  DNA/RNA synthesis precursors are especially vulnerable to damage induced by
reactive oxygen species occurring following oxidative stress. Guanosine
triphosphates are the prevalent oxidized nucleosites, which can be
misincorporated during replication, leading to mutations and cell death. Here,
we present a novel method based on micro-Raman spectroscopy, combined with ab
initio calculations, for the identification, detection, and quantification of
low concentrations of oxidized nucleotides. We also show that the Raman
signature in the terahertz spectral range (< 100 cm$^{-1}$) contains
information on the intermolecular assembly of guanine in tetrads, which allows
to further boost the oxidative damage detection limit. Eventually, we provide
evidence that similar analyses can be carried out on samples in very small
volumes at very low concentrations by exploiting the high sensitivity of
Surface Enhanced Raman Scattering combined with properly designed
superhydrophobic substrates. These results pave the way for employing such
advanced spectroscopic methods for quantitatively sensing the oxidative damage
of nucleotides in the cell.
