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DNA/RNA synthesis precursors are especially vulnerable to damage induced byreactive oxygen species occurring following oxidative stress. Guanosinetriphosphates are the prevalent oxidized nucleosites, which can bemisincorporated during replication, leading to mutations and cell death. Here,we present a novel method based on micro-Raman spectroscopy, combined with abinitio calculations, for the identification, detection, and quantification oflow concentrations of oxidized nucleotides. We also show that the Ramansignature in the terahertz spectral range (< 100 cm$^{-1}$) containsinformation on the intermolecular assembly of guanine in tetrads, which allowsto further boost the oxidative damage detection limit. Eventually, we provideevidence that similar analyses can be carried out on samples in very smallvolumes at very low concentrations by exploiting the high sensitivity ofSurface Enhanced Raman Scattering combined with properly designedsuperhydrophobic substrates. These results pave the way for employing suchadvanced spectroscopic methods for quantitatively sensing the oxidative damageof nucleotides in the cell.

analytical chemistry

Advanced Raman spectroscopy detection of oxidative damage in nucleic  acid bases: probing chemical changes and intermolecular interactions in  guanosine at ultralow concentration