Correlation between the Stereochemistry and Bioactivity in Octahedral Rhodium Prolinato Complexes

Rajathees Rajaratnam, Elisabeth K. Martin, Markus Doerr, Klaus Harms, Angela Casini, Eric Meggers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8111-8120
Number of pages10
JournalInorganic Chemistry
Volume54
Issue number16
DOIs
Publication statusPublished - 17-Aug-2015

Keywords

  • PROTEIN-KINASE INHIBITORS
  • PRECISION-CUT LIVER
  • ACUTE MYELOID-LEUKEMIA
  • GROWTH-FACTOR RECEPTOR
  • NECROSIS-FACTOR-ALPHA
  • METAL-COMPLEXES
  • AURORA KINASE
  • BIOORGANOMETALLIC CHEMISTRY
  • RUTHENIUM COMPLEXES
  • ENZYME-INHIBITOR

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