On-surface polymerization of natural amino acids: substrate engineering and monomer design

Poly(amino acids), protein analogues with amide backbones, have garnered wide attention due to their biodegradability and tunable physicochemical properties. However, the absence of an efficient polymerization strategy that combines simplified procedures with kinetic control for synthesizing poly(amino acids) remains a critical technical bottleneck, hindering their practical applications in advanced materials science. On-surface synthesis under ultra-high vacuum (UHV) conditions emerges as a promising avenue to overcome these challenges. In this review, we systematically review the design of monomers, synthetic methodologies, and network structures of surface-confined polyamides, emphasizing the pivotal roles of substrate engineering and monomer design in governing polymerization outcomes. We first elucidate the formation of surface-confined amide bonds and polyamide chains on noble metal substrates, involving acyl chloride-amine coupling for constructing one-dimensional linear polyamides and two-dimensional (2D) porous polyamide networks, and direct dehydration condensation of carboxyl and amino species. Additionally, we explore oligomerization pathways of natural amino acids, exemplified by the nickel-catalyzed formation of oligoprolines on the Au(111) surface. Looking forward, we propose that 2D materials, featuring tunable phase structures and versatile electronic properties, offer a transformative alternative to conventional metal substrates with limited modifiability. Meanwhile, natural amino acids, endowed with diverse functional side groups, present unique opportunities for synthesizing structurally complex polymer networks. By synergistically optimizing substrate properties and monomer structures, and harnessing advanced surface synthesis techniques, we aim to establish robust strategies for the substrate-confined catalytic precision synthesis of poly(amino acids). These advances are anticipated to unlock innovative applications in molecular electronics, nanoscale templating, and bio-inspired functional materials.