Regioselectivity in the adiabatic photocleavage of DNA-based oxetanes

[EN] Direct absorption of UVB light by DNA may induce formation of cyclobutane pyrimidine dimers and pyrimidine-pyrimidone (6-4) photoproducts. The latter arise from the rearrangement of unstable oxetane intermediates, which have also been proposed to be the electron acceptor species in the photoenzymatic repair of this type of DNA damage. In the present work, direct photolysis of oxetanes composed of substituted uracil (Ura) or thymine (Thy) derivatives and benzophenone (BP) have been investigated by means of transient absorption spectroscopy from the femtosecond to the microsecond time-scales. The results showed that photoinduced oxetane cleavage takes place through an adiabatic process leading to the triplet excited BP and the ground state nucleobase. This process was markedly affected by the oxetane regiochemistry (head-to-head, HH, vs. head-to-tail, HT) and by the nucleobase substitution; it was nearly quantitative for all investigated HH-oxetanes while it became strongly influenced by the substitution at positions 1 and 5 for the HT-isomers. The obtained results clearly confirm the generality of the adiabatic photoinduced cleavage of BP/Ura or Thy oxetanes, as well as its dependence on the regiochemistry, supporting the involvement of triplet exciplexes. As a matter of fact, when formation of this species was favored by keeping together the Thy and BP units after splitting by means of a linear linker, a transient absorption at similar to 400 nm, ascribed to the exciplex, was detected.Financial support from the Spanish Government (RYC-2015-17737 and CTQ2017-89416-R) and from the Conselleria d'Educacio Cultura i Esport (PROMETEO/2017/075 and GRISOLIAP/2017/005) is gratefully acknowledged.Blasco-Brusola, A.; Vayá Pérez, I.; Miranda Alonso, MÁ. (2020). Regioselectivity in the adiabatic photocleavage of DNA-based oxetanes. Organic & Biomolecular Chemistry. 18(44):9117-9123. https://doi.org/10.1039/D0OB01974GS91179123184

Influence of the linking bridge on the photoreactivity of benzophenone-thymine conjugates

