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This is the peer reviewed version of the following article: M. Lineros-Rosa, M. A. Miranda, V. Lhiaubet-Vallet, Chem. Eur. J. 2020, 26, 7205, which has been published in final form at https://doi.org/10.1002/chem.202000123. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. ; [EN] Photolabile protecting groups (PPGs) have been exploited in a wide range of chemical and biological applications, due to their ability to provide spatial and temporal control over light-triggered activation. In this work, we explore the concept of a new photocage compound based on the commercial UVA/UVB filter oxybenzone (OB; 2-hydroxy-4-methoxybenzophenone) for photoprotection and controlled release of carbonyl groups. The point here is that oxybenzone not only acts as a mere PPG, but also provides, once released, UV photoprotection to the carbonyl derivative. This design points to a possible therapeutic approach to reduce the severe photoadverse effects of drugs containing a carbonyl chromophore. ; This work was supported by the Spanish Government (project PGC2018-096684-B-I00) and the Universitat Politecnica de Valencia (FPI grant to M.L.-R.). Carmen Clemente Martínez is acknowledged for her technical help during the UPLC-HRMS experiments. ; Lineros-Rosa, M.; Miranda Alonso, MÁ.; Lhiaubet, VL. (2020). A Sunscreen-Based Photocage for Carbonyl Groups. Chemistry - A European Journal. 26(32):7205-7211. https://doi.org/10.1002/chem.202000123 ; S ; 7205 ; 7211 ; 26 ; 32 ; Silva, J. M., Silva, E., & Reis, R. L. (2019). Light-triggered release of photocaged therapeutics - Where are we now? Journal of Controlled Release, 298, 154-176. doi:10.1016/j.jconrel.2019.02.006 ; Klausen, M., Dubois, V., Verlhac, J., & Blanchard‐Desce, M. (2019). Tandem Systems for Two‐Photon Uncaging of Bioactive Molecules. ChemPlusChem, 84(6), 589-598. doi:10.1002/cplu.201900139 ; Brieke, C., Rohrbach, F., Gottschalk, A., Mayer, G., & Heckel, A. (2012). Light‐Controlled Tools. Angewandte ...

[EN] Photosensitization by drugs is a problem of increasing importance in modern life. This phenomenon occurs when a chemical substance in the skin is exposed to sunlight. Photosensitizing drugs are reported to cause severe skin dermatitis, and indeed, it is generally advised to avoid sunbathing and to apply sunscreen. In this context, the nonsteroidal anti-inflammatory drug (NSAID) diclofenac is a photosensitive drug, especially when administered in topical form. In this work, efforts have been made to design and study an innovative pro-drug/pro-filter system containing diclofenac and the UVA filter avobenzone in order to develop a safer use of this topical drug. The design is based on the presence of a well-established photoremovable phenacyl group in the avobenzone structure. Steady-state photolysis of the dyad in hydrogen-donor solvents, monitored by UV-Vis spectrophotometry and HPLC, confirms the simultaneous photorelease of diclofenac and avobenzone. Laser flash photolysis and phosphorescence emission experiments allow us to gain insight into the photoactive triplet excited-state properties of the dyad. Finally, it is shown that avobenzone provides partial photoprotection to diclofenac from photocyclization to carbazole derivatives. ; The present work was supported by the Spanish Government (CTQ2015-70164-P, BES-2013-066566), Generalitat Valenciana (Prometeo/2017/075). ; Aparici-Espert, MI.; Miranda Alonso, MÁ.; Lhiaubet, VL. (2018). Sunscreen-Based Photocages for Topical Drugs: A Photophysical and Photochemical Study of A Diclofenac-Avobenzone Dyad. Molecules. 23(3):1-11. https://doi.org/10.3390/molecules23030673 ; S ; 1 ; 11 ; 23 ; 3 ; Siegel, R. L., Miller, K. D., & Jemal, A. (2018). Cancer statistics, 2018. CA: A Cancer Journal for Clinicians, 68(1), 7-30. doi:10.3322/caac.21442 ; Curtius, K., Wright, N. A., & Graham, T. A. (2017). An evolutionary perspective on field cancerization. Nature Reviews Cancer, 18(1), 19-32. doi:10.1038/nrc.2017.102 ; Brem, R., Guven, M., & Karran, P. (2017). ...

