Nitrogen-15 and Fluorine-19 Relaxation Dynamics and Spin-Relayed SABRE-SHEATH Hyperpolarization of Fluoro-[15N3]metronidazole
Efficient 15N-hyperpolarization of [15N3]metronidazole was reported previously using the Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) technique. This hyperpolarized FDA-approved antibiotic is a potential contrast agent because it can be administered in a large dose and because previous studies revealed long-lasting HP states with exponential decay constant T1 values of up to 10 min. Possible hypoxia-sensing applications have been proposed using hyperpolarized [15N3]metronidazole. In this work, we report on the functionalization of [15N3]metronidazole with a fluorine-19 moiety via a one-step reaction to substitute the -OH group. SABRE-SHEATH hyperpolarization studies of fluoro-[15N3]metronidazole revealed efficient hyperpolarization of all three 15N sites with maximum %P15N values ranging from 4.2 to 6.2%, indicating efficient spin-relayed polarization transfer in microtesla fields via the network formed by 2J15N-15N. The corresponding 15N to 19F spin-relayed polarization transfer was found to be far less efficient with %P19F of 0.16%, i.e., more than an order of magnitude lower than that of 15N. Relaxation dynamics studies in microtesla fields support a spin-relayed polarization transfer mechanism because all 15N and 19F spins share the same T1 value of ca. 16-20 s and the same magnetic field profile for the SABRE-SHEATH polarization process. We envision the use of fluoro-[15N3]metronidazole as a potential hypoxia sensor. It is anticipated that under hypoxic conditions, the nitro group of fluoro-[15N3]metronidazole undergoes electronic stepwise reduction to an amino derivative. Ab initio calculations of 15N and 19F chemical shifts of fluoro-[15N3]metronidazole and its putative hypoxia-induced metabolites clearly indicate that the chemical shift dispersions of all three 15N sites and the 19F site are large enough to enable the envisioned hypoxia-sensing approaches.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:127 |
|---|---|
| Enthalten in: |
The journal of physical chemistry. A - 127(2023), 23 vom: 15. Juni, Seite 5018-5029 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kabir, Mohammad S H [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
140QMO216E |
|---|
| Anmerkungen: |
Date Completed 16.06.2023 Date Revised 16.06.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1021/acs.jpca.3c02317 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM357805267 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM357805267 | ||
| 003 | DE-627 | ||
| 005 | 20231226073402.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1021/acs.jpca.3c02317 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1192.xml |
| 035 | |a (DE-627)NLM357805267 | ||
| 035 | |a (NLM)37278605 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kabir, Mohammad S H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Nitrogen-15 and Fluorine-19 Relaxation Dynamics and Spin-Relayed SABRE-SHEATH Hyperpolarization of Fluoro-[15N3]metronidazole |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.06.2023 | ||
| 500 | |a Date Revised 16.06.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Efficient 15N-hyperpolarization of [15N3]metronidazole was reported previously using the Signal Amplification By Reversible Exchange in SHield Enabled Alignment Transfer (SABRE-SHEATH) technique. This hyperpolarized FDA-approved antibiotic is a potential contrast agent because it can be administered in a large dose and because previous studies revealed long-lasting HP states with exponential decay constant T1 values of up to 10 min. Possible hypoxia-sensing applications have been proposed using hyperpolarized [15N3]metronidazole. In this work, we report on the functionalization of [15N3]metronidazole with a fluorine-19 moiety via a one-step reaction to substitute the -OH group. SABRE-SHEATH hyperpolarization studies of fluoro-[15N3]metronidazole revealed efficient hyperpolarization of all three 15N sites with maximum %P15N values ranging from 4.2 to 6.2%, indicating efficient spin-relayed polarization transfer in microtesla fields via the network formed by 2J15N-15N. The corresponding 15N to 19F spin-relayed polarization transfer was found to be far less efficient with %P19F of 0.16%, i.e., more than an order of magnitude lower than that of 15N. Relaxation dynamics studies in microtesla fields support a spin-relayed polarization transfer mechanism because all 15N and 19F spins share the same T1 value of ca. 16-20 s and the same magnetic field profile for the SABRE-SHEATH polarization process. We envision the use of fluoro-[15N3]metronidazole as a potential hypoxia sensor. It is anticipated that under hypoxic conditions, the nitro group of fluoro-[15N3]metronidazole undergoes electronic stepwise reduction to an amino derivative. Ab initio calculations of 15N and 19F chemical shifts of fluoro-[15N3]metronidazole and its putative hypoxia-induced metabolites clearly indicate that the chemical shift dispersions of all three 15N sites and the 19F site are large enough to enable the envisioned hypoxia-sensing approaches | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Metronidazole |2 NLM | |
| 650 | 7 | |a 140QMO216E |2 NLM | |
| 650 | 7 | |a Nitrogen-15 |2 NLM | |
| 650 | 7 | |a Fluorine |2 NLM | |
| 650 | 7 | |a 284SYP0193 |2 NLM | |
| 650 | 7 | |a Nitrogen Isotopes |2 NLM | |
| 700 | 1 | |a Joshi, Sameer M |e verfasserin |4 aut | |
| 700 | 1 | |a Samoilenko, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Adelabu, Isaiah |e verfasserin |4 aut | |
| 700 | 1 | |a Nantogma, Shiraz |e verfasserin |4 aut | |
| 700 | 1 | |a Gelovani, Juri G |e verfasserin |4 aut | |
| 700 | 1 | |a Goodson, Boyd M |e verfasserin |4 aut | |
| 700 | 1 | |a Chekmenev, Eduard Y |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The journal of physical chemistry. A |d 1997 |g 127(2023), 23 vom: 15. Juni, Seite 5018-5029 |w (DE-627)NLM098261479 |x 1520-5215 |7 nnns |
| 773 | 1 | 8 | |g volume:127 |g year:2023 |g number:23 |g day:15 |g month:06 |g pages:5018-5029 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1021/acs.jpca.3c02317 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 127 |j 2023 |e 23 |b 15 |c 06 |h 5018-5029 | ||