Radiolysis in drug discovery: molecular modification, repurposing, and mechanistic insights.

INTRODUCTION: In drug discovery, exploring novel chemical space and elucidating precise molecular mechanisms are essential for successful lead identification. Radiation chemistry offers a highly versatile approach that spans both structural modification and mechanistic analysis. AREAS COVERED: This review examines gamma radiolysis as a robust engine for diversity-oriented molecular modification and drug repurposing, facilitating the structural diversification of natural scaffolds and the optimization of existing therapeutics. Conversely, pulse radiolysis is discussed as a high-precision analytical technique capturing the real-time kinetics of transient radical intermediates to establish quantitative structure-activity relationships (QSAR). The literature search encompasses radiolytic transformations of natural products and mechanistic studies employing pulse radiolysis. The literature search (up to June 2026) was conducted via PubMed and Google Scholar using keywords such as 'radiolysis' and 'structural modification. EXPERT OPINION: Radiolytic technologies provide crucial mechanistic insights to support lead optimization and rapidly generate novel scaffolds. Future integration of these tools with high-throughput screening and predictive computational modeling (e.g. DFT and machine learning) will overcome traditional purification bottlenecks, transforming radiation chemistry into an automated, 'on-demand' discovery workflow that significantly accelerates the drug discovery pipeline.