[EN] Photolyases are intriguing enzymes that take advantage of sunlight to restore lesions like cyclobutane pyrimidine dimers or (6-4) photoproducts. This work focused on the photoreductive process responsible for splitting of the azetidine ring proposed to occur during (6-4) photoproduct repair at a thymine-cytosine sequence. A model compound formed by photocycloaddition between thymine and 6-azauracil has been designed to mimic the elusive azetidine intermediate. The photoinduced electron transfer process has been investigated by means of steady-state and time-resolved fluorescence using photosensitizers with oxidation potentials in the singlet excited state ranging from -3.3 to -2.1V vs. SCE. Azetidine ring splitting and recovery of repaired bases were proven by HPLC analysis. ; The Spanish Government (CTQ2012-32621, CTQ2015-70164-P, RIRAAF RETICS RD12/0013/0009, Severo Ochoa program/SEV-2012-0267 and SVP-2013-068057 for A.B.F.-R. grant) and the Generalitat Valenciana (Prometeo II/2013/005) are gratefully acknowledged. We are indebted to Dr. G. Sastre for his collaboration in the mathematical treatment of some experimental results. ; Fraga Timiraos, AB.; Lhiaubet, VL.; Miranda Alonso, MÁ. (2016). Repair of a Dimeric Azetidine Related to the Thymine-Cytosine (6-4) Photoproduct by Electron Transfer Photoreduction. Angewandte Chemie International Edition. 55(20):6037-6040. https://doi.org/10.1002/anie.201601475 ; S ; 6037 ; 6040 ; 55 ; 20

A new mechanism of photosensitized formation of thymine (Thy) dimers is proposed, which involves generation of a delocalized triplet excited state as the key step. This is supported by chemical evidence obtained by combining one benzophenone and two Thy units with different degrees of freedom, whereby the photoreactivity is switched from a clean Paterno-Buchi reaction to a fully chemo-, regio-, and stereoselective [2+2] cycloaddition. ; Financial support from the Spanish Government (Grants SEV-2012-0267, CTQ2012-38754-C03-03, and CTQ2012-32621), Generalitat Valenciana (Prometeo Program), and Technical University of Valencia (Predoctoral FPI fellowship for P.M.) is gratefully acknowledged. ; Miró Richart, P.; Lhiaubet, VL.; Marín García, ML.; Miranda Alonso, MÁ. (2015). Photosensitized Thymine Dimerization via Delocalized Triplet Excited States. Chemistry - A European Journal. 21(47):17051-17056. doi:10.1002/chem.201502719 ; S ; 17051 ; 17056 ; 21 ; 47

Triplet-mediated pyrimidine (Pyr) dimerisation is a key process in photochemical damage to DNA. It 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 photophysical characterisation of the Pyr triplet excited states, as well as a brief discussion of the theoretical aspects. ; Financial support from the Spanish Government (CTQ2009-13699, CTQ2009-14196, JAE Doc fellowship for M. C. C. and Ramon y Cajal contract for V. L.-V.) and EU (CM0603) is gratefully acknowledged. ; Bosca Mayans, F.; Lhiaubet, VL.; Cuquerella Alabort, MC.; Miranda Alonso, MÁ. (2011). Photosensitised pyrimidine dimerisation in DNA. Chemical Science. 2(7):1219-1232. https://doi.org/10.1039/c1sc00088h ; S ; 1219 ; 1232 ; 2 ; 7 ; The Lancet Oncology. (2009). Beauty and the beast. The Lancet Oncology, 10(9), 835. doi:10.1016/s1470-2045(09)70243-8 ; Mouret, S., Baudouin, C., Charveron, M., Favier, A., Cadet, J., & Douki, T. (2006). Cyclobutane pyrimidine dimers are predominant DNA lesions in whole human skin exposed to UVA radiation. Proceedings of the National Academy of Sciences, 103(37), 13765-13770. doi:10.1073/pnas.0604213103 ; Setlow, R. B., Grist, E., Thompson, K., & Woodhead, A. D. (1993). Wavelengths effective in induction of malignant melanoma. Proceedings of the National Academy of Sciences, 90(14), 6666-6670. doi:10.1073/pnas.90.14.6666 ; Rochette, P. J. (2003). UVA-induced cyclobutane pyrimidine dimers form predominantly at thymine-thymine dipyrimidines and correlate with the mutation spectrum in rodent cells. Nucleic Acids Research, 31(11), 2786-2794. doi:10.1093/nar/gkg402 ; Mitchell, D. L., Fernandez, A. A., Nairn, ...

