{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:30:18Z","timestamp":1788489018746,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"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>Partially and exhaustively methylated \u03b2-cyclodextrins [(2-methyl)-\u03b2-CD (MCD), heptakis-(2,6-di-O-methyl)-\u03b2-CD (DIMEB), and heptakis-(2,3,6-tri-O-methyl)-\u03b2-CD (TRIMEB)] have been compared in the hydrolysis and enantiodiscrimination of benzodiazepine derivative (R)- or (S)-oxazepam hemisuccinate (OXEMIS), using nuclear magnetic resonance (NMR) spectroscopy as an investigation tool. After 6 h, MCD induced an 11% hydrolysis of OXEMIS, remarkably lower in comparison with underivatized \u03b2-CD (48%), whereas no hydrolysis was detected in the presence of DIMEB or TRIMEB after 24 h. DIMEB showed greater ability to differentiate OXEMIS enantiomers in comparison to TRIMEB, by contrast MCD did not produce any splitting of racemic OXEMIS resonances. Both enantiomers of OXEMIS underwent deep inclusion of their phenyl pendant into cyclodextrins cavities from their wider rims, but tighter complexes were formed by DIMEB with respect to TRIMEB.<\/jats:p>","DOI":"10.3390\/molecules26216347","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:31:26Z","timestamp":1634765486000},"page":"6347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hydrolysis and Enantiodiscrimination of (R)- and (S)-Oxazepam Hemisuccinate by Methylated \u03b2-Cyclodextrins: An NMR Investigation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9927-0953","authenticated-orcid":false,"given":"Andrea","family":"Cesari","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Chimiche, Universit\u00e0 di Padova, Via Marzolo 1, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6916-321X","authenticated-orcid":false,"given":"Federica","family":"Balzano","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Chimica Industriale, Universit\u00e0 di Pisa, Via Moruzzi 13, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6735-2711","authenticated-orcid":false,"given":"Gloria","family":"Uccello Barretta","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Chimica Industriale, Universit\u00e0 di Pisa, Via Moruzzi 13, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-6117","authenticated-orcid":false,"given":"Alessandra","family":"Recchimurzo","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica e Chimica Industriale, Universit\u00e0 di Pisa, Via Moruzzi 13, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","first-page":"214","article-title":"Benzodiazepine Pharmacology and Central Nervous System\u2013Mediated Effects","volume":"13","author":"Griffin","year":"2013","journal-title":"Ochsner J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.9740\/mhc.2016.05.120","article-title":"Benzodiazepine Use, Misuse, and Abuse: A Review","volume":"6","author":"Schmitz","year":"2016","journal-title":"Ment. Health Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0165-022X(02)00123-9","article-title":"Separation of oxazepam, lorazepam, and temazepam enantiomers by HPLC on a derivatized cyclodextrin-bonded phase: Application to the determination of oxazepam in plasma","volume":"54","author":"Hua","year":"2002","journal-title":"J. Biochem. Biophys. Methods"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1124\/dmd.30.11.1257","article-title":"Stereoselective Conjugation of Oxazepam by Human UDP-Glucuronosyltransferases (UGTs): S-Oxazepam Is Glucuronidated by UGT2B15, while R-Oxazepam Is Glucuronidated by UGT2B7 and UGT1A9","volume":"30","author":"Court","year":"2002","journal-title":"Drug Metab. Dispos."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1097\/00008571-199510000-00004","article-title":"Interindividual variability in the glucuronidation of (S) oxazepam contrasted with that of (R) oxazepam","volume":"5","author":"Patel","year":"1995","journal-title":"Pharmacogenetics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1124\/dmd.113.051656","article-title":"The Glucuronidation of R- and S-Lorazepam: Human Liver Microsomal Kinetics, UDP-Glucuronosyltransferase Enzyme Selectivity, and Inhibition by Drugs","volume":"41","author":"Uchaipichat","year":"2013","journal-title":"Drug Metab. Dispos."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/00008571-199502000-00005","article-title":"(S)Oxazepam glucuronidation is inhibited by Ketoprofen and other substrates of UGT2B7","volume":"5","author":"Patel","year":"1995","journal-title":"Pharmacogenetics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.59566\/IJBS.2006.2085","article-title":"Chiral drugs: An overview","volume":"2","author":"Nguyen","year":"2006","journal-title":"Int. J. Biomed. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1039\/C8OB02991A","article-title":"Racemization of oxazepam and chiral 1,4-benzodiazepines. DFT study of the reaction mechanism in aqueous solution","volume":"17","author":"Hok","year":"2019","journal-title":"Org. Biomol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/jps.2600781002","article-title":"Racemization Kinetics of Enantiomeric Oxazepams and Stereoselective Hydrolysis of Enantiomeric Oxazepam 3-Acetates in Rat Liver Microsomes and Brain Homogenate","volume":"78","author":"Yang","year":"1989","journal-title":"J. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1021\/jm00198a002","article-title":"Oxazepam esters. 1. Correlation between hydrolysis rates and brain appearance of oxazepam","volume":"22","author":"Maksay","year":"1979","journal-title":"J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1021\/acs.molpharmaceut.7b00405","article-title":"Oxazepam\u2013Dopamine Conjugates Increase Dopamine Delivery into Striatum of Intact Rats","volume":"14","author":"Cassano","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/S0021-9673(01)91610-3","article-title":"High-performance liquid chromatographic resolution of racemic 1,4-benzodiazepin-2-ones by means of a \u03b2-cyclodextrin silica bonded chiral stationary phase","volume":"506","author":"Bertucci","year":"1990","journal-title":"J. Chromatogr. