Why Nature Chose Phosphates

TLDR

Phosphate esters and anhydrides are ubiquitous in biology, serving roles in nucleic acids, metabolism, and energy transfer, but their negative charge and stability make them poorly reactive intermediates for organic chemists, who rely on more reactive species. The authors propose that multiply charged phosphates react via the monomeric metaphosphate ion PO₃⁻ as an intermediate. The study concludes that no other residue matches phosphate’s multifunctional role in biochemistry.

Abstract

Phosphate esters and anhydrides dominate the living world but are seldom used as intermediates by organic chemists. Phosphoric acid is specially adapted for its role in nucleic acids because it can link two nucleotides and still ionize; the resulting negative charge serves both to stabilize the diesters against hydrolysis and to retain the molecules within a lipid membrane. A similar explanation for stability and retention also holds for phosphates that are intermediary metabolites and for phosphates that serve as energy sources. Phosphates with multiple negative charges can react by way of the monomeric metaphosphate ion PO3- as an intermediate. No other residue appears to fulfill the multiple roles of phosphate in biochemistry. Stable, negatively charged phosphates react under catalysis by enzymes; organic chemists, who can only rarely use enzymatic catalysis for their reactions, need more highly reactive intermediates than phosphates.