title: Synthesis and biological characterization of new aminophosphonates for mitochondrial pH determination by (31)P 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 (31)P NMR properties and biological activities in vitro and in vivo were evaluated. The results showed a number of these mito-aminophosphonates exhibiting pKa values fitting the mitochondrial pH range, short relaxation, and chemical shift parameters compatible with sensitive (31)P 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.
authors: Aix-Marseille Université , CNRS UMR 7273, Equipe Sondes Moléculaires en Biologie et Stress Oxydant, Institut de Chimie Radicalaire, Marseille, France.
authors: Marcel
authors: M
authors: Culcasi
authors: Gilles
authors: G
authors: Casano
authors: Céline
authors: C
authors: Lucchesi
authors: Anne
authors: A
authors: Mercier
authors: Jean-Louis
authors: JL
authors: Clément
authors: Valérie
authors: V
authors: Pique
authors: Laure
authors: L
authors: Michelet
authors: Anja
authors: A
authors: Krieger-Liszkay
authors: Maxime
authors: M
authors: Robin
authors: Sylvia
authors: S
authors: Pietri
mesh_terms: D016475:3T3 Cells; D000818:Animals; D060326:Chemistry Techniques, Synthetic; D016825:Chlamydomonas reinhardtii / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008099:Liver / Q000166:cytology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism*; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D010477:Perfusion; D010539:Permeability; D051381:Rats
chemical_list: D063065:Organophosphonates