- Towards a green enantiomeric esterification of R/S-ketoprofen: A theoretical and experimental investigation
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Methanol, ethanol, 1- and 2-propanol were used as reactants and solvents in the esterification of R/S-ketoprofen catalyzed with Novozym 435. The interaction of the alcohols with Novozym 435 was studied at a molecular level through various spectroscopic techniques and molecular modeling. The results evidenced the dissolution of the polymeric support, loss of active protein, strong adsorption of the alcohols, modification of the secondary structure of the protein and smoothing of the inner structure of the biocatalyst's beads upon extended contact with the alcohols. Nevertheless, none of those drawbacks influences the specific activity and enantiomeric excess toward S(+)-enantiomer that remain unaltered upon extended contact with ethanol, 1- and 2-propanol as acyl acceptors. However, theoretical calculations demonstrated that methanol introduces steric and electronic hindrance within the step of the coordination of the R/S-ketoprofen with the catalytic triad.
- Toledo, María Victoria,José, Carla,Collins, Sebastián E.,Ferreira, María Luján,Briand, Laura E.
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- Binding of a chiral drug to a protein: An investigation of the 2-(3-benzoylphenyl)propionic acid/bovine serum albumin system by circular dichroism and fluorescence
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A combined approach using global analysis of circular dichroism multiwavelength data and time resolved fluorescence was applied to investigate the interaction of R-(-)- and S-(+)-ketoprofen with bovine serum albumin in buffer solution at neutral pH. A characterization of the most stable drug : protein adducts of 1:1 and 2:1 stoichiometry, as individual chemical species, was obtained. The stability constants and the absolute circular dichroism spectra of the diastereomeric complexes were determined. The spectra of the 1:1 conjugates are opposite in sign, those of the 2:1 complexes are both negative, but different in shape from each other (peaks at 358 and 342 nm for S-(+)- and R-(-)-ketoprofen, respectively). A tryptophan residue was shown to be involved in the binding of the drug, in the primary site for the R-(-) and in the secondary site for the S-(+) enantiomer, thereby showing that chiral recognition by the protein causes the site of highest affinity being not the same for both optical antipodes. The Owner Societies 2005.
- Monti, Sandra,Manoli, Francesco,Sortino, Salvatore,Morrone, Raffaele,Nicolosi, Giovanni
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- Chemoenzymatic synthesis of pure enantiomeric 2-aryl propionic acids
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A new chemoenzymatic procedure to obtain pure enantiomeric 2-arylpropionic acids is described. The one pot synthesis of (±)-2-arylpropionic acids is carried out by addition of dichlorocarbene to the C=O bond of arylmethylketones and hydrogenolysis of the additon product. The racemic mixture is resolved by enantiospecific hydrolysis of the racemic ethyl esters using native lipase from Candida rugosa. The good yields, the accessibility of the starting arylmethylketones and the stereospecificity of the enzymatic hydrolysis make the process interesting in order to obtain the same non steroidal antiinflammatory drugs such as Ibuprofen or Naproxen.
- Garcia,Del Campo,Llama,Sanchez-Montero,Sinisterra
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p. 8433 - 8440
(2007/10/02)
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