Synthesis and characterization of ruthenocene-containing complexes with biomedical applications

Abstract

Polysuccinimide was modified by reactions with aminopropyl morpholine and ethylenediamine to give a water-soluble biodegradable polymeric drug carrier. Ruthenocene has been functionalized in sixteen different reactions to ultimately give four ruthenocene-containing carboxylic acids of the form Rc(CH2)nCOOH (n = 0 – 3). These were covalently anchored to the amino-terminated side chains of the polyaspartamide carrier polymer utilizing the coupling agent O-benzotriazolyl-N,N,N’N’–tetramethyluronium hexafluorophosphate. These four new ruthenocene-polymer conjugates represent the first water-soluble ruthenocene peptide macromolecular conjugates ever made. XPS, 1H NMR spectroscopy and elemental analysis aided the characterisation of the new ruthenocene-containing polymers. A cyclic voltammetry study of all the ruthenocene-containing carboxylic acids in CH2Cl2/0.1 M [NBu4][B(C6F5)4] were carried out. Despite the use of this non-coordinating solvent/electrolyte system, none of the ruthenocene-containing carboxylic acids exhibited a chemical reversible Rc/Rc+ redox couple. The formal oxidation potentials of the free carboxylic acids were Eo = 776, 484, 494 and 516 mV vs. FcH/FcH+ for the acids containing zero, one, two and three CH2 spacer units between the ruthenocenyl and COOH functional groups respectively. One CH2 group was enough to eliminate any communication between these two functional groups. Electrochemistry in aqueous media was conducted on the ruthenocene-containing polymers. The oxidation potential of the polymer bound ruthenocene moiety ranged between 397 ≤ Epa ≤ 631 mV, with the latter, highest, oxidation potential belonging to the compound having no separator CH2 groups between the ruthenocenyl and CONH functional groups.