[EN] The propensity of 5-formyluracil and 5-formylcytosine, i.e. oxidative lesions and epigenetic intermediates, in acting as intrinsic DNA photosensitizers is unraveled by using a combination of molecular modeling, simulation and spectroscopy. Exploration of potential energy surfaces and non-adiabatic dynamics confirm a higher intersystem crossing rate for 5-formyluracil, whereas the kinetic models evidence different equilibria in the excited states for both compounds. ; Support from the Universite de Lorraine, CNRS and Spanish Government (PGC2018-096684-B-I00) is kindly acknowledged. A. F.-M. is grateful to Generalitat Valenciana (CTQ2017-87054-C2-2-P) and the European Social Fund for a postdoctoral contract (APOSTD/2019/149), M. L.-R. acknowledges the Universitat Politecnica de Valencia for the FPI grant. Calculations have been performed on the local LPCT computer center and on the Explor regional center in the framework of the project "Dancing under the light''. ; Francés-Monerris, A.; Lineros-Rosa, M.; Miranda Alonso, MÁ.; Lhiaubet, VL.; Monari, A. (2020). Photoinduced intersystem crossing in DNA oxidative lesions and epigenetic intermediates. Chemical Communications. 56(32):4404-4407. https://doi.org/10.1039/d0cc01132k ; S ; 4404 ; 4407 ; 56 ; 32 ; Madabhushi, R., Pan, L., & Tsai, L.-H. (2014). DNA Damage and Its Links to Neurodegeneration. Neuron, 83(2), 266-282. doi:10.1016/j.neuron.2014.06.034 ; Sage, E. (1993). DISTRIBUTION AND REPAIR OF PHOTOLESIONS IN DNA: GENETIC CONSEQUENCES AND THE ROLE OF SEQUENCE CONTEXT. Photochemistry and Photobiology, 57(1), 163-174. doi:10.1111/j.1751-1097.1993.tb02273.x ; Cadet, J., Sage, E., & Douki, T. (2005). Ultraviolet radiation-mediated damage to cellular DNA. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 571(1-2), 3-17. doi:10.1016/j.mrfmmm.2004.09.012 ; G. T. Wondrak , Skin stress response pathways: Environmental factors and molecular opportunities , Springer , 2016 ; Nakamura, J., Mutlu, E., Sharma, V., Collins, L., Bodnar, W., Yu, ...

