Theoretical Study on the Photo-Oxidation and Photoreduction of an Azetidine Derivative as a Model of DNA Repair

[EN] Photocycloreversion plays a central role in the study of the repair of DNA lesions, reverting them into the original pyrimidine nucleobases. Particularly, among the proposed mechanisms for the repair of DNA (6-4) photoproducts by photolyases, it has been suggested that it takes place through an intermediate characterized by a four-membered heterocyclic oxetane or azetidine ring, whose opening requires the reduction of the fused nucleobases. The specific role of this electron transfer step and its impact on the ring opening energetics remain to be understood. These processes are studied herein by means of quantum-chemical calculations on the two azetidine stereoisomers obtained from photocycloaddition between 6-azauracil and cyclohexene. First, we analyze the efficiency of the electron-transfer processes by computing the redox properties of the azetidine isomers as well as those of a series of aromatic photosensitizers acting as photoreductants and photo-oxidants. We find certain stereodifferentiation favoring oxidation of the cis-isomer, in agreement with previous experimental data. Second, we determine the reaction profiles of the ring-opening mechanism of the cationic, neutral, and anionic systems and assess their feasibility based on their energy barrier heights and the stability of the reactants and products. Results show that oxidation largely decreases the ring-opening energy barrier for both stereoisomers, even though the process is forecast as too slow to be competitive. Conversely, one-electron reduction dramatically facilitates the ring opening of the azetidine heterocycle. Considering the overall quantum-chemistry findings, N,N-dimethylaniline is proposed as an efficient photosensitizer to trigger the photoinduced cycloreversion of the DNA lesion model.This work has been funded by the Generalitat Valenciana and the European Social Fund through the postdoctoral contract APOSTD/2019/149 and the project GV/2020/226. It also was funded by the Spanish Ministerio de Ciencia e Innovacion (MICINN), projects CTQ2017-87054-C2-2-P and PGC2018-096684-B-I00, and a 2019 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation. The Foundation takes no responsibility for the opinions, statements, and contents of this project, which are entirely the responsibility of its authors. D.R.-S. is grateful to the Spanish MICINN for the "Ramon y Cajal" grant (Ref. RYC-2015-19234). M.N.-M. acknowledges the Generalitat Valenciana for the predoctoral grant (Ref. ACIF/2020/075).Navarrete-Miguel, M.; Francés-Monerris, A.; Miranda Alonso, MÁ.; Lhiaubet, VL.; Roca-Sanjuan, D. (2021). Theoretical Study on the Photo-Oxidation and Photoreduction of an Azetidine Derivative as a Model of DNA Repair. Molecules. 26(10):1-14. https://doi.org/10.3390/molecules26102911S114261

Tuned Pd/SiO 2 aerogel catalyst prepared by different synthesis techniques

Pd nanoparticles have been embedded on silica aerogel by using three different techniques. In each of them the metal was loaded in the matrix at different steps of the production: the direct synthesis, the wet impregnation and the supercritical impregnation of the previously dried aerogels. The resultant materials have been characterized to analyze the differences depending on the applied technique for its impregnation. Atomic absorption, nitrogen physisorption, X-ray diffraction, infrared spectroscopy and transmission electron microscopy where performed. In all the techniques the concentration of metal has been varied (from 0.13 to 1.61 % wt.) by modifying the concentration of the suspension (Pd-polyvinylpyrrolidone nanoparticles used in the direct synthesis) or of the solution of the metallic precursor (palladium acetylacetonate), both in the organic solvent and the supercritical media. The characterization had generally shown a good distribution of the metallic particles in the matrix, and the negligible effect of the metal on the textural properties. Finally, considerable variations where observed on the silanol groups on the surface of the catalysts. These materials were tested in D-glucose hydrogenation, observing significant differences on the performance of the catalyst depending on the synthesis technique employed.2018-06-06Spanish Ministry of Economy and Competitiveness project ENE2014-53459-

Release of Hydrogen from Nanoconfined Hydrides by Application of Microwaves

The release of hydrogen from solid hydrides by thermolysis can be improved by nanoconfinement of the hydride in a suitable micro/mesoporous support, but the slow heat transfer by conduction through the support can be a limitation. In this work, a C/SiO2 mesoporous material has been synthesized and employed as matrix for nanoconfinement of hydrides. The matrix showed high surface area and pore volume (386 m²/g and 1.41 cm³/g), which enabled the confinement of high concentrations of hydride. Furthermore, by modification of the proportion between C and SiO2, the dielectric properties of the complex could be modified, making it susceptible to microwave heating. As with this heating method the entire sample is heated simultaneously, the heat transfer resistances associated to conduction were eliminated. To demonstrate this possibility, ethane 1,2-diaminoborane (EDAB) was embedded on the C/SiO2 matrix at concentrations ranging from 11 to 31%wt using a wet impregnation method, and a device appropriate for hydrogen release from this material by application of microwaves was designed with the aid of a numerical simulation. Hydrogen liberation tests by conventional heating and microwaves were compared, showing that by microwave heating hydrogen release can be initiated and stopped in shorter times.2019-04-0

Release of Hydrogen from Nanoconfined Hydrides by Application of Microwaves

The release of hydrogen from solid hydrides by thermolysis can be improved by nanoconfinement of the hydride in a suitable micro/mesoporous support, but the slow heat transfer by conduction through the support can be a limitation. In this work, a C/SiO2 mesoporous material has been synthesized and employed as matrix for nanoconfinement of hydrides. The matrix showed high surface area and pore volume (386 m²/g and 1.41 cm³/g), which enabled the confinement of high concentrations of hydride. Furthermore, by modification of the proportion between C and SiO2, the dielectric properties of the complex could be modified, making it susceptible to microwave heating. As with this heating method the entire sample is heated simultaneously, the heat transfer resistances associated to conduction were eliminated. To demonstrate this possibility, ethane 1,2-diaminoborane (EDAB) was embedded on the C/SiO2 matrix at concentrations ranging from 11 to 31%wt using a wet impregnation method, and a device appropriate for hydrogen release from this material by application of microwaves was designed with the aid of a numerical simulation. Hydrogen liberation tests by conventional heating and microwaves were compared, showing that by microwave heating hydrogen release can be initiated and stopped in shorter times.2019-04-0

Experimental and Theoretical Study on the Cycloreversion of a Nucleobase-Derived Azetidine by Photoinduced Electron Transfer

