Pd(II)-Mediated Assembly of Porphyrin Channels in Bilayer Membranes

Abstract

A membrane-spanning bis(meso-3-pyridyl) porphyrin 1 has been synthesized, embedded in EYPC vesicles, and upon Pd(II) addition has been shown to form ionophores that allow the passage of anionic 5/6-carboxyfluorescein through membranes. The geometric matching of bis(meso-3-pyridyl) porphyrin 1 and trans-Pd(II) was designed to give a cyclic porphyrin trimer [PdCl(2)(1)](3). However, solution-phase studies showed that PdCl(2)(PhCN)(2) cross linked 1 into linear oligomers at porphyrin concentrations above 10 mM, although the formation of cyclic species was inferred from studies at concentrations below 2 μM. Fluorescence titrations showed that embedding porphyrin 1 in bilayers greatly reduced its affinity for Pd(II), but the combination of porphyrin 1 and Pd(II) gave an ionophoric species that increased the rate of 5/6-carboxyfluorescein (5/6-CF) transit through the phospholipid bilayer 12-fold. A maximum in the 5/6-CF release rate was observed at a Pd(II) concentration of 4 μM, and the application of a solution-phase binding model to the membrane phase showed that this peak in ionophoric activity corresponded to the greatest extent of porphyrin oligomerization. Further studies suggested these Pd(II)/porphyrin oligomers transported 5/6-CF via a channel mechanism.

Biomembrane Interactions of Functionalized Cryptophane‐A: Combined Fluorescence and 129Xe NMR Studies of a Bimodal Contrast Agent

“…A 2–4‐fold higher partitioning coefficient for the liquid‐crystalline phase indicated a preferential partitioning compared with the solid‐ordered phase, in which phospholipid alkyl tails are closely packed such that compounds are expelled from the membrane 43. 44 Interestingly, the partitioning coefficient for DPPC, which contains exclusively saturated fatty acid side chains, is much higher than for EYPC and POPC, which have both saturated and unsaturated fatty acid side chains. We presume that some of these trends can be rationalized by interplay of the penetration depth of the conjugate and the thickness of the bilayer.…”

Supramolecular Chemistry in the Biomembrane

“…In a parallel work, Webb and co‐workers synthesized bis‐5,15‐( meso ‐3‐pyridyl)porphyrin 23 , which was long enough to span the lipid bilayer membrane and self‐assemble into various oligomers in the presence of Pd II in solution . Transport experiments indeed showed dye efflux from carboxyfluorescein (CF)‐loaded vesicles, but not from vesicles containing fluorescein isothiocyanate–dextran.…”

“…In a parallel work, Webb and co-workers synthesized bis-5,15-(meso-3-pyridyl)porphyrin 23, which was long enough to span the lipid bilayer membrane and self-assemble into various oligomers in the presence of Pd II in solution. [53] Transport experiments indeed showed dye efflux from carboxyfluorescein (CF)-loaded vesicles, but not from vesicles containing fluores-cein isothiocyanate-dextran. This suggested that some of the oligomers might represent supramolecular boxes with cavities large enough to allow transport of species larger than that of metal ions (Figure 12).…”

Supramolecular Approaches to Combining Membrane Transport with Adhesion

“…To this end porphyrin 1 was synthesized, with the aim of adding adhesive groups after ester hydrolysis. 20 …”