[EN] 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 Paterno-Buchi (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 the key features are the strain associated with the reactive conformations and the participation of triplet exciplexes.Financial support from the Spanish Government (RYC-2015-17737 and CTQ2017-89416-R) and from the Conselleria d'Educació Cultura i Esport (PROMETEO/2017/075 and GRISOLIAP/2017/005) is gratefully acknowledged. The authors would like to thank the use of RIAIDT-USC analytical facilities for the X-ray crystallography analysis.Blasco-Brusola, A.; Vayá Pérez, I.; Miranda Alonso, MÁ. (2020). Influence of the linking bridge on the photoreactivity of benzophenone-thymine conjugates. The Journal of Organic Chemistry. 85(21):14068-14076. https://doi.org/10.1021/acs.joc.0c02088S14068140768521Kraemer, K. H. (1997). Sunlight and skin cancer: Another link revealed. Proceedings of the National Academy of Sciences, 94(1), 11-14. doi:10.1073/pnas.94.1.11Cadet, J., Mouret, S., Ravanat, J.-L., & Douki, T. (2012). Photoinduced Damage to Cellular DNA: Direct and Photosensitized Reactions†. Photochemistry and Photobiology, 88(5), 1048-1065. doi:10.1111/j.1751-1097.2012.01200.xRastogi, R. P., Richa, Kumar, A., Tyagi, M. B., & Sinha, R. P. (2010). Molecular Mechanisms of Ultraviolet Radiation-Induced DNA Damage and Repair. Journal of Nucleic Acids, 2010, 1-32. doi:10.4061/2010/592980Sinha, R. P., & Häder, D.-P. (2002). UV-induced DNA damage and repair: a review. Photochemical & Photobiological Sciences, 1(4), 225-236. doi:10.1039/b201230hChatterjee, N., & Walker, G. C. (2017). Mechanisms of DNA damage, repair, and mutagenesis. Environmental and Molecular Mutagenesis, 58(5), 235-263. doi:10.1002/em.22087Brash, D. E., & Haseltine, W. A. (1982). UV-induced mutation hotspots occur at DNA damage hotspots. Nature, 298(5870), 189-192. doi:10.1038/298189a0Taylor, J. S., & Cohrs, M. P. (1987). DNA, light, and Dewar pyrimidinones: the structure and biological significance to TpT3. Journal of the American Chemical Society, 109(9), 2834-2835. doi:10.1021/ja00243a052Taylor, J. S., Garrett, D. S., & Cohrs, M. P. (1988). Solution-state structure of the Dewar pyrimidinone photoproduct of thymidylyl-(3’ .fwdarw. 5’)-thymidine. Biochemistry, 27(19), 7206-7215. doi:10.1021/bi00419a007Kim, S. T., Malhotra, K., Smith, C. A., Taylor, J. S., & Sancar, A. (1994). Characterization of (6-4) photoproduct DNA photolyase. Journal of Biological Chemistry, 269(11), 8535-8540. doi:10.1016/s0021-9258(17)37228-9Li, J., Liu, Z., Tan, C., Guo, X., Wang, L., Sancar, A., & Zhong, D. (2010). Dynamics and mechanism of repair of ultraviolet-induced (6–4) photoproduct by photolyase. Nature, 466(7308), 887-890. doi:10.1038/nature09192Todo, T., Ryo, H., Yamamoto, K., Toh, H., Inui, T., Ayaki, H., … Ikenaga, M. (1996). Similarity Among the Drosophila (6-4)Photolyase, a Human Photolyase Homolog, and the DNA Photolyase-Blue-Light Photoreceptor Family. Science, 272(5258), 109-112. doi:10.1126/science.272.5258.109Todo, T., Takemori, H., Ryo, H., lhara, M., Matsunaga, T., Nikaido, O., … Nomura, T. (1993). A new photoreactivating enzyme that specifically repairs ultraviolet light-induced (6-4)photoproducts. Nature, 361(6410), 371-374. doi:10.1038/361371a0Todo, T., Tsuji, H., Otoshi, E., Hitomi, K., Sang-Tae Kim, & Ikenaga, M. (1997). Characterization of a human homolog of (6-4)photolyase. Mutation Research/DNA Repair, 384(3), 195-204. doi:10.1016/s0921-8777(97)00032-3Epe, B., Pflaum, M., & Boiteux, S. (1993). DNA damage induced by photosensitizers in cellular and cell-free systems. Mutation Research/Genetic Toxicology, 299(3-4), 135-145. doi:10.1016/0165-1218(93)90091-qMichaud, S., Hajj, V., Latapie, L., Noirot, A., Sartor, V., Fabre, P.-L., & Chouini-Lalanne, N. (2012). Correlations between electrochemical behaviors and DNA photooxidative properties of non-steroïdal anti-inflammatory drugs and their photoproducts. Journal of Photochemistry and Photobiology B: Biology, 110, 34-42. doi:10.1016/j.jphotobiol.2012.02.007Marguery, M. C., Chouini-Lalanne, N., Ader, J. C., & Paillous, N. (1998). Comparison of the DNA Damage Photoinduced by Fenofibrate and Ketoprofen, Two Phototoxic Drugs of Parent Structure. Photochemistry and Photobiology, 68(5), 679-684. doi:10.1111/j.1751-1097.1998.tb02529.xVinette, A. L., McNamee, J. P., Bellier, P. V., McLean, J. R. N., & Scaiano, J. C. (2003). Prompt and Delayed Nonsteroidal Anti-inflammatory Drug–photoinduced DNA Damage in Peripheral Blood Mononuclear Cells Measured with the Comet Assay¶. Photochemistry and Photobiology, 77(4), 390. doi:10.1562/0031-8655(2003)0772.0.co;2Lhiaubet, V., Gutierrez, F., Penaud–Berruyer, F., Amouyal, E., Daudey, J.