[EN] Azetidines are interesting compounds in medicine and chemistry as bioactive scaffolds and synthetic intermediates. However, photochemical processes involved in the generation and fate of azetidine-derived radical ions have scarcely been reported. In this context, the photoreduction of this four-membered heterocycle might be relevant in connection with the DNA (6-4) photoproduct obtained from photolyase. Herein, a stable azabipyrimidinic azetidine (AZT(m)), obtained from cycloaddition between thymine and 6-azauracil units, is considered to be an interesting model of the proposed azetidine-like intermediate. Hence, its photoreduction and photo-oxidation are thoroughly investigated through a multifaceted approach, including spectroscopic, analytical, and electrochemical studies, complemented by CASPT2 and DFT calculations. Both injection and removal of an electron result in the formation of radical ions, which evolve towards repaired thymine and azauracil units. Whereas photoreduction energetics are similar to those of the cyclobutane thymine dimers, photo-oxidation is clearly more favorable in the azetidine. Ring opening occurs with relatively low activation barriers (< 13 kcal mol(-1)) and the process is clearly exergonic for photoreduction. In general, a good correlation has been observed between the experimental results and theoretical calculations, which has allowed a synergic understanding of the phenomenon.The Spanish Government (CTQ2015-70164-P, CTQ2017-87054-C2-2-P, SVP-2013-068057 grants to A.B.F.-R. and RYC-2015-19234 grant to D.R.-S.) and the Valencia Regional Government (Prometeo/2017/075) are acknowledged for financial support. A.F.-M. is grateful to the Region Grand Est government (France) and the Universite de Lorraine for their financial support.Fraga-Timiraos, AB.; Francés-Monerris, A.; Rodríguez Muñiz, GM.; Navarrete-Miguel, M.; Miranda Alonso, MÁ.; Roca Sanjuan, D.; Lhiaubet, VL. (2018). Experimental and Theoretical Study on the Cycloreversion of a Nucleobase-Derived Azetidine by Photoinduced Electron Transfer. Chemistry - A European Journal. 24(57):15346-15354. https://doi.org/10.1002/chem.201803298S15346153542457Antermite, D., Degennaro, L., & Luisi, R. (2017). Recent advances in the chemistry of metallated azetidines. Organic & Biomolecular Chemistry, 15(1), 34-50. doi:10.1039/c6ob01665kCanu, N., Belin, P., Thai, R., Correia, I., Lequin, O., Seguin, J., … Gondry, M. (2018). Incorporation of Non-canonical Amino Acids into 2,5-Diketopiperazines by Cyclodipeptide Synthases. Angewandte Chemie International Edition, 57(12), 3118-3122. doi:10.1002/anie.201712536Canu, N., Belin, P., Thai, R., Correia, I., Lequin, O., Seguin, J., … Gondry, M. (2018). Incorporation of Non-canonical Amino Acids into 2,5-Diketopiperazines by Cyclodipeptide Synthases. Angewandte Chemie, 130(12), 3172-3176. doi:10.1002/ange.201712536Meyer, F. (2016). Trifluoromethyl nitrogen heterocycles: synthetic aspects and potential biological targets. Chemical Communications, 52(15), 3077-3094. doi:10.1039/c5cc09414cBrandi, A., Cicchi, S., & Cordero, F. M. (2008). Novel Syntheses of Azetidines and Azetidinones. Chemical Reviews, 108(9), 3988-4035. doi:10.1021/cr800325eCarreira, E. M., & Fessard, T. C. (2014). Four-Membered Ring-Containing Spirocycles: Synthetic Strategies and Opportunities. Chemical Reviews, 114(16), 8257-8322. doi:10.1021/cr500127bLopchuk, J. M., Fjelbye, K., Kawamata, Y., Malins, L. R., Pan, C.-M., Gianatassio, R., … Baran, P. S. (2017). Strain-Release Heteroatom Functionalization: Development, Scope, and Stereospecificity. Journal of the American Chemical Society, 139(8), 3209-3226. doi:10.1021/jacs.6b13229Hameed, A., Javed, S., Noreen, R., Huma, T., Iqbal, S., Umbreen, H., … Farooq, T. (2017). Facile and Green Synthesis of Saturated Cyclic Amines. Molecules, 22(10), 1691. doi:10.3390/molecules22101691Mehra, V., Lumb, I., Anand, A., & Kumar, V. (2017). Recent advances in synthetic facets of immensely reactive azetidines. RSC Adv., 7(72), 45763-45783. doi:10.1039/c7ra08884aKumarasamy, E., Kandappa, S. K., Raghunathan, R., Jockusch, S., & Sivaguru, J. (2017). Realizing an Aza Paternò-Büchi Reaction. Angewandte Chemie International Edition, 56(25), 7056-7061. doi:10.1002/anie.201702273Kumarasamy, E., Kandappa, S. K., Raghunathan, R., Jockusch, S., & Sivaguru, J. (2017). Realizing an Aza Paternò-Büchi Reaction. Angewandte Chemie, 129(25), 7162-7167. doi:10.1002/ange.201702273Schmid, S. C., Guzei, I. A., & Schomaker, J. M. (2017). A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines. Angewandte Chemie International Edition, 56(40), 12229-12233. doi:10.1002/anie.201705202Schmid, S. C., Guzei, I. A., & Schomaker, J. M. (2017). A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines. Angewandte Chemie, 129(40), 12397-12401. doi:10.1002/ange.201705202Diethelm, S., & Carreira, E. M. (2015). Total Synthesis of Gelsemoxonine through a Spirocyclopropane Isoxazolidine Ring Contraction. Journal of the American Chemical Society, 137(18), 6084-6096. doi:10.1021/jacs.5b02574Glawar, A. F. G., Jenkinson, S. F., Thompson, A. L., Nakagawa, S., Kato, A., Butters, T. D., & Fleet, G. W. J. (2013). 3-Hydroxyazetidine Carboxylic Acids: Non-Proteinogenic Amino Acids for Medicinal Chemists. ChemMedChem, 8(4), 658-666. doi:10.1002/cmdc.201200541Kagiyama, I., Kato, H., Nehira, T., Frisvad, J. C., Sherman, D. H., Williams, R. M., & Tsukamoto, S. (2015). Taichunamides: Prenylated Indole Alkaloids from Aspergillus taichungensis (IBT 19404). Angewandte Chemie International Edition, 55(3), 1128-1132. doi:10.1002/anie.201509462Kagiyama, I., Kato, H., Nehira, T., Frisvad, J. C., Sherman, D. H., Williams, R. M., & Tsukamoto, S. (2015). Taichunamides: Prenylated Indole Alkaloids from Aspergillus taichungensis (IBT 19404). Angewandte Chemie, 128(3), 1140-1144. doi:10.1002/ange.201509462Kato, N., Comer, E., Sakata-Kato, T., Sharma, A., Sharma, M., Maetani, M., … Corey, V. (2016). Diversity-oriented synthesis yields novel multistage antimalarial inhibitors. Nature, 538(7625), 344-349. doi:10.1038/nature19804Wang, X., Liu, C., Zeng, X., Wang, X., Wang, X., & Hu, Y. (2017). Ruthenium-Catalyzed Synthesis of Fused Tricyclic 1H-2,3-Dihydropyrimido[1,2-a]quinolines in One Step. Organic Letters, 19(13), 3378-3381. doi:10.1021/acs.orglett.7b01330Sarazen, M. L., & Jones, C. W. (2017). Insights into Azetidine Polymerization for the Preparation of Poly(propylenimine)-Based CO2 Adsorbents. Macromolecules, 50(23), 9135-9143. doi:10.1021/acs.macromol.7b02402Schnitzer, T., & Wennemers, H. (2017). Influence of theTrans/CisConformer Ratio on the Stereoselectivity of Peptidic Catalysts. Journal of the American Chemical Society, 139(43), 15356-15362. doi:10.1021/jacs.7b06194Kaiser, A., Mayer, K. K., Sellmer, A., & Wiegrebe, W. (2003). Electron Impact Induced Fragmentation of Aromatic Alkoxyimines II [5]. Formation and Transformation of Heterocyclic Radical Cations in the Gas Phase a. Monatshefte f�r Chemie / Chemical Monthly, 134(3), 343-354. doi:10.1007/s00706-002-0485-8Andreu, I., Delgado, J., Espinós, A., Pérez-Ruiz, R., Jiménez, M. C., & Miranda, M. A. (2008). Cycloreversion