{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:04:17Z","timestamp":1760151857556,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Symmetry"],"abstract":"<jats:p>The Cn molecular symmetry implicated by the schemes with which cyclodextrins (CDs), the well-known cyclic oligosaccharides, are introduced in the literature, is not valid. Numerous studies have shown that CDs are rather flexible with their macrocycle adopting various conformations that enable the inclusion complexation of guest molecules of various shapes. In this work, the loss and gain of the C7 symmetry of the heptakis (2, 3, 6-tri-O-methyl)-\u03b2-CD (TM-\u03b2-CD) is investigated by means of its conformation geometrical features in its hydrated form and upon complexation with molecules of different shapes. For this, the crystal structure of the inclusion complex of a bulky guest molecule (giberellic acid) in TM-\u03b2-CD is presented for the first time and compared with the previously determined crystal structures of monohydrated TM-\u03b2-CD and the inclusion complex of a linear monoterpenoid (geraniol) in TM-\u03b2-CD. The structural investigation was complemented by molecular dynamics simulations in an explicit solvent, based on the crystallographically determined models. The crucial role of the guest, in the symmetry gain of the host, reveals a pronounced induced-fit complexation mechanism for permethylated CDs.<\/jats:p>","DOI":"10.3390\/sym14102214","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:34:30Z","timestamp":1666312470000},"page":"2214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Molecular Symmetry of Permethylated \u03b2-Cyclodextrins upon Complexation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7402-0798","authenticated-orcid":false,"given":"Kostas","family":"Bethanis","sequence":"first","affiliation":[{"name":"Physics Laboratory, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1221-5167","authenticated-orcid":false,"given":"Elias","family":"Christoforides","sequence":"additional","affiliation":[{"name":"Physics Laboratory, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4683-8071","authenticated-orcid":false,"given":"Athena","family":"Andreou","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0919-0571","authenticated-orcid":false,"given":"Elias","family":"Eliopoulos","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos, 11855 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/polysaccharides3010001","article-title":"Cyclodextrins: Structural, Chemical, and Physical Properties, and Applications","volume":"3","author":"Poulson","year":"2022","journal-title":"Polysaccharides"},{"doi-asserted-by":"crossref","unstructured":"Fourmentin, S., Crini, G., and Lichtfouse, E. (2018). Cyclodextrin Fundamentals, Reactivity and Analysis, Springer. Environmental Chemistry for a Sustainable World.","key":"ref_2","DOI":"10.1007\/978-3-319-76159-6"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101408","DOI":"10.1016\/j.progpolymsci.2021.101408","article-title":"Cyclodextrin Polymers: Structure, Synthesis, and Use as Drug Carriers","volume":"118","author":"Liu","year":"2021","journal-title":"Prog. Polym. Sci."},{"doi-asserted-by":"crossref","unstructured":"Bruns, C.J. (2019). Exploring and Exploiting the Symmetry-Breaking Effect of Cyclodextrins in Mechanomolecules. Symmetry, 11.","key":"ref_4","DOI":"10.3390\/sym11101249"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6357","DOI":"10.1021\/jo00022a027","article-title":"Symmetry Breaking in Cyclodextrins: A Molecular Mechanics Investigation","volume":"56","author":"Lipkowitz","year":"1991","journal-title":"J. Org. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/anie.198003441","article-title":"Cyclodextrin Inclusion Compounds in Research and Industry","volume":"19","author":"Saenger","year":"1980","journal-title":"Angew. Chem. Int. Ed. Engl."},{"doi-asserted-by":"crossref","unstructured":"Dodziuk, H. (2006). Molecules with Holes\u2013Cyclodextrins. Cyclodextrins and Their Complexes, John Wiley & Sons, Ltd.","key":"ref_7","DOI":"10.1002\/3527608982"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/marc.201200017","article-title":"Formation of a Polypseudorotaxane via Self-Assembly of \u03b3-Cyclodextrin with Poly(N-Isopropylacrylamide)","volume":"33","author":"Wang","year":"2012","journal-title":"Macromol. Rapid Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1021\/ma200257z","article-title":"Recognition of Stereoregularity of Poly(Methacrylic Acid)s with \u03b3-Cyclodextrin","volume":"44","author":"Miura","year":"2011","journal-title":"Macromolecules"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"11523","DOI":"10.1038\/srep11523","article-title":"Engineering Cyclodextrin Clicked Chiral Stationary Phase for High-Efficiency Enantiomer Separation","volume":"5","author":"Tang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7545","DOI":"10.1021\/ja00336a039","article-title":"Topography of Cyclodextrin Inclusion Complexes, Part 20. Circular and Flip-Flop Hydrogen Bonding in.Beta.