{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:00:01Z","timestamp":1790686801377,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aces.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry \u0097 An Asian Journal"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Double\u2010masking strategies that layer classical prodrug chemistry with metal coordination offer a powerful route to widen the therapeutic window of reactive small molecules. Building on gossyzid, a pH\u2010activatable imine prodrug of the polyphenolic aldehyde gossypol, we introduce a family of gossyzid\u2013metal conjugates (GMCs) that implement orthogonal masking: gossypol is first protected as gossyzid, then \u201clocked\u201d within coordination environments formed with first\u2010row transition metal ions (Mn, Fe, Co, Ni, Cu, and Zn). Spectroscopic analyses, powder x\u2010ray diffraction, and thermogravimetric profiling support the formation of coordination architectures, rationalizing the mass\u2010spectrometric intractability of these species. Photophysical studies reveal metal\u2010dependent binding stoichiometries and affinities, establishing a tunable stability series across the GMCs. Using amino acids as competitive chelators, we demonstrate selective, triggerable de\u2010chelation of the metal node that regenerates gossyzid under tumor\u2010mimicking conditions; subsequent tumor\u2010microenvironment (TME)\u2010relevant acidolysis completes its activation to gossypol. Notably, only specific amino acids effectively unmask defined GMC subsets, enabling control over activation kinetics and extent. In triple\u2010negative breast cancer models, GMC cytotoxicity correlates with intrinsic metal\u2013ligand binding, thus showing the contributions of double masking. To our knowledge, this is the first systematic demonstration of amino\u2010acid\u2010triggered activation in double\u2010masked metal\u2013prodrug conjugates, with direct implications for the design of next\u2010generation, TME\u2010responsive prodrugs.<\/jats:p>","DOI":"10.1002\/asia.70910","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:58:50Z","timestamp":1790679530000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Amino Acid\u2010Triggered Activation of Double\u2010Masked Gossyzid\u2013Metal Conjugates: Metal\u2010Dependent Stability, Photophysical Properties, and Anticancer Activity"],"prefix":"10.1002","volume":"21","author":[{"given":"Megha","family":"Biswas","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences Indian Institute of Science Education and Research Berhampur, Laudigam, Konisi, District Ganjam  Berhampur Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaskar","family":"Sadhu","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences Indian Institute of Science Education and Research Berhampur, Laudigam, Konisi, District Ganjam  Berhampur Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Kajol","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences Indian Institute of Science Education and Research Berhampur, Laudigam, Konisi, District Ganjam  Berhampur Odisha India"},{"name":"Department of Biological Sciences Indian Institute of Science Education and Research Berhampur, Laudigam, Konisi, District Ganjam  Berhampur Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7729-6223","authenticated-orcid":false,"given":"Rakesh Kumar","family":"Pathak","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences Indian Institute of Science Education and Research Berhampur, Laudigam, Konisi, District Ganjam  Berhampur Odisha India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2468"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.22205"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.46"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010024\u201000914\u20107"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4MD00788C"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3MD00137G"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm500531z"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c00724"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4277"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2SC01003H"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00673A"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.01.016"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201041388\u20102"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.02.024"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4SC04555F"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010021\u201000910\u20107"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c01471"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202400309"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2024.216026"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169\u2010409X(89)90004\u20105"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01545"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202500232"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00209"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejic.201600908"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5DT02101D"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202203865"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2025.216847"},{"key":"e_1_2_7_29_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.11648\/j.cmr.20170606.13","article-title":"Selected Pharmacological Applications of 1st Row Transition Metal Complexes: A Review","volume":"6","author":"Hossain M. S.","year":"2017","journal-title":"Clinical Medicine Research"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ic202426v"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo201865x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac301821c"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201804161"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i2.298"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2024.04.019"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201905159"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.3c00753"},{"key":"e_1_2_7_38_1","first-page":"11721","article-title":"Design and Bio Evaluation of Schiff Base and Their Metal Complexes: A Green Route to Potential Anticancer Agents","volume":"11","author":"Thakkar K. J.","year":"2026","journal-title":"ACS Omega"},{"key":"e_1_2_7_39_1","first-page":"8123","article-title":"Synthesis and Spectroscopic Characterization of Schiff Base Metal Complexes, Biological Activity, and Molecular Docking Studies","volume":"9","author":"Venkatesh G.","year":"2024","journal-title":"ACS Omega"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2dt30432e"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10895\u2010005\u20102527\u20101"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202115580"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbmi.4c00001"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4OB00382A"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43479"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2020.213253"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2004.06.008"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrs.6490"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201063616\u20107"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010011\u20100483\u20105"}],"container-title":["Chemistry \u2013 An Asian Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aces.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/asia.70910","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aces.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/asia.70910","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aces.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/asia.70910","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:22:16Z","timestamp":1790684536000},"score":1,"resource":{"primary":{"URL":"https:\/\/aces.onlinelibrary.wiley.com\/doi\/10.1002\/asia.70910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":49,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/asia.70910"],"URL":"https:\/\/doi.org\/10.1002\/asia.70910","archive":["Portico"],"relation":{},"ISSN":["1861-4728","1861-471X"],"issn-type":[{"value":"1861-4728","type":"print"},{"value":"1861-471X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2025-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70910"}}