of Azetidines via Oxidative Electron Transfer. Steady-State and Time-Resolved Studies. Organic Letters, 10(22), 5207-5210. doi:10.1021/ol802181uFraga-Timiraos, A. B., Lhiaubet-Vallet, V., & Miranda, M. A. (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. doi:10.1002/anie.201601475Fraga-Timiraos, A. B., Lhiaubet-Vallet, V., & Miranda, M. A. (2016). Repair of a Dimeric Azetidine Related to the Thymine-Cytosine (6- 4) Photoproduct by Electron Transfer Photoreduction. Angewandte Chemie, 128(20), 6141-6144. doi:10.1002/ange.201601475Fraga-Timiraos, A., Rodríguez-Muñiz, G., Peiro-Penalba, V., Miranda, M., & Lhiaubet-Vallet, V. (2016). Stereoselective Fluorescence Quenching in the Electron Transfer Photooxidation of Nucleobase-Related Azetidines by Cyanoaromatics. Molecules, 21(12), 1683. doi:10.3390/molecules21121683Pérez-Ruiz, R., Jiménez, M. C., & Miranda, M. A. (2014). Hetero-cycloreversions Mediated by Photoinduced Electron Transfer. Accounts of Chemical Research, 47(4), 1359-1368. doi:10.1021/ar4003224Leo, E. A., Domingo, L. R., Miranda, M. A., & Tormos, R. (2006). Photogeneration and Reactivity of 1,n-Diphenyl-1,n-azabiradicals. The Journal of Organic Chemistry, 71(12), 4439-4444. doi:10.1021/jo0601967Cichon, M. K., Arnold, S., & Carell, T. (2002). A (6-4) Photolyase Model: Repair of DNA (6-4) Lesions Requires a Reduced and Deprotonated Flavin This work was supported by the Volkswagen Foundation, the Fonds der Chemischen Industry, and the Bundesministerium für Bildung und Forschung (BMBF: Neue Medien in der Bildung). Angewandte Chemie International Edition, 41(5), 767. doi:10.1002/1521-3773(20020301)41:53.0.co;2-bCichon, M. K., Arnold, S., & Carell, T. (2002). A (6-4) Photolyase Model: Repair of DNA (6-4) Lesions Requires a Reduced and Deprotonated Flavin. Angewandte Chemie, 114(5), 793-796. doi:10.1002/1521-3757(20020301)114:53.0.co;2-wPrakash, G., & Falvey, D. E. (1995). Model studies of the (6-4) photoproduct DNA photolyase: Synthesis and photosensitized splitting of a thymine-5,6-oxetane. Journal of the American Chemical Society, 117(45), 11375-11376. doi:10.1021/ja00150a050Joseph, A., & Falvey, D. E. (2002). Photoinduced electron transfer cleavage of oxetane adducts of uracil and cytosine. Photochemical & Photobiological Sciences, 1(9), 632-635. doi:10.1039/b201740gTrzcionka, J., Lhiaubet-Vallet, V., Paris, C., Belmadoui, N., Climent, M. J., & Miranda, M. A. (2007). Model Studies on a Carprofen Derivative as Dual Photosensitizer for Thymine Dimerization and (6–4) Photoproduct Repair. ChemBioChem, 8(4), 402-407. doi:10.1002/cbic.200600394Wu, Q.-Q., & Song, Q.-H. (2010). Photosensitized Splitting of Thymine Dimer or Oxetane Unit by a CovalentlyN-Linked Carbazole via Electron Transfer in Different Marcus Regions. The Journal of Physical Chemistry B, 114(30), 9827-9832. doi:10.1021/jp1035579Pérez-Ruiz, R., Miranda, M. A., Alle, R., Meerholz, K., & Griesbeck, A. G. (2006). An efficient carbonyl-alkene metathesis of bicyclic oxetanes: photoinduced electron transfer reduction of the Paternò–Büchi adducts from 2,3-dihydrofuran and aromatic aldehydes. Photochem. Photobiol. Sci., 5(1), 51-55. doi:10.1039/b513875bIzquierdo, M. A., Domingo, L. R., & Miranda, M. A. (2005). Theoretical Calculations on the Cycloreversion of Oxetane Radical Cations. The Journal of Physical Chemistry A, 109(11), 2602-2607. doi:10.1021/jp045832oMiranda, M. A., & Izquierdo, M. A. (2003). Chemical and transient spectroscopic evidence for C2–C3 cleavage of 2,3-diaryloxetane radical cations. Chemical Communications, (3), 364-365. doi:10.1039/b209500aMiranda, M. A., & Izquierdo, M. A. (2002). Stepwise Cycloreversion of Oxetane Radical Cations with Initial C−O Bond Cleavage. Journal of the American Chemical Society, 124(23), 6532-6533. doi:10.1021/ja025697yPérez-Ruiz, R., Sáez, J. A., Domingo, L. R., Jiménez, M. C., & Miranda, M. A. (2012). Oxetane Ring Enlargement through Nucleophilic Trapping of Radical Cations by Acetonitrile. Organic Letters, 14(22), 5700-5703. doi:10.1021/ol302717sGlas, A. F., Schneider, S., Maul, M. J., Hennecke, U., & Carell, T. (2009). Crystal Structure of the T(6-4)C Lesion in Complex with a (6-4) DNA Photolyase and Repair of UV-Induced (6-4) and Dewar Photolesions. Chemistry - A European Journal, 15(40), 10387-10396. doi:10.1002/chem.200901004Maul, M. J., Barends, T. R. M., Glas, A. F., Cryle, M. J., Domratcheva, T., Schneider, S., … Carell, T. (2008). Crystal Structure and Mechanism of a DNA (6-4) Photolyase. Angewandte Chemie International Edition, 47(52), 10076-10080. doi:10.1002/anie.200804268Maul, M. J., Barends, T. R. M., Glas, A. F., Cryle, M. J., Domratcheva, T., Schneider, S., … Carell, T. (2008). Röntgenkristallstruktur und Mechanismus der DNA-(6-4)-Photolyase. Angewandte Chemie, 120(52), 10230-10234. doi:10.1002/ange.200804268Faraji, S., & Dreuw, A. (2017). Insights into Light-driven DNA Repair by Photolyases: Challenges and Opportunities for Electronic Structure Theory. Photochemistry and Photobiology, 93(1), 37-50. doi:10.1111/php.12679Yamamoto, J., Plaza, P., & Brettel, K. (2017). Repair of (6-4) Lesions in DNA by (6-4) Photolyase: 20 Years of Quest for the Photoreaction Mechanism. Photochemistry and Photobiology, 93(1), 51-66. doi:10.1111/php.12696Zhang, M., Wang, L., & Zhong, D. (2017). Photolyase: Dynamics and Mechanisms of Repair of Sun-Induced DNA Damage. Photochemistry and Photobiology, 93(1), 78-92. doi:10.1111/php.12695Faraji, S., Zhong, D., & Dreuw, A. (2016). Characterization of the Intermediate in and Identification of the Repair Mechanism of (6- 4) Photolesions by Photolyases. Angewandte Chemie International Edition, 55(17), 5175-5178. doi:10.1002/anie.201511950Faraji, S., Zhong, D., & Dreuw, A. (2016). Characterization of the Intermediate in and Identification of the Repair Mechanism of (6- 4) Photolesions by Photolyases. Angewandte Chemie, 128(17), 5261-5264. doi:10.1002/ange.201511950Sancar, A. (2003). Structure and Function of DNA Photolyase and Cryptochrome Blue-Light Photoreceptors. Chemical Reviews, 103(6), 2203-2238. doi:10.1021/cr0204348Yamamoto, J., Martin, R., Iwai, S., Plaza, P., & Brettel, K. (2013). Repair of the (6-4) Photoproduct by DNA Photolyase Requires Two Photons. Angewandte Chemie International Edition, 52(29), 7432-7436. doi:10.1002/anie.201301567Yamamoto, J., Martin, R., Iwai, S., Plaza, P., & Brettel, K. (2013). Repair of the (6-4) Photoproduct by DNA Photolyase Requires Two Photons. Angewandte Chemie, 125(29), 7580-7584. doi:10.1002/ange.201301567Scannell, M. P., Fenick, D. J., Yeh, S.