Recognition‐Encoded Molecules: A Minimal Self‐Replicator

• Published in: Chemistry : a European journal 2024-12, Vol.30 (69), p.e202401667-n/a
• Main Authors: Rosa‐Gastaldo, Daniele, Maria Ara, Francesco, Dalla Valle, Andrea, Visentin, Giulia, Gabrielli, Luca
• Format: Article
• Language: English
• Subjects: Aldehydes; Aldehydes - chemistry; Aniline; Aniline Compounds - chemistry; Base Pairing; Chemical synthesis; Duplex; H-bonding; Hydrogen Bonding; Imines - chemistry; Kinetics; Nucleic acids; Nucleic Acids - chemistry; Oligoaniline; Oligonucleotides; Oligonucleotides - chemistry; Peptides; Phosphine; Phosphine oxide; Phosphines - chemistry; Recognition; Replication; Replication origins; Self-replicator
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202401667

Nucleic acids, with their unique duplex structure, which is key for information replication, have sparked interest in self‐replication's role in life's origins. Early template‐based replicators, initially built on short oligonucleotides, expanded to include peptides and synthetic molecules. We explore here the potential of a class of synthetic duplex‐forming oligoanilines, as self‐replicators. We have recently developed oligoanilines equipped with 2‐trifluoromethylphenol–phosphine oxide H‐bond base pairs and we investigate whether the imine formed between aniline and aldehyde complementary monomers can self‐replicate. Despite lacking a clear sigmoidal kinetic profile, control experiments with a methylated donor and a competitive inhibitor support self‐replication. Further investigations with the reduced aniline dimer demonstrate templated synthesis, revealing a characteristic parabolic growth. After showing sequence selective duplex formation, templated synthesis and the emergence of catalytic function, the self‐replication behaviour further suggests that the unique properties of nucleic acids can be paralleled by synthetic recognition‐encoded molecules. A minimal donor‐acceptor heterodimer, based on hydrogen bonding recognition, exhibits self‐replicating behaviour through imine formation between aniline and aldehyde complementary monomers. This further suggests that the unique properties of nucleic acids can be paralleled by synthetic recognition‐encoded molecules.