Cyclometalated Complexes of Platinum and Gold with Biological Properties: State-of-the-Art and Future Perspectives

Abstract

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.

Acridine-decorated cyclometallated gold(iii) complexes: synthesis and anti-tumour investigations

“…Slow diffusion of light petroleum into dichloromethane solutions of complexes 7 and 9 yielded crystals suitable for X-ray diffraction (Figure 3). In both compounds the square planar geometry of the gold(III) centres is slightly distorted due to the small bite angles of the cyclometalated ligand [respective C11-Au-N1 angles 81.1°(7) and 80.9° (9)]. In 7, the acridine-substituted nitrogen atom is in trans position to the nitrogen of the cyclometalated ligand, placing it on the same side as the tert-butyl substituent, while the O atom, as the weakest trans influence ligand, is trans to the stronger C-donor.…”

“…[4][5][6][7][8] In particular, cyclometalated gold(III) complexes have been attracting significant interest. 9,10 Both bidentate, (C^N) or tridentate, (C^N^C), (C^N^N) or (N^C^N) cyclometalated ligands have been used to stabilize the gold(III) centre, enabling the study of fundamental organometallic reactions, the characterization of catalytic intermediates, and the development of photoluminescent materials and of anticancer drug candidates. [11][12][13] Henderson and coworkers introduced a series of neutral cyclometalated (C^N)Au(N^N) chelate complexes containing phenylenediamine and ethylenediamine moieties, with the nitrogen atoms bearing electron-withdrawing moieties.…”

New Variations on the Theme of Gold(III) C∧N∧N Cyclometalated Complexes as Anticancer Agents: Synthesis and Biological Characterization

“…[4][5][6] Also intensely investigated are the applications of these complexes in the field of bioinorganic medicinal chemistry. 2,[7][8][9] Indeed, the superior stabilization of the gold(III) ion against reduction in aqueous solution, granted by C^N cyclometalated ligands with respect to, for example, N^N chelating ones, gave new impetus to the search of possible alternatives to platinum(II)-based anticancer agents. The first examples of cyclometalated Au III complexes as potential anticancer agents were those based on the C^N ligand 2-(N,N-dimethylamino)methylphenyl.…”

“…[10][11] Following these successful results, a number of other cyclometalated Au III complexes supported by C^N chelates as well as by C^N^N, N^C^N and C^N^C pincer ligands, endowed with promising anticancer properties and unique mechanisms of action, have been reported. 2,[7][8][9]12 These complexes also present the advantage of tolerating a large palette of ancillary ligands such as phosphanes, [13][14] NHCs, 15 and N-donor ligands, 16 enabling optimization of their biological properties. In general, for such different families of gold(III) cyclometalated compounds, interactions with protein targets are considered to be responsible for their observed anticancer effects, 9,[17][18] whereas interactions with DNA seem less relevant, with a few exceptions.…”

Gold and platinum alkynyl complexes for biomedical applications

“…73 However, the vast amount of work was devoted to the development of analogous species that mimic the coordination nature of the cisplatin, leaving organometallic complexes relegated to a second position. 74 Alternatively, organometallic platinum complexes and in particular alkynyl derivatives have lately demonstrated their capacity as anticancer agents, with excellent IC 50 values and in some cases exceeding that of cisplatin.…”