-R., & Falvey, D. E. (1997). Model Studies of DNA Photorepair:  Reduction Potentials of Thymine and Cytosine Cyclobutane Dimers Measured by Fluorescence Quenching. Journal of the American Chemical Society, 119(8), 1971-1977. doi:10.1021/ja963360oYeh, S. R., & Falvey, D. E. (1992). Model studies of DNA photorepair: energetic requirements for the radical anion mechanism determined by fluorescence quenching. Journal of the American Chemical Society, 114(18), 7313-7314. doi:10.1021/ja00044a063Pac, C., Ohtsuki, T., Shiota, Y., Yanagida, S., & Sakurai, H. (1986). Photochemical Reactions of Aromatic Compounds. XLII. Photosensitized Reactions of Some Selected Diarylcyclobutanes by Aromatic Nitriles and Chloranil. Implications of Charge-Transfer Contributions on Exciplex Reactivities. Bulletin of the Chemical Society of Japan, 59(4), 1133-1139. doi:10.1246/bcsj.59.1133Boussicault, F., Krüger, O., Robert, M., & Wille, U. (2004). Dissociative electron transfer to and from pyrimidine cyclobutane dimers: An electrochemical study. Org. Biomol. Chem., 2(19), 2742-2750. doi:10.1039/b406923dBoussicault, F., & Robert, M. (2008). Electron Transfer in DNA and in DNA-Related Biological Processes. Electrochemical Insights. Chemical Reviews, 108(7), 2622-2645. doi:10.1021/cr0680787Wenska, G., & Paszyc, S. (1990). Electron-acceptor-sensitized splitting of cyclobutane-type thymine dimers. Journal of Photochemistry and Photobiology B: Biology, 8(1), 27-37. doi:10.1016/1011-1344(90)85185-yFenick, D. J., Carr, H. S., & Falvey, D. E. (1995). Synthesis and Photochemical Cleavage of Cis-Syn Pyrimidine Cyclobutane Dimer Analogs. The Journal of Organic Chemistry, 60(3), 624-631. doi:10.1021/jo00108a026Pac, C., Miyamoto, I., Masaki, Y., Furusho, S., Yanagida, S., Ohno, T., & Yoshimura, A. (1990). CHLORANIL-PHOTOSENSITIZED MONOMERIZATION OF DIMETHYLTHYMINE CYCLOBUTANE DIMERS and EFFECT OF MAGNESIUM PERCHLORATE. Photochemistry and Photobiology, 52(5), 973-979. doi:10.1111/j.1751-1097.1990.tb01813.xNguyen, K. V., & Burrows, C. J. (2011). A Prebiotic Role for 8-Oxoguanosine as a Flavin Mimic in Pyrimidine Dimer Photorepair. Journal of the American Chemical Society, 133(37), 14586-14589. doi:10.1021/ja2072252Behrens, C., & Carell, T. (2003). Excess electron transfer in flavin-capped, thymine dimer-containing DNA hairpins. Chemical Communications, (14), 1632. doi:10.1039/b303805jCamp, J. R., Young, T., Hartman, R. F., & Rose, S. D. (1987). PHOTOSENSITIZATION OF PYRIMIDINE DIMER SPLITTING BY A COVALENTLY BOUND INDOLE. Photochemistry and Photobiology, 45(3), 365-370. doi:10.1111/j.1751-1097.1987.tb05388.xFrancés-Monerris, A., Segarra-Martí, J., Merchán, M., & Roca-Sanjuán, D. (2015). Complete-active-space second-order perturbation theory (CASPT2//CASSCF) study of the dissociative electron attachment in canonical DNA nucleobases caused by low-energy electrons (0-3 eV). The Journal of Chemical Physics, 143(21), 215101. doi:10.1063/1.4936574González-Ramírez, I., Segarra-Martí, J., Serrano-Andrés, L., Merchán, M., Rubio, M., & Roca-Sanjuán, D. (2012). On the N1–H and N3–H Bond Dissociation in Uracil by Low Energy Electrons: A CASSCF/CASPT2 Study. Journal of Chemical Theory and Computation, 8(8), 2769-2776. doi:10.1021/ct300153fRoca-Sanjuán, D., Merchán, M., Serrano-Andrés, L., & Rubio, M. (2008). Ab initio determination of the electron affinities of DNA and RNA nucleobases. The Journal of Chemical Physics, 129(9), 095104. doi:10.1063/1.2958286Durbeej, B., & Eriksson, L. A. (2000). Thermodynamics of the Photoenzymic Repair Mechanism Studied by Density Functional Theory. Journal of the American Chemical Society, 122(41), 10126-10132. doi:10.1021/ja000929jAparici-Espert, I., Garcia-Lainez, G., Andreu, I., Miranda, M. A., & Lhiaubet-Vallet, V. (2018). Oxidatively Generated Lesions as Internal Photosensitizers for Pyrimidine Dimerization in DNA. ACS Chemical Biology, 13(3), 542-547. doi:10.1021/acschembio.7b01097Pavlishchuk, V. V., & Addison, A. W. (2000). Conversion constants for redox potentials measured versus different reference electrodes in acetonitrile solutions at 25°C. Inorganica Chimica Acta, 298(1), 97-102. doi:10.1016/s0020-1693(99)00407-7Zhao, Y., & Truhlar, D. G. (2007). The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theoretical Chemistry Accounts, 120(1-3), 215-241. doi:10.1007/s00214-007-0310-xGaussian 09 Revision D.01 M. J. Frisch G. W. Trucks H. B. Schlegel G. E. Scuseria M. A. Robb J. R. Cheeseman G. Scalmani V. Barone G. A. Petersson H. Nakatsuji X. Li M. Caricato A. Marenich J. Bloino R. Janesko R. Gomperts B. Menucci H. P. Hratchian J. V. Ortiz A. F. Izmaylov D. Sonnenberg F. Williams-Young F. Ding F. Lipparini F. Edigi J. Goings B. Peng A. Petrone T. Henderson D. Ranasinghe V. G. Zakrzewski J. Gao N. Rega W. Zheng W. Liang M. Hada M. Ehara K. Toyota R. Fukuda M. Hasegawa T. Ishida T. Nakajima Y. Honda O. Kitao H. Nakai T. Vreven K. Throssell M. J. J. A. J. E. Peralta F. Ogliaro M. Bearpark J. J. Heyd E. Brothers K. N. Kudin V. N. Staroverov T. Keith R. Kobayashi J. Normand K. Raghavachari A. Rendell J. C. Burant S. S. Iyengar J. Tomasi M. Cossi J. M. Millam M. Klene C. Adamo R. Cammi J. W. Ochterski R. L. Martin K. Morokuma O. Farkas J. B. Foresman D. J. Fox Wallingford CT 2013.Aranda, J., Francés-Monerris, A., Tuñón, I., & Roca-Sanjuán, D. (2017). Regioselectivity of the OH Radical Addition to Uracil in Nucleic Acids. A Theoretical Approach Based on QM/MM Simulations. Journal of Chemical Theory and Computation, 13(10), 5089-5096. doi:10.1021/acs.jctc.7b00610Francés-Monerris, A., Merchán, M., & Roca-Sanjuán, D. (2014). Theoretical Study of the Hydroxyl Radical Addition to Uracil and Photochemistry of the Formed U6OH•Adduct. The Journal of Physical Chemistry B, 118(11), 2932-2939. doi:10.1021/jp412347kFrancés-Monerris, A., Merchán, M., & Roca-Sanjuán, D. (2016). Mechanism of the OH Radical Addition to Adenine from Quantum-Chemistry Determinations of Reaction Paths and Spectroscopic Tracking of the Intermediates. The Journal of Organic Chemistry, 82(1), 276-288. doi:10.1021/acs.joc.6b02393Isayev, O., Gorb, L., & Leszczynski, J. (2007). Theoretical calculations: Can Gibbs free energy for intermolecular complexes be predicted efficiently and accurately? Journal of Computational Chemistry, 28(9), 1598-1609. doi:10.1002/jcc.20696Andersson, K., Malmqvist, P., & Roos, B. O. (1992). Second‐order perturbation theory with a complete active space self‐consistent field reference function. The Journal of Chemical Physics, 96(2), 1218-1226. doi:10.1063/1.462209Roca-Sanjuán, D., Aquilante, F., & Lindh, R. (2011). Multiconfiguration second-order perturbation theory approach to strong electron correlation in chemistry and photochemistry. Wiley Interdisciplinary Reviews: Computational Molecular Science, 2(4), 585-603. doi:10.1002/wcms.97Forsberg, N., & Malmqvist, P.-Å. (1997). Multiconfiguration perturbation theory with imaginary level shift. Chemical Physics Letters, 274(1-3), 196-204. doi:10.1016/s0009-2614(97)00669-6Ghigo, G., Roos, B. O., & Malmqvist, P.-Å. (2004). A modified definition of the zeroth-order Hamiltonian in multiconfigurational perturbation theory (CASPT2). Chemical Physics Letters, 396(1-3), 142-149. doi:10.1016/j.cplett.2004.08.032Roca-Sanjuán, D., Rubio, M., Merchán, M., & Serrano-Andrés, L. (2006). Ab initiodetermination of the ionization potentials of DNA and RNA nucleobases. The Journal of Chemical Physics, 125(8), 084302. doi:10.1063/1.2336217Aquilante, F., Autschbach, J., Carlson, R. K., Chibotaru, L. F., Delcey, M. G., De Vico, L., … Lindh, R. (2015). Molcas8: New capabilities for multiconfigurational quantum chemical

