Molecular designs with PEG groups for water-solubilization of sparsely substituted porphyrins

Abstract

Molecular designs that achieve solubility of porphyrins in aqueous media are attractive for diverse applications. The presence of 4-sulfophenyl or 4-N-methylpyridinium groups at the four meso-positions is effective, but the use of fewer substituents is desirable for custom tailoring. Here, five target porphyrins (along with selected copper or zinc chelates) were prepared bearing PEG groups to understand how distinct designs affect aqueous solubility (where “PEG” refers to an oligoethylene glycol unit). One objective was to employ only one or two pegylated meso-aryl groups so that other meso-positions would be open for synthetic elaboration while retaining a compact structure. The key design features examined include (i) 2,6- versus 3,5-dipegylated aryl groups; (ii) one versus two 2,6-dipegylated aryl groups; (iii) a nonpolar versus ionizable terminus of the PEG moiety; and (iv) length of the PEG moiety. In each case, the PEG groups were attached on a porphyrin scaffold bearing one or two bis(2-propynyloxy)aryl groups. Assessment entailed octanol–aqueous solution partitioning (log P values) and aggregation over the concentration range of 0.2–200 μM. A trans-A₂ free base porphyrin bearing two 2,6-dialkoxyphenyl groups equipped with methyl-terminated PEG₆ groups gave ∼3 : 1 partitioning in water versus octanol but high overall solubility (at least 12 mM) in water alone; the analogous porphyrin with carboxylic acid-terminated PEG₆ groups gave >100 : 1 partitioning in phosphate-buffered saline (PBS, pH 7.4). A trans-AB porphyrin bearing a single 2,6-dialkoxyphenyl group equipped with carboxylic acid-terminated PEG₆ groups gave 43 : 1 partitioning in PBS versus octanol but was prone to self-aggregation at 20–200 μM in PBS alone. The results point to new molecular designs of potential value in the life sciences.