{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T19:23:31Z","timestamp":1784143411922,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,5,5]],"date-time":"2024-05-05T00:00:00Z","timestamp":1714867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Copper-catalyzed azide\u2013alkyne cycloaddition click (CuAAC) reaction is widely used to synthesize drug candidates and other biomolecule classes. Homogeneous catalysts, which consist of copper coordinated to a ligand framework, have been optimized for high yield and specificity of the CuAAC reaction, but CuAAC reaction with these catalysts requires the addition of a reducing agent and basic conditions, which can complicate some of the desired syntheses. Additionally, removing copper from the synthesized CuAAC-containing biomolecule is necessary for biological applications but inconvenient and requires additional purification steps. We describe here the design and synthesis of a PNN-type pincer ligand complex with copper (I) that stabilizes the copper (I) and, therefore, can act as a CuAAC catalyst without a reducing agent and base under physiologically relevant conditions. This complex was immobilized on two types of resin, and one of the immobilized catalyst forms worked well under aqueous physiological conditions. Minimal copper leaching was observed from the immobilized catalyst, which allowed its use in multiple reaction cycles without the addition of any reducing agent or base and without recharging with copper ion. The mechanism of the catalytic cycle was rationalized by density functional theory (DFT). This catalyst\u2019s utility was demonstrated by synthesizing coumarin derivatives of small molecules such as ferrocene and sugar.<\/jats:p>","DOI":"10.3390\/molecules29092148","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T14:26:11Z","timestamp":1715005571000},"page":"2148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development of Novel Immobilized Copper\u2013Ligand Complex for Click Chemistry of Biomolecules"],"prefix":"10.3390","volume":"29","author":[{"given":"Rene","family":"Kandler","sequence":"first","affiliation":[{"name":"Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yomal","family":"Benaragama","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Colombo, Colombo 00300, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1885-7627","authenticated-orcid":false,"given":"Manoranjan","family":"Bera","sequence":"additional","affiliation":[{"name":"Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Wang","sequence":"additional","affiliation":[{"name":"Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasheda Aktar","family":"Samiha","sequence":"additional","affiliation":[{"name":"Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. M. C.","family":"Sameera","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Colombo, Colombo 00300, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Das","sequence":"additional","affiliation":[{"name":"Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1328-1695","authenticated-orcid":false,"given":"Arundhati","family":"Nag","sequence":"additional","affiliation":[{"name":"Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/d41586-022-03087-8","article-title":"Chemists who invented revolutionary \u2018click\u2019 reactions win Nobel","volume":"610","author":"Castelvecchi","year":"2022","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1039\/b904091a","article-title":"Copper-catalyzed azide-alkyne cycloaddition (CuAAC) and beyond: New reactivity of copper(I) acetylides","volume":"39","author":"Hein","year":"2010","journal-title":"Chem. 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