-Cyclodextrin Undecahydrate: A Neutron Diffraction Study","volume":"106","author":"Betzel","year":"1984","journal-title":"J. Am. Chem. Soc."},{"doi-asserted-by":"crossref","unstructured":"Caira, M.R., Bourne, S.A., and Mzondo, B. (2017). Encapsulation of the Antioxidant R-(+)-\u03b1-Lipoic Acid in Permethylated \u03b1- and \u03b2-Cyclodextrins: Thermal and X-Ray Structural Characterization of the 1:1 Inclusion Complexes. Molecules, 22.","key":"ref_12","DOI":"10.3390\/molecules22060866"},{"doi-asserted-by":"crossref","unstructured":"Papaioannou, A., Christoforides, E., and Bethanis, K. (2019). Inclusion Complexes of Naringenin in Dimethylated and Permethylated \u03b2-Cyclodextrins: Crystal Structures and Molecular Dynamics Studies. Crystals, 10.","key":"ref_13","DOI":"10.3390\/cryst10010010"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10847-018-0824-y","article-title":"Structural Studies of the Inclusion Compounds of \u03b1-Naphthaleneacetic Acid in Heptakis(2,6-Di-O-Methyl)-\u03b2-Cyclodextrin and Heptakis(2,3,6-Tri-O-Methyl)-\u03b2-Cyclodextrin by X-Ray Crystallography and Molecular Dynamics","volume":"92","author":"Bethanis","year":"2018","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1007\/s00344-015-9546-1","article-title":"A Century of Gibberellin Research","volume":"34","author":"Hedden","year":"2015","journal-title":"J. Plant Growth Regul."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fpls.2011.00107","article-title":"Gibberellin Signaling in Plants\u2014The Extended Version","volume":"2","author":"Schwechheimer","year":"2012","journal-title":"Front. Plant Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s00425-018-2959-x","article-title":"Current Advances in Gibberellic Acid (GA3) Production, Patented Technologies and Potential Applications","volume":"248","author":"Camara","year":"2018","journal-title":"Planta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1002\/jsfa.10412","article-title":"Effects of Gibberellic Acid (GA3) Application before Anthesis on Rachis Elongation and Berry Quality and Aroma and Flavour Compounds in Vitis Vinifera L. \u201cCabernet Franc\u201d and \u201cCabernet Sauvignon\u201d Grapes","volume":"100","author":"Gao","year":"2020","journal-title":"J. Sci. Food Agric."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1093\/pcp\/pcaa104","article-title":"Gibberellin Metabolism and Signaling: Targets for Improving Agronomic Performance of Crops","volume":"61","author":"Gao","year":"2020","journal-title":"Plant Cell Physiol."},{"doi-asserted-by":"crossref","unstructured":"Caira, M.R., Griffith, V.J., Nassimbeni, L.R., and van Oudtshoorn, B. (1994). Unusual 1C4 Conformation of a Methylglucose Residue in Crystalline Permethyl-[Small Beta]-Cyclodextrin Monohydrate. J. Chem. Soc. Perkin Trans. 2, 2071\u20132072.","key":"ref_20","DOI":"10.1039\/P29940002071"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1002\/(SICI)1521-3773(19981231)37:24<3404::AID-ANIE3404>3.0.CO;2-G","article-title":"Closure of the Cavity in Permethylated Cyclodextrins through Glucose Inversion, Flipping, and Kinking","volume":"37","author":"Steiner","year":"1998","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127350","DOI":"10.1016\/j.molstruc.2019.127350","article-title":"X-ray Crystallography and Molecular Dynamics Studies of the Inclusion Complexes of Geraniol in \u03b2-Cyclodextrin, Heptakis (2,6-Di-O-Methyl)-\u03b2-Cyclodextrin and Heptakis (2,3,6-Tri-O-Methyl)-\u03b2-Cyclodextrin","volume":"1202","author":"Christoforides","year":"2020","journal-title":"J. Mol. Struct."},{"unstructured":"Sheldrick G, M. (2013). SAINT, Version 8.37, Bruker AXS Inc.","key":"ref_23"},{"unstructured":"Sheldrick, G.M. (2012). SADABS, Bruker AXS Inc.","key":"ref_24"},{"unstructured":"Sheldrick, G.M. (2008). XPREP, Bruker AXS Inc.","key":"ref_25"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1107\/S0907444909038360","article-title":"Experimental Phasing with It SHELXC\/It D\/It E: Combining Chain Tracing with Density Modification","volume":"66","author":"Sheldrick","year":"2010","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal structure refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. C Struct. