{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:35:03Z","timestamp":1783510503130,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Zagreb"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Aiming toward a novel, noninvasive technique, with a real-time potential application in the monitoring of the complexation of steroidal neuromuscular blocker drugs Vecuronium (Vec) and Rocuronium (Roc) with sugammadex (SDX, medication for the reversal of neuromuscular blockade induced by Vec or Roc in general anesthesia), we developed proof-of-principle methodology based on surface-enhanced Raman spectroscopy (SERS). Silver nanoparticles prepared by the reduction of silver ions with hydroxylamine hydrochloride were used as SERS-active substrates, additionally aggregated with calcium nitrate as needed. The Vec and Roc SERS spectra were obtained within the biorelevant 5 \u00d7 10\u22127\u20131 \u00d7 10\u22124 M range, as well as the SERS of SDX, though the latter was observed only in the presence of the aggregating agent. SDX\/drug complexes at a 1\/1 molar ratio revealed significant spectral changes in the vibrational bands of the SDX glucose rings and the drug steroid rings, implying that the insertion of Vec and Roc molecules into the SDX cavity was not only driven by attractive electrostatic interactions between the positively charged cyclic unit of the drug and the negative carboxylate groups of cyclodextrin but also supported by hydrophobic interactions between the host cyclodextrin and the guest drug molecule. The observed changes in SERS signals are applicable in biorelevant conditions and support further studies of SDX\/drug complexes in vivo.<\/jats:p>","DOI":"10.3390\/molecules30020231","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T05:17:08Z","timestamp":1736399828000},"page":"231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Encapsulation of Vecuronium and Rocuronium by Sugammadex Investigated by Surface-Enhanced Raman Spectroscopy"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8820-649X","authenticated-orcid":false,"given":"Adriana","family":"Ken\u0111el","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9933-446X","authenticated-orcid":false,"given":"Ivo","family":"Piantanida","sequence":"additional","affiliation":[{"name":"Institute Ru\u0111er Bo\u0161kovi\u0107, Division of Organic Chemistry & Biochemistry, Bijeni\u010dka Cesta 54, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1179-2253","authenticated-orcid":false,"given":"Sne\u017eana","family":"Miljani\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJM199506223322507","article-title":"New neuromuscular blocking drugs","volume":"332","author":"Hunter","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/1521-3773(20020118)41:2<265::AID-ANIE265>3.0.CO;2-Q","article-title":"A novel concept of reversing neuromuscular block: Chemical encapsulation of Rocuronium Bromide by a cyclodextrin-based synthetic host","volume":"41","author":"Bom","year":"2002","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.mpaic.2021.04.010","article-title":"Neuromuscular blocking agents and reversal agents","volume":"22","author":"Hunter","year":"2021","journal-title":"Anaesth. Intensiv. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1093\/bja\/76.4.481","article-title":"Rocuronium: The newest aminosteroid neuromuscular blocking drug","volume":"76","author":"Hunter","year":"1996","journal-title":"Br. J. Anaesth."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1097\/ALN.0000000000004442","article-title":"Encapsulation dynamics of neuromuscular blocking drugs by Sugammadex","volume":"138","author":"Irani","year":"2023","journal-title":"Anesthesiology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1097\/ACO.0000000000000891","article-title":"The future of neuromuscular blocking agents","volume":"33","author":"Blobner","year":"2020","journal-title":"Curr. Opin. Anaesthesiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Si, S., Zhao, X., Su, F., Lu, H., Zhang, D., Sun, L., Wang, F., and Xu, L. (2023). New advances in clinical application of neostigmine: No longer focusing solely on increasing skeletal muscle strength. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1227496"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.molliq.2018.06.033","article-title":"Theoretical studies on themechanismof sugammadex for the reversal of aminosteroid-induced neuromuscular blockade","volume":"265","author":"Li","year":"2018","journal-title":"J. Mol. Liq."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jcrc.2008.10.010","article-title":"Preclinical pharmacology of sugammadex","volume":"24","author":"Bom","year":"2009","journal-title":"J. Crit. Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/BF03256937","article-title":"Assessment of the potential for displacement interactions with Sugammadex. A pharmacokinetic-pharmacodynamic modelling approach","volume":"31","author":"Zwiers","year":"2011","journal-title":"Clin. Drug Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jclinane.2017.06.006","article-title":"Sugammadex efficacy for reversal of rocuronium- and vecuronium-induced neuromuscular blockade: A pooled analysis of 26 studies","volume":"41","author":"Herring","year":"2017","journal-title":"J. Clin. Anesth."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jphotobiol.2014.08.019","article-title":"Biophysical study on the interaction of an anesthetic, vecuronium bromide with human serum albumin using spectroscopic and calorimetric methods","volume":"140","author":"Zhu","year":"2014","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s10337-011-1945-2","article-title":"Determination of Vecuronium Bromide in Pharmaceuticals: Development, Validation and Comparative Study of HPLC and CZE Analytical Methods","volume":"73","author":"Gomes","year":"2011","journal-title":"Chromatographia"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kooijman, H., van Geerestein, V.J., van der Sluis, P., Kanters, J.A., Kroon, J., Funke, C.W., and Kelder, J. (1991). Molecular structure of vecuronium bromide, a neuromuscular blocking agent. Crystal structure, molecular mechanics and NMR investigations. J. Chem. Soc. Perkin Trans. 2, 1581\u20131586.","DOI":"10.1039\/p29910001581"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108928","DOI":"10.1016\/j.steroids.2021.108928","article-title":"Vecuronium bromide and its ad-vanced intermediates: A crystallographic and spectroscopic study","volume":"176","author":"Ciceri","year":"2021","journal-title":"Steroids"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.33320\/maced.pharm.bull.2011.57.002","article-title":"Determination of Rocuronium bromide by hydrophilic interaction liquid chromatography (HILIC)","volume":"57","author":"Nakov","year":"2011","journal-title":"Maced. Pharm. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.chroma.2006.12.041","article-title":"Simultaneous determination of rocuronium and its eight impurities in pharmaceutical preparation using high-performance liquid chromatography with amperometric detection","volume":"1149","author":"Boruta","year":"2007","journal-title":"J. Chromatogr. A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/chromsci\/bms252","article-title":"Analysis of rocuronium in human whole blood and tissues using liquid chromatography\u2013tandem mass spectrometry","volume":"51","author":"Cho","year":"2013","journal-title":"J. Chromatogr. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jpba.2013.11.032","article-title":"Analysis of rocuronium in human plasma by liquid chromatography\u2013tandem mass spectrometry with application in clinical pharmacokinetics","volume":"90","author":"Lauretti","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/mrc.1008","article-title":"An NMR study of cyclodextrin complexes of the steroidal neuromuscular blocker drug rocuronium bromide","volume":"40","author":"Cameron","year":"2002","journal-title":"Magn. Reson. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1021\/acsnano.9b04224","article-title":"Present and future of surface-enhanced Raman scattering","volume":"14","author":"Langer","year":"2020","journal-title":"ACS Nano"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pilot, R., Signorini, R., Durante, C., Orian, L., Bhamidipati, M., and Fabris, L. (2019). A review on surface-enhanced raman scattering. Biosensors, 9.","DOI":"10.3390\/bios9020057"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1021\/acssuschemeng.0c09296","article-title":"One-Pot Synthesis of a Three-Dimensional Au-Decorated Cellulose Nanocomposite as a Surface-Enhanced Raman Scattering Sensor for Selective Detection and in Situ Monitoring","volume":"9","author":"Hu","year":"2021","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"122117","DOI":"10.1016\/j.matchemphys.2019.122117","article-title":"Nystatin complexation with \u03b2-cyclodextrin: Spectroscopic evaluation of inclusion by FT-Raman, photoacoustic spectroscopy, and 1H NMR","volume":"239","author":"Somer","year":"2020","journal-title":"Mater. Chem. Phys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.molstruc.2010.08.008","article-title":"Spectroscopic and theoretical study on inclusion complexation of beta-cyclodextrin with permethrin","volume":"981","author":"Li","year":"2010","journal-title":"J. Mol. Struct."