Vibrational Stark Effect Probes for Nucleic Acids

The vibrational Stark effect (VSE) has proven to be an effective method for the study of electric fields in proteins via the use of infrared probes. To explore the use of VSE in nucleic acids, we investigated the Stark spectroscopy of nine structurally diverse nucleosides. These nucleosides contained nitrile or azide probes in positions that correspond to both the major and minor grooves of DNA. The nitrile probes showed better characteristics and exhibited absorption frequencies over a broad range; that is, from 2253 cm-1 for 2‘-O-cyanoethyl ribonucleosides 8 and 9 to 2102 cm-1 for a 13C-labeled 5-thiocyanatomethyl-2‘-deoxyuridine 3c. The largest Stark tuning rate observed was |Δμ| = 1.1 cm-1/(MV/cm) for both 5-cyano-2‘-deoxyuridine 1 and N2-nitrile-2‘-deoxyguanosine 7. The latter is a particularly attractive probe because of its high extinction coefficient (ε = 412 M-1cm-1) and ease of incorporation into oligomers.