title: Octahedral rhodium(III) complexes as kinase inhibitors: Control of the relative stereochemistry with acyclic tridentate ligands.
abstract: Octahedral metal complexes are attractive structural templates for the design of enzyme inhibitors as has been demonstrated, for example, with the development of metallo-pyridocarbazoles as protein kinase inhibitors. The octahedral coordination sphere provides untapped structural opportunities but at the same time poses the drawback of dealing with a large number of stereoisomers. In order to address this challenge of controlling the relative metal-centered configuration, the synthesis of rhodium(III) pyridocarbazole complexes with facially coordinating acyclic tridentate ligands was investigated. A strategy for the rapid synthesis of such complexes is reported, the diastereoselectivities of these reactions were investigated, the structure of several complexes were determined by X-ray crystallography, the high kinetic stability of such complexes in thiol-containing solutions was demonstrated in (1)H-NMR experiments, and the protein kinase inhibition ability of this class of complexes was confirmed. It can be concluded that the use of multidentate ligands is currently maybe the most practical strategy to avoid a large number of possible stereoisomers in the course of exploiting octahedral coordination spheres as structural templates for the design of bioactive molecules.
authors: Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35043 Marburg, Germany.
authors: Stefan
authors: S
authors: Mollin
authors: Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35043 Marburg, Germany.
authors: Radostan
authors: R
authors: Riedel
authors: Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35043 Marburg, Germany.
authors: Klaus
authors: K
authors: Harms
authors: Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35043 Marburg, Germany; College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, People's Republic of China. Electronic address: meggers@chemie.uni-marburg.de.
authors: Eric
authors: E
authors: Meggers
mesh_terms: D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D056831:Coordination Complexes; D008024:Ligands; D047428:Protein Kinase Inhibitors; D012238:Rhodium
keywords: Enzyme inhibition; Protein kinases; Rh complexes; Stereochemistry; Synthesis