{"doi":"10.1021/jacs.1c05547","title":"Enabling <i>In Vivo</i> Photocatalytic Activation of Rapid Bioorthogonal Chemistry by Repurposing Silicon-Rhodamine Fluorophores as Cytocompatible Far-Red Photocatalysts","abstract":"Chromophores that absorb in the tissue-penetrant far-red/near-infrared window have long served as photocatalysts to generate singlet oxygen for photodynamic therapy. However, the cytotoxicity and side reactions associated with singlet oxygen sensitization have posed a problem for using long-wavelength photocatalysis to initiate other types of chemical reactions in biological environments. Herein, silicon-Rhodamine compounds (SiRs) are described as photocatalysts for inducing rapid bioorthogonal chemistry using 660 nm light through the oxidation of a dihydrotetrazine to a tetrazine in the presence of trans-cyclooctene dienophiles. SiRs have been commonly used as fluorophores for bioimaging but have not been applied to catalyze chemical reactions. A series of SiR derivatives were evaluated, and the Janelia Fluor-SiR dyes were found to be especially effective in catalyzing photooxidation (typically 3%). A dihydrotetrazine/tetrazine pair is described that displays high stability in both oxidation states. A protein that was site-selectively modified by trans-cyclooctene was quantitatively conjugated upon exposure to 660 nm light and a dihydrotetrazine. By contrast, a previously described methylene blue catalyst was found to rapidly degrade the protein. SiR-red light photocatalysis was used to cross-link hyaluronic acid derivatives functionalized by dihydrotetrazine and trans-cyclooctenes, enabling 3D culture of human prostate cancer cells. Photoinducible hydrogel formation could also be carried out in live mice through subcutaneous injection of a Cy7-labeled hydrogel precursor solution, followed by brief irradiation to produce a stable hydrogel. This cytocompatible method for using red light photocatalysis to activate bioorthogonal chemistry is anticipated to find broad applications where spatiotemporal control is needed in biological environments.","journal":"Journal of the American Chemical Society","year":2021,"id":149304,"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":109,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9438,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":608867,"name":"He Zhang","orcid":"0000-0002-5084-9892","position":1,"is_corresponding":false},{"id":634893,"name":"Tao Zhang","orcid":"0000-0001-6855-0162","position":2,"is_corresponding":false},{"id":635770,"name":"Xiaoyu Zou","orcid":null,"position":3,"is_corresponding":false},{"id":291084,"name":"Hui Wang","orcid":"0000-0002-2346-8621","position":4,"is_corresponding":false},{"id":635771,"name":"Julia E. Rosenberger","orcid":null,"position":5,"is_corresponding":false},{"id":443864,"name":"Raghu Vannam","orcid":"0000-0002-6665-8548","position":6,"is_corresponding":false},{"id":635772,"name":"William S. Trout","orcid":null,"position":7,"is_corresponding":false},{"id":259888,"name":"Jonathan B. Grimm","orcid":"0000-0003-0331-4200","position":8,"is_corresponding":false},{"id":249822,"name":"Luke D. Lavis","orcid":"0000-0002-0789-6343","position":9,"is_corresponding":false},{"id":634894,"name":"Colin Thorpe","orcid":"0000-0001-8238-0112","position":10,"is_corresponding":false},{"id":443867,"name":"Xinqiao Jia","orcid":"0000-0002-3564-5576","position":11,"is_corresponding":false},{"id":258567,"name":"Zibo Li","orcid":"0000-0002-1063-0298","position":12,"is_corresponding":false},{"id":324007,"name":"Joseph M. Fox","orcid":"0000-0002-8258-1640","position":13,"is_corresponding":false},{"id":377227,"name":"Chuanqi Wang","orcid":"0009-0006-1439-7397","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-18T23:42:51.282401Z","pmid":"34250803","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":[]}