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Table 1. Sequences and properties of the peptide dendrimers synthesizedAA 1 AA 2 AA 3 AA 4 AA 5 AA 6 MScalc.Yield(%)MSfoundCharge(pH 7)2a Asp Ala Val Ala Thr Glu 2285.3 13.0 2285.2 - 52e Asp Ala Val Glu Thr Glu 2401.4 13.2 2401.0 - 72h Ser His Ala His Thr Gln 2463.6 2.2 2463.5 02p Lys Ala Val Leu Lys Arg 2599.1 12.9 2599.0 + 9Negatively charged (2a, 2e), neutral hydrophilic (2h) and strongly positively charged (2p)sequences have been synthesized on solid-phase and purified by RP-HPLC (Table 1).The metal binding properties of the peptide dendrimers have been tested by UV-Vismeasurements, detecting bipyridyl/metal interactions by the shift in the bipyridylabsorption band. Spectrophotometric titrations with Cu(II), Ni(II) and Zn(II) in HEPESbuffer, pH 6.5, have detected the formation of stable 1:1 complexes (K f 10 5 -10 6 M -1 ) for alldendrimers tested.By titrating neutral or negatively charged dendrimers with Fe(II), the characteristicMLCT band of low-spin tris-bipyridyl iron complexes is observed in the visible region(Figure 2, top right). Moreover, from the presence of isosbestic points it can be deducedthat such complexes are the only species formed. The 2:1 dendrimer/metal stoichiometryrequired for interaction of an iron center with three bipyridyl ligands has been confirmed byJob plot analyses [6] of complex formation (Figure 2, bottom right). On the other hand, forthe positively charged dendrimer 2p, neither the shift in the bipyridyl absorption band northe band in the visible region are observed under the same conditions, suggesting that thisdendrimer does not bind the metal.Some metal/dendrimer mixtures have been analyzed by LC-MS: in addition to thepeaks of the free dendrimers formed by complex hydrolysis under the acidic elutionconditions, peaks due to metal complexes with the stoichiometry predicted by the UVexperiments have been detected. Interestingly, in the case of the 2e/Fe(II) mixture, peaksdue to different regio- and stereo-isomers of the 2:1 complex appear, as well as peaks dueto 1:1 complexes formed as hydrolysis intermediates.In the 2:1 dendrimer/Fe(II) complexes the two dendrimer ligands are not equivalent:the first one has both bipyridyl moieties bound to the metal, the second one has onebipyridyl bound to the metal and the other not engaged in binding. The two freecoordination sites of such bipyridyl could chelate a further metal ion, allowing theformation of more complex molecular architectures.AcknowledgmentsFinancial support from the Swiss National Science Fondation for the research project, as well as fromthe Nachwuchsförderungskommission of the Faculty of Natural Philosophy of the University of Bernefor the participation of Piero Geotti-Bianchini to the Symposium, are gratefully acknowledged.References1. Crespo, L., Sanclimens, G., Pons, M. Giralt, E., Royo, M., Albericio, F. Chem. Rev. 105, 1663-1681(2005).2. Darbre, T., Reymond, J.-L. Acc. Chem. Res. 39, 925-934 (2006).3. Javor, S., Delort, E., Darbre, T., Reymond, J.-L. J. Am. Chem. Soc. 129, 13238-13246 (2007).4. Costas, M., Mehn, M.P., Jensen, M.P., Que, L. Jr. Chem. Rev. 104, 939-986 (2004).5. Uhlich, N.A., Sommer, P., Bühr, C., Schürch, S., Reymond, J.-L., Darbre, T. Chem. Commun. 6237-6239 (2009).6. Huang, C.Y. Meth. Enzymol. 87, 509-525 (1982).625