Non-enzymatic ribonucleotide reduction in the prebiotic context.

Area of Science:

• Astrobiology
• Prebiotic Chemistry
• Computational Chemistry

Background:

• Prebiotic chemistry models explain RNA and protein precursor formation, but not DNA precursors.
• Deoxynucleotides, DNA's building blocks, are currently synthesized via enzymatic reduction of ribonucleotides.
• Ribonucleotide reductases, the enzymes involved, are radical enzymes, suggesting radical-based prebiotic pathways may exist.

Purpose of the Study:

• To investigate potential non-enzymatic prebiotic routes for deoxynucleotide formation.
• To explore radical-mediated mechanisms for ribonucleotide reduction in a prebiotic environment.
• To characterize the energetics of proposed non-enzymatic pathways using computational chemistry.

Main Methods:

• Computational chemistry was employed to model reaction mechanisms.
• Several potential non-enzymatic pathways for ribonucleotide reduction were characterized.
• The study focused on a putative hydrogen sulfide (H2S)/hydrosulfuryl radical (HS(.) ) environment.

Main Results:

• A bio-inspired mechanistic cycle involving a keto intermediate and disulfide (HSSH) production was found to be potentially viable.
• An alternative pathway via an enol intermediate showed similar energetic requirements.
• Non-cyclical pathways generating the HSS(.) radical demonstrated a significantly increased thermodynamic driving force (approx. 70 kJ/mol).

Conclusions:

• Non-enzymatic pathways, particularly those involving radical intermediates and hydrogen sulfide, offer plausible routes for prebiotic deoxynucleotide synthesis.
• The increased thermodynamic favorability of non-cyclical pathways warrants further investigation for early Earth chemistry.
• These findings contribute to understanding the origins of DNA building blocks in the absence of complex enzymes.