15N Hyperpolarization of Imidazole-15N2 for Magnetic Resonance pH Sensing via SABRE-SHEATH

Roman V Shchepin; Danila A Barskiy; Aaron M Coffey; Thomas Theis; Fan Shi; Warren S Warren; Boyd M Goodson; Eduard Y Chekmenev

doi:10.1021/acssensors.6b00231

¹⁵N Hyperpolarization of Imidazole-¹⁵N₂ for Magnetic Resonance pH Sensing via SABRE-SHEATH

ACS Sens. 2016 Jun 24;1(6):640-644. doi: 10.1021/acssensors.6b00231. Epub 2016 Apr 14.

Authors

Roman V Shchepin¹, Danila A Barskiy¹, Aaron M Coffey¹, Thomas Theis², Fan Shi³, Warren S Warren², Boyd M Goodson⁴, Eduard Y Chekmenev⁵

Affiliations

¹ Vanderbilt University Institute of Imaging Science (VUIIS), Department of Radiology, Department of Biomedical Engineering, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University , Nashville, Tennessee 37232-2310, United States.
² Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
³ Department of Chemistry and Biochemistry and Materials Technology Center, Southern Illinois University , Carbondale, Illinois 62901, United States.
⁴ Department of Chemistry and Biochemistry and Materials Technology Center, Southern Illinois University, Carbondale, Illinois 62901, United States; Department of Chemistry and Biochemistry and Materials Technology Center, Southern Illinois University, Carbondale, Illinois 62901, United States.
⁵ Vanderbilt University Institute of Imaging Science (VUIIS), Department of Radiology, Department of Biomedical Engineering, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University, Nashville, Tennessee 37232-2310, United States; Vanderbilt University Institute of Imaging Science (VUIIS), Department of Radiology, Department of Biomedical Engineering, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University, Nashville, Tennessee 37232-2310, United States; Vanderbilt University Institute of Imaging Science (VUIIS), Department of Radiology, Department of Biomedical Engineering, and Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University, Nashville, Tennessee 37232-2310, United States; Russian Academy of Sciences, Moscow, Leninskiy Prospekt 14, 119991, Russia.

Abstract

¹⁵N nuclear spins of imidazole-¹⁵N₂ were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A ¹⁵N NMR signal enhancement of ∼2000-fold at 9.4 T is reported using parahydrogen gas (∼50% para-) and ∼0.1 M imidazole-¹⁵N₂ in methanol:aqueous buffer (∼1:1). Proton binding to a ¹⁵N site of imidazole occurs at physiological pH (pK_a ∼ 7.0), and the binding event changes the ¹⁵N isotropic chemical shift by ∼30 ppm. These properties are ideal for in vivo pH sensing. Additionally, imidazoles have low toxicity and are readily incorporated into a wide range of biomolecules. ¹⁵N-Imidazole SABRE-SHEATH hyperpolarization potentially enables pH sensing on scales ranging from peptide and protein molecules to living organisms.

Keywords: 15N; NMR; chemical shift; hyperpolarization; imidazole; pH sensing; parahydrogen.

Abstract

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