Characterization of Locally Excited and Charge-Transfer States of the Anticancer Drug Lapatinib by Ultrafast Spectroscopy and Computational Studies

This is the peer reviewed version of the following article: I. Vayá, I. Andreu, E. Lence, C. González-Bello, M. Consuelo Cuquerella, M. Navarrete-Miguel, D. Roca-Sanjuán, M. A. Miranda, Chem. Eur. J. 2020, 26, 15922, which has been published in final form at https://doi.org/10.1002/chem.202001336. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] Lapatinib (LAP) is an anticancer drug, which is metabolized to theN- and O-dealkylated products (N-LAP andO-LAP, respectively). In view of the photosensitizing potential of related drugs, a complete experimental and theoretical study has been performed on LAP,N-LAP andO-LAP, both in solution and upon complexation with human serum albumin (HSA). In organic solvents, coplanar locally excited (LE) emissive states are generated; they rapidly evolve towards twisted intramolecular charge-transfer (ICT) states. By contrast, within HSA only LE states are detected. Accordingly, femtosecond transient absorption reveals a very fast switching (ca. 2 ps) from LE (lambda(max)=550 nm) to ICT states (lambda(max)=480 nm) in solution, whereas within HSA the LE species become stabilized and live much longer (up to the ns scale). Interestingly, molecular dynamics simulation studies confirm that the coplanar orientation is preferred for LAP (or to a lesser extentN-LAP) within HSA, explaining the experimental results.Financial support from the Spanish Government (RYC-2015-17737, CTQ2017-89416-R, ISCIII grants RD16/0006/0004, PI16/01877 and CPII16/00052, SAF2016-75638-R, RYC-2015-19234, CTQ2017-87054-C2-2-P, and MDM-2015-0538), Conselleria d'Educacio Cultura i Esport (PROMETEO/2017/075), the Xunta de Galicia [ED431B 2018/04 and Centro singular de investigacion de Galicia accreditation 2019-2022 (ED431G 2019/03)] and the European Regional Development Fund is gratefully acknowledged. We thank the Centro de Supercomputacion de Galicia (CESGA) for use of the Finis Terrae computer.Vayá Pérez, I.; Andreu Ros, MI.; Lence, E.; González-Bello, C.; Cuquerella Alabort, MC.; Navarrete-Miguel, M.; Roca-Sanjuán, D.... (2020). Characterization of Locally Excited and Charge-Transfer States of the Anticancer Drug Lapatinib by Ultrafast Spectroscopy and Computational Studies. Chemistry - A European Journal. 26(68):15922-15930. https://doi.org/10.1002/chem.202001336S15922159302668Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394-424. doi:10.3322/caac.21492Nicholson, R. ., Gee, J. M. ., & Harper, M. . (2001). EGFR and cancer prognosis. European Journal of Cancer, 37, 9-15. doi:10.1016/s0959-8049(01)00231-3Yashiro, M., Qiu, H., Hasegawa, T., Zhang, X., Matsuzaki, T., & Hirakawa, K. (2011). An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells. British Journal of Cancer, 105(10), 1522-1532. doi:10.1038/bjc.2011.397Gonzalez, G., & Lage, A. (2007). Cancer Vaccines for Hormone/Growth Factor Immune Deprivation:A Feasible Approach for Cancer Treatment. Current Cancer Drug Targets, 7(3), 229-241. doi:10.2174/156800907780618310Sigismund, S., Avanzato, D., & Lanzetti, L. (2017). Emerging functions of the EGFR in cancer. Molecular Oncology, 12(1), 3-20. doi:10.1002/1878-0261.12155Thomas, R., & Weihua, Z. (2019). Rethink of EGFR in Cancer With Its Kinase Independent Function on Board. Frontiers in Oncology, 9. doi:10.3389/fonc.2019.00800MEDINA, P., & GOODIN, S. (2008). Lapatinib: A dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clinical Therapeutics, 30(8), 1426-1447. doi:10.1016/j.clinthera.2008.08.008Nolting, M., Schneider-Merck, T., & Trepel, M. (2014). Lapatinib. Small Molecules in Oncology, 125-143. doi:10.1007/978-3-642-54490-3_7Schroeder, R., Stevens, C., & Sridhar, J. (2014). Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer. Molecules, 19(9), 15196-15212. doi:10.3390/molecules190915196Spector, N. L., Xia, W., Burris, H., Hurwitz, H., Dees, E. C., Dowlati, A., … Bacus, S. (2005). Study of the Biologic Effects of Lapatinib, a Reversible Inhibitor of ErbB1 and ErbB2 Tyrosine Kinases, on Tumor Growth and Survival Pathways in Patients With Advanced Malignancies. Journal of Clinical Oncology, 23(11), 2502-2512. doi:10.1200/jco.2005.12.157Krasner, J. (1972). Drug-Protein Interaction. Pediatric Clinics of North America, 19(1), 51-63. doi:10.1016/s0031-3955(16)32666-9Peters, T. (1995). Ligand Binding by Albumin. All About Albumin, 76-132. doi:10.1016/b978-012552110-9/50005-2Molins-Molina, O., Lence, E., Limones-Herrero, D., González-Bello, C., Miranda, M. A., & Jiménez, M. C. (2019). Identification of a common recognition center for a photoactive non-steroidal antiinflammatory drug in serum albumins of different species. Organic Chemistry Frontiers, 6(1), 99-109. doi:10.1039/c8qo01045eMolins-Molina, O., Pérez-Ruiz, R., Lence, E., González-Bello, C., Miranda, M. A., & Jiménez, M. C. (2019). Photobinding of Triflusal to Human Serum Albumin Investigated by Fluorescence, Proteomic Analysis, and Computational Studies. Frontiers in Pharmacology, 10. doi:10.3389/fphar.2019.01028Monteiro, A. F., Rato, M., & Martins, C. (2016). Drug-induced photosensitivity: Photoallergic and phototoxic reactions. Clinics in Dermatology, 34(5), 571-581. doi:10.1016/j.clindermatol.2016.05.006Vayá, I., Andreu, I., Monje, V. T., Jiménez, M. C., & Miranda, M. A. (2015). Mechanistic Studies on the Photoallergy Mediated by Fenofibric Acid: Photoreactivity with Serum Albumins. Chemical Research in Toxicology, 29(1), 40-46. doi:10.1021/acs.chemrestox.5b00357Vayá, I., Lhiaubet-Vallet, V., Jiménez, M. C., & Miranda, M. A. (2014). Photoactive assemblies of organic compounds and biomolecules: drug–protein supramolecular systems. Chem. Soc. Rev., 43(12), 4102-4122. doi:10.1039/c3cs60413fIshikawa, T., Kamide, R., & Niimura, M. (1994). Photoleukomelanodermatitis (Kobori) Induced by Afloqualone. The Journal of Dermatology, 21(6), 430-433. doi:10.1111/j.1346-8138.1994.tb01768.xKabir, M. Z., Mukarram, A. K., Mohamad, S. B., Alias, Z., & Tayyab, S. (2016). Characterization of the binding of an anticancer drug, lapatinib to human serum albumin. Journal of Photochemistry and Photobiology B: Biology, 160, 229-239. doi:10.1016/j.jphotobiol.2016.04.005Shen, G.