Unnatural benzocrown ether amino acids as recognition and signalling units for the fluorescent sensing of metallic cations

Abstract

Crown ethers are known for their interesting binding properties with metallic and organic cations and have been applied in the design of chemosensors, molecular machines and supramolecular polymers.1 Amino acids, and hence peptides, also display ability to complex metal ions through nitrogen, oxygen and sulphur donor atoms at the main and side chain, thus 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 vivo and in vitro.2 Examples of amino acids combined with crown ether units have been used in the recognition of ammonium ions, amino acids and peptides and in the formation of artificial channels across membranes for ion transport.3 Therefore, following our research on the synthesis and application of fluorimetric probes for cations based on heterocycles, crown ethers and amino acids,4 we now report the evaluation of a new benzoxazolyl-alanine, functionalised with different benzocrown ether coordinating units and different (hetero)aromatic bridges (phenyl, thienyl or furyl) as fluorimetric chemosensors for the recognition of metallic cations such as Na+, Ca2+, Cu2+, Cd2+, Co2+, Cr3+, Zn2+, Hg2+, Fe2+, Fe3+, Ni2+ and Pd2+. Spectrofluorimetric titrations were carried out in acetonitrile and revealed that the benzocrown-benzoxazolyl-alanine derivatives 1-4 were highly fluorescent and displayed a quenching of fluorescence (CHEQ effect) upon binding to the different cations.