Prebiotic Roles of Formaldehyde as an Activating Agent and a Building Block in Solid-State Peptide Modification

Signal transduction by gaseous small molecules is an essential process in modern living systems, where the gasotransmitters relay cellular signals to bio(macro)molecules through covalent bond formation. However, the origin or a primordial version of such signaling events in abiotic worlds has been poorly understood to date. Through examination of chemical reactivities between formaldehyde and cyclic dipeptide/diketopiperazine derivatives in prebiotically relevant solid-state environments, this study demonstrates that the gaseous small molecule may serve not only as a mere building block for the abiotic construction of biomolecules but also as an activating agent that transforms the inert peptide into reactive, prebiotically important chemical species. In addition, superiority of solid-state reactions or mechanochemistry to solution-based reaction conditions described in this article may be an indication of potential significance of the mechanical force-induced chemistry for chemical evolution, in particular for abiotic emergence of polypeptides.