Hyperpolarizing Concentrated Metronidazole 15NO2 Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime

Roman V. Shchepin; Jonathan R. Birchall; Nikita V. Chukanov; Kirill V. Kovtunov; Igor V. Koptyug; Thomas Theis; Warren S. Warren; Juri G. Gelovani; Boyd M. Goodson; Sepideh Shokouhi; Matthew S. Rosen; Yi Fen Yen; Wellington Pham; Eduard Y. Chekmenev

doi:10.1002/chem.201901192

Hyperpolarizing Concentrated Metronidazole ¹⁵NO₂ Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime

Roman V. Shchepin, Jonathan R. Birchall, Nikita V. Chukanov, Kirill V. Kovtunov, Igor V. Koptyug, Thomas Theis, Warren S. Warren, Juri G. Gelovani, Boyd M. Goodson, Sepideh Shokouhi, Matthew S. Rosen, Yi Fen Yen, Wellington Pham, Eduard Y. Chekmenev

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

The NMR hyperpolarization of uniformly ¹⁵N-labeled [¹⁵N₃]metronidazole is demonstrated by using SABRE-SHEATH. In this antibiotic, the ¹⁵NO₂ group is hyperpolarized through spin relays created by ¹⁵N spins in [¹⁵N₃]metronidazole, and the polarization is transferred from parahydrogen-derived hydrides over six chemical bonds. In less than a minute of parahydrogen bubbling at approximately 0.4 μT, a high level of nuclear spin polarization (P_15N) of around 16 % is achieved on all three ¹⁵N sites. This product of ¹⁵N polarization and concentration of ¹⁵N spins is around six-fold better than any previous value determined for ¹⁵N SABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state persists for tens of minutes (relaxation time, T₁≈10 min). A novel synthesis of uniformly ¹⁵N-enriched metronidazole is reported with a yield of 15 %. This approach can potentially be used for synthesis of a wide variety of in vivo metabolic probes with potential uses ranging from hypoxia sensing to theranostic imaging.

Original language	English
Pages (from-to)	8829-8836
Number of pages	8
Journal	Chemistry - A European Journal
Volume	25
Issue number	37
DOIs	https://doi.org/10.1002/chem.201901192
Publication status	Published - 2 Jul 2019

Keywords

hyperpolarization
isotopic labeling
nitrogen heterocycles
NMR spectroscopy
SABRE
spin relays
NMR SIGNAL AMPLIFICATION
PARA-HYDROGEN
SPIN DYNAMICS
SENSITIVITY
TO-NOISE RATIO
PARAHYDROGEN
REVERSIBLE EXCHANGE
N-15 HYPERPOLARIZATION
MAGNETIC-RESONANCE

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10.1002/chem.201901192

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Shchepin, R. V., Birchall, J. R., Chukanov, N. V., Kovtunov, K. V., Koptyug, I. V., Theis, T., Warren, W. S., Gelovani, J. G., Goodson, B. M., Shokouhi, S., Rosen, M. S., Yen, Y. F., Pham, W., & Chekmenev, E. Y. (2019). Hyperpolarizing Concentrated Metronidazole ¹⁵NO₂ Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime. Chemistry - A European Journal, 25(37), 8829-8836. https://doi.org/10.1002/chem.201901192

Shchepin, Roman V. ; Birchall, Jonathan R. ; Chukanov, Nikita V. ; Kovtunov, Kirill V. ; Koptyug, Igor V. ; Theis, Thomas ; Warren, Warren S. ; Gelovani, Juri G. ; Goodson, Boyd M. ; Shokouhi, Sepideh ; Rosen, Matthew S. ; Yen, Yi Fen ; Pham, Wellington ; Chekmenev, Eduard Y. / Hyperpolarizing Concentrated Metronidazole ¹⁵NO₂ Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime. In: Chemistry - A European Journal. 2019 ; Vol. 25, No. 37. pp. 8829-8836.

@article{5fcf1f38406544e9860f5b79bfe700ff,

title = "Hyperpolarizing Concentrated Metronidazole 15NO2 Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime",

abstract = "The NMR hyperpolarization of uniformly 15N-labeled [15N3]metronidazole is demonstrated by using SABRE-SHEATH. In this antibiotic, the 15NO2 group is hyperpolarized through spin relays created by 15N spins in [15N3]metronidazole, and the polarization is transferred from parahydrogen-derived hydrides over six chemical bonds. In less than a minute of parahydrogen bubbling at approximately 0.4 μT, a high level of nuclear spin polarization (P15N) of around 16 % is achieved on all three 15N sites. This product of 15N polarization and concentration of 15N spins is around six-fold better than any previous value determined for 15N SABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state persists for tens of minutes (relaxation time, T1≈10 min). A novel synthesis of uniformly 15N-enriched metronidazole is reported with a yield of 15 %. This approach can potentially be used for synthesis of a wide variety of in vivo metabolic probes with potential uses ranging from hypoxia sensing to theranostic imaging.",

keywords = "hyperpolarization, isotopic labeling, nitrogen heterocycles, NMR spectroscopy, SABRE, spin relays, NMR SIGNAL AMPLIFICATION, PARA-HYDROGEN, SPIN DYNAMICS, SENSITIVITY, TO-NOISE RATIO, PARAHYDROGEN, REVERSIBLE EXCHANGE, N-15 HYPERPOLARIZATION, MAGNETIC-RESONANCE",

