Designer ligands. Part 12.¹ Synthesis and evaluation of novel palladium(II)–selective ligand systems

Abstract

The discovery of the anti-tumour platinum complexes, cisplatin 2 and carboplatin 3 has highlighted the potential of platinum-selective ligands in medicine -not only as anti-cancer agents, but also as "rescue agents" to remove the nephrotoxic platinum from the body. 4 Apparently, platinum is complexed by sulfur-rich proteins and enzymes in the kidney, and various sulfur-containing amide ligands have been developed to remove platinum from such biomolecules. 4 Separation of the valuable platinum group metals (PGM) from base metals, such as iron, copper, nickel and cobalt, 5 is also typically achieved by solvent extraction, using PGM-selective ligands. Our own research on metal-selective ligands has been concerned with the development of systems capable of selectively chelating nickel, 6 copper, 7 silver, 8 or platinum group metals 9,10 in the presence of specified metal contaminants. In this communication, we discuss: the synthesis of novel ligands; the development of molecularly imprinted polymers (MIPs); and an evaluation of their PGM extraction potential.Desirable ligand-design criteria for the solvent extraction of metal ions include: solubility in organic solvents; ready synthesis; and cost effectiveness -criteria, which we hoped would be reflected in the ligand systems targeted in this study. The ligands 1 and 2 were also designed to incorporate several important structural features, viz., S-and N-donor atoms for metal chelation; an aromatic ring to increase lipophilicity; an amide function for platinum and palladium selectivity; substituents (R) to fine-tune N-donor capacity; and additional sulfur donors for multidentate coordination with the metal centre. Results and discussion Ligand synthesisSynthesis of the known ligands 1 11 and the novel analogues 2 involved two phases, viz., formation of the monomeric mercaptoacetanilides 5a-f (Scheme 1) and their subsequent condensation with the 1,2-dibromoethane or 1,3-dibromopropane. The mercaptoacetanilides 5a-f were obtained in 40-60% yield (following recrystallisation) by heating 1:1 mixtures of mercaptoacetic acid 3 with the corresponding anilines 4a-f under a gentle stream of dry nitrogen gas. 11,12 While oxidation to the disulfides was normally obviated under these conditions, use of 1-naphthylamine 4g resulted in the formation of the disulfide 6g as the sole product. 13 In the second phase, the mercaptoacetanilides 5a-f were coupled with 1,2-dibromoethane or 1,3-dibromopropane in methanolic potassium hydroxide. Recrystallisation from ethanol or, in some cases, flash chromatography and recrystallisation generally afforded the diamides 1a-f and 2a-f in reasonable yields (30-60%).Molecularly imprinted polymers (MIPs) have found use in separation methodology, 14 and as drug−receptor-binding 15 and antibody-binding 16 mimics. Moreover, as heterogeneous metalselective extractants, 17 they offer significant potential advantages over the use of classical homogeneous systems, in that separation of the metal may be effected directly from aqueous solution without resort...

Molecular imprinting science and technology: a survey of the literature for the years 2004-2011

“…This may rightly be deemed a daunting task. Nonetheless, MIP‐based catalytic systems and the use of MIPs in synthesis continue to evolve . Recent reports of several systems with significant catalytic power bodes well for the continued development in this sector.…”

Designer ligands: The search for metal ion selectivity

“…Preliminary solvent extraction studies 24 using some of these and other related ligands indicated, in general, significant selectivity for palladium(II) over copper(II), nickel(II) and cobalt(II) and, in subsequent studies, 25 attention was given to the application of MIP technology in the construction of PGMselective MIPs (Scheme 4).…”