Expanded combinatorial formation of porphyrin macrocycles in aqueous solution containing vesicles. A prebiotic model

Abstract

The role of combinatorial processes in the origin of life remains relatively unexplored. In a chemical model for the possible prebiogenesis of tetrapyrrole macrocycles reported previously, a tandem combinatorial reaction of two diones (substituents = methyl, acetic acid) and two aminoketones (substituents = ethyl, propanoic acid) afforded up to 538 porphyrins (upon oxidation of the corresponding porphyrinogens). The reaction was performed at a 1 : 1 ratio of hydrophobic and hydrophilic substituents in each pool of reactants, and the resulting porphyrins partitioned in ∼1 : 1 ratio between aqueous solution and phosphatidylcholine vesicle membranes. Here, a change in the ratio of hydrophobic and hydrophilic substituents of the [2 × 2] reaction gave corresponding changes in the polarity profile of the resulting porphyrins (3.5–9.0% yield). Reaction of four diones and four aminoketones (bearing hydrophilic or hydrophobic substituents) in the presence of lipid vesicles followed by photooxidation afforded porphyrins in 8.7% yield. The resulting porphyrins partitioned in ∼1 : 1 ratio between phosphatidylcholine vesicles and aqueous solution, as observed previously for the [2 × 2] reaction. Both the aqueous fraction and the vesicles fraction were photochemically active as evidenced by the fluorescence quantum yield (Φf ∼ 0.1). Software (PorphyrinViLiGe) for virtual library generation indicates that the [4 × 4] reaction affords up to 131 464 porphyrins. The relative insensitivity of physicochemical properties (partitioning, photoactivity) toward combinatorial expansion may be a valuable yet unappreciated attribute for prebiotic functionality.