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8024","DOI":"10.1021\/ac400639y","article-title":"Cyclodextrins in Analytical Chemistry: Host\u2013Guest Type Molecular Recognition","volume":"85","author":"Szente","year":"2013","journal-title":"Anal. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kfoury, M., Landy, D., and Fourmentin, S. (2018). Characterization of Cyclodextrin\/Volatile Inclusion Complexes: A Review. Molecules, 23.","DOI":"10.3390\/molecules23051204"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1007\/s10311-020-01156-w","article-title":"130 years of cyclodextrin discovery for health, food, agriculture, and the industry: A review","volume":"19","author":"Fourmentin","year":"2021","journal-title":"Environ. Chem. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lee, J.-U., Lee, S.-S., Lee, S., and Bin Oh, H. (2020). Noncovalent Complexes of Cyclodextrin with Small Organic Molecules: Applications and Insights into Host\u2013Guest Interactions in the Gas Phase and Condensed Phase. Molecules, 25.","DOI":"10.3390\/molecules25184048"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Periasamy, R. (2021). Cyclodextrin-based molecules as hosts in the formation of supramolecular complexes and their practical ap-plications\u2014A review. J. Carbohydr. Chem., 135\u2013155.","DOI":"10.1080\/07328303.2021.1967970"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"116332","DOI":"10.1016\/j.trac.2021.116332","article-title":"Application of enantioselective separation techniques to bioanalysis of chiral drugs and their metabolites","volume":"143","author":"Chankvetadze","year":"2021","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_20","first-page":"115761","article-title":"Chiral analysis in food science","volume":"123","author":"Bueno","year":"2019","journal-title":"Trends Anal. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"580","DOI":"10.3311\/PPch.18067","article-title":"Cyclodextrins as Dominant Chiral Selective Agents in the Capillary Separation Techniques","volume":"65","author":"Juvancz","year":"2021","journal-title":"Period. Polytech. Chem. Eng."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115639","DOI":"10.1016\/j.trac.2019.115639","article-title":"Chiral recognition in separation sciences: Part I: Polysaccharide and cyclodextrin selectors","volume":"120","author":"Scriba","year":"2019","journal-title":"Trends Anal. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hancu, G., Papp, L., T\u00f3th, G., and Kelemen, H. (2021). The Use of Dual Cyclodextrin Chiral Selector Systems in the Enantioseparation of Pharmaceuticals by Capillary Electrophoresis: An Overview. Molecules, 26.","DOI":"10.3390\/molecules26082261"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117517","DOI":"10.1016\/j.carbpol.2020.117517","article-title":"Negatively charged cyclodextrins: Synthesis and applications in chiral analysis-A review","volume":"256","author":"Guo","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"355","DOI":"10.2174\/1573411016999200525144506","article-title":"Role of Chromatograph-based Analytical Techniques in Quantification of Chiral Compounds: An Update","volume":"17","author":"Gunjal","year":"2021","journal-title":"Curr. Anal. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115691","DOI":"10.1016\/j.trac.2019.115691","article-title":"Recent advances in cyclodextrins-based chiral-recognizing platforms","volume":"121","author":"Wang","year":"2019","journal-title":"Trends Anal. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wenzel, T.J. (2018). Differentiation of Chiral Compounds Using NMR Spectroscopy, John Wiley & Sons. [2nd ed.].","DOI":"10.1002\/9781119324782"},{"key":"ref_28","unstructured":"Polavarapu, P.L. (2018). Chiral Analysis by NMR Spectroscopy: Chiral Solvating Agents. Chiral Analysis: Advances in Spectroscopy, Chromatography and Emerging Methods, Elsevier."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/jps.2600570109","article-title":"Influence of Cyclodextrins on Ester Hydrolysis","volume":"57","author":"Chin","year":"1968","journal-title":"J. Pharm. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.ijpharm.2017.06.009","article-title":"Effects of cyclodextrins on the chemical stability of drugs","volume":"531","author":"Popielec","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/BF00708879","article-title":"The effect of cyclodextrins on the hydrolysis of carboxylic acid esters","volume":"20","author":"Trotta","year":"1994","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"119698","DOI":"10.1016\/j.ijpharm.2020.119698","article-title":"2-Methyl-\u03b2-cyclodextrin grafted ammonium chitosan: Synergistic effects of cyclodextrin host and polymer backbone in the interaction with amphiphilic prednisolone phosphate salt as revealed by NMR spectroscopy","volume":"587","author":"Cesari","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_33","first-page":"533","article-title":"Molecular complexes: Part 18\u2014A nuclear magnetic resonance adaptation of the continuous variation (job) method of stoicheiometry determination","volume":"82","author":"Homer","year":"1986","journal-title":"J. Chem. Soc. Faraday Trans. 1 Phys. Chem. Condens. Phases"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1039\/TF9656101626","article-title":"Interaction of electron acceptors with bases: Part 15\u2014Determination of association constants of organic charge-transfer complexes by n.m.r. spectroscopy","volume":"61","author":"Foster","year":"1965","journal-title":"Trans. Faraday Soc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:19:38Z","timestamp":1760167178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/21\/6347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":34,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["molecules26216347"],"URL":"https:\/\/doi.org\/10.3390\/molecules26216347","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]}}}