[EN] Interaction of nucleic acids with light is a scientific question of paramount relevance not only in the understanding of life functioning and evolution, but also in the insurgence of diseases such as malignant skin cancer and in the development of biomarkers and novel light-assisted therapeutic tools. This work shows that the UVA portion of sunlight, not absorbed by canonical DNA nucleobases, can be absorbed by 5-formyluracil (ForU) and 5-formylcytosine (ForC), two ubiquitous oxidatively generated lesions and epigenetic intermediates present in living beings in natural conditions. We measure the strong propensity of these molecules to populate triplet excited states able to transfer the excitation energy to thymine-thymine dyads, inducing the formation of cyclobutane pyrimidine dimers (CPDs). By using steady-state and transient absorption spectroscopy, NMR, HPLC, and theoretical calculations, we quantify the differences in the triplet-triplet energy transfer mediated by ForU and ForC, revealing that the former is much more efficient in delivering the excitation energy and producing the CPD photoproduct. Although significantly slower than ForU, ForC is also able to harm DNA nucleobases and therefore this process has to be taken into account as a viable photosensitization mechanism. The present findings evidence a rich photochemistry crucial to understand DNA damage photobehavior. ; Support from the Universite de Lorraine, CNRS, regional (Prometeo/2017/075) and Spanish Government (PGC2018-096684-B-I00, CTQ2017-87054-C2-2-P) is kindly acknowledged. A. F.-M. is grateful to Generalitat Valenciana and the European Social Fund (postdoctoral contract APOSTD/2019/149 and project GV/2020/226) for financial support. M. L.-R. acknowledges the Universitat Politecnica de Valencia for the FPI grant. All calculations have been performed on the local LPCT computer center and on the Explor regional center in the framework of the project "Dancing under the light". ; Lineros-Rosa, M.; Francés-Monerris, A.; Monari, A.; Miranda ...

The efficiency of thymine (Thy) and uracil (Ura) to form cyclobutane pyrimidine dimers (CPDs) in solution, upon UV irradiation differs by one order of magnitude. This could to be partially related to the steric hindrance induced by the methyl at C5 in thymine. The aim of the present work is to establish the influence of a bulky moiety at this position on the photoreactivity of pyrimidines. With this purpose, photosensitization with benzophenone and acetone of a 5-tert-butyl uracil derivative (1) and the equivalent Thy (2) has been compared. Introduction of the tert-butyl group completely blocks CPD formation. Moreover, the mechanistic insight obtained by laser flash photolysis is in accordance with the observed photoreactivity. ; Financial support by the Spanish Government (CTQ2012-32621, CTQ2015-70164-P and contract JAE-Predoc 2011-00740 to V. V.-C.) and the Generalitat Valenciana (PROMETEOII/2013/005) is gratefully acknowledged. ; Vendrell Criado, V.; Lhiaubet, VL.; Yamaji, M.; Cuquerella Alabort, MC.; Miranda Alonso, MÁ. (2016). Blocking cyclobutane pyrimidine dimer formation by steric hindrance. Organic and Biomolecular Chemistry. 14(17):4110-4115. https://doi.org/10.1039/c6ob00382f ; S ; 4110 ; 4115 ; 14 ; 17

4110 4115 14 17 ; Senia ; The efficiency of thymine (Thy) and uracil (Ura) to form cyclobutane pyrimidine dimers (CPDs) in solution, upon UV irradiation differs by one order of magnitude. This could to be partially related to the steric hindrance induced by the methyl at C5 in thymine. The aim of the present work is to establish the influence of a bulky moiety at this position on the photoreactivity of pyrimidines. With this purpose, photosensitization with benzophenone and acetone of a 5-tert-butyl uracil derivative (1) and the equivalent Thy (2) has been compared. Introduction of the tert-butyl group completely blocks CPD formation. Moreover, the mechanistic insight obtained by laser flash photolysis is in accordance with the observed photoreactivity. Financial support by the Spanish Government (CTQ2012-32621, CTQ2015-70164-P and contract JAE-Predoc 2011-00740 to V. V.-C.) and the Generalitat Valenciana (PROMETEOII/2013/005) is gratefully acknowledged. Vendrell Criado, V.; Lhiaubet, VL.; Yamaji, M.; Cuquerella Alabort, MC.; Miranda Alonso, MÁ. (2016). Blocking cyclobutane pyrimidine dimer formation by steric hindrance. Organic and Biomolecular Chemistry. 14(17):4110-4115. doi:10.1039/c6ob00382f

