Thiolato-bridged dinuclear arene ruthenium complexes and their potential as anticancer drugs

• The discovery and synthesis of thiolato bridged dinuclear arene ruthenium complexes are described and discussed.
• The complexes can be obtained as mono-, di-, or trithiolato complexes.
• Trithiolato complexes are among the most cytotoxic ruthenium ever reported.
• One trithiolato complex, diruthenium-1, significantly prolongs the survival of tumor-bearing mice.
• Trithiolato complexes do not hydrolyze and remain inert toward amino acids, proteins, and nucleotides.
• Conjugation to various biological active moieties is expected to increase their and cellular uptake and selectivity.

Water-soluble arene ruthenium complexes have been intensively studied as cytotoxic compounds for the last fifteen years, notably owing to the promising in vitro and in vivo evaluations of, respectively, RAPTA-C (η6-p-MeC6H4Pri)Ru(P-pta)Cl2 (pta = 1,3,5-triaza-7-phospha-tricyclo-[3.3.1.1]decane) from Dyson's laboratory, and the (η6-arene)Ru(en)Cl]+ (en = ethylenediamine, RAED) family of compounds from Sadler's laboratory. In this account we describe the discovery of thiolato-bridged dinuclear arene ruthenium complexes and highlight subsequent developments in the field, including their syntheses, structures, and the recent strategies for the design of thiolato-bridged dinuclear arene ruthenium bioconjugates.

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