Identification of methylated cytidines using terahertz spectroscopy

Abstract The potential role of terahertz (THz) spectroscopy in identifying and manipulating DNA methylation, a key cancer biomarker, is currently being debated. This study investigates the THz spectra of both methylated and demethylated cytidines to resolve this issue using quantum calculations. Our findings confirm that the methylation of cytidines can be identified by the spectral features in the THz region, which we attribute to the rotational motion of the methyl group. This result validates THz spectroscopy as a potential diagnostic tool for the early stage of cancer. However, the calculated bond dissociation energy for the demethylation C‐C bond is approximately 106.5 kcal/mol, which corresponds to several orders of magnitude higher than the energy of a single THz photon, making direct demethylation via a single‐photon process energetically unfeasible. Hence, we conclude that while THz spectroscopy is a promising tool for identifying the methylation of DNA, its proposed therapeutic application for inducing the demethylation of the 5‐methylcytidines is unlikely.