-F., Liu, T.-T., Wang, Q., Jiang, M., & Shi, J.-H. (2015). Spectroscopic and molecular docking studies of binding interaction of gefitinib, lapatinib and sunitinib with bovine serum albumin (BSA). Journal of Photochemistry and Photobiology B: Biology, 153, 380-390. doi:10.1016/j.jphotobiol.2015.10.023Wilson, J. N., Liu, W., Brown, A. S., & Landgraf, R. (2015). Binding-induced, turn-on fluorescence of the EGFR/ERBB kinase inhibitor, lapatinib. Organic & Biomolecular Chemistry, 13(17), 5006-5011. doi:10.1039/c5ob00239gLi, M.-D., Yan, Z., Zhu, R., Phillips, D. L., Aparici-Espert, I., Lhiaubet-Vallet, V., & Miranda, M. A. (2018). Enhanced Drug Photosafety by Interchromophoric Interaction Owing to Intramolecular Charge Separation. Chemistry - A European Journal, 24(25), 6654-6659. doi:10.1002/chem.201800716Vayá, I., Bonancía, P., Jiménez, M. C., Markovitsi, D., Gustavsson, T., & Miranda, M. A. (2013). Excited state interactions between flurbiprofen and tryptophan in drug–protein complexes and in model dyads. Fluorescence studies from the femtosecond to the nanosecond time domains. Physical Chemistry Chemical Physics, 15(13), 4727. doi:10.1039/c3cp43847cAndersson, K., Malmqvist, P., & Roos, B. O. (1992). Second‐order perturbation theory with a complete active space self‐consistent field reference function. The Journal of Chemical Physics, 96(2), 1218-1226. doi:10.1063/1.462209Andersson, K., Malmqvist, P. A., Roos, B. O., Sadlej, A. J., & Wolinski, K. (1990). Second-order perturbation theory with a CASSCF reference function. The Journal of Physical Chemistry, 94(14), 5483-5488. doi:10.1021/j100377a012Roca-Sanjuán, D., Aquilante, F., & Lindh, R. (2011). Multiconfiguration second-order perturbation theory approach to strong electron correlation in chemistry and photochemistry. Wiley Interdisciplinary Reviews: Computational Molecular Science, 2(4), 585-603. doi:10.1002/wcms.97In:http://www.ccdc.cam.ac.uk/solutions/csd-discovery/components/gold/(accessed January 22 2020).Zunszain, P. A., Ghuman, J., Komatsu, T., Tsuchida, E., & Curry, S. (2003). BMC Structural Biology, 3(1), 6. doi:10.1186/1472-6807-3-6D. A. Case R. M. Betz D. S. Cerutti T. E. Cheatham T. A. Darden R. E. Duke T. J. Giese H. Gohlke A. W. Goetz N. Homeyer S. Izadi P. Janowski J. J. Kaus A. Kovalenko T. S. Lee S. LeGrand P. Li C. Lin T. Luchko R. Luo B. Madej D. Mermelstein K. M. M. Merz G. Monard H. Nguyen H. Nguyen I. Omelyan A. Onufriev D. R. R. Roe A. Roitberg C. Sagui C. L. Simmerling W. M. Botello-Smith J. Swails R. Walker J. Wang R. M. Wolf X. Wu L. Xiao P. A. Kollman AMBER2016 University of California San Francisco.Wybranowski, T., Cyrankiewicz, M., Ziomkowska, B., & Kruszewski, S. (2008). The HSA affinity of warfarin and flurbiprofen determined by fluorescence anisotropy measurements of camptothecin. Biosystems, 94(3), 258-262. doi:10.1016/j.biosystems.2008.05.034Itoh, T., Saura, Y., Tsuda, Y., & Yamada, H. (1997). Stereoselectivity and enantiomer-enantiomer interactions in the binding of ibuprofen to human serum albumin. Chirality, 9(7), 643-649. doi:10.1002/(sici)1520-636x(1997)9:73.0.co;2-8Pérez-Ruíz, R., Lence, E., Andreu, I., Limones-Herrero, D., González-Bello, C., Miranda, M. A., & Jiménez, M. C. (2017). A New Pathway for Protein Haptenation by β-Lactams. Chemistry - A European Journal, 23(56), 13986-13994. doi:10.1002/chem.201702643Gaussian 09 Revision D.01 M. J. Frisch G. W. Trucks H. B. Schlegel G. E. Scuseria M. A. Robb J. R. Cheeseman G. Scalmani V. Barone B. Mennucci G. A. Petersson H. Nakatsuji M. Caricato X. Li H. P. Hratchian A. F. Izmaylov J. Bloino G. Zheng J. L. Sonnenberg M. Hada M. Ehara K. Toyota R. Fukuda J. Hasegawa M. Ishida T. Nakajima Y. Honda O. Kitao H. Nakai T. Vreven J. J. A. Montgomery J. E. Peralta F. Ogliaro M. Bearpark J. J. Heyd E. Brothers K. N. Kudin V. N. Staroverov R. Kobayashi J. Normand K. Raghavachari A. Rendell J. C. Burant S. S. Iyengar J. Tomasi M. Cossi N. Rega J. M. Millam M. Klene J. E. Knox J. B. Cross V. Bakken C. Adamo J. Jaramillo R. Gomperts R. E. Stratmann O. Yazyev A. J. Austin R. Cammi C. Pomelli J. W. Ochterski R. L. Martin K. Morokuma V. G. Zakrzewski G. A. Voth P. Salvador J. J. Dannenberg S. Dapprich A. D. Daniels Ö. Farkas J. B. Foresman J. V. Ortiz J. Cioslowski D. J. Fox 2013 Wallingford CT.Aquilante, F., Autschbach, J., Carlson, R. K., Chibotaru, L. F., Delcey, M. G., De Vico, L., … Lindh, R. (2015). Molcas 8: New capabilities for multiconfigurational quantum chemical calculations across the periodic table. Journal of Computational Chemistry, 37(5), 506-541. doi:10.1002/jcc.24221Forsberg, N., & Malmqvist, P.-Å. (1997). Multiconfiguration perturbation theory with imaginary level shift. Chemical Physics Letters, 274(1-3), 196-204. doi:10.1016/s0009-2614(97)00669-6W. L. DeLano in The PyMOL Molecular Graphics System.http://www.pymol.org/

