Significant impacts of metal ions from ancient oceans on nucleoside phosphorylation

Nucleotides, such as 5'-AMP and ATP, are essential biomolecules in modern organisms. The phosphorylation of nucleosides to generate nucleotides occurs in complex prebiotic environments, where metal ions played a pivotal role, particularly in the metal-rich ancient oceans. Investigating the impact of prebiotic metal ions on nucleotide formation is critical to understanding their contributions to chemical evolution. Herein, we examined adenosine phosphorylation in the presence of various metal ions (Mn²⁺, Fe²⁺, Fe³⁺, Co²⁺, Ni²⁺, and Mg²⁺) under wet-dry cycling conditions. The results reveal that these systems can produce 5'-AMP, 2'/3'-AMP, 2',3'-cAMP, ADP, ATP, c-di-AMP, and the oligomeric nucleotide pApA. The yields of these nucleotides varied depending on the metal ions present and were lower than in the metal-free system. The concentrations and combinations of metal ions in a solution markedly impact the levels of nucleotides. Notably, 5'-AMP emerged as the dominant product, exhibiting high 5'-regioselectivity, strongly supporting the RNA world hypothesis. Moreover, Co²⁺ and Ni²⁺ enhanced nucleotide cyclization, while iron proved crucial for oligonucleotide formation. Intriguingly, hydrolysis experiments revealed nucleotides interconversion. Furthermore, metal accelerated hydrolysis of nucleotides compared to the metal-free system, directly impacting the efficiency and final yield of nucleoside phosphorylation. These findings underscore the multifaced role of metal ions in regulating phosphorylation, facilitating hydrolysis, and promoting nucleotides interconversion, thereby advancing our understanding of prebiotic chemical evolution and providing empirical support for environments rich in metals, as plausible settings for the emergence of primordial RNA-based life.