title: Correlation between the Stereochemistry and Bioactivity in Octahedral Rhodium Prolinato Complexes.
abstract: Controlling the relative and absolute configuration of octahedral metal complexes constitutes a key challenge that needs to be overcome in order to fully exploit the structural properties of octahedral metal complexes for applications in the fields of catalysis, materials sciences, and life sciences. Herein, we describe the application of a proline-based chiral tridentate ligand to decisively control the coordination mode of an octahedral rhodium(III) complex. We demonstrate the mirror-like relationship of synthesized enantiomers and differences between diastereomers. Further, we demonstrate, using the established pyridocarbazole pharmacophore ligand as part of the organometallic complexes, the importance of the relative and absolute stereochemistry at the metal toward chiral environments like protein kinases. Protein kinase profiling and inhibition data confirm that the proline-based enantiopure rhodium(III) complexes, despite having all of the same constitution, differ strongly in their selectivity properties despite their unmistakably mutual origin. Moreover, two exemplary compounds have been shown to induce different toxic effects in an ex vivo rat liver model.
authors.affiliation: †Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, 35043 Marburg, Germany.
authors.forename: Rajathees
authors.initials: R
authors.lastname: Rajaratnam
authors.affiliation: †Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, 35043 Marburg, Germany.
authors.forename: Elisabeth K
authors.initials: EK
authors.lastname: Martin
authors.affiliation: †Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, 35043 Marburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Dörr
authors.affiliation: †Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, 35043 Marburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Harms
authors.affiliation: ‡Department of Pharmacokinetics, Toxicology and Targeting, Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, The Netherlands.|§Cardiff School of Chemistry, University of Cardiff, Park Place, Cardiff CF10 3A, U.K.
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.affiliation: †Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse 4, 35043 Marburg, Germany.|∥College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, People's Republic of China.
authors.forename: Eric
authors.initials: E
authors.lastname: Meggers
mesh_terms: D000818:Animals; D006801:Humans; D008099:Liver / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D009942:Organometallic Compounds; D047428:Protein Kinase Inhibitors; D012238:Rhodium