Unveiling Luminescent Ir and Rh N-Heterocyclic Carbene Complexes: Structure, Photophysical Specifics, and Cellular Localization in the Endoplasmic Reticulum.

Complexes of Rh and Ir of the [M(COD)(NHC)X] type (where M=Rh or Ir, COD=1,5-cyclooctadiene, NHC=N-heterocyclic carbene, and X=halide) have recently shown promising cytotoxic activities against several cancer cell lines. Initial mechanism of action studies provided some knowledge about their interaction with DNA and proteins. However, information about their cellular localization remains scarce owing to luminescence quenching within this complex type.

A Combined Spectroscopic and Protein Crystallography Study Reveals Protein Interactions of Rh(NHC) Complexes at the Molecular Level.

While most Rh-N-heterocyclic carbene (NHC) complexes currently investigated in anticancer research contain a Rh(III) metal center, an increasing amount of research is focusing on the cytotoxic activity and mode of action of square-planar [RhCl(COD)(NHC)] (where COD = 1,5-cyclooctadiene) which contains a Rh(I) center. The enzyme thioredoxin reductase (TrxR) and the protein albumin have been proposed as potential targets, but the molecular processes taking place upon protein interaction remain elusive. Herein, we report the preparation of peptide-conjugated and its nonconjugated parent [RhCl(COD)(NHC)] complexes, an in-depth investigation of both their stability in solution, and a crystallographic study of protein interaction.

Luminescent Bimetallic Ir /Au Peptide Bioconjugates as Potential Theranostic Agents.

Invited for the cover of this issue are Vanesa Fernández-Moreira, Nils Metzler-Nolte, M. Concepción Gimeno and co-workers at Universidad de Zaragoza and Ruhr-Universität Bochum. The image depicts the reported bimetallic bioconjugates as planes directing the gold fragment towards the target (lysosomes).

Luminescent Bimetallic Ir /Au Peptide Bioconjugates as Potential Theranostic Agents.

Diverse iridium peptide bioconjugates and the corresponding iridium/gold bimetallic complexes have been synthesized starting from a cyclometallated carboxylic acid substituted Ir complex [Ir(ppy) (Phen-5-COO)] by solid phase peptide synthesis (SPPS). The selected peptide sequences were an enkephalin derivative Tyr-Gly-Gly-Phe-Leu together with the propargyl-substituted species Tyr-Gly-Pgl-Phe-Leu to allow gold coordination (Pgl: propyrgyl-glycine, HC≡C-Gly), and a specific short peptide, Ala-Cys-Ala-Phen, containing a cysteine residue. Introduction of the gold center has been achieved via a click reaction with the alkynyl group leading to an organometallic Au-C(triazole) species, or by direct coordination to the sulfur atom of the cysteine.

On the interaction of N-heterocyclic carbene Ir complexes with His and Cys containing peptides.

In contrast to their rhodium(i) and iridium(iii) analogues, examples of iridium(i) complexes are only poorly investigated in the context of anti-cancer research. Recently we reported on the cytotoxic activity of [Ir(+I)(COD)(NHC)Cl] complexes (NHC: N-heterocyclic carbene, COD: 1,5-cycloactodiene) and their unusual oxidative interaction with cytochrome c and lysozyme. To get further insight into the molecular basis of this interaction a methylated histidine (His) derivative was synthesized, which could be used in solid phase peptide chemistry leading to a peptide-imidazolium salt.