Synthesis and Biological Characterization of New Aminophosphonates for Mitochondrial pH Determination by 31P NMR Spectroscopy
Abstract
A series of mitochondria targeted α-aminophosphonates
combining a diethoxyphosphoryl group and an
alkyl chain-connected triphenylphosphonium bromide tail
were designed and synthesized, and their pH-sensitive 31P
NMR properties and biological activities in vitro and in vivo
were evaluated. The results showed a number of these mitoaminophosphonates
exhibiting pKa values fitting the mitochondrial
pH range, short relaxation, and chemical shift parameters
compatible with sensitive 31P NMR detection, and low
cytotoxicity on green algae and murine fibroblasts cell cultures.
Of these, two selected compounds demonstrated to distribute at NMR detectable levels within the cytosolic and mitochondrial
sites following their perfusion to isolated rat livers, with no detrimental effects on cell energetics and aerobic respiration. This
study provided a new molecular scaffold for further development of in situ spectroscopic real-time monitoring of mitochondrion/
cytosol pH gradients.