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The X\u2010ray structure of <jats:bold>Mn2<\/jats:bold> confirmed its distorted octahedral geometry. <jats:bold>Mn1<\/jats:bold> and <jats:bold>Mn2<\/jats:bold>, for the first time, showed US\u2010triggered release of CO and ROS generation (<jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub> and <jats:sup>\u22c5<\/jats:sup>OH) in an aqueous solution from any Mn(I)\u2010tricarbonyl complexes, indicating its potential for synergetic CO gas therapy and sonodynamic therapy. The above\u2010mentioned in\u2010solution chemistry was successfully translated into <jats:italic>in\u2005vitro<\/jats:italic> cellular models. These complexes showed unprecedented US\u2010triggered toxicity against T\u2010cell lymphoma and human breast cancer cells (IC<jats:sub>50<\/jats:sub> for <jats:bold>Mn2<\/jats:bold>&lt;1\u2005\u03bcM) while were minimally toxic without US or against normal spleen and human embryonic kidney cells. <jats:bold>Mn2<\/jats:bold> was ca. 12 fold more anticancer active than <jats:bold>Mn1<\/jats:bold>, indicating that the ferrocene conjugation augmented the US sensitivity. The apoptotic sonotoxicity of <jats:bold>Mn2<\/jats:bold> was due to US\u2010promoted mitochondrial depolarization via ROS generation and CO release. The apoptosis was triggered by caspase 3 activation. This is the first report of Mn(I)\u2010tricarbonyl\u2010based sonosensitizers for cancer SDT. Overall, this study, for the first time, establishes the effectiveness of 3d metal carbonyls in SDT.<\/jats:p>","DOI":"10.1002\/chem.202403454","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T10:20:19Z","timestamp":1730888419000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Sonodynamic Cancer Therapy by Mn(I)\u2010tricarbonyl Complexes via Ultrasound\u2010triggered CO Release and ROS Generation"],"prefix":"10.1002","volume":"31","author":[{"given":"Ashish","family":"Kumar Yadav","sequence":"first","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology (BHU) Varanasi  Uttar Pradesh 221005 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virendra","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Zoology Institute of Science, Banaras Hindu University, Varanasi  Uttar Pradesh 221005 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagar","family":"Acharjee","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology (BHU) Varanasi  Uttar Pradesh 221005 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukanta","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Bombay  Mumbai, Maharashtra 400076 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4393-4447","authenticated-orcid":false,"given":"Rajesh","family":"Kushwaha","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology (BHU) Varanasi  Uttar Pradesh 221005 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnab","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology Bombay  Mumbai, Maharashtra 400076 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biplob","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Zoology Institute of Science, Banaras Hindu University, Varanasi  Uttar Pradesh 221005 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samya","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Chemistry Indian Institute of Technology (BHU) Varanasi  Uttar Pradesh 221005 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202004883"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201511432"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2022.214860"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.12.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2020.111122"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.poly.2023.116778"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202209136"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja3084434"},{"key":"e_1_2_9_9_1","unstructured":"\u00a0"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00403D"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202301074"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3CS00227F"},{"key":"e_1_2_9_13_1","unstructured":"\u00a0"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja413063e"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202200597"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202319966"},{"key":"e_1_2_9_17_1","unstructured":"\u00a0"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1CC06769A"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202100615"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c02485"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201311225"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9SC03166A"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7580707"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.6b02623"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-021-01910-7"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphotobiol.2020.111787"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/es0617800"},{"key":"e_1_2_9_28_1","first-page":"391","volume":"4","author":"Casida M. 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