Narrow Results

Ketenes are excellent precursors for catalytic asymmetric reactions, creating chiral centers mainly through addition across their C=C bonds. Density functional theory (DFT) calculations at the MO6/LACVP* and B3LYP/LACVP* levels of theory were employed in a systematic investigation of the peri-, chemo- and regio-selectivity of the addition of transition metal oxo complexes of the type ReO₃L(L=Cl^-, O^-, OCH₃, CH₃) to substituted ketenes O=C=C(CH₃)(X) [X=CH₃, H, CN, Ph] with the aim of elucidating the effects of substituents on the mechanism of the reactions. The [2 + 2] addition pathway across the C=C or C=O (depending on the ligand) is the most preferred in the reactions of dimethyl ketene with all the metal complexes studied. The [2 + 2] pathway is also the most preferred in the reactions of ReO₃Cl with all the substituted ketenes studied except when X=Cl. Thus of all the reactions studied, it is only the reaction of ReO₃Cl with O=C=C(CH₃)(Cl) that prefers the [3 + 2] addition pathway. Reactions of dimethyl ketene with ReO₃L favors addition across C=O bonds of the ketene when L=O^- and CH₃ but favors addition across C=C bonds when L=OCH₃ and Cl. In the reactions of ReO₃Cl with substituted ketenes, addition across C=O bonds is favored only when X=H while addition across C=C bonds is favored when X=CH₃, Cl, Ph, CN. The reactions of dimethyl ketene with ReO₃L will most likely lead to the formation of an ester precursor in each case. A zwitterionic intermediate is formed in the reactions except in the reactions of . The order in the activation energies of the reactions of dimethyl ketenes with the metal complexes ReO₃L with respect to changing ligand L is O^- < CH₃O^- < Cl^- < CH₃ while the order in reaction energies is CH₃ < CH₃O^- < O^- < Cl^-. For the reactions of substituted ketenes with ReO₃Cl, the order in activation barriers is CH₃ < Ph < CN < Cl < H while the reaction energies follow the order Cl < CH₃ < H < Ph < CN. In the reactions of dimethyl ketenes with ReO₃L, the trend in the selectivity of the reactions with respect to ligand L is Cl^- < CH₃O^- < CH₃ < O^- while the trend in selectivity is CH₃ < CN < Cl < Ph in the reactions of ReO₃Cl with substituted ketenes. It is seen that reactions involving a change in oxidation state of metal from the reactant to product have high activation barriers while reactions that do not involve a change in oxidation state have low activation barriers. For both [3 + 2] and [2 + 2] additions, low activation barriers are obtained when the substituent on the ketene is electron-donating while high activation barriers are obtained when the substituent is electron-withdrawing.

Rett Syndrome is a rare genetic disorder exclusively seen in girls. Approximately 95% of RTT cases is caused by mutations in the MeCP2 gene which codes for Methyl-CpG-binding protein 2 (MeCP2). In this review, first, a brief introductory review of Rett Syndrome, MeCP2 protein structure and function, mutation types and frequencies, and phenotype–genotype relationships were provided. After that, the current knowledge on the wild-type and mutant MeCP2 protein structure and dynamics as well as its binding to DNA is reviewed. The review particularly focuses on computational (such as molecular dynamics) and experimental (such as electrophoretic mobility shift assays) studies on the MeCP2 binding to different types of DNA as well as the computational and experimental (such as circular dichroism) studies on the stability changes upon mutations. In the end, a brief opinion on future outlook for further computational studies is provided.