Chapter 3 - Phosphine–copper(I) complexes as anticancer agents: design, synthesis, and physicochemical characterization. Part I

Abstract

Copper complexes represent one of the prospective groups of metal-based drugs proposed as an alternative to platinum drugs in the treatment of cancer. Part I analyzes the route followed by our research group in the syntheses of hydrophilic phosphine–copper(I) complexes. Beyond classical characterization in the solid and solution states, additional physicochemical studies have established the thermodynamic stability of these complexes as copper(I) species in aqueous media. A class of homoleptic phosphine complexes of general formula [Cu(PR3)4]+ (PR3tertiary phosphine) has also disclosed intriguing kinetic lability. Hence, copper(I) can be transchelated from [Cu(PR3)n]+ inorganic scaffolds (n≤4) into amino-acidic sequences typical of copper transporters. Within this approach, we hypothesize that an amount of copper exceeding its normal homeostasis could be selectively loaded into tumor cells for antiproliferative purposes, whilst leaving unaffected nontumor cells.