"Engineering Metal Ion Photocages to Investigate Zinc Signaling and Homeostasis"
Metal ions are essential to numerous processes that sustain life. Among these important roles, metal ions carry the signals that enable learning, memory, and movement. While the functions of loosely bound metal ions like sodium, potassium and calcium are well-established, the role of vesicular zinc, which was found in neurons decades ago, in signal transduction remain ambiguous. Despite the lack of definitive mechanisms, circumstantial evidence suggests zinc can modulate the activity of a variety of ion channels, and zinc interactions with cell surface receptors may lead to a variety of intracellular responses. Photocaged complexes are chemical tools that trap zinc until a light source releases the metal ion at the desired time and location; however, the properties of early photocages for zinc were not compatible with many biological applications. We have been combining principles of metal chelator design with the photoreactivity of xanthone and nitrophenylacetic acid derivatives. Taking advantage of a light-induced decarboxylation reaction, zinc can be released inside cells with an appropriate light source.