Overriding Phthalate Decomposition When Exploring Mycophenolic Acid Intermediates as Selenium-Based ROS Biological Probes.

Hypochlorous (OCl) acid is the most well-known bacterial oxidant to be produced by neutrophils. Excess amounts of OCl can cause various disorders in living systems. Herein, we have designed, synthesized, and characterized two novel organoselenium-based target molecules ( and ) based on a synthetic intermediate of mycophenolic acid for the aqueous detection of OCl. Probe has been recently reported (. . , , 3557-3561); both probes show immediate "turn-on" fluorescence (<1 s) upon the addition of OCl, display an increase in the fluorescence quantum yield (3.7-fold in and 11.6-fold in ), and are completely soluble in aqueous media without the help of any cosolvent. However, a decrease in the "turn-on" intensity with the oxidized version of in cell assays due to the anhydride/phthalate functionality suggests that probe degradation occurs based on hydrolytic action (a probe degradation half-life of ∼1500 s at 15 μM and 150 μM OCl). Thus, the change of "anhydride" to "methylamide" begets , which possesses more stability without sacrificing its water solubility properties and responses at short times. Further studies suggest that is highly stable within physiological pH (pH = 7.4). Surprisingly, in live cell experiments involving U-2 OS cells and HeLa cells, accumulated and aggregated in lipid droplets and gives a "turn-on" fluorescence response. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays confirmed that is not toxic. Cuvette aggregation studies were also performed (tetrahydrofuran/HO) to demonstrate aggregation-induced fluorescence at longer times. Our current hypothesis is that the "turn-on" fluorescence effect is caused by the aggregation-induced emission mechanism available for . In this case, in tandem, we reanalyzed the derivative to compare and contrast cell localization as imaged by confocal microscopy; fluorescence emission occurs in the absence of, or prior to, Se oxidation.