Catalytic diversification upon metal scavenging in a prebiotic model for formation of tetrapyrrole macrocycles

Abstract

A prebiotic model for the formation of tetrapyrrole macrocycles was examined in aqueous solution containing representative Earth-available metals [Mg(II), Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II) and Pd(II)]. First, a hydrophilic porphyrin (uroporphyrin I) was found to undergo metalation with all metals examined except Mg(II). Second, a competition experiment among the eight metals with uroporphyrin in limiting quantity afforded preferential metalation with Mn(II), Co(II), Cu(II) and Ni(II). A multicomponent analysis method enabled absorption spectrophotometric detection of 8 distinct uroporphyrins (7 metallo-, 1 free base) in a single mixture. Third, a dione–aminoketone reaction was performed in aqueous solution containing the metals followed by photooxidation in the presence of a quinone. The reaction proceeds through multiple stages: (1) dione–aminoketone condensation to give a pyrrole equipped for self-condensation, (2) tetramerization of the pyrrole and cyclization to give uroporphyrinogens, (3) 6e⁻/6H⁺ dehydrogenation (e.g., photooxidation) to give the uroporphyrins, and (4) metalation of the uroporphyrins. The presence versus absence of metals resulted in lower yields, yet Mn(II), Fe(II), Co(II), Cu(II) and Zn(II) each individually gave the corresponding metallouroporphyrin [with trivalent metals observed in three cases: Mn(III), Fe(III), and Co(III)]. Analogous reaction in the presence of all eight metals together gave the free base, Mn(III), and Zn(II) chelates whereas other metal chelates could not be reliably detected by absorption spectroscopy or mass spectrometry. Such metalloporphyrins greatly broaden the accessible redox levels, catalytic avenues, and photochemical features versus those of the free base porphyrins. Taken together, scavenging of metals is expected to increase the functional diversity of tetrapyrroles on early Earth.