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1107\/S0021889811043202","article-title":"ShelXle: A Qt graphical user interface for SHELXL","volume":"44","author":"Sheldrick","year":"2011","journal-title":"J. Appl. Crystallogr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1107\/S0907444904011679","article-title":"PRODRG: A Tool for High-Throughput Crystallography of Protein\u2013Ligand Complexes","volume":"60","year":"2004","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1107\/S0021889807067908","article-title":"Mercury CSD 2.0\u2014New Features for the Visualization and Investigation of Crystal Structures","volume":"41","author":"Macrae","year":"2008","journal-title":"J. Appl. Crystallogr."},{"unstructured":"Schr\u00f6dinger, LLC (2015). The PyMOL Molecular Graphics System, Version 1.8, Schrodinger, LLC.","key":"ref_31"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1107\/S0021889808042726","article-title":"OLEX2: A Complete Structure Solution, Refinement and Analysis Program","volume":"42","author":"Dolomanov","year":"2009","journal-title":"J. Appl. Crystallogr."},{"key":"ref_33","first-page":"198","article-title":"An Overview of the Amber Biomolecular Simulation Package","volume":"3","author":"Case","year":"2012","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15103","DOI":"10.1039\/c1cp20854c","article-title":"Molecular Dynamics Studies of Native and Substituted Cyclodextrins in Different Media: 1. Charge Derivation and Force Field Performances","volume":"13","author":"Cezard","year":"2011","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","article-title":"Automatic Atom Type and Bond Type Perception in Molecular Mechanical Calculations","volume":"25","author":"Wang","year":"2006","journal-title":"J. Mol. Graph. Model."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and Dynamics of the TIP3P, SPC, and SPC\/E Water Models at 298 K","volume":"105","author":"Mark","year":"2001","journal-title":"J. Phys. Chem. A"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"3rd PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.Py: An Efficient Program for End-State Free Energy Calculations","volume":"8","author":"Miller","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molstruc.2018.02.037","article-title":"Crystal Structures and Molecular Dynamics Studies of the Inclusion Compounds of \u03b2-Citronellol in \u03b2-Cyclodextrin, Heptakis(2,6-Di-O-Methyl)-\u03b2-Cyclodextrin and Heptakis(2,3,6-Tri-O-Methyl)-\u03b2-Cyclodextrin","volume":"1161","author":"Fourtaka","year":"2018","journal-title":"J. Mol. Struct."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"130169","DOI":"10.1016\/j.molstruc.2021.130169","article-title":"Inclusion of Citral Isomers in Native and Methylated Cyclodextrins: Structural Insights by X-Ray Crystallography and Molecular Dynamics Simulation Analysis","volume":"1234","author":"Fourtaka","year":"2021","journal-title":"J. Mol. Struct."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10847-012-0145-5","article-title":"Permethylated \u03b2-Cyclodextrin\/Pesticide Complexes: X-Ray Structures and Thermogravimetric Assessment of Kinetic Parameters for Complex Dissociation","volume":"75","author":"Cruickshank","year":"2013","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1107\/S2052520616003954","article-title":"The Cambridge Structural Database","volume":"72","author":"Groom","year":"2016","journal-title":"Acta Crystallogr. Sect. B Struct. Sci. Cryst. Eng. Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1002\/ejoc.200800829","article-title":"Unique Regioselective Binding of Permethylated \u03b2-Cyclodextrin with Azobenzene Derivatives","volume":"2009","author":"Shi","year":"2009","journal-title":"Eur. J. Org. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s10847-012-0164-2","article-title":"Inclusion Compounds of Plant Growth Regulators in Cyclodextrins, Part VII: Study of the Crystal Structures of 2-Naphthylacetic Acid Encapsulated in \u03b2-Cyclodextrin and Heptakis(2,3,6-Tri-O-Methyl)-\u03b2-Cyclodextrin Complexes by X-Ray Crystallography","volume":"75","author":"Triantafyllopoulou","year":"2013","journal-title":"J. Incl. Phenom. Macrocycl. Chem."}],"container-title":["Symmetry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-8994\/14\/10\/2214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:58:04Z","timestamp":1760144284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-8994\/14\/10\/2214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["sym14102214"],"URL":"https:\/\/doi.org\/10.3390\/sym14102214","relation":{},"ISSN":["2073-8994"],"issn-type":[{"type":"electronic","value":"2073-8994"}],"subject":[],"published":{"date-parts":[[2022,10,20]]}}}