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Unlocking Biomolecule Modification with Light‐Promoted Photocatalyst‐Free Approaches: Current Tools, Challenges, and Perspectives

Year: 2025

Type: article

Abstract: Bioconjugation has emerged as a powerful tool in modern chemical biology for creating new molecules with applications in both research and therapeutics. The modification of biomacromolecules—such as proteins, peptides, nucleic acids, carbohydrates, and related biomolecules—contributes to various fields, including biochemistry and materials science, with relevance to the development of biopharmaceuticals, such as antibody–drug conjugates. Over the past two decades, there has been a growing interest in developing simpler, milder, site‐selective, and high‐yielding synthetic protocols. Among these, photoinduced methods stand out, as light is a sustainable energy source that enables the formation of highly reactive intermediates under mild reaction conditions, typically well tolerated in bioconjugation. In recent years, photocatalyzed light‐induced chemical processes have been extensively explored. However, reactions that proceed without external photocatalysts are especially appealing, particularly from economic and sustainability viewpoints. This Perspective article discusses the strategies developed over the past decade for photocatalyst‐free photoinduced bioconjugation, with special focus on the formation of electron‐donor/electron‐acceptor complexes. Both biomolecule synthesis and late‐stage functionalization will be addressed. Experimental limitations and the applicability of these protocols in biocompatible contexts will be evaluated. Beyond macromolecules, monomeric units, such as amino acids and nucleotides, are also considered.

Source: ChemistryEurope

DOI: 10.1002/ceur.202500284

Authors: Milene Hornink, Maria Eduarda C. Thedy, Eugénie Romero, Gary A. Molander