Development of novel 19F NMR pH indicators: synthesis and evaluation of a series of fluorinated vitamin B6 analogues.
We have synthesized a series of novel fluorinated vitamin B6 analogues (6-fluoropyridoxol derivatives) as potential 19F NMR pH indicators for use in vivo. Modifications included addition of aldehyde, carboxyl or aminomethyl groups at the 4- or 5-ring position, and examination of a trifluoromethyl moiety as an internal chemical shift standard. The variation in chemical shift with respect to acid-base titration showed pKa values in the range 7.05-9.5 with a chemical shift sensitivity in the range 7.4-12 ppm. Several of the molecules readily cross cell membranes providing estimates of both intra- and extra-cellular pH in whole blood. 6-Fluoropyridoxamine (6-FPAM) exhibits a pKa = 7.05, which is closer to normal physiological pH than the parent molecule 6-fluoropyridoxol (6-FPOL) (pKa = 8.2), and should thus, be useful for precise and accurate measurements of pH in vivo. Enhanced spectral resolution for 6-FPAM over 6-FPOL is demonstrated in whole blood and the perfused rat heart.
He
S
S
University of Texas-Southwestern Medical Center, Dallas 75235, USA.
Mason
R P
RP
Hunjan
S
S
Mehta
V D
VD
Arora
V
V
Katipally
R
R
Kulkarni
P V
PV
Antich
P P
PP
D000818:Animals; D005069:Evaluation Studies as Topic; D005461:Fluorine; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats
D005461:Fluorine; D011736:Pyridoxine