Dimetallic functionalities in liposome bilayers

A dicopper(II) complex can be covalently linked to palmitate/palmitoyl-oleoyl-phosphatidylcholine (PA/POPC) liposomes using the following one-pot strategy: preformed [Cu ₂(bpbp)(PA)](ClO ₄) ₂ (bpbp ^- = 2,6-bis((N,N′-bis(2-picolyl)amino)methyl)-4-tertbutylphenolato) was incorporated into POPC liposomes with a loading of up to 10 mol%. Despite its shape and charge, the decoration of PA/POPC liposomes with {Cu ₂(bpbp)} ³⁺ did not disrupt the liposome structure; however, the mean liposome diameter increased from about 130 nm (0 mol% dicopper complex) to about 150 nm (10 mol% dicopper complex). Single-crystal X-ray structures furnish snapshots of the pH-dependent solution state derivatives of {Cu ₂(bpbp)} ³⁺, and model the structure of the [Cu ₂(bpbp)(PA)] ²⁺ head group at the surface of the liposomes. An impressive plasticity in the intramolecular non-bonded Cu.Cu distance for these ions, ranging from 3 to 4 Å, in [Cu ₂(bpbp)OH] ²⁺, [Cu ₂(bpbp)(OAc)(H ₂O)] ²⁺ and [Cu ₂(bpbp)(H ₂O) ₂] ³⁺ allows for their utility as labile reagents in water. Remarkably, the flexible dicopper site is selective for a single carboxylate ligand, so that [Cu ₂(bpbp)(PA)] ²⁺ is favoured even in the presence of other chemically similar oxoanions, such as CO ₃ ^2-, HCO ₃ ^-, NO ₃ ^-, ClO ₄ ^-, ReO ₄ ^- and CF ₃SO ₃ ^-.