New Amino Acid-Based Thiosemicarbazones and Hydrazones: Synthesis and Evaluation as Fluorimetric Chemosensors in Aqueous Mixtures

Abstract

Bearing in mind the interest in the development and application of amino acids/peptides as bioinspired systems for sensing, a series of new phenylalanine derivatives bearing thiosemicarbazone and hydrazone units at the side chain were synthesised and evaluated as fluorimetric chemosensors for ions. Thiosemicarbazone and hydrazone moieties were chosen because they are considered both proton-donor and proton-acceptor, which is an interesting feature in the design of chemosensors. The obtained compounds were tested for the recognition of organic and inorganic anions (such as AcO^-, F^-, Cl^-, Br^-, I^-, ClO₄^-, CN^-, NO₃^-, BzO^-, OH^-, H₂PO₄^- and HSO₄^-) and of alkaline, alkaline-earth, and transition metal cations, (such as Na⁺, K⁺, Cs⁺, Ag⁺, Cu⁺, Cu²⁺, Ca²⁺, Cd²⁺, Co²⁺, Pb²⁺, Pd²⁺, Ni²⁺, Hg²⁺, Zn²⁺, Fe²⁺, Fe³⁺ and Cr³⁺) in acetonitrile and its aqueous mixtures in varying ratios via spectrofluorimetric titrations. The results indicate that there is a strong interaction via the donor N, O and S atoms at the side chain of the various phenylalanines, with higher sensitivity for Cu²⁺, Fe³⁺ and F^- in a 1:2 ligand-ion stoichiometry. The photophysical and metal ion-sensing properties of these phenylalanines suggest that they might be suitable for incorporation into peptide chemosensory frameworks.

Keywords: chemosensors; fluorescence; hydrazone; phenylalanine; thiosemicarbazone; unnatural amino acids.