Water is essential for life as we know it, but it has paradoxically been considered inimical to the emergence of life. Proteins and nucleic acids have sustained evolution and life for billions of years, but both are condensation polymers, suggesting that their formation requires the elimination of water. This presents intrinsic challenges at the origins of life, including how condensation polymer synthesis can overcome the thermodynamic pressure of hydrolysis in water and how nucleophiles can kinetically outcompete water to yield condensation products. The answers to these questions lie in balancing thermodynamic activation and kinetic stability. For peptides, an effective strategy is to directly harness the energy trapped in prebiotic molecules, such as nitriles, and avoid the formation of fully hydrolysed monomers. In this Review, we discuss how chemical energy can be built into precursors, retained, and released selectively for polymer synthesis. Looking to the future, the outstanding goals include how nucleic acids can be synthesized, avoiding the formation of fully hydrolysed monomers and what caused information to flow from nucleic acids to proteins.
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