-P., Poteau, R., … Paillous, N. (2000). Spectroscopic and theoretical studies of the excited states of fenofibric acid and ketoprofen in relation with their photosensitizing properties. New Journal of Chemistry, 24(6), 403-410. doi:10.1039/a909539jLhiaubet, V., Paillous, N., & Chouini-Lalanne, N. (2001). Comparison of DNA Damage Photoinduced by Ketoprofen, Fenofibric Acid and Benzophenone via Electron and Energy Transfer¶. Photochemistry and Photobiology, 74(5), 670. doi:10.1562/0031-8655(2001)0742.0.co;2Cuquerella, M. C., Lhiaubet-Vallet, V., Cadet, J., & Miranda, M. A. (2012). Benzophenone Photosensitized DNA Damage. Accounts of Chemical Research, 45(9), 1558-1570. doi:10.1021/ar300054eBignon, E., Marazzi, M., Besancenot, V., Gattuso, H., Drouot, G., Morell, C., … Monari, A. (2017). Ibuprofen and ketoprofen potentiate UVA-induced cell death by a photosensitization process. Scientific Reports, 7(1). doi:10.1038/s41598-017-09406-8Boscá, F., & Miranda, M. A. (1998). New Trends in Photobiology (Invited Review) Photosensitizing drugs containing the benzophenone chromophore. Journal of Photochemistry and Photobiology B: Biology, 43(1), 1-26. doi:10.1016/s1011-1344(98)00062-1Rogers, J. E., & Kelly, L. A. (1999). Nucleic Acid Oxidation Mediated by Naphthalene and Benzophenone Imide and Diimide Derivatives:  Consequences for DNA Redox Chemistry. Journal of the American Chemical Society, 121(16), 3854-3861. doi:10.1021/ja9841299Surana, K., Chaudhary, B., Diwaker, M., & Sharma, S. (2018). Benzophenone: a ubiquitous scaffold in medicinal chemistry. MedChemComm, 9(11), 1803-1817. doi:10.1039/c8md00300aCuquerella, M. C., Lhiaubet-Vallet, V., Bosca, F., & Miranda, M. A. (2011). Photosensitised pyrimidine dimerisation in DNA. Chemical Science, 2(7), 1219. doi:10.1039/c1sc00088hBlasco-Brusola, A., Navarrete-Miguel, M., Giussani, A., Roca-Sanjuán, D., Vayá, I., & Miranda, M. A. (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. doi:10.1039/d0cp03084hBurrows, C. J., & Muller, J. G. (1998). Oxidative Nucleobase Modifications Leading to Strand Scission. Chemical Reviews, 98(3), 1109-1152. doi:10.1021/cr960421sBelmadoui, N., Climent, M. J., & Miranda, M. A. (2006). Photochemistry of a naphthalene–thymine dyad in the presence of acetone. Tetrahedron, 62(7), 1372-1377. doi:10.1016/j.tet.2005.11.035Bonancía, P., Vayá, I., Climent, M. J., Gustavsson, T., Markovitsi, D., Jiménez, M. C., & Miranda, M. A. (2012). Excited-State Interactions in Diastereomeric Flurbiprofen–Thymine Dyads. The Journal of Physical Chemistry A, 116(35), 8807-8814. doi:10.1021/jp3063838Encinas, S., Climent, M. J., Gil, S., Abrahamsson, U. O., Davidsson, J., & Miranda, M. A. (2004). Singlet Excited-State Interactions in Naphthalene-Thymine Dyads. ChemPhysChem, 5(11), 1704-1709. doi:10.1002/cphc.200400262Belmadoui, N., Encinas, S., Climent, M. J., Gil, S., & Miranda, M. A. (2006). Intramolecular Interactions in the Triplet Excited States of Benzophenone–Thymine Dyads. Chemistry - A European Journal, 12(2), 553-561. doi:10.1002/chem.200500345Dumont, E., Wibowo, M., Roca-Sanjuán, D., Garavelli, M., Assfeld, X., & Monari, A. (2015). Resolving the Benzophenone DNA-Photosensitization Mechanism at QM/MM Level. The Journal of Physical Chemistry Letters, 6(4), 576-580. doi:10.1021/jz502562dDelatour, T., Douki, T., D’Ham, C., & Cadet, J. (1998). Photosensitization of thymine nucleobase by benzophenone through energy transfer, hydrogen abstraction and one-electron oxidation. Journal of Photochemistry and Photobiology B: Biology, 44(3), 191-198. doi:10.1016/s1011-1344(98)00142-0Tamai, N., Asahi, T., & Masuhara, H. (1992). Intersystem crossing of benzophenone by femtosecond transient grating spectroscopy. Chemical Physics Letters, 198(3-4), 413-418. doi:10.1016/0009-2614(92)85074-kGut, I. G., Wood, P. D., & Redmond, R. W. (1996). Interaction of Triplet Photosensitizers with Nucleotides and DNA in Aqueous Solution at Room Temperature. Journal of the American Chemical Society, 118(10), 2366-2373. doi:10.1021/ja9519344Miro, P., Gomez‐Mendoza, M., Sastre, G., Cuquerella, M. C., Miranda, M. A., & Marin, M. L. (2019). Generation of the Thymine Triplet State by Through‐Bond Energy Transfer. Chemistry – A European Journal, 25(28), 7004-7011. doi:10.1002/chem.201900830Joseph, A., Prakash, G., & Falvey, D. E. (2000). Model Studies of the (6−4) Photoproduct Photolyase Enzyme:  Laser Flash Photolysis Experiments Confirm Radical Ion Intermediates in the Sensitized Repair of Thymine Oxetane Adducts. Journal of the American Chemical Society, 122(45), 11219-11225. doi:10.1021/ja002541uMartínez, L. J., & Scaiano, J. C. (1997). Transient Intermediates in the Laser Flash Photolysis of Ketoprofen in Aqueous Solutions:  Unusual Photochemistry for the Benzophenone Chromophore. Journal of the American Chemical Society, 119(45), 11066-11070. doi:10.1021/ja970818tPerez-Ruiz, R., Groeneveld, M., van Stokkum, I. H. M., Tormos, R., Williams, R. M., & Miranda, M. A. (2006). Fast transient absorption spectroscopy of the early events in photoexcited chiral benzophenone–naphthalene dyads. Chemical Physics Letters, 429(1-3), 276-281. doi:10.1016/j.cplett.2006.07.077Martens, J.; Maison, W.; Schlemminger, I.; Westerhoff, O.; Groger, H. Preparation of Precursors for PNA monomers. WO20000028642000

