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Novel alanines bearing a heteroaromatic side chain: synthesis and studies on fluorescent chemosensing of metal cations with biological relevance

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Abstract

A family of novel thienylbenzoxazol-5-yl-l-alanines, consisting of an alanine core bearing a benzoxazole at the side chain with a thiophene ring at position 2, substituted with different (hetero)aryl substituents, was synthesised to study the tuning of the photophysical and chemosensory properties of the resulting compounds. These novel heterocyclic alanines 3a–f and a series of structurally related bis-thienylbenzoxazolyl-alanines 3g–j were evaluated for the first time in the recognition of selected metal cations with environmental, medicinal and analytical interest such as Co2+, Cu2+, Zn2+ and Ni2+, in acetonitrile solution, with the heterocycles at the side chain acting simultaneously as the coordinating and reporting units, via fluorescence changes. This behaviour can be explained by the involvement of the electron donor heteroatoms in the recognition event, through complexation of the metal cations. The spectrofluorimetric titrations showed that thienylbenzoxazolyl-alanines 3a–j and 4a,b were non-selective fluorimetric chemosensors for the above-mentioned cations, with the best results being obtained for the interaction of Cu2+ with bis-alanine 3j and deprotected alanines 4a,b. The encouraging photophysical and metal ion sensing properties of these thienylbenzoxazolyl-alanines suggest that they can be used to obtain bioinspired fluorescent reporters for metal ion such as peptides/proteins with chemosensory/probing ability.

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Acknowledgements

Thanks are due to Fundação para a Ciência e Tecnologia (FCT) for a PhD grant to R. C. M. Ferreira (SFRH/BD/86408/2012), and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support through the Chemistry Research Centre of the University of Minho (Ref. UID/QUI/00686/2013 and UID/QUI/0686/2016). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005 with funds from POCI 2010 (FEDER) and FCT.

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  1. Centre of Chemistry, University of Minho, Campus of Gualtar, 4710-057, Braga, Portugal

    Rosa Cristina M. Ferreira, Maria Manuela M. Raposo & Susana P. G. Costa

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  1. Rosa Cristina M. Ferreira
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  2. Maria Manuela M. Raposo
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  3. Susana P. G. Costa
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Correspondence to Susana P. G. Costa.

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Ferreira, R.C.M., Raposo, M.M.M. & Costa, S.P.G. Novel alanines bearing a heteroaromatic side chain: synthesis and studies on fluorescent chemosensing of metal cations with biological relevance. Amino Acids 50, 671–684 (2018). https://doi.org/10.1007/s00726-018-2549-z

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