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.

Norfloxacin (NFX) photosensitizes formation of thymine dimers (T<>T) in DNA, while its N(4') acetyl derivative (ANFX) does not. This is evident from the observation of single-strand breaks after enzymatic treatment with T4 endonuclease V and subsequent gel electrophoresis. The triplet energies of NFX and ANFX are estimated at 273 and 268 kJ/mol, respectively, on the basis of triplet-triplet energy transfer quenching by a set of biphenyl and naphthalene derivatives. Hence, the triplet energy of thymine in DNA (i.e., the value for a photosensitizer to produce T<>T) can be estimated at 270 kJ/mol.

aTriplet-mediated pyrimidine (Pyr) dimerisation is a key process in photochemical damage to DNA. 5It may occur in the presence of a photosensitiser, provided that a number of requirements are fulfilled, such as favourable intersystem crossing quantum yield and high triplet energy. The attention has been mainly focused on cyclobutane pyrimidine dimers, as they are by far the most relevant Pyr photoproducts obtained by sensitisation. The present perspective deals with the involved chemistry, not only in DNA but also in its simple building blocks. It also includes the 10 photophysical characterisation of the Pyr triplet excited states, as well as a brief discussion of the theoretical aspects.

A series of fluoroquinolones (FQs), including enoxacin (ENX), pefloxacin (PFX), norfloxacin (NFX), its N(4')-acetyl derivative (ANFX), ofloxacin (OFX), and rufloxacin (RFX) have been investigated to determine their potential as DNA photosensitizers via thymine cyclobutane dimer (T<>T) formation in DNA. At fluoroquinolone concentrations and light doses insufficient to produce direct single strand breaks, ENX, PFX, and NFX were able to produce T<>T dimers in DNA, revealed by enzymatic treatment with T4 endonuclease V. By contrast, ANFX, OFX, and RFX were inefficient in this assay. The absolute values of the triplet energies of ENX, PFX, NFX, ANFX, OFX, and RFX were estimated by means of laser flash photolysis, using flurbiprofen, 4-biphenylcarboxylic acid, and naproxen as energy acceptors. They were found to be 273, 269, 269, 265, 262, and 253 kJ/mol, respectively. Other triplet excited state properties of the FQs, including quantum yields and lifetimes, were also studied. All the results indicate that the threshold ET value required for a given compound to become a potential DNA photosensitizer via T<>T formation is in the range defined by the triplet energies of NFX and ANFX (265-269 kJ/mol). This provides the basis for an alert rule: any chemical (drugs, cosmetics, pesticides, etc.) with higher ET has to be considered with regard to its potential photogenotoxicity.

Elsevier Nardi, G.; Manet, I.; Monti, S.; Miranda Alonso, MÁ.; Lhiaubet-Vallet, V. (2014 oxygen gives rise to a EPR detectable TEMPO signal that is not associated with singlet oxygen production. This knowledge is essential for an appropriate and error-free application of the TEMPO/EPR method in chemical, biological and medical studies.

In most sunscreens, the presence of two UV filters usually leads to synergistic effects regarding both the final performance and photostabilization of the active principles. However, this may also result in an accelerated decomposition if a photoreaction occurs between the single components. Thus, the understanding of photophysics and photochemistry of UV filter combinations is important to improve sunscreen photostability. In this context, photoreactivity of a commonly used UVA filter, namely tert-butylmethoxydibenzoylmethane (BM-DBM, also known as avobenzone, Parsol 1789, etc.), has been studied in the presence of six commercial solar filters: octyl methoxycinnamate, bis-ethylhexyloxyphenol methoxyphenyl triazine, octocrylene, diethylamino hydroxybenzoyl hexyl benzoate, octyl triazone and dioctyl butamido triazone. To achieve this goal, a mechanism-based strategy has been designed in order to investigate the photostability of sunscreens in a more systematic way, taking into account different processes: tautomerization of BM-DBM, formation of triplet excited state of BM-DBM in its diketo form and its quenching in the presence of UV filters, reactivity of UV filters under triplet photosensitization, quenching of singlet oxygen by UV filters and degradation of the latter under singlet oxygenation conditions.

Novel sunscreens are required providing active protection in the UVA and UVB regions. On the other hand, there is an increasing concern about the photosafety of UV filters, as some of them are not sufficiently photostable. Avobenzone is one of the most frequently employed sunscreen ingredients, but it has been reported to partially decompose after irradiation. In the present work, photophysical and photochemical studies on a methylated avobenzone-derivative have shown that the diketo form is responsible for photodegradation. A transient absorption was observed at 380 nm after laser flash photolysis excitation at 308 nm. It was assigned to the triplet excited state of the diketo form, as inferred from quenching by oxygen and b-carotene. This transient also interacted with key building blocks of biomolecules by triplet-triplet energy transfer (in the case of thymidine) or electron transfer processes (for 2¢-deoxyguanosine, tryptophan and tyrosine). Irradiation of the avobenzone derivative in the presence of a triazine UV-B filter (E-35852) diminished the undesirable effects of the compound by an efficient quenching of the triplet excited state. Thus, sunscreen formulations including triplet quenchers could provide effective protection from the potential phototoxic and photoallergic effects derived from poor photostability of avobenzone.

A remarkable stereodifferentiation has been observed in the interaction between the excited triplet state of carprofen (CP) and human serum albumin (HSA). Time-resolved measurements using laser flash photolysis reveal the presence of two components with different lifetimes in triplet decay. This is explained by complexation of CP to the two possible HSA binding sites. The shorter-lived components are ascribed to the CP/HSA complexes in site I, where stereodifferentiation is more important (tauR/tauS ca. 4). This is correlated with formation of a dehalogenated photoproduct upon steady-state photolysis.