Role of Acid in the Co-oligomerization of Formaldehyde and Pyrrole

[Image: see text] Building on previous work (J. Phys. Chem. A2017,121, 8154–8166) under neutral conditions, we examined the co-oligomerization of CH(2)O and pyrrole to form porphryinogen under acidic conditions using density functional theory (B3LYP//6-311G**). Thermodynamically, we found that azafulvene intermediates were significantly stabilized under highly acidic conditions. Kinetically, energy barriers were lowered for C–C bond formation, discriminating in favor of reactions that lead to porphyrinogen. However, it was challenging to satisfactorily combine our thermodynamic and kinetic profiles into a unified free-energy profile because of difficulties in optimizing transition states of cationic species involving proton hops. Instead, we used neutral carboxylic acids as a proxy to study how energy barriers changed. By combining data from both neutral and acidic conditions, we estimate a free-energy profile for the initial steps of oligomerization under milder acidic conditions more relevant to prebiotic chemistry.