Heterometallic Multinuclear Complexes as Anti‐Cancer Agents‐An Overview of Recent Developments

Abstract

This review provides a critical assessment of the advances made in the development of heterometallic multinuclear complexes as potential chemotherapeutic agents, with the aim of providing a starting point for future investigators. The combination of the classical transition metals (Pt, Ru and Au) with other metal moieties has the potential to result in complexes with improved pharmacokinetic and pharmacodynamic properties. This enables selective targeting of the bio- [a] 3434 Figure 2. The Pt II -Ru III complexes, IT127 and AH-197, [35] and the macrocyclic rectangles investigated by Chi and colleagues. [36] The IC 50 (μM) values reported are shown below the chemical structures.

Therapeutic and Diagnostic Applications of Multimetallic Rhenium(I) Tricarbonyl Complexes

“…Perhaps more importantly, there is a lack of investigation on the mechanism of action of heterometallic anticancer complexes in general. [29] Because of the paucity of the studies mentioned above, many compounds are arbitrarily prepared rather than rationally designed.…”

“…Additionally, the stability of heterometallic complexes under physiological conditions is often not examined, which makes it difficult to tell whether the activity comes from the intact complex or individual mononuclear fragments. Perhaps more importantly, there is a lack of investigation on the mechanism of action of heterometallic anticancer complexes in general [29] . Because of the paucity of the studies mentioned above, many compounds are arbitrarily prepared rather than rationally designed.…”

“…Multimetallic complexes, in general, have found useful biological applications because they leverage the distinct properties of different metal centers simultaneously. [29][30][31] In the context of Re(CO) 3 complexes, both homonuclear, which contain multiple Re centers, and heteronuclear, which contain Re and a different metal center, multimetallic compounds have been reported. In this Minireview, we will summarize the therapeutic and diagnostic applications of these Re(CO) 3 -containing multimetallic complexes.…”

“…Although other multimetallic complexes of this type have been reported for catalytic applications, [32] we are only focusing on complexes that have been used in a biological setting. Readers are referred elsewhere for reviews on the biological applications of mononuclear Re(CO) 3 complexes, [1][2][3][4][5][6][7] multimetallic complexes in a more general sense, [29][30][31] and rhenium complexes where Re exists in oxidation states III, IV, V and VII. [6,33]…”

“…Given the valuable therapeutic and diagnostic properties of the Re(CO) 3 core, there has been a significant interest in using this fragment in conjunction with other metal centers. Multimetallic complexes, in general, have found useful biological applications because they leverage the distinct properties of different metal centers simultaneously [29–31] . In the context of Re(CO) 3 complexes, both homonuclear, which contain multiple Re centers, and heteronuclear, which contain Re and a different metal center, multimetallic compounds have been reported.…”