Selective Photocatalytic C‐H oxidation of 5‐methylcytosine in DNA

Selective C‐H activation on complex biological macromolecules is a key goal in the field of organic chemistry. It requires thermodynamically challenging chemical transformations to be delivered in mild, aqueous conditions. 5‐Methylcytosine (5mC) is a fundamentally important epigenetic modification in DNA that has major implications for biology and has emerged as a vital biomarker. Selective functionalisation of 5mC would enable new chemical approaches to tag, detect and map DNA methylation to enhance the study and exploitation of this epigenetic feature. We demonstrate the first example of direct and selective chemical oxidation of 5mC to 5‐formylcytosine (5fC) in DNA, employing a photocatalytic system. This transformation was used to selectively tag 5mC. We also provide proof‐of‐concept for deploying this chemistry for single‐base resolution sequencing of 5mC and genetic bases adenine (A), cytosine (C), guanine (G), thymine (T) in DNA on a next‐generation sequencing system. This work exemplifies how photocatalysis has the potential to transform the analysis of DNA.