Revenue management software in the hotel sector

La disponibilidad de software se ha erigido como un requisito fundamental para la aplicación de Revenue Management desde sus inicios. El gran volumen y variedad de datos requeridos para la adopción de decisiones de Revenue Management ha impulsado el desarrollo de soluciones, tanto genéricas que hemos denominado software de Revenue Management, como específicas, nombradas como herramientas de Revenue Management; en el contexto nacional e internacional. En este trabajo se analiza la evolución y la utilización de ambos tipos en función de la pertenencia o no a cadena hotelera. A nivel internacional se aprecia la difusión, en etapas tempranas de la implantación de Revenue Management, de software genérico. Centrándonos en el caso de España, actualmente se usa un mayor número de herramientas. Se identifican cinco software de Revenue Management mayoritariamente utilizados por cadenas hoteleras (EasyRMS, Synergy, Price Match, Ideas y ARMS); y 25 herramientas de apoyo (shoppers, channel managers, entre otros)que aseguran estar utilizando actualmente un elevado porcentaje de los hoteles que pertenecen a cadenas (93%) y todos los independientes (100%).The availability of software has constituted a fundamental requirement for the application of Revenue Management from its beginnings. The great volume and the variety of data required to adopt Revenue Management decisions has boosted the development of solutions in the national and international contexts that are both generic – which we have called Revenue Management software - and specific –Revenue Management tools. In this work, we analyse the evolution and the use of both types according to belonging to a hotel chain or not. At the international level, the diffusion of generic software is noted in the early stages of implementing Revenue Management. Centring on the case of Spain, more tools are currently used. Five software of Revenue Management have been identified, mainly utilised by hotel chains (EasyRMS, Synergy, Price Match, Ideas and ARMS), and 25 support tools (shoppers, channel managers, among others). The last ones are to a greater or lesser extent employed by a high percentage of the hotels that belong to chains (93%) and all those which are independent (100%)

