Effect of inhibitors on the catalyzed dehydration of HCO3- by copper(II) complexes re-evaluated

In a recent paper by Cheng and co-workers (Sun, Y.-J.; Zang, L. Z.; Cheng, P.; Lin, H.-K.; Yan, S.-P.; Sun, W.; Liao, D.-Z.; Jiang, Z.-H.; Shen, P.-W. Inorg. Chem. 2003, 42, 508-515), kinetic evidence for inhibitor effects of specific ligands on the catalyzed dehydration of HCO3- by copper(II) complexes of the type [Tp(Ph)]CuX (X- = OH-, N3-, and NCS-) was reported. The analysis of the kinetic data is not correct, and a re-evaluation shows that the claimed catalytic activity of the studied complexes on the dehydration reaction of bicarbonate is indeed questionable. Furthermore, the apparent inhibitor effect of specific selected ligands in the Cu(II) complexes does not seem to exist at all and is based on a wrong interpretation of the kinetic data.     

Palladium catalyzed Suzuki C-C couplings in an ionic liquid: nanoparticles responsible for the catalytic activity

A new family of functionalized ligands derived from norborn-5-ene-2,3-dicarboxylic anhydride has been used in Suzuki C-C cross-couplings between aryl boronic acids and aryl bromide derivatives in [BMI][PF(6)] (BMI=1-n-butyl-3-methyl-imidazolium), using palladium acetate as catalytic precursor. High conversions and yields are obtained when amine ligands containing hydroxy groups are involved. TEM analyses after catalysis show the formation of small nanoparticles, in contrast to the agglomerates observed when nanoparticles are intentionally preformed, with a consequent decrease in the catalytic activity in the latter case. Some tests, including the correlation effect between solvent and ligand, are carried out to try to identify the true nature of the catalyst. All the results obtained suggest that formation of nanoparticles is required to lead to a catalytically active system.     

Electron microscopic study of dehydration transformations. II. The formation of “superstructures” on the dehydration of goethite and diaspore

It is shown that the satellites observed in the diffraction pattern of the dehydrated single crystal of the mineral goethite, which were previously attributed to a “superstructure,” are better interpreted in terms of small angle scattering by a “texture” of the dehydration product hematite. This texture consists of rows of cavities parallel to the H(003) = G(100) planes with an average distance of 30–50 Å, depending on the stage of the transformation, in a highly twinned hematite matrix. In corundum resulting from the dehydration of diaspore a more isotropic texture is formed and the diffraction pattern exhibits “halos” instead of rows of satellite spots.     

Molecular dynamics simulation study reveals polar nature of pathogenic mutations responsible for stabilizing active conformation of kinase domain in leucine-rich repeat kinase II

The kinase domain of LRRK2 is increasingly gaining attention as a promising therapeutic target due to pathogenic mutation leading to development of Parkinson’s disease. Mutation in G2019S and I2020T increases the kinase activity, while A2016T mutation causes drug resistance. Increased kinase activity of LRRK2 has been associated with deposition of tau and α-synuclein proteins. However, mechanism responsible for increase in activity due to mutation is not known. In the present study, extensive molecular dynamics study has been performed on both wild and mutant homology models of DYG-In (active) conformation of the kinase domain of LRRK2 in the absence/presence of ATP at the active site to study the behavior of DYG loop. In absence of ATP, it is observed that G2019S and I2020T mutants stabilize DYG loop by increasing formation of hydrogen bond with neighboring residues, mainly with GLU 1920 and ILE 1991, respectively. In ATP-kinase complex, DYG loop also increases hydrogen bonding with neighboring residues in mutant LRRK2. The study indicates that polar side chain of mutated residues increases the polarity of DYG loop, causing an increase in hydrogen bonding with neighboring residues to stabilize the active conformation of kinase domain in LRRK2. The binding free energy of ATP is found to be higher in mutated kinase as compared to wild, due to more stable kinase domain.     

Crucial dependence of chemiluminescence efficiency on the syn/anti conformation for intramolecular charge-transfer-induced decomposition of bicyclic dioxetanes bearing an oxidoaryl group

Thermally stable rotamers of bicyclic dioxetanes bearing 6-hydroxynaphthalen-1-yl (anti-5a and syn-5a), 3-hydroxynaphthalen-1-yl (anti-5b and syn-5b), and 5-hydroxy-2-methylphenyl groups (anti-5c and syn-5c) were synthesized. These dioxetanes underwent TBAF (tetrabutylammonium fluoride)-induced decomposition accompanied by the emission of light in DMSO and in acetonitrile at 25 °C. For all three pairs of rotamers, the chemiluminescence efficiency Φ(CL) for anti-5 was 8-19 times higher than that for syn-5, and the rate of CTID (charge-transfer-induced decomposition) for anti-5 was faster than that for syn-5. The chemiluminescence spectra of the rotamers for 5a and 5c, respectively, were different. This discrepancy in the chemiluminescence spectra between rotamers can presumably be attributed to the difference in the structures of de novo keto imide anti-14 and syn-14 in an excited state, which inherit the structures of the corresponding intermediary anionic dioxetanes anti-13 and syn-13. The important difference in chemiluminescence efficiency between anti-5 and syn-5 is discussed from the viewpoint of a chemiexcitation mechanism for CTID of oxidophenyl-substituted dioxetane.     

Identification of photolabeled peptides for the acceptor substrate binding domain of beta 1,4-galactosyltransferase.

We successfully applied a carbene-generating N-acetylglucosamine derivative carrying a biotinyl group to the radioisotope-free identification of peptides within bovine UDP-galactose: N-acetylglucosamine beta 1,4-galactosyltransferase (GalT, EC 2.4.1.38) catalytic domain. Owing to the low yield of cross-linking, conventional photoaffinity labeling experiments usually encounter a thorny problem in attempting to isolate labeled components from very complex mixtures. A biotin tag introduced with our photoaffinity probe enabled us to separate the photolabeled protein from a large amount of coexisting unlabeled GalT. The introduction of biotin was also useful for the radioisotope-free detection of a labeled protein based on a highly sensitive chemiluminescent technique. We developed a novel poly(vinylidene difluoride) membrane for the identification of labeled peptides in a simple dot blot assay. Using this membrane, we successfully identified biotinyl peptides among a number of HPLC separated fragments derived from the protease digestion of photolabeled GalT proteins. The sequence analysis revealed that the biotin tag was incorporated within a tryptic GalT fragment of Y197-R208. Our approach yields, for the first time, information on the acceptor substrate binding-site fragment in this enzyme, that has been difficult to obtain using other approaches. These data are consistent with previous suggestions concerning the GalT acceptor site and clearly demonstrate the effectiveness of our approach for rapid identification of photolabeled peptides.