Development of Chemical Probes for Studying K+ in biology

Potassium (K+) occupies 4% of human body mass and is the most abundant intracellular cation. Potassium plays a vital role in regulating intracellular fluid volume, fluid transportation, and neuron signaling. Abnormal K+ fluctuations may lead to diseases such as anorexia, bulimia, heart disease, diabetes, and epilepsy. Recent study also has shown elevated level of K+ channel mutation in cancer cells. However, the physiology of K+ is insufficiently understood, due to the absence of ways to measure the change of K+ in cellular fluids with high spatial and temporal fidelity. This dissertation chronicles the design and applications of novel imaging probes and strategies for probing K+ both intracellularly and extracellularly. This work describes the first ratiometric probe and a new fluorescent turn-on probe for imaging intracellular K+; both probes utilize novel lariat-ether modified crown ether structure as K+ binding ionophore. Additionally, this work describes development of a new imaging tool for detecting H2O2 utilizing bioluminescence resonance energy transfer