8-hydroxyquinoline derivatives as fluorescent sensors for total intracellular magnesium

Although magnesium is essential for a number of cellular processes such as proliferation and death, its distribution and intracellular compartmentalization have not yet been thoroughly elucidated, mainly because of the inadequacy of the available techniques to map intracellular magnesium distribution. For this reason, particular interest has been recently demonstrated by a family of fluorescent molecules, the DCHQ series (Diaza-18-Crown-16 8-Hydroxyquinoline), that have shown an affinity and specificity for magnesium higher than all the other commercial probes, thus permitting the detection of the total intracellular magnesium [1]. The synthesis of the DCHQ compounds has been optimized by using microwave heating [2]: this approach allowed us to easily modify the basic structure with the introduction of various functional groups to obtain a number of derivatives with improved features of fluorescence, uptake and localization with respect to the original compound (DCHQ1). Fluorescence quantum yield has been enhanced via introduction of aromatic side groups (DCHQ7 and 13), that contemporary conferred improved features of uptake, since the probes are highly retained inside the cells after washings. Enhanced uptake has also been achieved with DCHQ12, a DCHQ-AM derivative that is recognized by the intracellular esterases. DCHQ11, with two long hydrophobic side chains, instead, allowed a better staining of the membranes due to its high affinity to the lipophilic environments. Results show the potentiality of these new fluorescent probes in providing novel insight in the study of intracellular magnesium homeostasis.