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0924-2031(90)80041-2","article-title":"Spectroscopic studies on \u03b2-cyclodextrin","volume":"1","author":"Egyed","year":"1990","journal-title":"Vib. Spectrosc."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mosier-Boss, P.A. (2017). Review of SERS substrates for chemical sensing. Nanomaterials, 7.","DOI":"10.3390\/nano7060142"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jcis.2013.07.066","article-title":"Effects of cations and anions as aggregating agents on SERS detection of cotinine (COT) and trans-3\u2032-hydroxycotinine (3HC)","volume":"410","author":"Han","year":"2013","journal-title":"J. Colloid Interface Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7405","DOI":"10.1021\/jp052184f","article-title":"Surface-enhanced Raman spectroscopy as a probe of competitive binding by anions to citrate-reduced silver colloids","volume":"109","author":"Bell","year":"2005","journal-title":"J. Phys. Chem. A"},{"key":"ref_30","first-page":"509","article-title":"Specific and selective SERS active sites generation on silver nanoparticles by cationic and anionic adatoms","volume":"70","author":"Stefancu","year":"2018","journal-title":"Rom. Rep. Phys."},{"key":"ref_31","unstructured":"Dollish, F.R., Fateley, W.G., and Bentley, F.F. (1974). Characteristic Raman Frequencies of Organic Compounds, John Wiley & Sons. [1st ed.]."},{"key":"ref_32","unstructured":"Nes, W.D., and Parish, E.J. (1989). Raman spectra of steroids. Analysis of Sterols and Other Biologically Significant Steroids, Academia Press, Inc.. [1st ed.]."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0022-2860(83)80009-X","article-title":"Laser Raman spectra of some representative hormonal steroids","volume":"102","author":"Pouskouleli","year":"1983","journal-title":"J. Mol. Struct."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.molstruc.2011.05.014","article-title":"FT-IR, FT-Raman spectra and scaled quantum mechanical study of 4-amino-1-benzylpiperidine","volume":"998","author":"Chandra","year":"2011","journal-title":"J. Mol. Struct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s11051-006-9122-5","article-title":"Piperidine adsorption on two different silver electrodes: A combined surface enhanced Raman spectroscopy and density functional theory study","volume":"9","author":"Hao","year":"2007","journal-title":"J. Nanoparticle Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cplett.2015.09.003","article-title":"Conformational analysis of morpholine studied using Raman spectroscopy and density functional theoretical calculations","volume":"639","author":"SenGupta","year":"2015","journal-title":"Chem. Phys. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"20596","DOI":"10.1021\/jp206544a","article-title":"Conformations of morpholine in liquid and adsorbed on gold nanoparticles explored by raman spectroscopy and theoretical calculations","volume":"115","author":"Xie","year":"2011","journal-title":"J. Phys. Chem. C"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.saa.2008.02.032","article-title":"pH-dependent Raman study of pyrrole and its vibrational analysis using DFT calculations","volume":"71","author":"Singh","year":"2008","journal-title":"Spectrochim. Acta A"},{"key":"ref_39","first-page":"5468","article-title":"Electrochemical polymerization and Raman study of polypyrrole and polyaniline thin films","volume":"7","author":"Abdullah","year":"2012","journal-title":"Int. J. Phys. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Raffaini, G., Elli, S., Catauro, M., and D\u2019angelo, A. (2024). Different drug mobilities in hydrophobic cavities of host\u2013guest complexes between \u03b2-Cyclodextrin and 5-fluorouracil at different stoichiometries: A molecular dynamics study in water. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115888"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0032-9592(03)00258-9","article-title":"Cyclodextrins and their uses: A review","volume":"39","year":"2004","journal-title":"Process Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.1021\/jp027460u","article-title":"A new method for fast preparation of highly surface-enhanced Raman scattering (SERS) active silver colloids at room temperature by reduction of silver nitrate with hydroxylamine hydrochloride","volume":"107","author":"Leopold","year":"2003","journal-title":"J. Phys. Chem. B"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/2\/231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:25:20Z","timestamp":1759919120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/2\/231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["molecules30020231"],"URL":"https:\/\/doi.org\/10.3390\/molecules30020231","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]}}}