A direct comparison of azide and nitrile vibrational probes

Abstract

The synthesis of 2'-azido-5-cyano-2'-deoxyuridine, N(3)CNdU (1), from trityl-protected 2'-amino-2'-deoxyuridine was accomplished in four steps with a 12.5% overall yield. The IR absorption positions and profiles of the azide and nitrile group of N(3)CNdU were investigated in 14 different solvents and water/DMSO solvent mixtures. The azide probe was superior to the nitrile probe in terms of its extinction coefficient, which is 2-4 times larger. However, the nitrile IR absorbance profile is generally less complicated by accidental Fermi resonance. The IR frequencies of both probes undergo a substantial red shift upon going from water to aprotic solvents such as THF or DMSO. DFT calculations supported the hypothesis that the molecular origin of the higher observed frequency in water is primarily due to hydrogen bonds between the probes and water molecules.

Figure 1

FTIR absorbance spectra of N₃CNdU dissolved in water, tetrahydrofuran (THF), or methanol recorded at 293 K with a concentration of 50 mM. The maximum absorbance of each spectrum has been normalized to unity and the spectra have been offset for comparison.

Figure 2

A. FTIR absorbance spectra of N₃CNdU in water/DMSO mixtures ranging from 0 to 100% water in 12.5% increments recorded at 293 K with a concentration of 50 mM. The maximum absorbance of each spectrum has been normalized to unity and the spectra have been offset for comparison. B. Dependence of the position of maximum absorbance of the azide IR absorbance band on solvent composition. C. Dependence of the nitrile IR absorbance band position on solvent composition.

Scheme 1