{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T13:58:09Z","timestamp":1762955889127,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>A new type of biomimetic templated copolymer has been prepared by reverse addition fragmentation chain transfer polymerization (RAFT) in dioxane. The initial formulation includes the template fluorescein, N-isopropylacrylamide (NIPAM, 84 mol %), methacrylic acid (MAA, 5-mol %), 4-vinylpyridine (4-VP, 9 mmol %), and N,N\u2032-methylenebis(acrylamide) (MBA, 2 mol %). PolyNIPAM is a thermosensitive polymer that comes out of aqueous solution above its lower critical solution temperature forming hydrophobic \u2018crosslinks\u2019. MAA and 4-VP interact in dioxane forming acid\u2013base crosslinks. The excess 4-VP serves as a recognition monomer organizing around the template fluorescein to form a binding site that is held in place by the noncovalent and covalent crosslinks. The MBA is a covalent crosslinker. The RAFT agent in the resulting copolylmer was reduced to a thiol and attached to gold nanoparticles. The gold nanoparticle bound copolymer binds fluorescein completely in less than two seconds with an affinity constant greater than 108 M\u22121. A reference copolymer prepared with the same monomers by the same procedure binds fluorescein much more weakly.<\/jats:p>","DOI":"10.3390\/s18051330","type":"journal-article","created":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T11:15:39Z","timestamp":1524654939000},"page":"1330","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Rapid, High Affinity Binding by a Fluorescein Templated Copolymer Combining Covalent, Hydrophobic, and Acid\u2013Base Noncovalent Crosslinks"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5370-8286","authenticated-orcid":false,"given":"Casey J.","family":"Grenier","sequence":"first","affiliation":[{"name":"Tekscan, Inc., 307 W. First St., Boston, MA 02127, USA"}]},{"given":"Anthony","family":"Timberman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of New Hampshire, Durham NH 03824, USA"}]},{"given":"Rongfang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of New Hampshire, Durham NH 03824, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1222-7320","authenticated-orcid":false,"given":"John","family":"Csoros","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of New Hampshire, Durham NH 03824, USA"}]},{"given":"Alex","family":"Papantones","sequence":"additional","affiliation":[{"name":"Boston Analytical, 14 Manor Parkway, Salem, NH 03079, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3226-2470","authenticated-orcid":false,"given":"Leila F.","family":"Deravi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA"}]},{"given":"W. Rudolf","family":"Seitz","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of New Hampshire, Durham NH 03824, USA"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0021-9673(02)00058-4","article-title":"Molecular recognition through the exact placement of functional groups on non-covalent molecularly imprinted polymers","volume":"950","author":"Lu","year":"2002","journal-title":"J. Chromatogr. A"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1021\/cr990099w","article-title":"Molecularly imprinted polymers and their use in biomimetic sensors","volume":"100","author":"Haupt","year":"2000","journal-title":"Chem. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5417","DOI":"10.1016\/j.polymer.2010.09.037","article-title":"Molecularly imprinted polymers synthesized via semi-covalent imprinting with sacrificial spacer for imprinting phenols","volume":"51","author":"Qi","year":"2010","journal-title":"Polymer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.snb.2014.09.094","article-title":"Molecularly imprinted polymer nanoparticles in chemical sensing\u2013Synthesis, characterisation and application","volume":"207","author":"Wackerlig","year":"2015","journal-title":"Sens. Actuators B Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/03602550701304784","article-title":"Selective Adsorption and Recognition by Molecularly Imprinted Polymer: A Study on Molecular Self-Assembly and its Effect on Selectivity","volume":"46","author":"Liao","year":"2007","journal-title":"Polym.-Plast. Technol. Eng."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/jmr.2347","article-title":"Molecular imprinting science and technology: A survey of the literature for the years 2004\u20132011","volume":"27","author":"Whitcombe","year":"2014","journal-title":"J. Mol. Recognit."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1021\/acs.macromol.5b02602","article-title":"A Critical Appraisal of RAFT-Mediated Polymerization-Induced Self-Assembly","volume":"49","author":"Canning","year":"2016","journal-title":"Macromolecules"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Marinesco, S., and Dale, N. (2013). Molecularly Imprinted Polymers: Promising Advanced Materials for In Vivo Sensing. Microelectrode Biosensors, Humana Press.","DOI":"10.1007\/978-1-62703-370-1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1039\/C5TB02620B","article-title":"A molecularly imprinted polymer as an antibody mimic with affinity for lysine acetylated peptides","volume":"4","author":"Yang","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1021\/ac401251j","article-title":"Bioapplications for Molecularly Imprinted Polymers","volume":"86","author":"Schirhagl","year":"2014","journal-title":"Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1021\/ac9013989","article-title":"Diagnostics for the developing world: Microfluidic paper-based analytical devices","volume":"82","author":"Martinez","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S1381-5148(01)00050-5","article-title":"Molecularly imprinted microspheres as antibody binding mimics","volume":"48","author":"Ye","year":"2001","journal-title":"React. Funct. Polym."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.1021\/jo961784v","article-title":"Molecular imprinting utilizing an amide functional group for hydrogen bonding leading to highly efficient polymers","volume":"62","author":"Yu","year":"1997","journal-title":"J. Org. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.1021\/ac0105686","article-title":"Characterization of molecularly imprinted polymers with the Langmuir-Freundlich isotherm","volume":"73","author":"Umpleby","year":"2001","journal-title":"Anal. