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Table 1. Yields, UV-vis absorption data, irradiation times (t irr , in min) and rate constants(k, in min -1 ) for the photolysis of conjugates 2a-d at different wavelengths in MeOH/aq.HEPES buffer (80:20)Cpd.Yield(%)UV-visλ max (nm)254 nm 300 nm 350 nm 419 nmt irr k t irr k t irr k t irr k2a 73 395 30.0 0.10 100.7 0.03 45.7 0.07 36.6 0.082b 80 384 8.3 0.35 10.3 0.30 10.4 0.28 9.8 0.322c 74 401 0.5 4.74 0.7 4.49 0.5 6.61 0.4 7.192d 50 385 0.5 6.22 0.7 4.06 0.6 4.94 0.6 5.10The photocleavage of thiocoumarin 2a and thioquinolone 2b-d phenylalanine conjugateswas studied in MeOH/aq. HEPES buffer (80:20) at different wavelengths of irradiation, in aRayonet RPR-100 reactor with lamps of 254, 300, 350 and 419 nm, resulting in thequantitative release of Z-Phe-OH and photo by-products related to the heterocycle.Cleavage kinetics parameters were obtained from plots of peak area, determined byHPLC/UV monitoring, of the starting material versus irradiation time, with a linearcorrelation suggesting a first order reaction. Rate constants were obtained by the linear leastsquares methodology for a straight line. The irradiation time was the time necessary for theconsumption of the starting material until less than 10% of the initial area was detected(Table 1).It was found that the thiocarbonyl analogues 2 cleaved significantly faster and atlonger wavelengths than the precursor carbonyl compounds 1 [3] and within the thionatedseries, the quinolone conjugates released the amino acid more efficiently when compared tothe coumarin conjugate (between 60-140 times faster depending on the wavelength,compare 2a with 2d). Considering the influence of the methoxy substituent at the quinolonemoiety, the results indicated that it had a positive effect on the photocleavage properties ofthe corresponding conjugates (between 14-20 times faster, compare 2b with 2c and 2d).The position of the methoxy group was irrelevant for the rate constant at all wavelengths ofirradiation (compare 2c and 2d).In summary, thionated coumarin and quinolone phenylalanine conjugates 2 werereadily obtained in fair to good yields through a one-step reaction and upon photolysis itwas found that the thionated conjugates 2 cleaved significantly faster than the parentconjugates 1 at 419 nm [3] and cleavage kinetics parameters were obtained. The cleavageof the ester bond and the quantitative release of the amino acid in short irradiation times atall considered wavelengths of irradiation suggests that thionated quinolone derivatives 2b-dmay be considered as promising alternatives as photocleavable protecting groups forcarboxylic acids. Fast photolysis at 419 nm for quinolone conjugates 2b-d is particularlyinteresting, since this wavelength is the most suitable for practical caging strategies as itavoids cell damage due to short wavelengths.AcknowledgmentsThanks are due to Foundation for Science and Technology (FCT-Portugal) for financial supportthrough project PTDC/QUI/69607/2006 (FCOMP-01-0124-FEDER-007449) and a PhD grant toA.S.C. Fonseca (SFRH/BD/32664/2006). The NMR spectrometer Bruker Avance III 400 is part of theNational NMR Network and was purchased in the framework of the National Program for ScientificRe-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT.References1. Mayer, G., et al. Angew. Chem. Int. Ed. 45, 4900-4921 (2006).2. (a) Hagen, V., et al. Angew. Chem. Int. Ed. 44, 7887-7891 (2005); (b) Geissler, D., et al. Angew.Chem. Int. Ed. 44, 1195-1198 (2005); (c) Furuta, T., et al. ChemBioChem 5, 1119-1128 (2004); (d)Shembekar, V.R., et al. Biochemistry 46, 5479-5484 (2007); (e) Gilbert, D., et al. ChemBioChem 8,89-97 (2007); (f) Fonseca, A.S.C., et al. Tetrahedron 63, 1353-1359 (2007); (g) Fernandes, M.J.G.,et al. Tetrahedron 64, 3032-3038 (2008); (h) Soares, A.M.S., et al. Amino Acids 39, 121-133 (2010).3. Fonseca, A.S.C., et al. Amino Acids 39, 699-712 (2010).9