Aqueous–membrane partitioning of β-substituted porphyrins encompassing diverse polarity

Abstract

Understanding the partitioning of organic molecules between aqueous solution and lipid membranes is critical to problems in fields ranging from drug design to environmental science to studies of the origin of life. Here, six β-substituted porphyrins of diverse polarity were examined for partitioning between the membranes of phosphatidylcholine vesicles and aqueous solution. The porphyrins include uroporphyrin I (number of carboxylic acid substituents = 8), heptacarboxylic acid porphyrin I (7), hexacarboxylic acid porphyrin I (6), coproporphyrin I (4), mesoporphyrin IX (2) and etioporphyrin I (0). The porphyrins were examined individually and collectively. In each case, size-exclusion chromatography was used to separate a porphyrins/vesicles fraction and a porphyrins/aqueous fraction. Each fraction was analyzed quantitatively by reversed-phase HPLC with fluorescence detection or by UV-Visible absorption spectroscopy to give partition coefficients. The partition coefficients for the six porphyrins also were calculated (clog P) using seven software programs: ACD/Labs, ALOGPS 2.1, Chemdraw, Molinspiration, KowWin, MarvinSketch, and XLOGP3. For perspective, clog P values for seven other porphyrins and 18 non-porphyrins also were calculated. Wide variation among programs was observed for almost all of the porphyrins and non-porphyrins of similar molecular weight. The dearth of porphyrins with requisite substituent patterns for experimental examination and the unreliability of calculation preclude definitive predictions concerning partitioning of unknown porphyrins; however, the results afford heuristics to predict aqueous–membrane partitioning of diverse β-substituted porphyrins.