrium constants for the luciferin-metal ion system vary in the order, depository divalent transition metal ions > alkali metal ions. The equilibrium constants for the ternary complexes formed between metal ions and a mixture of lucifcrin and luciferase are larger than that of binary complexes but vary in the same order. Steady state fluorometric titration's of luciferin further confirmed its complexation with metal ions. The single absorption maximum of firefly luciferase at 278 nm originating from tyrosine was split into a doublet in presence of transition metal ions. The absorption maximum at lower wavelength is attributed to the H-bond raptured free tyrosine denatured conformation of the luciferase while the longer wavelength band to tyrosine- transition metal ion complex. Difference spectra of luciferase metal ion complex yielded change in the molar extinction coefficients from which the number of tyrosine molecules exposed to aqueous solution by the perturbant metal ions are evaluated following the Donovan model. The number of tyrosine molecules exposed to the aqueous medium as a result of conformational change in the enzyme are 4, 3, 3, 2 and 3 by Hg²⁺,Mn²⁺, Co²⁺, Cd²⁺ and Cs⁺ respectively. The denaturation constants calculated for the luciferase-metal ion complexes vary between 0.152 and 0.570 and follow the order of Hg²⁺> Cs⁺> Cd²⁺> Co²⁺> Mn²⁺. Steady state fluorescence data reveal that the metal ions quench the fluorescence of enzyme by complexation with the side chain residues of the excited state tyro sine. Profound change in the UV CD spectrum of luciferin and luciferase in presence of metal ions was attributed to the conformational change in the substrate and enzyme. Thus the inhibition of luciferase activity in the firefly bioluminescence by metal ions is attributed to the quaternary complex formed between metal ion-luciferin-luciferase and ATP near or around the active site of the enzyme. Page(s): 256-267

X-band electron paramagnetic resonance spectra of pig serum albumin-copper(II) and pig serum albumin-copper(II)-amino acid systems

Tue, 01 Aug 2000 00:00:00 GMT

Title: X-band electron paramagnetic resonance spectra of pig serum albumin-copper(II) and pig serum albumin-copper(II)-amino acid systems Authors: Patel, R N; Pandeya, K B Abstract: EPR spectra of the binary, PSA-copper(II) (1:1 and 2:1) and ternary systems, PSA-copper(II) -amino acid (1:1:1) have been studied. In binary system, two distinct EPR features have been observed, one of the features (towards the low field), showing broad and overlapping signals is attributed to non-specific bonding of copper(II) to albumin and other feature (towards higher field), showing sharp intense signals is attributed to specific bonding. The change from non-specific to specific bonding is favoured by increase in pH as well as by increase in protein concentration. Observed pH for transition from non-specific binding is 10.00 <pH < 11.30. A better resolution of nitrogen hyperfine couplings are obtained for both binary, PSA-Cu(II) (1:1 and 2:1) and ternary PSA-Cu(II)-amino ac id (1:1:1) systems. Seven and more than seven nitrogen superhyperfine lines are observed in g region of binary and ternary systems respectively. Page(s): 251-255

Dye-mediated photodynamic inactivation of Bacillus subtilis cells: Involvement of singlet oxygen and superoxide radicals

Tue, 01 Aug 2000 00:00:00 GMT

Title: Dye-mediated photodynamic inactivation of Bacillus subtilis cells: Involvement of singlet oxygen and superoxide radicals Authors: Dube, Alok; Bansal, Harsha; Gupta, Pradeep K Abstract: Studies were carried out on the photodynamic inactivation of Bacillus subtilis cells by He-Ne laser irradiation in presence of methylene blue and toluidine blue. Electron paramagnetic resonance (EPR) measurements show decrease in the cell membrane nuidity due to photodynamic damage of the lipophilic compartments. Study of cell damage in presence of sodium azide, D₂O and glutathione as well as measurements on singlet oxygen/free radical generation by EPR show that with toluidine blue, singlet oxygen is the major reactive species leading to cell membrane damage. No free radical generation was observed in toluidine blue mediated photodamage. However, with methylene blue our observations suggest that the photodamage arises due to both singlet oxygen mediated membrane damage and intracellular damage by superoxide radical. Page(s): 245-250