Cytosine (Cyt) exhibits a short S₁ excited state lifetime of ~120 ps upon UV photoexcitation to its 0-0 band. Increasing the vibrational energy in the S₁ state rapidly decreases the lifetime to <1 ps. Studying cytosine derivatives allows to unravel the mechanism responsible for this fast deactivation. We have measured the supersonic jet-cooled S₀  S₁ vibronic spectra [1] of Cyt, 5-methylcytosine (5MCyt) and 5-fluorocytosine (5FCyt). 5FCyt, which is better known under its trade name "flucytosine" is an anti-tumor prodrug and a systemic antifungal drug [2,3].
The bands in the n₁ and n₂ low-frequency out-of-plane vibrations of 5MCyt and 5FCyt extend to an excess vibrational energy that is 2 - 5 times higher than for cytosine. This implies (1) that n₁ and n₂ are the promoting modes for the S₁  S₀ internal conversion in Cyt and (2) that substitution at the C-5 position may slow down this process by orders of magnitude.

This work was carried out by Simon Lobsiger, Maria Trachsel and Takuya Den in the group of Prof. Samuel Leutwyler.

References:

1. S. Lobsiger, M. Trachsel, S. T. Den, T. Schär, S. Leutwyler;
   to be published.
2. A. Vermes, H.-J. Guchelaar, J. Dankert;
   "Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions"
   J. Antimicrob. Chemother., 46, 171-179, (2000); doi:10.1093/jac/46.2.171.
3. P. D. Boucher, M. M. Im, S. O. Freytag, D. S. Shewach;
   "A Novel Mechanism of Synergistic Cytotoxicity with 5-Fluorocytosine and Ganciclovir in Double Suicide Gene Therapy"
   Cancer Res., 66, 3230-3237, (2006); doi:10.1158/0008-5472.CAN-05-3033.