Triplet excited states as chiral reporter for the binding of drugs to transport proteins

[EN] The triplet excited state of flurbiprofen methyl ester (FBPMe) has been used as a chiral reporter for the two binding sites of human serum albumin (HSA). The occupation level of the binding sites has been estimated from regression analysis of the triplet decays at several [FBPMe]/[HSA] ratios. The data agree with two high affinity binding sites (I and II) that are populated to a different extent. A remarkable stereodifferentiation has been found in the drug triplet lifetimes within the protein microenvironment.The UPV (Grant PI 2003-0522 and fellowship to I.V.), the MEC (Grant CTQ2004-03811), and Generalitat Valenciana (Grant GV2004-0536 and Grupos03/082) are gratefully acknowledged for financial support.Jiménez Molero, MC.; Miranda Alonso, MÁ.; Vayá Pérez, I. (2005). Triplet excited states as chiral reporter for the binding of drugs to transport proteins. Journal of the American Chemical Society. 127(29):10134-10135. https://doi.org/10.1021/ja0514489S10134101351272

Stereodifferentiation in the fluorescence of naproxen-arginine salts in the solid state

[EN] Three stereoisomeric salts of naproxen (NPX) with arginine (Arg), namely (S)-NPX/(S)-Arg, (R)-NPX/(S)-Arg and (S)NPX/(R)-Arg, have been prepared, and their fluorescence spectra recorded in solution and in the solid state. While the emission properties in solution did not show significant differences with lambda(max) = 355 nm, tau(F) (MeOH) ca. 11.5 ns and tau(F) (H2O) ca. 9 ns (as NPX/Na), the (R)-NPX/(S)-Arg and (S)-NPX/(R)-Arg solid salts displayed red-shifted fluorescence spectra With maxima at 375 mn and tau(F) = 1.1 ns. By contrast, the behaviour of solid (S)-NPX/(S)-Arg was similar to that of NPX/Na With; ax = 355 nm and tau(F) ca. 5.5 ns. These results are explained based on the X-ray crystal structures and attributed to formation of NPX excimers emitting at longer wavelengths. Accordingly, such excimer emission was also observed in the fluorescence spectrum of a model NPX dyad in solution.The UPV (PI 2003-0522 and predoctoral fellowship to I.V.), the MYCT (Grant CTQ2004-03811) the Generalitat Valenciana (Grupos03/082 and GV04B-468) are gratefully acknowledged for financial support. We also thank our colleague Dr. M. L. Marin for providing a gift of (2-methoxynaphthalen-6-yl)acetic acid and Dr. A. Llamas (Unidade de Raios X de la Universidade de Santiago de Compostela) for the X-ray measurements.Vayá Pérez, I.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2005). Stereodifferentiation in the fluorescence of naproxen-arginine salts in the solid state. Tetrahedron Asymmetry. 16(12):2167-2171. https://doi.org/10.1016/j.tetasy.2005.05.018S21672171161

Transient absorption spectroscopy for determining multiple site occupancy in drug-protein conjugates. A comparison between human and bovine serum albumins using flurbiprofen methyl ester as probe