Un acercamiento a los desafíos del aprendizaje virtual en tiempos de COVID-19

The challenges of virtual learning in times of COVID-19 were analyzed at the Faculty of Secondary Education of the "Félix Varela Morales" Pedagogical Headquarters, of the Marta Abreu de Las Villas Central University, located in the city of Santa Clara, Villa Clara Cuba between the years 2020-2021. The Materialist Dialectic was used as a general method, and the methods of the historical-logical, analytical-synthetic and inductive-deductive theoretical level. Bibliographic sources were reviewed including journal articles, books, research reports and documents that deal with the subject mainly between the years 2020-2021. Among the main results, the need to work in the direction of three great challenges stands out: the efficient use of technological resources available in Cuban universities, the preparation of teachers and students for virtual learning and the didactic organization of each one of the subjects. It is concluded that an approach to these three challenges of virtual learning in times of pandemic is required.Se analizaron los desafíos del aprendizaje virtual en tiempos de COVID-19 en la Facultad de Enseñanza Media de la Sede Pedagógica “Félix Varela Morales”, de la Universidad Central Marta Abreu de Las Villas, situada en la ciudad de Santa Clara, Villa Clara Cuba entre los años 2020-2021. Se utilizó como método general el Dialéctico Materialista, y los métodos del nivel teórico histórico-lógico, analítico-sintético e inductivo-deductivo. Se revisaron fuentes bibliográficas entre artículos de&nbsp; revistas, libros, informes de investigación y documentos que tratan la temática fundamentalmente entre los años 2020-2021. Entre los principales resultados se destaca la necesidad de trabajar en la dirección de tres grandes desafíos: la utilización eficiente de los recursos tecnológicos de que se disponen en las universidades cubanas, la preparación de docentes y estudiantes para el aprendizaje virtual y la organización didáctica de cada una de las asignaturas. Se concluye que se requiere un acercamiento a estos tres desafíos del aprendizaje virtual en tiempos de pandemia

