Fructose controlled ionophoric activity of a cholate-boronic acid.

Wulff-type boronic acids have been shown to act as ionophores at pH 8.2 by transporting Na(+) through phospholipid bilayers. A cholate-boronic acid conjugate was synthesised and shown to be an ionophore, although the hydroxyl-lined face of the cholate moiety did not enhance ion transport. Mechanistic studies suggested a carrier mechanism for Na(+) transport. The addition of fructose (>5 mM) strongly inhibited ionophoric activity of the cholate-boronic acid conjugate, mirrored by a strong decrease in the ability of this compound to partition into an organic phase. Modelling of the partitioning and ion transport data, using a fructose/boronic acid binding constant measured at pH 8.2, showed a good correlation with the extent of fructose/boronic acid complexation and suggested high polarity fructose/boronic acid complexes are poor ionophores. The sensitivity of ion transport to fructose implies that boronic acid-based antibiotic ionophores with activity modulated by polysaccharides in the surrounding environment may be accessible.

Pd(II)-mediated assembly of porphyrin channels in bilayer membranes.

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.