{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:09:54Z","timestamp":1792163394285,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NC State University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A targeted strategy for treating cancer is antibody-directed enzyme prodrug therapy, where the enzyme attached to the antibody causes conversion of an inactive small-molecule prodrug into an active drug. A limitation may be the diffusion of the active drug away from the antibody target site. A related strategy with radiotherapeutics entails enzymatically promoted conversion of a soluble to insoluble radiotherapeutic agent, thereby immobilizing the latter at the target site. Such a molecular brachytherapy has been scarcely investigated. In distinct research, the advent of molecular designs for aggregation-induced emission (AIE) suggests translational use in molecular brachytherapy. Here, several 2-(2-hydroxyphenyl)benzothiazole substrates that readily aggregate in aqueous solution (and afford AIE) were elaborated in this regard. In particular, (1) the 2-(2-hydroxyphenyl) unit was derivatized to bear a pegylated phosphodiester that imparts water solubility yet undergoes enzymatic cleavage, and (2) a p-phenol unit was attached to the benzo moiety to provide a reactive site for final-step iodination (here examined with natural abundance iodide). The pegylated phosphodiester-iodinated benzothiazole undergoes conversion from aqueous-soluble to aqueous-insoluble upon treatment with a phosphatase or phosphodiesterase. The aggregation is essential to molecular brachytherapy, whereas the induced emission of AIE is not essential but provides a convenient basis for research development. Altogether, 21 compounds were synthesized (18 new, 3 known via new routes). Taken together, blending biomedical strategies of enzyme prodrug therapy with materials chemistry concerning substances that undergo AIE may comprise a step forward on the long road toward molecular brachytherapy.<\/jats:p>","DOI":"10.3390\/molecules27248682","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T03:23:49Z","timestamp":1670556229000},"page":"8682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tailoring the AIE Chromogen 2-(2-Hydroxyphenyl)benzothiazole for Use in Enzyme-Triggered Molecular Brachytherapy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4330-1271","authenticated-orcid":false,"given":"Zhiyuan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7593-310X","authenticated-orcid":false,"given":"Jinghuai","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5558-0810","authenticated-orcid":false,"given":"Kathy-Uyen","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0809-6492","authenticated-orcid":false,"given":"Jayden C.","family":"Eppley","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittipan","family":"Siwawannapong","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-2040","authenticated-orcid":false,"given":"Jonathan S.","family":"Lindsey","sequence":"additional","affiliation":[{"name":"Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","unstructured":"Halperin, E.C., Perez, C.A., and Brady, L.W. 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