Regiochemical memory in the adiabatic photolysis of thymine-derived oxetanes. A combined ultrafast spectroscopic and CASSCF/CASPT2 computational study

[EN] The photoinduced cycloreversion of oxetanes has been thoroughly investigated in connection with the photorepair of the well-known DNA (6-4) photoproducts. In the present work, the direct photolysis of the two regioisomers arising from the irradiation of benzophenone (BP) and 1,3-dimethylthymine (DMT), namely the head-to-head (HH-1) and head-to-tail (HT-1) oxetane adducts, has been investigated by combining ultrafast spectroscopy and theoretical multiconfigurational quantum chemistry analysis. Both the experimental and computational results agree with the involvement of an excited triplet exciplex(3)[BPMIDLINE HORIZONTAL ELLIPSISDMT]* for the photoinduced oxetane cleavage to generate(3)BP* and DMT through an adiabatic photochemical reaction. The experimental signature of(3)[BPMIDLINE HORIZONTAL ELLIPSISDMT]* is the appearance of an absorption band atca.400 nm, detected by femtosecond transient absorption spectroscopy. Its formation is markedly regioselective, as it is more efficient and proceeds faster for HH-1 (similar to 2.8 ps) than for HT-1 (similar to 6.3 ps). This is in line with the theoretical analysis, which predicts an energy barrier to reach the triplet exciplex for HT-1, in contrast with a less hindered profile for HH-1. Finally, the more favorable adiabatic cycloreversion of HH-1 compared to that of HT-1 is explained by its lower probability to reach the intersystem crossing with the ground state, which would induce a radiationless deactivation process leading either to a starting adduct or to a dissociated BP and DMT.Financial support from the Spanish Government (RYC-2015-17737, CTQ2017-89416-R, RYC-2015-19234, CTQ2017-87054-C2-2-P, and MDM-2015-0538), from the Conselleria d'Educacio, Investigacio, Cultura i Esport (PROMETEO/2017/075 and GRISOLiAP/2017/005) and from the Universitat de Valencia (postdoctoral grant within the "Atraccio de Talent 2019" Program for A. G.) is gratefully acknowledged. This work was also supported by a 2019 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation. The Foundation takes no responsibility for the opinions, statements, and contents of this project, which are entirely the responsibility of its authors.Blasco-Brusola, A.; Navarrete-Miguel, M.; Giussani, A.; Roca-Sanjuan, D.; Vayá Pérez, I.; Miranda Alonso, MÁ. (2020). Regiochemical memory in the adiabatic photolysis of thymine-derived oxetanes. A combined ultrafast spectroscopic and CASSCF/CASPT2 computational study. Physical Chemistry Chemical Physics. 22(35):20037-20042. https://doi.org/10.1039/d0cp03084hS2003720042223

Administración de riesgos. Volumen VIII. Ensayos sobre modelos, mercados y riesgos financieros

Desde 2019 ya se vislumbraba un panorama económico y financiero incierto, y se proyectaban diversos escenarios que abarcaban desde una desaceleración de la economía mundial para 2020, hasta una fuerte recesión debido a factores como: incremento en los déficit fiscales, tanto en naciones desarrolladas como emergentes; inestabilidad cambiaria, incertidumbre y volatilidad en los mercados financieros, caída en los precios del petróleo y un descenso en el volumen del comercio internacional y la actividad industrial, entre los principales indicadores. Sin embargo, ningún pronóstico previó que la inestabilidad económica y financiera sería provocada por una crisis sanitaria como lo es la pandemia del COVID-19. Se prevé que la economía mundial se recuperé durante 2021, a medida que el confinamiento y restricciones de movilidad de la población desaparezcan y conforme se intensifiquen las campañas de vacunación. Ante este panorama, es de esperarse que exista inestabilidad económica y financiera en los próximos años. Por tanto, el estudio de la situación financiera nacional e internacional, a través de los mercados e instrumentos financieros, y los riesgos financieros y económicos inherentes a su operación bajo condiciones de incertidumbre, continúan siendo temas de estudio prioritarios. Considerando lo anterior, este volumen está integrado por tres partes que tratan diversos enfoques sobre modelos, mercados y riesgos financieros. En la primera parte se presenta una reflexión crítica de uno de los principales modelos utilizados en las finanzas, el modelo de fijación de precios, CAPM. La segunda parte, trata la volatilidad de los mercados bursátiles de países miembros del Mercado Integrado Latinoamericano, MILA, los mercados petroleros y el mercado cambiario. En la última parte se analizan distintos tipos de riesgos financieros en diferentes contextos y mercados.Marissa R. Martínez-Preece; Carlos Zubieta-Badillo; Francisco López-Herrera, coordinadores

Anafilaxia en niños y adultos: prevención, diagnóstico y tratamiento

La anafilaxia es una condición que requiere asistencia inmediata para su resolución, se puede presentar en diferentes entornos: consultorio, hospital, escuela, hogar o en algún otro espacio público. La información aquí contenida forma parte de lineamientos conocidos sobre prevención, diagnóstico y tratamiento. Se abordan aspectos epidemiológicos, desencadenantes, factores de riesgo y cofactores; se explican de una manera didáctica los mecanismos fisiopatológicos que se traducen en fenotipos de presentación. Se enfatiza el diagnóstico clínico con base en criterios ya establecidos, se mencionan clasificaciones para evaluar la gravedad de la reacción, así como el rol de las pruebas clínicas o de laboratorio. Como aspectos de relevancia, se abordan el tratamiento de primera elección con adrenalina, instrucciones sobre autoinyectores y diferentes elementos para el tratamiento complementario y de segunda elección. También se refieren aspectos a considerar al dar de alta a un paciente y medidas de seguimiento, con un énfasis preventivo en la comunidad. Finalmente, se menciona el abordaje en el consultorio de alergia para decidir sobre opciones de inmunomodulación. ABSTRACT Anaphylaxis is a condition that requires immediate assistance for its resolution, it can occur in different settings: office, hospital, school, home or some other public space. The information contained herein forms part of known guidelines on prevention, diagnosis and treatment. Epidemiological aspects, triggers, risk factors and co-factors are addressed; physiopathological mechanisms that are translated into presentation phenotypes are explained in a didactic way. Clinical diagnosis is emphasized based on established criteria, classifications are mentioned to evaluate the severity of the reaction, as well as the role of clinical or laboratory tests. As relevant aspects, the first choice treatment with adrenaline, instructions on auto-injectors and different elements for the complementary and second choice treatment are dealt with. They also refer to aspects to consider when discharging a patient and followup measures, with a preventive emphasis on the community. Finally, the allergy clinic approach to deciding on immunomodulation options is mentione