Aza-Crown-Based Macrocyclic Probe Design for "PET-off" Multi-Cu²⁺ Responsive and "CHEF-on" Multi-Zn²⁺ Sensor:...

The work represents a rare example of an aza-crown-based macrocyclic chemosensor, H₂DTC (H₂DTC = 1,16-dihydroxy-tetraaza-30-crown-8) for the selective detection of both Zn²⁺ and Cu²⁺ in HEPES buffer medium (pH 7.4). H₂DTC exhibits a fluorescence response for both Zn²⁺ and Cu²⁺ ions. The reversibility of the chemosensor in its binding with Zn²⁺ and Cu²⁺ ions is also examined using a Na₂EDTA solution. H₂DTC exhibits a chelation-enhanced fluorescence (CHEF) effect in the presence of Zn²⁺ ions and a quenching effect (CHEQ) in the presence of paramagnetic Cu²⁺ ions. Furthermore, the geometry and spectral properties of H₂DTC and the chemosensor bound to Zn²⁺ have been studied by DFT and TDDFT calculations. The limit of detection (LOD) values are 0.11 × 10^-9 and 0.27 × 10^-9 M for Cu²⁺ and Zn²⁺, respectively. The formation constants for the Zn²⁺ and Cu²⁺ complexes have been measured by pH-potentiometry in 0.15 M NaCl in 70:30 (v:v) water:ethanol at 298.1 K. UV-vis absorption and fluorometric spectral data and pH-potentiometric titrations indicate 1:1 and 2:1 metal:chemosensor species. In the solid state H₂DTC is able to accommodate up to four metal ions, as proved by the crystal structures of the complexes [Zn₄(DTC)(OH)₂(NO₃)₄] (1) and {[Cu₄(DTC)(OCH₃)₂(NO₃)₄]·H₂O} (2). H₂DTC can be used as a potential chemosensor for monitoring Zn²⁺ and Cu²⁺ ions in biological and environmental media with outstanding accuracy and precision. The propensity of H₂DTC to detect intracellular Cu²⁺ and Zn²⁺ ions in the triple negative human breast cancer cell line MDA-MB-468 and in HeLa cells has been determined by fluorescence cell imaging.