A Tandem Chemical Vapor Deposition Platform for the Solvent‐Free Synthesis of Polypeptide Architectures

The precise engineering of surfaces decorated with polypeptides is critical for advanced diagnostics, biomedical coatings, and cellular interfaces. However, conventional methods are plagued by the need for solvents, multistep procedures, substrate limitations, and the abundance of side reactions. Here, we report that two-step chemical vapor polymerization can result in the fast, efficient, and substrate-independent synthesis of polypeptide films without the use of solvents or excipients. The first step involves deposition of an initiator layer, i.e., poly(4-amino-p-xylylene), via chemical vapor deposition (CVD) polymerization of 4,16-diamino[2.2]paracyclophane. The second step involves evaporation and ring-opening polymerization of N-carboxy anhydrides. This fully integrated CVD approach ensures substrate-independent, conformal growth of poly(propargyl-(S)-glycine) and poly(O-propargyl-(S)-tyrosine) films of up to 198 nm thickness. The use of CVD processes eliminates the concern of side reactions, such as transfer and termination reactions, and is a prerequisite for the successful peptide micropatterning, demonstrated in this study. Successful peptide growth and post-polymerization modifications via click chemistry were confirmed by time-of-flight secondary mass spectrometry, x-ray photoelectron spectroscopy, and infrared spectroscopy. The application of entirely solvent-free workflows to develop biomacromolecular coatings, such as the polypeptide films demonstrated in this study, addresses a critical gap in the pursuit of advanced and scalable biologization methods.