Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques

D. I. Potapenko, M. A. Foster, David John Lurie, I. A. Kirilyuk, James McDonald Strachan Hutchison, I. A. Grigor'ev, E. G. Bagryanskaya, V. V. Khramtsov

Research output: Contribution to journalArticle

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Abstract

New improved pH-sensitive nitroxides were applied for in vivo studies. An increased stability of the probes towards reduction was achieved by the introduction of the bulky ethyl groups in the vicinity of the paramagnetic N-O fragment. In addition, the range of pH sensitivity of the approach was extended by the synthesis of probes with two ionizable groups, and, therefore, with two pK(a) values. Stability towards reduction and spectral characteristics of the three new probes were determined in vitro using 290 MHz radiofrequency (RF)- and X-band electron paramagnetic resonance (EPR), longitudinally detected EPR (LODEPR), and field-cycled dynamic nuclear polarization (FC-DNP) techniques. The newly synthesized probe, 4-[bis(2-hydroxyethyl)amino]-2-pyridine-4-yl-2,5,5-triethyl-2,5-,dihydro-1H-imidazol-oxyl, was found to be the most appropriate for the application in the stomach due to both higher stability and convenient pH sensitivity range from pH 1.8 to 6. LODEPR, FC-DNP and proton-electron double resonance imaging (PEDRI) techniques were used to detect the nitroxide localization and acidity in the rat stomach. Improved probe characteristics allowed us to follow in vivo the drug-induced perturbation in the stomach acidity and its normalization afterwards during I h or longer period of time. The results show the applicability of the techniques for monitoring drug pharmacology and disease in the living animals. (c) 2006 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)1-11
Number of pages10
JournalJournal of Magnetic Resonance
Volume182
DOIs
Publication statusPublished - 2006

Keywords

  • nitroxide
  • in vivo EPR techniques
  • in vivo pH measurement
  • stomach acidity
  • IN-VIVO
  • INTRACELLULAR PH
  • EXTRACELLULAR PH
  • RESONANCE-SPECTROSCOPY
  • MAGNETIC-RESONANCE
  • PROBES
  • SPIN
  • SERIES
  • VITRO
  • HOMEOSTASIS

Cite this

Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques. / Potapenko, D. I.; Foster, M. A.; Lurie, David John; Kirilyuk, I. A.; Hutchison, James McDonald Strachan; Grigor'ev, I. A.; Bagryanskaya, E. G.; Khramtsov, V. V.

In: Journal of Magnetic Resonance, Vol. 182, 2006, p. 1-11.

Research output: Contribution to journalArticle

Potapenko, D. I. ; Foster, M. A. ; Lurie, David John ; Kirilyuk, I. A. ; Hutchison, James McDonald Strachan ; Grigor'ev, I. A. ; Bagryanskaya, E. G. ; Khramtsov, V. V. / Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques. In: Journal of Magnetic Resonance. 2006 ; Vol. 182. pp. 1-11.
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abstract = "New improved pH-sensitive nitroxides were applied for in vivo studies. An increased stability of the probes towards reduction was achieved by the introduction of the bulky ethyl groups in the vicinity of the paramagnetic N-O fragment. In addition, the range of pH sensitivity of the approach was extended by the synthesis of probes with two ionizable groups, and, therefore, with two pK(a) values. Stability towards reduction and spectral characteristics of the three new probes were determined in vitro using 290 MHz radiofrequency (RF)- and X-band electron paramagnetic resonance (EPR), longitudinally detected EPR (LODEPR), and field-cycled dynamic nuclear polarization (FC-DNP) techniques. The newly synthesized probe, 4-[bis(2-hydroxyethyl)amino]-2-pyridine-4-yl-2,5,5-triethyl-2,5-,dihydro-1H-imidazol-oxyl, was found to be the most appropriate for the application in the stomach due to both higher stability and convenient pH sensitivity range from pH 1.8 to 6. LODEPR, FC-DNP and proton-electron double resonance imaging (PEDRI) techniques were used to detect the nitroxide localization and acidity in the rat stomach. Improved probe characteristics allowed us to follow in vivo the drug-induced perturbation in the stomach acidity and its normalization afterwards during I h or longer period of time. The results show the applicability of the techniques for monitoring drug pharmacology and disease in the living animals. (c) 2006 Elsevier Inc. All rights reserved.",
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AU - Potapenko, D. I.

