Influence of the Linking Bridge on the Photoreactivity of Benzophenone–Thymine Conjugates

Abstract

Benzophenone (BP) is present in a variety of bioactive molecules. This chromophore is able to photosensitize DNA damage, where one of the most relevant BP/DNA interactions occurs with thymine (Thy). In view of the complex photoreactivity previously observed for dyads containing BP covalently linked to thymidine, the aim of this work is to investigate whether appropriate changes in the nature of the spacer could modulate the intramolecular BP/Thy photoreactivity, resulting in an enhanced selectivity. Accordingly, the photobehavior of a series of dyads derived from BP and Thy, separated by linear linkers of different length, has been investigated by steady-state photolysis, as well as femtosecond and nanosecond transient absorption spectroscopy. Irradiation of the dyads led to photoproducts arising from formal hydrogen abstraction or Paternò-Büchi (PB) photoreaction, with a chemoselectivity that was clearly dependent on the nature of the linking bridge; moreover, the PB process occurred with complete regio-and stereoselectivity. The overall photoreactivity increased with the length of the spacer and correlated well with the rate constants estimated from the BP triplet lifetimes. A reaction mechanism explaining these results is proposed, where key features are the strain associated with the reactive conformations and the participation of triplet exciplexes. ASSOCIATED CONTENTSupporting Information. 1 H and 13 C NMR spectra of the synthesized dyads and intermediates. UV, femtosecond transient absorption and laser flash photolysis spectra and kinetics. X-Ray crystallography data for Ox-D10.

Regioselectivity in the adiabatic photocleavage of DNA-based oxetanes

“…Thus, photolysis of the dyad 1 containing the BP and Thy chromophores linked through a sugar moiety resulted in the formation of HH-6, HT-6, HH-7 and HT-7, 26 whereas HH-8 was obtained from irradiation of dyad 2, where BP and Thy are connected through a linear chain of ten linking atoms. 30 Steady state photolysis of oxetanes HH-6, HT-6, HH-7 and HT-7 gave rise in all cases to dyad 1 as the only photoproduct, whereas, under the same conditions, oxetane HH-8 led cleanly to dyad 2.…”

“…Hence, oxetane HH-8 was also submitted to femtosecond transient absorption measurements ( exc = 280 nm), which fully confirmed formation of the triplet excited state of the BP-derived chromophore with maximum at ca. 530 nm 30 (see Fig. 6A and B).…”

“…Finally, the photophysical properties of HH-8 were investigated and compared to those of dyad 2. 30 Kinetic analysis of the transient peaking at 530 nm in the ns-s time-scale upon LFP at 266 nm revealed that the decay traces in both systems could be fitted by a Please do not adjust margins…”

“…In view of the photoreactivity observed for the nucleobasederived oxetanes as a function of the substitution at positions 1 and 5, the photobehavior of polycyclic oxetanes (see Figure 1B) whose splitting could lead to BP and Thy chromophores covalently linked through a spacer of different nature was also investigated. Their synthesis was achieved following the reported procedures, 26,30 by means of the Paternò-Büchi photoreaction between the BP and Thy units of the precursor dyads 1 and 2 (see Fig. 4).…”

Mechanisms and energetics for hydrogen abstraction of thymine photosensitized by benzophenone from theoretical principles

“…Paterno `-Bu ¨chi cycloaddition links the carbonyl group on the BZP and the carbon-carbon double bond on the thymine to generate oxetane adducts with regioselectivity. 16,17 Triplettriplet energy transfer produces the triplet thymine which can easily bind to the other thymine forming a thymine dimer. 18,19 An electron transfer forms a thymine cation radical which reacts with oxygen and H 2 O to form thymine glycol.…”