{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:17:34Z","timestamp":1771049854205,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H05099"],"award-info":[{"award-number":["16H05099"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H04609"],"award-info":[{"award-number":["18H04609"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20H04767"],"award-info":[{"award-number":["20H04767"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20H02701"],"award-info":[{"award-number":["20H02701"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["SENTAN"],"award-info":[{"award-number":["SENTAN"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Hydrogen sulfide and its oxidation products are involved in many biological processes, and sulfane sulfur compounds, which contain sulfur atoms bonded to other sulfur atom(s), as found in hydropersulfides (R-S-SH), polysulfides (R-S-Sn-S-R), hydrogen polysulfides (H2Sn), etc., have attracted increasing interest. To characterize their physiological and pathophysiological roles, selective detection techniques are required. Classically, sulfane sulfur compounds can be detected by cyanolysis, involving nucleophilic attack by cyanide ion to cleave the sulfur\u2013sulfur bonds. The generated thiocyanate reacts with ferric ion, and the resulting ferric thiocyanate complex can be easily detected by absorption spectroscopy. Recent exploration of the properties of sulfane sulfur compounds as both nucleophiles and electrophiles has led to the development of various chemical techniques for detection, isolation, and bioimaging of sulfane sulfur compounds in biological samples. These include tag-switch techniques, LC-MS\/MS, Raman spectroscopy, and fluorescent probes. Herein, we present an overview of the techniques available for specific detection of sulfane sulfur species in biological contexts.<\/jats:p>","DOI":"10.3390\/biom11111553","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:29:46Z","timestamp":1634765386000},"page":"1553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Recent Advances in Detection, Isolation, and Imaging Techniques for Sulfane Sulfur-Containing Biomolecules"],"prefix":"10.3390","volume":"11","author":[{"given":"Honami","family":"Echizen","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eita","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenjiro","family":"Hanaoka","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1523\/JNEUROSCI.16-03-01066.1996","article-title":"The possible role of hydrogen sulfide as an endogenous neuromodulator","volume":"16","author":"Abe","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/med.21433","article-title":"Toward Hydrogen Sulfide Based Therapeutics: Critical Drug Delivery and Developability Issues","volume":"38","author":"Zheng","year":"2018","journal-title":"Med. Res. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nchembio.1834","article-title":"Biogenesis of reactive sulfur species for signaling by hydrogen sulfide oxidation pathways","volume":"11","author":"Mishanina","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Giles, G.I., Nasim, M.J., Ali, W., and Jacob, C. (2017). The reactive sulfur species concept: 15 years on. Antioxidants, 6.","DOI":"10.3390\/antiox6020038"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kimura, H. (2021). Hydrogen Sulfide (H2S) and Polysulfide (H2Sn) Signaling: The First 25 Years. Biomolecules, 11.","DOI":"10.3390\/biom11060896"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0076-6879(87)43009-7","article-title":"Sulfane Sulfur","volume":"143","author":"Wood","year":"1987","journal-title":"Methods Enzymol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/bj2640625","article-title":"Sulphane sulphur in biological systems: A possible regulatory role","volume":"264","author":"Toohey","year":"1989","journal-title":"Biochem. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ab.2011.01.044","article-title":"Sulfur signaling: Is the agent sulfide or sulfane?","volume":"413","author":"Toohey","year":"2011","journal-title":"Anal. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12789","DOI":"10.3390\/molecules190812789","article-title":"Thiosulfoxide (Sulfane) sulfur: New chemistry and new regulatory roles in biology","volume":"19","author":"Toohey","year":"2014","journal-title":"Molecules"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7606","DOI":"10.1073\/pnas.1321232111","article-title":"Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling","volume":"111","author":"Ida","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"45995","DOI":"10.1038\/srep45995","article-title":"Polysulfides (H2Sn) produced from the interaction of hydrogen sulfide (H2S) and nitric oxide (NO) activate TRPA1 channels","volume":"7","author":"Miyamoto","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e10695","DOI":"10.15252\/emmm.201910695","article-title":"Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology","volume":"11","author":"Ide","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1039\/C5MB00216H","article-title":"Persulfides: Current knowledge and challenges in chemistry and chemical biology","volume":"11","author":"Park","year":"2015","journal-title":"Mol. Biosyst."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/35055104","article-title":"Protein S-nitrosylation: A physiological signal for neuronal nitric oxide","volume":"3","author":"Jaffrey","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.freeradbiomed.2008.09.034","article-title":"Detection of protein S-nitrosylation with the biotin-switch technique","volume":"46","author":"Forrester","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"ra72","DOI":"10.1126\/scisignal.2000464","article-title":"HS signals through protein S-Sulfhydration","volume":"2","author":"Mustafa","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1021\/cb4001052","article-title":"Persulfide reactivity in the detection of protein S-sulfhydration","volume":"8","author":"Pan","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"ra86","DOI":"10.1126\/scisignal.2002329","article-title":"H2S-induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response","volume":"4","author":"Krishnan","year":"2011","journal-title":"Sci. Signal."