Article pubs.acs.org/JACS
Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
The Photoaddition of a Psoralen to DNA Proceeds via the Triplet State Janina Diekmann,† Julia Gontcharov,‡ Sascha Fröbel,†,§ Christian Torres Ziegenbein,†,∥ Wolfgang Zinth,‡ and Peter Gilch*,† †
Institut für Physikalische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany Lehrstuhl für BioMolekulare Optik, Fakultät für Physik and Center for Integrated Protein Science Munich CIPSM, Ludwig-Maximilians-Universität München, Oettingenstrasse 67, 80538 München, Germany
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S Supporting Information *
ABSTRACT: Psoralens are natural compounds that serve in the light dependent treatment of certain skin diseases (PUVA therapy). They are DNA intercalators that upon photoexcitation form adducts with thymine bases. For one psoralen derivative, 4′-aminomethyl-4,5′,8-trimethylpsoralen (AMT), the photoreactions are characterized here by nanosecond UV−vis and IR absorption spectroscopy. The triplet state of AMT is identified as the reactive one. On the 1−10 μs time scale this local triplet state transforms into a triplet biradical bearing one single bond between the addends. Within ∼50 μs this biradical forms the final adduct featuring a cyclobutane ring. This kinetic behavior is in stark contrast to the closely related photoaddition of two thymine moieties within the DNA. Origins of the differences are discussed.
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Scheme 1. Structure of the Psoralen Derivative AMT,a the Thymine Base of the DNA, and One of the Two Diastereomeric cis-syn-Photoadducts on the Furan Side
INTRODUCTION Ultraviolet (UV) light can trigger chemical reactions in DNA, whichif not repaired enzymaticallyirreversibly damage the carrier of the genetic code.1 Various of these DNA photolesions have been identified. The most abundant one is the cyclobutane pyrimidine dimer (CPD) formed between two thymine bases adjacent on the DNA strand.2 The formation of this lesion was traced by femtosecond UV pump infrared (IR) probe spectroscopy.3,4 The experiments showed that the CPD formation after UV−C absorption occurs within a few 100 fs via an excited singlet state as a precursor. This implies that the ring forms in a concerted Woodward−Hoffmann5 type way. Studies on the dimerization via the triplet state are hampered by the small quantum yield of this state for direct excitation.2,6 Higher populations of the thymine triplet state can be attained by sensitization.7 Experiments with direct6 and sensitized7 excitation indicated that the efficiency for dimerization starting from the triplet state is small; i.e.,
