Organometallic Complexes: New Tools for Chemotherapy

Abstract

The importance of organometallics can be noticed by their presence in all life organisms. The most known natural organometallic molecule is vitamin B12, a porphyrin containing a cobalt atom, useful for several enzymatic transformations. Based on the remarkable properties of this class of compounds, a new area of medicinal research was developed. Gérard Jaouen was the first to introduce the term of "bioorganometallic chemistry" in 1985 although the first organometallic therapeutical was Salvarsan®, discovered by Paul Ehrlich (Nobel Prize in Medicine in 1908). Bioorganometallic chemistry consists of the synthesis and the study of organometallic complexes, complexes with at least one metal-carbon bond, in a biological and medicinal interest. This field of research was accentuated by the discovery of the ferrocene in 1951 by Pauson and Kealy, confirmed in 1952 by Wilkinson (Nobel Prize in 1973). Today, bioorganometallic chemistry includes 5 main domains: (1) organometallic therapeuticals, (2) toxicology and environment, (3) molecular recognition in aqueous phases, (4) enzymes, proteins and peptides, (5) bioanalysis and pharmaceutical sensors. In this review, we focused on organometallic therapeuticals. The exceptional properties of organometallics are first described and then, an overview on the main organometallic complexes used for drug design is presented. This review gives an idea how organometallics can be used for the rational design of new drugs.

An Iridium(III) Complex Inhibits JMJD2 Activities and Acts as a Potential Epigenetic Modulator

“…The methoxy groups of 1 also generated a resonance at 57.2 ppm in the 13 C NMR spectrum in acetone-d 6 All complexes were synthesized and tested as racemic mixtures of enantiomers. To demonstrate that the cyclometalated iridium(III) complexes used in this study are substitutionally inert, the stability of the complexes were investigated by 1 complexes were stable in DMSO-d 6 /D 2 O (9:1; 5 mM) at 298 K for at least seven days, as verified by 1 H NMR spectroscopy. Similarly, UV−vis absorption spectroscopy also showed that the complexes were stable in acetonitrile/Tris-HCl buffer/ (8:2; 10 μM) at 298 K for at least 7 days.…”

The antimalarial ferroquine: from bench to clinic

“…But the clinical development of new compounds is often been stopped for various reasons: toxicity, chemistry, pharmacology, or economics, and less than one in ten promising molecules that have entered the pipeline reaches the stage of clinical studies. In the mid- 90 s, we extended the strategy developed by Gérard Jaouen (Vessieres et al , 1988) in anticancer therapy to antimalarial therapy (see Chavain & Biot, 2010 for review). The main antimalarials in current use (CQ, quinine, mefloquine, artemisinin, atovaquone) were modified by introduction of a ferrocenyl moiety in their chemical structure.…”

Main-Group Medicinal Chemistry Including Li and Bi*

“…While it is estimated that about 70% of organic drugs are bioinspired or are derivatives of natural products, 1 putative metal-based drugs are normally synthetic. 13 Reflecting growing interest, reviews are also available describing the development of organometallic compounds as therapeutic agents [14][15][16] and, intriguingly, of metal-organic frameworks (MOFs) which may function as drug carriers, that is a new type of drug delivery system. Despite the dominance of organic molecules in chemotherapy, it is of interest that modern chemotherapy is widely acknowledged to have begun with the work of Paul Ehrlich who investigated the efficacy of arsenic compounds for the treatment of, for example, African trypanosominasis.…”