Although the carcinogenic potential of ultraviolet radiation is well-known, UV light may interact with
DNA by direct absorption or through
photosensitization by endogenous or exogenous chromophores. These chromophores can extend the "active" fraction of the solar spectrum to the UVA region and beyond, which means that
photosensitizers increase the probability of developing
skin cancer upon exposure to sunlight. Therefore researchers would like to understand the mechanisms involved in photosensitized DNA damage both to anticipate possible photobiological risks and to design tailor-made photoprotection strategies. In this context, photosensitized DNA damage can occur through a variety of processes including electron transfer,
hydrogen abstraction, triplet-triplet energy transfer, or generation of
reactive oxygen species. In this Account, we have chosen
benzophenone (BP) as a classical and paradigmatic chromophore to illustrate the different lesions that
photosensitization may prompt in
nucleosides, in
oligonucleotides, or in
DNA. Thus, we discuss in detail the accumulated mechanistic evidence of the BP-photosensitized reactions of
DNA or its building blocks obtained by our group and others. We also include
ketoprofen (KP), a BP-derivative that possesses a chiral center, to highlight the stereodifferentiation in the key photochemical events, revealed through the dynamics of the reactive triplet excited state ((3)KP*). Our results show that irradiation of the BP chromophore in the presence of
DNA or its components leads to nucleobase oxidations,
cyclobutane pyrimidine dimer formation, single strand breaks, DNA-
protein cross-links, or abasic sites. We attribute the manifold photoreactivity of BP to its well established photophysical properties: (i) it absorbs UV light, up to 360 nm; (ii) its intersystem crossing quantum yield (ϕ(ISC)) is almost 1; (iii) the energy of its nπ* lowest triplet excited state (E(T)) is ca. 290 kJ mol(-1); (iv) it produces
singlet oxygen ((1)O(2)) with a quantum yield (ϕ(Δ)) of ca. 0.3. For electron transfer and
singlet oxygen reactions, we focused on
guanine, the nucleobase with the lowest oxidation potential. Among the possible oxidative processes, electron transfer predominates. Conversely, triplet-triplet energy transfer occurs mainly from (3)BP* to
thymine, the base with the lowest lying triplet state in
DNA. This process results in the formation of
cyclobutane pyrimidine dimers, but it also competes with the Paternò-Büchi reaction in nucleobases or
nucleosides, giving rise to oxetanes as a result of crossed cycloadditions. Interestingly, we have found significant stereodifferentiation in the quenching of the KP triplet excited state by both 2'-deoxyguanosine and
thymidine. Based on these results, this chromophore shows potential as a (chiral) probe for the investigation of electron and triplet energy transport in
DNA.