The renaissance of metal -aminophenolates: From amphiphilic materials to antitumor drugs

Bidentate hydrophilic copper(II)-containing head groups with hydrophobic alkyl and alkoxo tails present a potential as precursors for redox-responsive Langmuir-Blodgett films. All systems were characterized by means of elemental, spectrometric, spectroscopic, and electrochemical techniques, and their amphiphilic properties were probed by means of compression isotherms and Brewster angle microscopy. Core flexibility improved Langmuir film formation resulting in a higher formal collapse pressure and showed excellent reversibility of the ligand-based processes.;Furthermore, the stabilization of a bivalent oxidation state in cobalt complexes of aminophenolate-based asymmetric tridentate ligands with iodo- and bromo-substituents is studied. The two synthesized complexes were characterized by means of several spectroscopic and spectrometric techniques. Both metallosurfactants exhibit amphiphilic properties and organization, as shown by compression isothems and Brewster angle microscopy, but exhibit dissimilar collapse mechanisms. Langmuir-Blodgett films are readily obtained and were characterized by equilibrium contact angle and atomic force microscopy.;In addition, various nickel(II), copper(II), and zinc(II) metallosurfactants were synthesized and characterized in an attempt to establish how coordination modes and protonation preferences relate to amphiphilic behavior. Careful choice of the metal ion leads to control of surfactant-to-metal ratio, selection of coordination modes and structural properties, and the understanding of the protonation preferences of the ligands.;Moreover, a general approach toward amphiphilic systems bearing multimetallic clusters and their ability to form Langmuir-Blodgett films is presented. The synthetic strategy to stabilize these clusters involves the use of a ligand containing an N2O-donor set and long octadecanoic chains to obtain carboxylate-supported complexes. These species were thoroughly characterized, and had their structures solved by X-ray crystallography. We describe the amphiphilic properties of the ligand and the cluster-containing systems by means of area vs. pressure isotherms and show that these cluster-bearing species can be transferred onto solid substrates yielding homogeneous Langmuir-Blodgett films, as characterized by atomic force microscopy and contact angle measurements. Furthermore, the amphiphilic properties are enhanced by varying the subphase conditions in a new generation of bi- and tetracupric species. These changes include temperature, pH, and incorporation of the coligand terephthalate ion.;Proteasomal inhibition and tumor cell apoptosis induction was observed when human C4-2B prostate cancer cells are treated with various nickel(II), copper(II), and zinc(II) metallodrugs. The chymotryspin-like activity is fourfold more potent than that recently reported by our group for gallium species and suggests the use of transition metal complexes that specifically target the proteasome as a novel route to anticancer therapy. A thorough study that encompasses the synthesis, spectrometric and spectroscopic characterization and pharmacological evaluation of a series of complexes was carried out.