Paley's watchmaker analogy and prebiotic synthetic chemistry in surfactant assemblies. Formaldehyde scavenging by pyrroles leading to porphyrins as a case study

Abstract

The formation of elaborate molecules is regarded as an essential first step in prebiotic chemistry, but how such transformations could spontaneously occur, particularly in dilute aqueous conditions, remains poorly understood. Here, micromolar concentrations of a 3,4-dialkylpyrrole and excess formaldehyde in aqueous micellar solution (pH 7) at 25 or 50 °C were found to give good yield (up to 40%) of the lipophilic octaalkylporphyrin. The reaction occurs despite a mean occupancy number of ∼0.1 pyrrole molecules/micelle, and <1 of 10,000 micelles initially containing the requisite 4 pyrrole molecules to form the porphyrin assuming a (random) Poisson distribution. Yields of up to 13% were observed in large, unilamellar phosphatidylcholine vesicles, wherein there are ∼15,000 pyrrole molecules per vesicle membrane. Double-labeling crossover experiments (of 3,4-diethylpyrrole and 3,4-dimethylpyrrole) examined by mass spectrometry revealed facile exchange processes of reactive constituents among both micelle and vesicle surfactant assemblies. Together, the exchange of pyrrolic reactants among micelles and the thermodynamic driving force for tetrapyrrole formation overcome the apparent statistical odds against reaction. The fruitful exchange, accumulation and reaction of minute quantities of reactants in aqueous-surfactant assemblies suggest a general means for formation of prebiotically valuable constituents, even when the statistical odds at the outset are overwhelmingly improbable.

Porphinogen Formation from the Co-Oligomerization of Formaldehyde and Pyrrole: Free Energy Pathways

“…To simulate milder conditions (neutral pH) and plausibly lower concentrations (μM) of reactants, Lindsey and co-workers added micelles/vesicles to neutral solutions of formaldehyde and an alkylpyrrole, thereby synthesizing porphyrins in up to 40% yield. 4 The simplest porphyrin that can be formed from the cooligomerization of formaldehyde and unsubstituted pyrrole is porphin, C 20 H 14 N 4 (Figure 1, left). The first synthesis of porphin from these starting materials was reported by Rothemund in 1935.…”

Chlorophyll-Inspired Red-Region Fluorophores: Building Block Synthesis and Studies in Aqueous Media

“…Inspection shows that most micelles are empty, and among those that contain a chlorin, relatively few (1.8% or 3.2% for H 2 C3 or H 2 C6 , respectively) contain more than one chlorin. Prior treatments of Poissonian distributions of tetrapyrroles in micelles include bacteriochlorophyll a [ 53 ] or chlorophyll a [ 54 ] in Triton-X100 micelles; octaalkylporphyrins in cetyl trimethylammonium chloride or sodium dodecyl sulfate (SDS) [ 55 ]; chlorophyll a (and derivatives thereof) [ 56 ] in Triton-X100, sodium bis(2-ethylhexyl)sufosuccinate (AOT) or SDS [ 57 ]; and synthetic chlorins and bacteriochlorins in Triton-X100, CTAB or SDS [ 13 ]. The topic of porphyrins in membranes has been reviewed [ 58 , 59 ].…”

“…The distributions of tetrapyrroles in micelles should not be regarded as static, given that hydrophobic solutes typically undergo extensive exchange among micelles; for example, substrates such as dodecylpyrene undergo extensive exchange in minutes–hours among SDS micelles [ 60 ]. The exchange of solutes between micelles [ 55 , 61 , 62 , 63 , 64 , 65 ] can entail exchange through the aqueous solution, fusion–fission of micelles, and/or micellar fission. The prevalence of a given mechanism depends on the micellar surface charge, aqueous ionic strength, and solute polarity.…”

Carbon dioxide photoreduction in prebiotic environments

“…Vesicles could be used as microreactors to drive a chemical evolution. Moreover, their synthesis could require formaldehyde [40], that is achievable through the reduction of carbon dioxide.…”