Correlation between the Stereochemistry and Bioactivity in Octahedral Rhodium Prolinato Complexes

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.