cytochrome-c-t and carbene

A cytochrome

Topics: Biocatalysis; Cytochromes c; Hydrogen; Methane; Molecular Structure; Nitrogen; Silicon

N-heterocyclic carbenes-modified half-sandwich iridium(III) complex [(η

Topics: A549 Cells; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Coordination Complexes; Cytochromes c; Drug Screening Assays, Antitumor; HeLa Cells; Heterocyclic Compounds; Humans; Iridium; Lung Neoplasms; Lysosomes; Methane; Microscopy, Confocal; Mitochondria; Organometallic Compounds

Enzymes that catalyze carbon-silicon bond formation are unknown in nature, despite the natural abundance of both elements. Such enzymes would expand the catalytic repertoire of biology, enabling living systems to access chemical space previously only open to synthetic chemistry. We have discovered that heme proteins catalyze the formation of organosilicon compounds under physiological conditions via carbene insertion into silicon-hydrogen bonds. The reaction proceeds both in vitro and in vivo, accommodating a broad range of substrates with high chemo- and enantioselectivity. Using directed evolution, we enhanced the catalytic function of cytochrome c from Rhodothermus marinus to achieve more than 15-fold higher turnover than state-of-the-art synthetic catalysts. This carbon-silicon bond-forming biocatalyst offers an environmentally friendly and highly efficient route to producing enantiopure organosilicon molecules.

Topics: Bacterial Proteins; Biocatalysis; Carbon; Cytochromes c; Directed Molecular Evolution; Hydrogen Bonding; Methane; Organosilicon Compounds; Rhodothermus; Silicon; Substrate Specificity

A new NHC iridium(I) complex (1) showing significant antiproliferative properties in vitro is described here. Its crystal structure, solution behaviour and interactions with the model proteins cytochrome c (cyt c) and lysozyme were investigated. High resolution ESI-MS measurements suggest that this iridium(i) complex acts as a prodrug and binds cyt c tightly through an unusual "oxidative" mechanism. Eventually, an iridium(III)-NHC fragment is found associated to the protein.

Topics: Cell Proliferation; Cell Survival; Coordination Complexes; Cytochromes c; HEK293 Cells; Heterocyclic Compounds; HT29 Cells; Humans; Iridium; MCF-7 Cells; Methane; Muramidase; Oxidation-Reduction