This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry B, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/jp076960q[EN] Laser flash photolysis (LFP) has been used to determine the degree of binding of (S)- or (R)-flurbiprofen methyl ester (FBPMe) to human and bovine serum albumins (HSA and BSA, respectively). Regression analysis of the triplet decay of the drug (lambda = 360 nm) in the presence of the proteins led to a satisfactory fitting when considering a set of three lifetimes; the corresponding A(free), A(I) and A(II) preexponential coefficients can be correlated with the presence of FBPMe in the bulk solution and within the two known binding sites. The most remarkable differences between HSA and BSA were found under nonsaturating conditions; thus, when the [FBPMe]/[SA] ratio was 1: 1, all the drug was bound to HSA, whereas 20-30% of it remained free in the bulk solution in the presence of BSA. The UP approach was also applicable to the study of more complex FBPMe/HSA/BSA mixtures; the obtained results were in good agreement with the previous findings in FBPMe/HSA and FBPMe/BSA systems. This suggests the possibility of making use of the transient triplet-triplet absorption for investigating the distribution of a drug between several compartments in different host biomolecules.Financial support from the MCYT (CTQ2004-03811 and CTQ2007-67010) and the Generalitat Valenciana (GV06/099) is gratefully acknowledged. I.V. thanks MEC for a fellowship.Vayá Pérez, I.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2008). Transient absorption spectroscopy for determining multiple site occupancy in drug-protein conjugates. A comparison between human and bovine serum albumins using flurbiprofen methyl ester as probe. The Journal of Physical Chemistry B. 112(9):2694-2699. doi:10.1021/jp076960qS26942699112

Characterization of the lowest singlet and triplet states of S-Flurbiprofen

[EN] The photophysical properties of S-flurbiprofen [S-2-fluoro-alpha-methyl-4-biphenylacetic acid], a nonsteroidal anti-inflammatory drug, have been examined using steady-state and time-resolved spectroscopic techniques. The energy of its first singlet excited state is 99 kcal mol(-1). The fluorescence quantum yields and lifetimes (at 300 nm) have been determined in acetonitrile, methanol, hexane and PBS; they are in the range 0.15 2.0.co;2Castell, J. V., Gómez-Lechón, M. J., Miranda, M. A., & Morera, I. M. (1992). Phototoxicity of non-steroidal anti-inflammatory drugs: in vitro testing of the photoproducts of Butibufen and Flurbiprofen. Journal of Photochemistry and Photobiology B: Biology, 13(1), 71-81. doi:10.1016/1011-1344(92)80041-sLewis, F. D., Bassani, D. M., Caldwell, R. A., & Unett, D. J. (1994). Singlet State Cis,Trans Photoisomerization and Intersystem Crossing of 1-Arylpropenes. Journal of the American Chemical Society, 116(23), 10477-10485. doi:10.1021/ja00102a014Wintgens, V., Johnston, L. J., & Scaiano, J. C. (1988). Use of a photoreversible fulgide as an actinometer in one- and two-laser experiments. Journal of the American Chemical Society, 110(2), 511-517. doi:10.1021/ja00210a034S. L. Murov , I.Carmichael and G. L.Hug, Handbook of Photochemistry, Marcel Dekker, Inc., New York, 2nd edn., 1993S. S. Adams , B. J.Armitage and J. S.Nicholson, Hydroxybiphenyl compounds, Ger. Offen., 1974, 54 pp., CODEN: GWXXBX DE 2329125 19740103 CAN 82:16565 AN 1975:16565Fasani, E., Barberis Negra, F. F., Mella, M., Monti, S., & Albini, A. (1999). Photoinduced C−F Bond Cleavage in Some Fluorinated 7-Amino-4-quinolone-3-carboxylic Acids. The Journal of Organic Chemistry, 64(15), 5388-5395. doi:10.1021/jo982456tAlbini, A., & Monti, S. (2003). Photophysics and photochemistry of fluoroquinolones. Chemical Society Reviews, 32(4), 238. doi:10.1039/b209220

Use of triplet excited states for the study of drug binding to human and bovine serum albumins