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.3390\/ijms14011207","article-title":"Consequences of Morphology on Molecularly Imprinted Polymer-Ligand Recognition","volume":"14","author":"Rosengren","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1134\/S1607672915050038","article-title":"Electrosynthesis and binding properties of molecularly imprinted poly-O-phenylenediamine as artificial antibodies for electroanalysis of myoglobin","volume":"464","author":"Shumyantseva","year":"2015","journal-title":"Dokl. Biochem. Biophys."},{"key":"ref_17","unstructured":"Friedman, M. (2013). Protein Crosslinking: Nutritional and Medical Consequences, Springer Science & Business Media."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5683","DOI":"10.1039\/C5TB01021G","article-title":"A zwitterionic polymer as a novel inhibitor of protein aggregation","volume":"3","author":"Rajan","year":"2015","journal-title":"J. Mater. Chem. B"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40262-012-0018-5","article-title":"The clinical relevance of plasma protein binding changes","volume":"52","author":"Roberts","year":"2013","journal-title":"Clin. Pharmacokinet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/0009-2509(92)80210-4","article-title":"Electrostatic effects on protein partitioning: Simultaneous effect of pH and polymer molecular weight","volume":"47","author":"Forciniti","year":"1992","journal-title":"Chem. Eng. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1039\/b704590e","article-title":"Swellable theophylline selective microparticles for sensing applications","volume":"132","author":"Fan","year":"2007","journal-title":"Analyst"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jmr.1163","article-title":"N-isopropylacrylamide as a functional monomer for noncovalent molecular imprinting","volume":"25","author":"Ansell","year":"2012","journal-title":"J. Mol. Recognit."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1021\/ja973070n","article-title":"Molecular specific swelling change of hydrogels in accordance with the concentration of guest molecules","volume":"120","author":"Watanabe","year":"1998","journal-title":"J. Am. Chem. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4092","DOI":"10.1103\/PhysRevLett.80.4092","article-title":"Globule-to-Coil Transition of a Single Homopolymer Chain in Solution","volume":"80","author":"Wu","year":"1998","journal-title":"Phys. Rev. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tang, L., Jin, J.K., Qin, A., Yuan, W.Z., Mao, Y., Mei, J., Sun, J.Z., and Tang, B.Z. (2009). A fluorescent thermometer operating in aggregation-induced emission mechanism: Probing thermal transitions of PNIPAM in water. Chem. Commun., 4974\u20134976.","DOI":"10.1039\/b907382e"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8916","DOI":"10.1021\/jp0690603","article-title":"Effects of Hofmeister Anions on the LCST of PNIPAM as a Function of Molecular Weight","volume":"111","author":"Zhang","year":"2007","journal-title":"J. Phys. Chem. C"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7069","DOI":"10.1021\/ma071359b","article-title":"Temperature-induced phase transition of well-defined cyclic poly(N-isopropylacrylamide) s in aqueous solution","volume":"40","author":"Qiu","year":"2007","journal-title":"Macromolecules"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ijpharm.2003.12.013","article-title":"Poly(N-isopropylacrylamide) copolymers for constant temperature controlled drug delivery","volume":"273","author":"Eeckman","year":"2004","journal-title":"Int. J. Pharmaceut."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1295\/polymj.37.565","article-title":"pH and temperature-sensitive behaviors of poly(4-vinyl pyridine-co-N-isopropyl acrylamide) microgels","volume":"37","author":"Kim","year":"2005","journal-title":"Polym. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8016","DOI":"10.1021\/ma00128a007","article-title":"Synthesis and Characterization of Thermo- and Chemomechanically Responsive Poly(N-isopropylacrylamide-co-methacrylic acid) Hydrogels","volume":"28","author":"Brazel","year":"1995","journal-title":"Macromolecules"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0079-6700(92)90023-R","article-title":"Poly(N-isopropylacrylamide): Experiment, theory and application","volume":"17","author":"Schild","year":"1992","journal-title":"Progress Polym. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1080\/10601326808051910","article-title":"Solution properties of poly(N-isopropylacrylamide)","volume":"2","author":"Heskins","year":"1968","journal-title":"J. Macromol. Sci. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0021-9673(02)00360-6","article-title":"Non-covalent and semi-covalent molecularly imprinted polymers for selective on-line solid-phase extraction of 4-nitrophenol from water samples","volume":"963","author":"Caro","year":"2002","journal-title":"J. Chromatogr. A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.1021\/la034459t","article-title":"Modification of Gold Surfaces with Water-Soluble (Co)polymers Prepared via Aqueous Reversible Addition-Fragmentation Chain Transfer (RAFT) Polymerization","volume":"19","author":"Sumerlin","year":"2003","journal-title":"Langmuir"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11562","DOI":"10.1021\/ja020556h","article-title":"Facile Preparation of Transition Metal Nanoparticles Stabilized by Well-Defined (Co)polymers Synthesized via Aqueous Reversible Addition-Fragmentation Chain Transfer Polymerization","volume":"124","author":"Lowe","year":"2002","journal-title":"J. Am. Chem. Soc."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/18\/5\/1330\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:02:06Z","timestamp":1760194926000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/18\/5\/1330"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,25]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["s18051330"],"URL":"https:\/\/doi.org\/10.3390\/s18051330","relation":{},"ISSN":["1424-8220"],"issn-type":[{"type":"electronic","value":"1424-8220"}],"subject":[],"published":{"date-parts":[[2018,4,25]]}}}