AU - Foster, M. A.

AU - Lurie, David John

AU - Kirilyuk, I. A.

AU - Hutchison, James McDonald Strachan

AU - Grigor'ev, I. A.

AU - Bagryanskaya, E. G.

AU - Khramtsov, V. V.

PY - 2006

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N2 - New improved pH-sensitive nitroxides were applied for in vivo studies. An increased stability of the probes towards reduction was achieved by the introduction of the bulky ethyl groups in the vicinity of the paramagnetic N-O fragment. In addition, the range of pH sensitivity of the approach was extended by the synthesis of probes with two ionizable groups, and, therefore, with two pK(a) values. Stability towards reduction and spectral characteristics of the three new probes were determined in vitro using 290 MHz radiofrequency (RF)- and X-band electron paramagnetic resonance (EPR), longitudinally detected EPR (LODEPR), and field-cycled dynamic nuclear polarization (FC-DNP) techniques. The newly synthesized probe, 4-[bis(2-hydroxyethyl)amino]-2-pyridine-4-yl-2,5,5-triethyl-2,5-,dihydro-1H-imidazol-oxyl, was found to be the most appropriate for the application in the stomach due to both higher stability and convenient pH sensitivity range from pH 1.8 to 6. LODEPR, FC-DNP and proton-electron double resonance imaging (PEDRI) techniques were used to detect the nitroxide localization and acidity in the rat stomach. Improved probe characteristics allowed us to follow in vivo the drug-induced perturbation in the stomach acidity and its normalization afterwards during I h or longer period of time. The results show the applicability of the techniques for monitoring drug pharmacology and disease in the living animals. (c) 2006 Elsevier Inc. All rights reserved.

AB - New improved pH-sensitive nitroxides were applied for in vivo studies. An increased stability of the probes towards reduction was achieved by the introduction of the bulky ethyl groups in the vicinity of the paramagnetic N-O fragment. In addition, the range of pH sensitivity of the approach was extended by the synthesis of probes with two ionizable groups, and, therefore, with two pK(a) values. Stability towards reduction and spectral characteristics of the three new probes were determined in vitro using 290 MHz radiofrequency (RF)- and X-band electron paramagnetic resonance (EPR), longitudinally detected EPR (LODEPR), and field-cycled dynamic nuclear polarization (FC-DNP) techniques. The newly synthesized probe, 4-[bis(2-hydroxyethyl)amino]-2-pyridine-4-yl-2,5,5-triethyl-2,5-,dihydro-1H-imidazol-oxyl, was found to be the most appropriate for the application in the stomach due to both higher stability and convenient pH sensitivity range from pH 1.8 to 6. LODEPR, FC-DNP and proton-electron double resonance imaging (PEDRI) techniques were used to detect the nitroxide localization and acidity in the rat stomach. Improved probe characteristics allowed us to follow in vivo the drug-induced perturbation in the stomach acidity and its normalization afterwards during I h or longer period of time. The results show the applicability of the techniques for monitoring drug pharmacology and disease in the living animals. (c) 2006 Elsevier Inc. All rights reserved.

KW - nitroxide

KW - in vivo EPR techniques

KW - in vivo pH measurement

KW - stomach acidity

KW - IN-VIVO

KW - INTRACELLULAR PH

KW - EXTRACELLULAR PH

KW - RESONANCE-SPECTROSCOPY

KW - MAGNETIC-RESONANCE

KW - PROBES

KW - SPIN

KW - SERIES

KW - VITRO

KW - HOMEOSTASIS

U2 - 10.1016/j.jmr.2006.06.002

DO - 10.1016/j.jmr.2006.06.002

M3 - Article

VL - 182

SP - 1

EP - 11

JO - Journal of Magnetic Resonance

JF - Journal of Magnetic Resonance

SN - 1090-7807

ER -