Development of novel 19F NMR pH indicators: Synthesis and evaluation of a series of fluorinated vitamin B6 analogues

Sha He, Ralph P. Mason, Sandeep Hunjan, Vimal D. Mehta, Veera Arora, Revathi Katipally, Padmakar V. Kulkarni, Peter P. Antich

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 pK(a) values in the range 7.05-9.5 with a chemical shift sensitivity in the range 7.4-12ppm. 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 pK(a)=7.05, which is closer to normal physiological pH than the parent molecule 6-fluoropyridoxol (6-FPOL) (pK(a)=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. Copyright (C) 1998 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1631-1639
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume6
Issue number9
DOIs
StatePublished - Sep 1998

Fingerprint

Vitamin B 6
Chemical shift
Nuclear magnetic resonance
Blood
Molecules
Spectral resolution
Cell membranes
Titration
Aldehydes
Rats
Derivatives
Acids
Cell Membrane

Keywords

  • F NMR
  • Fluoropyridoxamine
  • Fluoropyridoxol
  • pH
  • Vitamin B

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Development of novel 19F NMR pH indicators : Synthesis and evaluation of a series of fluorinated vitamin B6 analogues. / He, Sha; Mason, Ralph P.; Hunjan, Sandeep; Mehta, Vimal D.; Arora, Veera; Katipally, Revathi; Kulkarni, Padmakar V.; Antich, Peter P.

In: Bioorganic and Medicinal Chemistry, Vol. 6, No. 9, 09.1998, p. 1631-1639.

Research output: Contribution to journalArticle

He, Sha ; Mason, Ralph P. ; Hunjan, Sandeep ; Mehta, Vimal D. ; Arora, Veera ; Katipally, Revathi ; Kulkarni, Padmakar V. ; Antich, Peter P. / Development of novel 19F NMR pH indicators : Synthesis and evaluation of a series of fluorinated vitamin B6 analogues. In: Bioorganic and Medicinal Chemistry. 1998 ; Vol. 6, No. 9. pp. 1631-1639.
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