The Design of Terbium-Based Chemosensors for the Selective Detection of Zinc Ions

As zinc is a vital structural component of several metalloproteinases, problems with Zn2+ metabolism are associated with numerous disorders, including prostate cancer, cerebral ischemia, Alzheimers disease (AD), and epilepsy. To study the roles of Zn2+ in vivo, it is desirable to have probes that can detect Zn2+ with high selectivity and sensitivity. The fluorescence lifetimes of typical organic compounds, including common zinc-selective fluorescent sensor molecules, are in the nanosecond region. In addition, biological material is highly complex and usually bears numerous fluorescent groups. Therefore, luminescent stains based on organic dye molecules, although highly sensitive, are not completely adequate in view of the difficulty in separating the fluorescence of the stain from that of the sample. On the other hand, luminescent lanthanide complexes have large Stokes shifts and long luminescence lifetimes in the order of milliseconds. In this proposed study, terbium-based luminescent sensors (14) for the detection of Zn2+ in aqueous solutions will be developed. The proposed chemosensors (14) feature 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) rings, which will encapsulate the terbium ion (Tb3+), and the high-affinity Zn2+-binding moieties bis[(2-pyridyl)methyl]-amine (DPA) and bis[(2-quinolinyl)methyl]-amine) (DQA) to chelate Zn2+. The proposed sensor design is based on the sensitization of Tb3+ via excitation of the covalently attached phenyl chromophore, that is, the antenna (possessing both * and n* transitions). The resulting sensitization of the Tb3+ 5D4 excited state, with the coincidental characteristic line-like emission of Tb3+, is expected to change when Zn2+ binds to the DPA and DQA, Zn2+ chelators. The perturbation of energy sensitization processes (the antenna effect) when the sensor binds Zn2+ would induce changes in both the fluorescence lifetimes and emission intensities of the lanthanide complex. A photophysical evaluation of chemosensors (14) for the detection of Zn2+ will be studied. The binding affinity of Zn2+ to each of the fluorescent probes (14) and the efficacy of Zn2+ analysis by fluorescence spectroscopy will also be investigated. In addition, investigation of the effect of various competing cations (Hg2+, Ni2+, Ca2+, K+) on the luminescence intensity of 14 to assess their selectivity for Zn2+ will also be explored. Our proposed chemosensors 14 are expected to be water-soluble and could be used to detect zinc ions in environmental and biomedical monitoring. Such sensors could be potential armament to prevent and cure diseases associated with imbalanced zinc levels