Thermodynamic Constraints on Glycerol-Based Proto-Nucleotides: Phosphate Versus Arsenate in Early Backbone Evolution

Area of Science:

• Astrobiology
• Origin of Life Research
• Computational Chemistry

Background:

• The formation of RNA and DNA required prebiotic nucleoside and nucleotide synthesis.
• The ribose-phosphate backbone of RNA/DNA is unstable in water, suggesting simpler precursors may have existed.

Purpose of the Study:

• To investigate the thermodynamic feasibility of glycerol-based nucleosides and nucleotides as potential proto-nucleic acid building blocks.
• To compare two distinct assembly pathways for these glycerol-based molecules.
• To assess the energetic viability of arsenate as a phosphate substitute.

Main Methods:

• Utilized semiempirical prescreening and density functional theory (DFT) calculations.
• Evaluated Gibbs free energy for glycerol-based nucleoside and nucleotide formation.
• Examined two assembly pathways: classic (glycerol-linker-base) and alternative (glycerol-base-linker).

Main Results:

• Glycerol-derived nucleosides and nucleotides are thermodynamically favorable in both vacuum and aqueous solutions.
• The classic assembly pathway is more favorable for nucleotide formation than the alternative.
• Arsenate substitution for phosphate shows minor energetic differences but suggests a less stable backbone, implying hydrolytic disadvantages.

Conclusions:

• Glycerol-based backbones are plausible candidates for early proto-nucleic acid chemistry.
• Phosphate's selection over arsenate may be due to greater kinetic persistence and hydrolytic stability, not thermodynamic instability.
• These findings provide insights into the chemical evolution leading to modern nucleic acids.