Synthetic unnatural amino acids as fluorimetric probes for metallic cations

Abstract

Molecular recognition is the basis for most biological functions and in recent years the research on compounds capable of recognizing and binding organic and inorganic molecules involved in biological pathways has evolved to mimic as much aspossible the natural mechanisms of organization [1]. The design of peptides that coordinate metals, by incorporation of modified amino acids, has potential for applications as varied as the study on protein-protein interactions mediated by metals, protein binding to nanoparticles and metal surfaces, and the development of selective chemosensors for metals for use in vivoand in vitro[2]. For the synthesis of peptide based chemosensors, fluorescent ligands which are mostly heteroaromatic ring systems often substituted by potentially chelating groups which act as both the recognition and signalling site can be used, as reported recently for ligands capable to chelate various metal ions and whose complexes possess diversified photophysical properties [3]. Bearing these facts in mind and following our research interests that include the synthesis and application of fluorimetric probes for metallic cations based on heterocycles and amino acids, namely benzoxazolyl-alanines, thiadiazolyl-, benzothiazolyl- and benzimidazolyl-asparagines [4], we now report the evaluation of unnatural alanine derivatives as fluorimetric chemosensors for the recognition of metallic cations with analytical, biological, and medicinal relevance, through the introduction of oxygen and nitrogen heterocycles ascoordinating/reporting units in an alanine core in order to obtain new chemosensors. Benzoxazolyl-alanines 1-3 with an imidazolyl moiety with different substituents were synthesised and evaluated for their ability to respond, viachanges in the fluorescence spectra, in the presence of biologically important alkaline, alkaline-earth and transition metallic cations through spectrofluorometric titrations and also by 1H NMR titrations.