Amino-Substituted 2,2'-Bipyridine Ligands as Fluorescent Indicators for ZnII and Applications for Fluorescence Imaging of Prostate Cells.

ZnII concentrations in malignant prostate tissues are much lower than in benign or healthy, suggesting that ZnII levels are a potential biomarker for prostate cancer (PCa). Five 2,2'-bipyridine ligands were synthesized containing amino substituents with varying electron-donating ability for investigation as fluorescent ZnII indicators. The excited state characteristics of the ligands were explored by UV/Vis and fluorescence spectroscopy. 3,3'-Diamino-2,2'-bipyridine (1) was previously shown to be weakly fluorescent as a result of π→π* transitions. The other four ligands have properties consistent with an n→π* intraligand charge transfer excited state. Strongly donating amino and aminophenyl (2 and 4) substituents gave low quantum yields, while weaker donating benzimidazole substituents (6 and 7) gave high quantum yields. Absorption and fluorescence wavelengths underwent bathochromic shifts upon ZnII binding in a majority of cases. Quantum yields drastically increased upon ZnII binding for 1 and 2, but decreased for 4, 6, and 7. Compounds 6 and 7 were incubated with PC-3, DU 145 and BPH-1 cells to determine their ZnII sensing abilities in a biological system. Weak fluorescence was observed in BPH-1 cells and subsequent incubation with ZnII caused fluorescence intensity to increase. No fluorescence was observed in PCa cell lines. Further investigation of these ligands may allow for quantitative determination of ZnII concentrations in ex vivo tissue samples.