Title:Cyclometalated Complexes of Platinum and Gold with Biological Properties: State-of-the-Art and Future Perspectives
Volume: 25
Issue: 4
Author(s): Sophie Jurgens, Fritz E. Kuhn and Angela Casini*
Affiliation:
- School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT,United Kingdom
Keywords:
Organometallic, cyclometalation, gold, platinum, cancer therapy, anticancer agents.
Abstract: Background: The inherent problems accompanying chemotherapy necessitate
the development of new anticancer approaches. The development of compounds that can
disrupt cancerous cellular machinery by novel mechanisms, via interactions with proteins
and non-canonical DNA structures (e.g. G-quadruplexes), as well as by alteration of the
intracellular redox balance, is nowadays focus of intense research. In this context, organometallic
compounds of the noble metals Pt and Au have become prominent experimental
therapeutic agents. This review provides an overview of the Pt(II) and Au(III) cyclometalated
compounds with a chelating ring containing a strong C-M σ -bond to improve
the stability of the compounds with respect to ligand exchange reactions and biological
reduction. Furthermore, these properties can be easily tuned by modification of either
the anionic cyclometalated or the ancillary ligands. Special focus has been set to
C^N, C^N^C, C^N^N and C^N^S platinum(II) and gold(III) pincer complexes regarding
their synthesis and biological mechanisms of action as anticancer agents.
Methods: A structured search of both chemical and medicinal databases for peerreviewed
research literature has been conducted. The quality of retrieved papers was appraised
using standard tools. The synthesis as well as the chemical and biological properties
of the described compounds were carefully reviewed and described. The findings
were outlined using a conceptual framework.
Results: In this review we included 155 papers, the majority originating from high-impact
papers on the synthesis and biological modes of platinum(II) and gold(III) compounds.
Among them, 17 papers were highlighted to give an introduction to the use of Pt and Au
compounds with medicinal properties, mainly focussing on coordination compounds. The
synthesis and medicinal properties of organometallic compounds of various metals (such
as Fe, Ru, Ti) were outlined in 51 papers. These compounds included metallocenes, metallo-
arenes, metallo-carbonyls, metallo-carbenes (e.g. N-heterocyclic carbenes), and alkynyl
complexes. The C^N, C^N^C, C^N^N and C^N^S pincer complexes of platinum(
II) (46 papers) and gold(III) (44 papers) were discussed concerning their synthesis,
stability and advantages to develop therapeutic compounds. We strove to show the consistent
development of C^N, C^N^C, C^N^N and C^N^S platinum(II) and gold(III) pincer
complexes regarding their synthesis and biological modes from the early beginnings to
the most recent findings.
Conclusion: This review supplies a profound overview of the development of organometallic
compounds for medicinal purposes, setting special focus to the synthesis and
stability of C^N, C^N^C, C^N^N and C^N^S pincer complexes of platinum(II) and
gold(III) and their use as anticancer agents.