},{"key":"ref_19","first-page":"1","article-title":"A novel persulfide detection method reveals protein persulfide- and polysulfide-reducing functions of thioredoxin and glutathione systems","volume":"2","author":"Pader","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1002\/anie.201305876","article-title":"Detection of protein S-sulfhydration by a tag-switch technique","volume":"53","author":"Zhang","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1021\/ol301370s","article-title":"Methylsulfonyl benzothiazole (MSBT): A selective protein thiol blocking reagent","volume":"14","author":"Zhang","year":"2012","journal-title":"Org. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.molcel.2011.10.021","article-title":"Hydrogen sulfide-linked sulfhydration of NF-\u03baB mediates its antiapoptotic actions","volume":"45","author":"Sen","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1039\/C5SC04818D","article-title":"Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation","volume":"7","author":"Wedmann","year":"2016","journal-title":"Chem. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/bph.14330","article-title":"Inorganic hydrogen polysulfides: Chemistry, chemical biology and detection","volume":"176","author":"Liu","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/bph.14394","article-title":"Speciation of reactive sulfur species and their reactions with alkylating agents: Do we have any clue about what is present inside the cell?","volume":"176","author":"Ida","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.bbagen.2013.05.037","article-title":"Chemical aspects of hydrogen sulfide measurements in physiological samples","volume":"1840","author":"Nagy","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1136\/thoraxjnl-2016-209359","article-title":"Production of reactive persulfide species in chronic obstructive pulmonary disease","volume":"72","author":"Numakura","year":"2017","journal-title":"Thorax"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-01311-y","article-title":"Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics","volume":"8","author":"Akaike","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sawa, T., Motohashi, H., Ihara, H., and Akaike, T. (2020). Enzymatic regulation and biological functions of reactive cysteine persulfides and polysulfides. Biomolecules, 10.","DOI":"10.3390\/biom10091245"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41467-017-00605-5","article-title":"Exact mass analysis of sulfur clusters upon encapsulation by a polyaromatic capsular matrix","volume":"8","author":"Matsuno","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1039\/C7CS00238F","article-title":"Electromagnetic theories of surface-enhanced Raman spectroscopy","volume":"46","author":"Ding","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9518","DOI":"10.1021\/acs.analchem.6b02081","article-title":"A Single Nanoprobe for Ratiometric Imaging and Biosensing of Hypochlorite and Glutathione in Live Cells Using Surface-Enhanced Raman Scattering","volume":"88","author":"Wang","year":"2016","journal-title":"Anal. Chem."},{"key":"ref_33","first-page":"68","article-title":"Intraoperative brain cancer detection with Raman spectroscopy in humans","volume":"4","author":"Banerjee","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-03899-1","article-title":"Gold-nanof\u00e8ve surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival","volume":"9","author":"Shiota","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101926","DOI":"10.1016\/j.redox.2021.101926","article-title":"On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity","volume":"41","author":"Honda","year":"2021","journal-title":"Redox Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.1021\/acs.analchem.8b04634","article-title":"Developing polysulfide-sensitive gfps for real-time analysis of polysulfides in live cells and subcellular organelles","volume":"91","author":"Hu","year":"2019","journal-title":"Anal. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1039\/c3sc50754h","article-title":"New fluorescent probes for sulfane sulfurs and the application in bioimaging","volume":"4","author":"Chen","year":"2013","journal-title":"Chem. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1021\/jacs.5b10494","article-title":"Biosynthesis and Reactivity of Cysteine Persulfides in Signaling","volume":"138","author":"Yadav","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep14774","article-title":"Identification of H2S3 and H2S produced by 3-mercaptopyruvate sulfurtransferase in the brain","volume":"5","author":"Kimura","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1039\/C6CC08372B","article-title":"Development of a reversible fluorescent probe for reactive sulfur species, sulfane sulfur, and its biological application","volume":"53","author":"Takano","year":"2017","journal-title":"Chem. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7257","DOI":"10.1021\/ja502968x","article-title":"Rational design and bioimaging applications of highly selective fluorescence probes for hydrogen polysulfides","volume":"136","author":"Liu","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13961","DOI":"10.1002\/anie.201506887","article-title":"The Development of Fluorescent Probes for Visualizing Intracellular Hydrogen Polysulfides","volume":"54","author":"Chen","year":"2015","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/jn\/134.3.489","article-title":"Glutathione Metabolism and Its Implications for Health","volume":"134","author":"Wu","year":"2004","journal-title":"J. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1021\/ja043919h","article-title":"Evolution of fluorescein as a platform for finely tunable fluorescence probes","volume":"127","author":"Urano","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nrm3391","article-title":"H2S signalling through protein sulfhydration and beyond","volume":"13","author":"Paul","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18003","DOI":"10.1021\/ja207851s","article-title":"Development of a highly selective fluorescence probe for hydrogen sulfide","volume":"133","author":"Sasakura","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"40227","DOI":"10.1038\/srep40227","article-title":"Discovery and Mechanistic Characterization of Selective Inhibitors of H2S-producing Enzyme: 3-Mercaptopyruvate Sulfurtransferase (3MST) Targeting Active-site Cysteine Persulfide","volume":"7","author":"Hanaoka","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/11\/1553\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:19:35Z","timestamp":1760167175000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/11\/1553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["biom11111553"],"URL":"https:\/\/doi.org\/10.3390\/biom11111553","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]}}}