[EN] The photochemical properties of itraconazole (1), a broad-spectrum antifungal agent, have been investigated in connection with reported skin photosensitivity disorders. Steady state photolysis, fluorescence and phosphorescence experiments have been performed to understand photoreactivity of 1 in biological media. The drug is unstable under UVB irradiation, suffering a primary dehalogenation of the 2,4-dichlorophenyl moiety that occurs mainly at the ortho-position. In poorly H-donating solvents, such as acetonitrile, the major photoproduct arises from intramolecular attack of the initially generated aryl radical towards the triazole ring. In addition, reduced compounds resulting from homolytic cleavage of the C-Cl bond in ortho or para positions and subsequent H-abstraction from the medium are obtained to a lesser extent. In good H-donating solvents, such as ethanol, the main photoproducts are formed by reductive dehalogenation. Furthermore, irradiation of a model dyad containing a tryptophan unit and the reactive 2,4-dichlorophenyl moiety of itraconazole leads to formation of a new covalent link between these two substructures revealing that homolysis of the C-Cl bond of 1 can result in alkylation of reactive amino acid residues of proteins, leading to formation of covalent photoadducts. Therefore, it has been established that the key process in the photosensitization by itraconazole is cleavage of the carbon-halogen bond, which leads to aryl radicals and chlorine atoms. These highly reactive species might be responsible for extensive free radical-mediated biological damage, including lipid peroxidation or photobinding to proteins. ; Merck Sharp & Dohme, Spanish Government (CTQ2009-13699, CTQ2012-32621, CTQ2012-38754-C03-03, RyC-2007-00476, PFIS FI09/00312), Generalitat Valenciana (Prometeo Program) and CAPES (post-doctoral fellowship of P. A. S. Programa de Pos-Graduacao em Quimica da UFRJ, Brazil) are gratefully acknowledged for financial support. ; Nardi, G.; Marín García, ML.; De Souza, PA.; ...

[EN] Using a sunscreen-based photocage, we have demonstrated that it is possible to prevent photodegradation of a bioactive compound and to achieve its controlled photorelease. The concept has been proven linking avobenzone, one of the most important UVA blockers, to ketoprofen, which is a representative example of a photosensitive drug. ; Spanish Government (CTQ2015-70164-P, RIRAAF RETICS RD12/0013/0009, Severo Ochoa program/SEV-2012-0267 and BES-2013-066566), Generalitat Valenciana (Prometeo II/2013/005) and VLC/Campus Microcluster "Interacciones Luz-Farmaco en Sistemas Biologicos y Reacciones Adversas'' are gratefully acknowledged. ; Aparici-Espert, MI.; Cuquerella Alabort, MC.; Paris, C.; Lhiaubet ., VL.; Miranda Alonso, MÁ. (2016). Photocages for protection and controlled release of bioactive compounds. Chemical Communications. 52(99):14215-14218. https://doi.org/10.1039/c6cc08175d ; S ; 14215 ; 14218 ; 52 ; 99 ; H. H. Tonnesen , Photostability of Drugs and Drug Formulations, CRC Press LLC, 2nd edn, 2004 ; Rehan Zaheer, M., Gupta, A., Iqbal, J., Zia, Q., Ahmad, A., Roohi, ., … Aliev, G. (2016). Molecular Mechanisms of Drug Photodegradation and Photosensitization. Current Pharmaceutical Design, 22(7), 768-782. doi:10.2174/1381612822666151209151408 ; Klinge, S. A., & Sawyer, G. A. (2013). Effectiveness and Safety of Topical versus Oral Nonsteroidal Anti-inflammatory Drugs: A Comprehensive Review. The Physician and Sportsmedicine, 41(2), 64-74. doi:10.3810/psm.2013.05.2016 ; Moore, D. E. (2002). Drug-Induced Cutaneous Photosensitivity. Drug Safety, 25(5), 345-372. doi:10.2165/00002018-200225050-00004 ; Drucker, A. M., & Rosen, C. F. (2011). Drug-Induced Photosensitivity. Drug Safety, 34(10), 821-837. doi:10.2165/11592780-000000000-00000 ; V. Lhiaubet-Vallet and M. A.Miranda, CRC Handbook of Organic Photochemistry and Photobiology, CRC Press, Boca Raton, 3rd edn, 2012, ch. 66, vol. 2, p. 1541 ; Bagheri, H., Lhiaubet, V., Montastruc, J. L., & Chouini-Lalanne, N. (2000). Photosensitivity to ...

