{"doi":"10.1021/acs.jpcb.4c07877","title":"<sup>15</sup>N SABRE-SHEATH and NMR/DFT Characterization of Amino-Metronidazole, a Metabolic Product of the Antibiotic and Prospective Hypoxia Contrast Agent Metronidazole","abstract":"The antibiotic metronidazole (MNZ) has gained interest as a potential MRI contrast agent for imaging hypoxia. 15 N-labeled MNZ can be efficiently hyperpolarized via SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei), but the envisioned MRI approach requires that MNZ rapidly undergoes structural changes in hypoxic environments with significant 15 N frequency differences manifested in its downstream metabolic products. We have performed NMR studies of the anticipated metabolic product amino-MNZ (despite anticipated stability concerns) accompanied by computational density functional theory (DFT) studies to predict the 15 N chemical shifts of different relevant species. Direct hyperpolarization of sparse naturally abundant 15 N spins in amino-MNZ via SABRE-SHEATH (enhancement up to ∼9400 fold), along with 1 H-decoupled 15 N NMR, allowed comparison with both 15 N 3 -MNZ and naturally abundant MNZ. The results show significant 15 N shift differences that agree with the DFT predictions. Taken together, the results show that it should be possible to readily distinguish the parent MNZ from product amino-MNZ in envisioned MRI approaches at clinically relevant magnetic fields.","journal":"The Journal of Physical Chemistry B","year":2025,"id":530972,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1260260,"name":"Md Shahabuddin Alam","orcid":"0000-0002-5366-3321","position":1,"is_corresponding":false},{"id":1076656,"name":"Mohammad Shah Hafez Kabir","orcid":"0000-0003-4952-8730","position":2,"is_corresponding":false},{"id":1260741,"name":"Anthony F. Petrilla","orcid":null,"position":3,"is_corresponding":false},{"id":1260740,"name":"Zahid Siraj","orcid":null,"position":4,"is_corresponding":false},{"id":477788,"name":"Thomas Theis","orcid":"0000-0001-6779-9978","position":5,"is_corresponding":false},{"id":402028,"name":"Eduard Y. Chekmenev","orcid":"0000-0002-8745-8801","position":6,"is_corresponding":false},{"id":402030,"name":"Boyd M. Goodson","orcid":"0000-0001-6079-5077","position":7,"is_corresponding":false},{"id":753812,"name":"Ishani M. Senanayake","orcid":"0009-0003-4772-2983","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T02:51:10.077559Z","pmid":"39843250","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}