author = "Shchepin, {Roman V.} and Birchall, {Jonathan R.} and Chukanov, {Nikita V.} and Kovtunov, {Kirill V.} and Koptyug, {Igor V.} and Thomas Theis and Warren, {Warren S.} and Gelovani, {Juri G.} and Goodson, {Boyd M.} and Sepideh Shokouhi and Rosen, {Matthew S.} and Yen, {Yi Fen} and Wellington Pham and Chekmenev, {Eduard Y.}",

note = "{\textcopyright} 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2019",

month = jul,

day = "2",

doi = "10.1002/chem.201901192",

language = "English",

volume = "25",

pages = "8829--8836",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "Wiley-VCH Verlag",

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Shchepin, RV, Birchall, JR, Chukanov, NV, Kovtunov, KV, Koptyug, IV, Theis, T, Warren, WS, Gelovani, JG, Goodson, BM, Shokouhi, S, Rosen, MS, Yen, YF, Pham, W & Chekmenev, EY 2019, 'Hyperpolarizing Concentrated Metronidazole ¹⁵NO₂ Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime', Chemistry - A European Journal, vol. 25, no. 37, pp. 8829-8836. https://doi.org/10.1002/chem.201901192

Hyperpolarizing Concentrated Metronidazole ¹⁵NO₂ Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime. / Shchepin, Roman V.; Birchall, Jonathan R.; Chukanov, Nikita V.; Kovtunov, Kirill V.; Koptyug, Igor V.; Theis, Thomas; Warren, Warren S.; Gelovani, Juri G.; Goodson, Boyd M.; Shokouhi, Sepideh; Rosen, Matthew S.; Yen, Yi Fen; Pham, Wellington; Chekmenev, Eduard Y.

In: Chemistry - A European Journal, Vol. 25, No. 37, 02.07.2019, p. 8829-8836.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Hyperpolarizing Concentrated Metronidazole 15NO2 Group over Six Chemical Bonds with More than 15 % Polarization and a 20 Minute Lifetime

AU - Shchepin, Roman V.

AU - Birchall, Jonathan R.

AU - Chukanov, Nikita V.

AU - Kovtunov, Kirill V.

AU - Koptyug, Igor V.

AU - Theis, Thomas

AU - Warren, Warren S.

AU - Gelovani, Juri G.

AU - Goodson, Boyd M.

AU - Shokouhi, Sepideh

AU - Rosen, Matthew S.

AU - Yen, Yi Fen

AU - Pham, Wellington

AU - Chekmenev, Eduard Y.

PY - 2019/7/2

Y1 - 2019/7/2

N2 - The NMR hyperpolarization of uniformly 15N-labeled [15N3]metronidazole is demonstrated by using SABRE-SHEATH. In this antibiotic, the 15NO2 group is hyperpolarized through spin relays created by 15N spins in [15N3]metronidazole, and the polarization is transferred from parahydrogen-derived hydrides over six chemical bonds. In less than a minute of parahydrogen bubbling at approximately 0.4 μT, a high level of nuclear spin polarization (P15N) of around 16 % is achieved on all three 15N sites. This product of 15N polarization and concentration of 15N spins is around six-fold better than any previous value determined for 15N SABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state persists for tens of minutes (relaxation time, T1≈10 min). A novel synthesis of uniformly 15N-enriched metronidazole is reported with a yield of 15 %. This approach can potentially be used for synthesis of a wide variety of in vivo metabolic probes with potential uses ranging from hypoxia sensing to theranostic imaging.

AB - The NMR hyperpolarization of uniformly 15N-labeled [15N3]metronidazole is demonstrated by using SABRE-SHEATH. In this antibiotic, the 15NO2 group is hyperpolarized through spin relays created by 15N spins in [15N3]metronidazole, and the polarization is transferred from parahydrogen-derived hydrides over six chemical bonds. In less than a minute of parahydrogen bubbling at approximately 0.4 μT, a high level of nuclear spin polarization (P15N) of around 16 % is achieved on all three 15N sites. This product of 15N polarization and concentration of 15N spins is around six-fold better than any previous value determined for 15N SABRE-derived hyperpolarization. At 1.4 T, the hyperpolarized state persists for tens of minutes (relaxation time, T1≈10 min). A novel synthesis of uniformly 15N-enriched metronidazole is reported with a yield of 15 %. This approach can potentially be used for synthesis of a wide variety of in vivo metabolic probes with potential uses ranging from hypoxia sensing to theranostic imaging.

KW - hyperpolarization

KW - isotopic labeling

KW - nitrogen heterocycles

KW - NMR spectroscopy

KW - SABRE

KW - spin relays

KW - NMR SIGNAL AMPLIFICATION

KW - PARA-HYDROGEN

KW - SPIN DYNAMICS

KW - SENSITIVITY

KW - TO-NOISE RATIO

KW - PARAHYDROGEN

KW - REVERSIBLE EXCHANGE

KW - N-15 HYPERPOLARIZATION

KW - MAGNETIC-RESONANCE

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U2 - 10.1002/chem.201901192

DO - 10.1002/chem.201901192

M3 - Article

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JO - Chemistry - A European Journal

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