{"doi":"10.1021/jacs.2c01809","title":"Selective Isotope Labeling and LC-Photo-CIDNP Enable NMR Spectroscopy at Low-Nanomolar Concentration","abstract":"NMR spectroscopy is a powerful tool to investigate molecular structure and dynamics. The poor sensitivity of this technique, however, limits its ability to tackle questions requiring dilute samples. Low-concentration photochemically induced dynamic nuclear polarization (LC-photo-CIDNP) is an optically enhanced NMR technology capable of addressing the above challenge by increasing the detection limit of aromatic amino acids in solution up to 1000-fold, either in isolation or within proteins. Here, we show that the absence of NMR-active nuclei close to a magnetically active site of interest (e.g., the structurally diagnostic 1Hα–13Cα pair of amino acids) is expected to significantly increase LC-photo-CIDNP hyperpolarization. Then, we exploit the spin-diluted tryptophan isotopolog Trp-α-13C-β,β,2,4,5,6,7-d7 and take advantage of the above prediction to experimentally achieve a ca 4-fold enhancement in NMR sensitivity over regular LC-photo-CIDNP. This advance enables the rapid (within seconds) detection of 20 nM concentrations or the molecule of interest, corresponding to a remarkable 3 ng detection limit. Finally, the above Trp isotopolog is amenable to incorporation within proteins and is readily detectable at a 1 μM concentration in complex cell-like media, including Escherichia coli cell-free extracts.","journal":"Journal of the American Chemical Society","year":2022,"id":246421,"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":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":882448,"name":"Siyu Li","orcid":"0000-0001-5979-8633","position":1,"is_corresponding":false},{"id":883029,"name":"Clayton A. Mickles","orcid":null,"position":2,"is_corresponding":false},{"id":730191,"name":"Valeria Guzmán‐Luna","orcid":"0000-0002-2242-5953","position":3,"is_corresponding":false},{"id":882449,"name":"Kenji Sugisaki","orcid":"0000-0002-1950-5725","position":4,"is_corresponding":false},{"id":431041,"name":"Clayton M. Thompson","orcid":null,"position":5,"is_corresponding":false},{"id":883030,"name":"Hung H. Dang","orcid":null,"position":6,"is_corresponding":false},{"id":390171,"name":"Silvia Cavagnero","orcid":"0000-0002-4290-2331","position":7,"is_corresponding":false},{"id":748479,"name":"Hanming Yang","orcid":"0000-0003-0488-2656","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T00:23:43.438539Z","pmid":"35700317","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":[]}