[EN] The photophysics and photochemistry of the beta-lapachone derived diphenyldihydrodioxin 3 were investigated using steady-state and time resolved techniques. Laser excitation of 3 leads to the formation of its cation radical 4 (absorption maxima at 410 and 450 nm and a lifetime of 10 mu s), which was confirmed by its thermal generation employing tris(2,4-dibromophenyl)-aminium hexachloroantimonate (BAHA) as the electron acceptor. The cation radical 4 was also formed via the triplet excited state of 3 through a triplet sensitized process using benzophenone (E-T = 69 kcal mol(-1)) as the sensitizer. ; Financial support by the Spanish Government (grant CTQ2012-32621) is gratefully acknowledged. We thank Prof. Julia Pérez-Prieto for making available the laser flash photolysis facilities at the University of Valencia. BB thanks Coordena- ção de Aperfeiçoamento do Pessoal do Ensino Superior (CAPES-Brazil) for a graduate fellowship. JCN-F thanks Generalitàt Valenciana for a Visiting Professor fellowship. ; Netto Ferreira, JC.; Lhiaubet ., VL.; Bernades, B.; Ferreira, ABB.; Miranda Alonso, MÁ. (2014). Photophysics and photochemistry of the beta-lapachone derived diphenyldihydrodioxin: generation and characterization of its cation radical. Photochemical & Photobiological Sciences. 13(12):1655-1660. https://doi.org/10.1039/C4PP00231H ; S ; 1655 ; 1660 ; 13 ; 12

[EN] In this work, the attention is focused on UVA-photosensitized reactions triggered by a DNA chromophore-containing lesion, namely 5-formyluracil. This is a major oxidatively generated lesion that exhibits an enhanced light absorption in the UVB-UVA region. The mechanistic study combining photochemical and photobiological techniques shows that irradiation of S-formyluracil leads to a triplet excited state capable of sensitizing formation of cyclobutane pyrimidine dimers in DNA via a triplet-triplet energy transfer. This demonstrates for the first time that oxidatively generated DNA damage can behave as an intrinsic sensitizer and result in an important extension of the active fraction of the solar spectrum with photocarcinogenic potential. Overall, this raises the question of an aggravated photomutagenicity of the 5-formyluracil lesion. ; The present work was supported by Spanish Government (CTQ2015-70164-P, Severo Ochoa program/SEV-2012-0267, BES-2013-066566, CSIC 2016801007), Instituto de Salud Carlos III (RD16/0006/0030, FIS PI16/01877), Generalitat Valenciana (Prometeo/2017/075). ; Aparici-Espert, MI.; García-Laínez, G.; Andreu Ros, MI.; Miranda Alonso, MÁ.; Lhiaubet, VL. (2018). Oxidatively Generated Lesions as Internal Photosensitizers for Pyrimidine Dimerization in DNA. ACS Chemical Biology. 13(3):542-547. https://doi.org/10.1021/acschembio.7b01097 ; S ; 542 ; 547 ; 13 ; 3

