Fluorinated alpha-methylamino acids as 19F NMR indicators of intracellular pH

A series of nontoxic, fluorinated amino acids and their methyl esters have been used to measure intracellular pH in human peripheral blood lymphocytes by 19F NMR. Mono-, di-, and trifluoro alpha-methylalanines and their methyl esters have been characterized with respect to their spectra, the pH dependence of their fluorine resonances, and the effects of temperature and cations on the NH2pKa values. These pH indicators can be used singly or in combination to determine intracellular vs. extracellular pH profiles over a wide range (greater than 2 pH units) of extracellular pH.