Transmembrane Chloride Transport by Diphosphine-Pd(II) Complexes: Effect of the Ligand Geometry

Transmembrane chloride transport is a fundamental biological process, and its impairment is at the origin of severe genetic diseases such as cystic fibrosis. Synthetic anion carriers able to transport chloride and other anions across biological membranes are considered as putative candidates for treating these syndromes. We have proposed diphosphine-Pd(II) complexes as a new class of anion carriers and in this contribution we have investigated the ionophoric activity of a family of Pd(II) complexes with diphosphine chelating ligands differing for the ligand bite angle that is varied from 71 degrees (dppm) to 98 degrees (dppb). Moreover, in the case of the dppe ligand we also investigated the effect of the introduction in the ligand structure of alkyl substituents of increasing length and hydrophobicity and of electron donor and withdrawing substituents. All the complexes investigated are able to transport chloride across the phospholipid membrane of liposomes and the most important parameter influencing their relative efficacy is the lipophilicity of the complex with the highest activity observed for [Pd(pEt-dppe)Cl-2]. On the contrary the bite angle of the ligand appears to be not relevant while the activity is diminished by the insertion of both EWG and EDG groups on the phenyl substituents of the phosphine ligands. Finally, also Ni(II) and Cu(I) complexes display ionophoric activity demonstrating that the transport ability of metal complexes is not limited to Pd(II) metal ion.