{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:08:07Z","timestamp":1760854087030},"reference-count":33,"publisher":"Walter de Gruyter GmbH","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The unique ability of the bioorthogonal pairs to withstand and unaffect biological processes while maintaining high selectivity towards each other sparked the interest in better probing and controlling biological functions. In early years, <jats:italic>trans-<\/jats:italic>cyclooctene (TCO)\/tetrazine ligation readily standed out by encompassing most of the bioorthogonal criteria such as its excellent biocompatibility, selectivity and efficiency, and as a result of high HOMO-LUMO gap. Modifications on the TCO scaffold such as cyclopropanation render bicyclononene-based TCOs with high enhancement of its reactivity, whereas other modifications focused on improving the solubility, stability, or enabling the scaffold to act as <jats:italic>click<\/jats:italic>-to-release drug delivery system. The implementation of facile methods to enhance its versatility is essential for potentiating drug-delivery strategies and expanding the dynamic range of bioorthogonal on\/off control. Considering the remarkable properties of bicyclononene-based TCOs we envisioned that the incorporation of an additional vector for functionalization at the cyclopropane moiety could allow access to more complex and double-functionalized TCO probes. Herein we report the synthesis and study of a double-functionalizable strained <jats:italic>trans-<\/jats:italic>cyclooctenes for tetrazine bioorthogonal reactions.<\/jats:p>","DOI":"10.1515\/pac-2019-0201","type":"journal-article","created":{"date-parts":[[2019,5,18]],"date-time":"2019-05-18T16:24:02Z","timestamp":1558196642000},"page":"15-23","source":"Crossref","is-referenced-by-count":9,"title":["Synthesis and reactivity\/stability study of double-functionalizable strained <i>trans<\/i>-cyclooctenes for tetrazine bioorthogonal reactions"],"prefix":"10.1515","volume":"92","author":[{"given":"Jo\u00e3o M. J. M.","family":"Ravasco","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa) , Faculty of Pharmacy, Universidade de Lisboa , Av. Prof. Gama Pinto , 1649-003 Lisboa , Portugal"}]},{"given":"Jaime A. 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