Ratiometric Fluorescent Sensor Based on Inhibition of Resonance for Detection of Cadmium in Aqueous Solution and Living Cells

Although cadmium has been recognized as a highly toxic heavy metal and poses many detrimental effects on human health, the Cd2+-uptake and nosogenesis mechanisms are still insufficiently understood, mainly because of the lack of facile analytical methods for monitoring changes in the environmental and intracellular Cd2+ concentrations with high spatial and temporal reliability. To this end, we present the design, synthesis, and photophysical properties of a cadmium sensor, DQCd1 based on the fluorophore 4-isobutoxy-6-(dimethylamino)-8-methoxyquinaldine (model compound 1). Preliminary investigations indicate that 1 could be protonated under neutral media and yield a resonance process over the quinoline fluorophore. Upon excitation at 405 nm, 1 shows a strong fluorescence emission at 554 nm with a quantum yield of 0.17. Similarly, DQCd1 bears properties comparable to its precursor. It exhibits fluorescence emission at 558 nm (Phi(f) = 0.15) originating from the monocationic species under physiological conditions. Coordination with Cd2+ causes quenching of the emission at 558 nm and simultaneously yields a significant hypsochromic shift of the emission maximum to 495 nm (Phi(f) = 0.11) due to inhibition of the resonance process. Thus, a single-excitation, dual-emission ratiometric measurement with a large blue shift in emission (Delta lambda = 63 nm) and remarkable changes in the ratio (F-495 nm/F-558 nm) of the emission intensity (R/R-0 up to 15-fold) is established. Moreover, the sensor DQCd1 exhibits very high sensitivity for Cd2+ (K-d = 41 pM) and excellent selectivity response for Cd2+ over other heavy- and transition-metal ions and Na+, K+, Mg2+ and Ca2+ at the millimolar level. Therefore, DQCd1 can act as a ratiometric fluorescent sensor for Cd2+ through inhibition of the resonance process. Confocal microscopy and cytotoxicity experiments indicate that DQCd1 is cell-permeable and noncytotoxic under our experimental conditions. It can indeed visualize the changes of intracellular Cd2+ in living cells using dual-emission ratiometry.