We perform site-specific isotopic-edited IR experiments on TA-DNA. This is a well-studied duplex that is shown to form two tandem A-T Hoogsteen base pairs at positions T6 and A7 when a drug molecule, echinomycin, is intercalated into adjacent GC nucleobases at positions C4, G5, C8, & G9 (Figure ). We installed a single labeled T 13 C4=O into TA-DNA and extracted the frequencies of the individual TC4=O bond (Figure , S1). We preliminary assign these two major signals at 1720 cm -1 and 1670 cm -1 in the T C4 edited spectra to atomic displacements from in-phase TC4=O (1720 cm -1 ) and out-of-phase TC4=O (1670 cm -1 ) stretching. The major signal at 1720 cm -1 was previously assigned to the localized TC2=O; however, the observation of this signal in the T 13 C4 edited spectra indicates that there are contributions from the C4=O group during the vibration observed via isotope editing in the duplex (~25% by our calculation).