Although it is generally accepted that amino acids were present on the prebiotic Earth, the mechanism by which α-amino acids were condensed into polypeptides before the emergence of enzymes remains unsolved. Here, we demonstrate a prebiotically plausible mechanism for peptide (amide) bond formation that is enabled by α-hydroxy acids, which were likely present along with amino acids on the early Earth. Together, α-hydroxy acids and α-amino acids form depsipeptides—oligomers with a combination of ester and amide linkages—in model prebiotic reactions that are driven by wet–cool/dry–hot cycles. Through a combination of ester–amide bond exchange and ester bond hydrolysis, depsipeptides are enriched with amino acids over time. These results support a long-standing hypothesis that peptides might have arisen from ester-based precursors.

Biopolymers exist within living cells as far-fromequilibrium metastable polymers. Living systems must constantly invest energy for biopolymer synthesis. In the earliest stages of life on Earth, the complex molecular machinery that contemporary life employs for the synthesis and maintenance of polymers did not exist. Thus, a major question regarding the origin of life is how the first far-from-equilibrium polymers emerged from a prebiotic "pool" of monomers. Here, we describe a proof-of-principle system, in which L-malic acid monomers form far-from-equilibrium, metastable oligoesters via repeated, cyclic changes in hydration and temperature. Such cycles would have been associated with day−night and/or seasonal cycles on the early Earth. In our model system, sample heating, which promotes water evaporation and ester bond formation, drives polymerization. Even though periodic sample rehydration and heating in the hydrated state promotes ester bond hydrolysis, successive iterations of wet−dry cycles result in polymer yields and molecular weight distributions in excess of that observed after a single drying cycle. We term this phenomenon a "polymerization ratchet". We have quantitatively characterized the "ratchet" of our particular system. Ester bond formation rates and oligoester hydrolysis rates were determined for temperatures ranging from 60 to 95°C. Based on these rates, a mathematical model was developed using polycondensation kinetics, from which conditions were predicted for oligoester growth. This model was verified experimentally by the demonstration that L-malic acid monomers subjected to multiple wet−dry cycles form oligoesters, which reach a steady-state concentration and mean length after several cycles. The concentration of oligoesters that persist between subsequent steady-state cycles depends on the temperature and durations of the dry and wet phases of the cycle. These results provide insights regarding the potential for very simple systems to exhibit features that would have been necessary for initiation of polymer evolution, before the emergence of genomes or enzymes.

Hold the water! Deep‐eutectic solvents (DESs) are nonvolatile media suitable for a wide range of chemical reactions. The discovery that nucleic acids can form duplex, triplex, and G‐quadruplex structures (which in some cases differ from those adopted in aqueous media) in a water‐free DES (see picture) opens the enticing possibility that catalytic nucleic acids and enzyme–nucleic acid complexes could also be used in these solvents.

The RNA World hypothesis is central to many current theories regarding the origin and early evolution of life. However, the formation of RNA by plausible prebiotic reactions remains problematic. Formidable challenges include glycosidic bond formation between ribose and the canonical nucleobases, as well as the inability of nucleosides to mutually select their pairing partners from a complex mixture of other molecules prior to polymerization. Here we report a one-pot model prebiotic reaction between a pyrimidine nucleobase (2,4,6-triaminopyrimidine, TAP) and ribose, which produces TAP-ribose conjugates in high yield (60-90%). When cyanuric acid (CA), a plausible ancestral nucleobase, is mixed with a crude TAP+ribose reaction mixture, micrometer-length supramolecular, noncovalent assemblies are formed. A major product of the TAP+ribose reaction is a β-ribofuranoside of TAP, which we term TARC. This nucleoside is also shown to efficiently form supramolecular assemblies in water by pairing and stacking with CA. These results provide a proof-of-concept system demonstrating that several challenges associated with the prebiotic emergence of RNA, or pre-RNA polymers, may not be as problematic as widely believed.

Hydrogen cyanide polymerizes readily under a variety of conditions and significant prebiotic roles have been suggested for these polymers due to the abundance of HCN in universe. However, the structures of HCN polymers have been more speculative than grounded in experimental data. Here we show that 13 C and 15 N solid state NMR spectra of polymers formed in neat HCN are inconsistent with the previously proposed structures and suggest instead that the polymers are formed by simple monomer addition, first in head-to-tail fashion to form linear, conjugated chains, and then laterally to form saturated two-dimensional networks. This interpretation of the NMR spectra finds support in other information about the polymerization of neat HCN, including the presence of free radicals. As expected from the literature, formation of the HCN tetramer, diaminomaleonitrile, is also observed, but only when the reaction is catalyzed exclusively by base and then in crystalline form.