Regioselective Oxidation Catalysis in Synthetic Phospholipid Vesicles. Membrane-Spanning Steroidal Metalloporphyrins

A membrane-spanning porphyrin has been synthesized by attaching four 3β-hydroxy-5-cholenic acid moieties to,β,α,β-meso-tetrakis(o-aminophenyl)porphyrin. The resulting steroidal porphyrin, H₂ChP, and the corresponding metalloporphyrins, MChP, were shown by gel permeation chromatography,³¹P NMR, and differential scanning calorimetry to intercalate into vesicle bilayers. The steroidal porphyrin was found to be in a well-defined and highly ordered microenvironment within the bilayer. The anisotropic ESR spectra of Cu¹¹(ChP) in orientated bilayer assemblies on Mylar film clearly indicated that the plane of the porphyrin ring was parallel to the plane defined by the bilayer-water interface. The porphyrin ring was also found to be in the middle of the bilayer with fluctuations of ±3-4 Å around the center. This was shown by use of tethered imidazole ligands of the general formula Im(CH₂)_nCOOH as molecular probes. Ligation to Co¹¹(ChP) could be monitored by ESR as a function of the length of the tethered ligand and conclusively demonstrated that only ligands where n > 6 were able to coordinate to the metal. Iron(III) and manganese(III) steroidal porphyrins were then used as regioselective epoxidation and hydroxylation catalysts. Diolefinic sterols were epoxidized exclusively at the side chain. Epoxidation of polyunsaturated fatty acids was preferred by a ratio of 2/1 at the more hydrophobic terminus and it was found that by increasing the rigidity of the bilayer by the addition of cholesterol the selectivity could be raised to 9/1. Finally, it was shown that cholesterol could be selectively hydroxylated at the C₂₅tertiary carbon.