[EN] The triplet excited states of (S)- and (R)-flurbiprofen (FBP) have been used as reporters for the microenvironments experienced within the binding sites of human and bovine serum albumins. Regression analysis of triplet decay provides valuable information on the degree of protection that these excited states are afforded from attack by a second FBP molecule, oxygen, or other reagents. The multiexponential fitting of these decays can be satisfactorily correlated with the distribution of the drug among the two binding sites and its presence as the noncomplexed form in the bulk solution. This assignment has been confirmed by using (S)-ibuprofen or capric acid as selective site II replacement probes. Triplet lifetimes and site occupancy are sensitive to the type of serum albumin employed (human versus bovine). Finally, the binding behaviour of (S)- and (R)-FBP exhibits little stereoselectivity.Financial support from the MCYT (CTQ2004-03811) and the Generalitat Valenciana (GV06/099) isgratefully acknowledged. I.V. and C.J.B. thank “Ministerio de Educación y Ciencia” for a fellowship.Vayá Pérez, I.; Bueno Alejo, CJ.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2006). Use of triplet excited states for the study of drug binding to human and bovine serum albumins. ChemMedChem. 1(9):1015-1020. https://doi.org/10.1002/cmdc.200600061S101510201

Influence of the spacer on the photoreactivity of flurbiprofen-tyrosine dyads

[EN] The photoreactivity of diastereomeric dyads containing (S)- or (R)-flurbiprofen (FBP) and (S)-Tyr, either directly linked (1) or separated by a cyclic spacer (3) has been investigated. The main feature is a remarkable intramolecular quenching of FBP fluorescence, especially in 1. The process is clearly configuration dependent, being more efficient for the (R,S)- diastereomer in 1 and for the (S,S)-analogue in 3. Noteworthy, exciplex emission is detected in the 380-500 nm region in the case of 3. Fluorescence decay kinetics from the femtosecond to the nanosecond time-domains provides evidence for the dynamic nature of the quenching. In agreement with the steady-state and time-resolved observations, molecular modelling points to a more favourable geometric arrangement of the two interacting chromophores in 1 than in 3.Financial support from the Spanish Government (CTQ2013-47872-C2-1-P), EU (PCIG12GA-2012-334257, LASERLAB-EUROPE grant agreement no. 284464, EU FP7, and MSCA- 657465) and Generalitat Valenciana (PROMETEOII/2013/005) is gratefully acknowledged.Vayá Pérez, I.; Gustavsson, T.; Markovitsi, D.; Miranda Alonso, MÁ.; Jiménez Molero, MC. (2016). Influence of the spacer on the photoreactivity of flurbiprofen-tyrosine dyads. Journal of Photochemistry and Photobiology A: Chemistry. 322:95-101. https://doi.org/10.1016/j.jphotochem.2016.03.006S9510132

La formación del profesorado. Nuevos enfoques desde la teoría y la historia de la educación

Producción CientíficaLa formación del profesorado y su impacto sobre la calidad de los sistemas educativos tienen un lugar destacado en las agendas tanto políticas como educativas de la Unión Europea. Se perciben como elementos cruciales para reformas educativas y economías sostenibles en el marco del gran esfuerzo europeo de conseguir una posición de liderazgo en un mundo globalizado. Por lo tanto, existe un gran debate sobre la necesidad de mejorar la formación del profesorado para asegurar los logros del alumnado. Por otro lado, se discute también si las políticas neo-liberales efectivamente llevan a la de-profesionalización del profesorado y a la homogenización de la educación. Este es el sentido que ha impulsado la edición de esta monografía que incluye ensayos basados en las líneas actuales de investigación de los miembros del Grupo Extremeño de Investigación en Teoría e Historia de la Educación y de otros investigadores de varias universidades españolas que trabajan sobre la formación del profesorado. Los diferentes capítulos ofrecen reflexiones desde la teoría y la historia de la Educación relacionados con la calidad de la formación del profesorado, y los intentos recientes y contemporáneos de renovar dicha formación.Departamento de Didáctica de las Ciencias Experimentales, de las Ciencias Sociales y de la Matemátic