DM-nitrophen AM ester is caged magnesium.

There have been several reports using DM-nitrophen to photorelease calcium inside cells by both one (UV) and 2-photon photolysis [Nature (2004) 431: 195-199; Cell Calcium (2006) 39: 65-73; Gastroenterology (2002) 122:415-27]. DM-nitrophen is a caged calcium I made as postdoc in 1988. It is based upon EDTA, so has a very high affinity for calcium (so far so good) and a moderate affinity for magnesium (Dooh!!). Thus, in a normal intracellular milieu DM-nitrophen is caged magnesium. (Modeling says it is about 95% loaded with magnesium.) Thus, the calcium-induced calcium release reported in these papers must arise from photodamage of cells (either of the SR or PM), not from uncaging of calcium. The real give away in the work from the Nathanson lab in which they “load” cells with the free acid of DM-nitrophen, then use 2-photon uncaging to elicit CICR. It is clearly impossible for a small organic molecule with 4 negative charges to penetrate the plasma membrane, else why would Roger Tsien bothered developing AM-ester loading of calcium chelators?