[EN] Electron transfer involving nucleic acids and their derivatives is an important field in bioorganic chemistry, specifically in connection with its role in the photo-driven DNA damage and repair. Four-membered ring heterocyclic oxetanes and azetidines have been claimed to be the intermediates involved in the repair of DNA (6-4) photoproduct by photolyase. In this context, we examine here the redox properties of the two azetidine isomers obtained from photocycloaddition between 6-aza-1,3-dimethyluracil and cyclohexene. Steady-state and time-resolved fluorescence experiments using a series of photoreductants and photooxidants have been run to evaluate the efficiency of the electron transfer process. Analysis of the obtained quenching kinetics shows that the azetidine compounds can act as electron donors. Additionally, it appears that the cis isomer is more easily oxidized than its trans counterpart. This result is in agreement with electrochemical studies performed on both azetidine derivatives. ; Spanish Government (CTQ2015-70164-P, RIRAAF RETICS RD12/0013/0009, Red de Fotoquimica Biologica CTQ2015-71896-REDT, Severo Ochoa program/SEV-2012-0267 and SVP-2013-068057 for A. B. F.-R. grant) and Generalitat Valenciana (Prometeo II/2013/005) are gratefully acknowledged. ; Fraga-Timiraos, AB.; Rodríguez Muñiz, GM.; Peiro-Penalba, V.; Miranda Alonso, MÁ.; Lhiaubet, VL. (2016). Stereoselective Fluorescence Quenching in the Electron Transfer Photooxidation of Nucleobase-Related Azetidines by Cyanoaromatics. Molecules. 21(12). https://doi.org/10.3390/molecules21121683 ; S ; 21 ; 12 ; Arnold, A. R., Grodick, M. A., & Barton, J. K. (2016). DNA Charge Transport: from Chemical Principles to the Cell. Cell Chemical Biology, 23(1), 183-197. doi:10.1016/j.chembiol.2015.11.010 ; Jia, C., Ma, B., Xin, N., & Guo, X. (2015). Carbon Electrode–Molecule Junctions: A Reliable Platform for Molecular Electronics. Accounts of Chemical Research, 48(9), 2565-2575. doi:10.1021/acs.accounts.5b00133 ; Beratan, D. N., Liu, C., ...

21 12 ; S ; [EN] Electron transfer involving nucleic acids and their derivatives is an important field in bioorganic chemistry, specifically in connection with its role in the photo-driven DNA damage and repair. Four-membered ring heterocyclic oxetanes and azetidines have been claimed to be the intermediates involved in the repair of DNA (6-4) photoproduct by photolyase. In this context, we examine here the redox properties of the two azetidine isomers obtained from photocycloaddition between 6-aza-1,3-dimethyluracil and cyclohexene. Steady-state and time-resolved fluorescence experiments using a series of photoreductants and photooxidants have been run to evaluate the efficiency of the electron transfer process. Analysis of the obtained quenching kinetics shows that the azetidine compounds can act as electron donors. Additionally, it appears that the cis isomer is more easily oxidized than its trans counterpart. This result is in agreement with electrochemical studies performed on both azetidine derivatives. Spanish Government (CTQ2015-70164-P, RIRAAF RETICS RD12/0013/0009, Red de Fotoquimica Biologica CTQ2015-71896-REDT, Severo Ochoa program/SEV-2012-0267 and SVP-2013-068057 for A. B. F.-R. grant) and Generalitat Valenciana (Prometeo II/2013/005) are gratefully acknowledged. Fraga-Timiraos, AB.; Rodríguez Muñiz, GM.; Peiro-Penalba, V.; Miranda Alonso, MÁ.; Lhiaubet, VL. (2016). Stereoselective Fluorescence Quenching in the Electron Transfer Photooxidation of Nucleobase-Related Azetidines by Cyanoaromatics. Molecules. 21(12). https://doi.org/10.3390/molecules21121683 Arnold, A. R., Grodick, M. A., & Barton, J. K. (2016). DNA Charge Transport: from Chemical Principles to the Cell. Cell Chemical Biology, 23(1), 183-197. doi:10.1016/j.chembiol.2015.11.010 Jia, C., Ma, B., Xin, N., & Guo, X. (2015). Carbon Electrode–Molecule Junctions: A Reliable Platform for Molecular Electronics. Accounts of Chemical Research, 48(9), 2565-2575. doi:10.1021/acs.accounts.5b00133 Beratan, D. N., Liu, C., Migliore, A., ...