Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin-steroid interaction

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dc.contributor.authorCaira, Mino R
dc.contributor.authorBourne, Susan A
dc.contributor.authorSamsodien, Halima
dc.contributor.authorSmith, Vincent J
dc.date.accessioned2021-10-08T06:20:12Z
dc.date.available2021-10-08T06:20:12Z
dc.date.issued2014
dc.description.abstractThe interaction between the potent anticancer agent 2-methoxyestradiol (2ME) and a series of cyclodextrins (CDs) was investigated in the solid state using thermal analysis and X-ray diffraction, while the possibility of enhancing its poor aqueous solubility with CDs was probed by means of equilibrium solubility and dissolution rate measurements. Single crystal X-ray diffraction studies of the inclusion complexes between 2ME and the derivatised cyclodextrins heptakis(2,6-di-O-methyl)-β-CD (DIMEB) and heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) revealed for the first time the nature of the encapsulation of a bioactive steroid by representative CD host molecules. Inclusion complexation invariably involves insertion of the D-ring of 2ME from the secondary side of each CD molecule, with the 17-OH group generally hydrogen bonding to a host glycosidic oxygen atom within the CD cavity, while the A-ring and part of the B-ring of 2ME protrude from the secondary side. In the case of the TRIMEB·2ME complex, there is evidence that complexation proceeds with mutual conformational adaptation of host and guest molecules. The aqueous solubility of 2ME was significantly enhanced by CDs, with DIMEB, TRIMEB, randomly methylated β-CD and hydroxypropyl-β-CD being the most effective hosts. The 2:1 host-guest β-CD inclusion complex, prepared by two methods, yielded very rapid dissolution in water at 37 °C relative to untreated 2ME, attaining complete dissolution within 15 minutes (co-precipitated complex) and 45 minutes (complex from kneading).
dc.identifier.apacitationCaira, M. R., Bourne, S. A., Samsodien, H., & Smith, V. J. (2014). Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin-steroid interaction. <i>Beilstein Journal of Organic Chemistry</i>, 11(1), 2616 - 2630. http://hdl.handle.net/11427/34223en_ZA
dc.identifier.chicagocitationCaira, Mino R, Susan A Bourne, Halima Samsodien, and Vincent J Smith "Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin-steroid interaction." <i>Beilstein Journal of Organic Chemistry</i> 11, 1. (2014): 2616 - 2630. http://hdl.handle.net/11427/34223en_ZA
dc.identifier.citationCaira, M.R., Bourne, S.A., Samsodien, H. & Smith, V.J. 2014. Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin-steroid interaction. <i>Beilstein Journal of Organic Chemistry.</i> 11(1):2616 - 2630. http://hdl.handle.net/11427/34223en_ZA
dc.identifier.issn1860-5397
dc.identifier.issn2195-951X
dc.identifier.ris TY - Journal Article AU - Caira, Mino R AU - Bourne, Susan A AU - Samsodien, Halima AU - Smith, Vincent J AB - The interaction between the potent anticancer agent 2-methoxyestradiol (2ME) and a series of cyclodextrins (CDs) was investigated in the solid state using thermal analysis and X-ray diffraction, while the possibility of enhancing its poor aqueous solubility with CDs was probed by means of equilibrium solubility and dissolution rate measurements. Single crystal X-ray diffraction studies of the inclusion complexes between 2ME and the derivatised cyclodextrins heptakis(2,6-di-O-methyl)-β-CD (DIMEB) and heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) revealed for the first time the nature of the encapsulation of a bioactive steroid by representative CD host molecules. Inclusion complexation invariably involves insertion of the D-ring of 2ME from the secondary side of each CD molecule, with the 17-OH group generally hydrogen bonding to a host glycosidic oxygen atom within the CD cavity, while the A-ring and part of the B-ring of 2ME protrude from the secondary side. In the case of the TRIMEB·2ME complex, there is evidence that complexation proceeds with mutual conformational adaptation of host and guest molecules. The aqueous solubility of 2ME was significantly enhanced by CDs, with DIMEB, TRIMEB, randomly methylated β-CD and hydroxypropyl-β-CD being the most effective hosts. The 2:1 host-guest β-CD inclusion complex, prepared by two methods, yielded very rapid dissolution in water at 37 °C relative to untreated 2ME, attaining complete dissolution within 15 minutes (co-precipitated complex) and 45 minutes (complex from kneading). DA - 2014 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - Beilstein Journal of Organic Chemistry LK - https://open.uct.ac.za PY - 2014 SM - 1860-5397 SM - 2195-951X T1 - Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin-steroid interaction TI - Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin-steroid interaction UR - http://hdl.handle.net/11427/34223 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34223
dc.identifier.vancouvercitationCaira MR, Bourne SA, Samsodien H, Smith VJ. Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin-steroid interaction. Beilstein Journal of Organic Chemistry. 2014;11(1):2616 - 2630. http://hdl.handle.net/11427/34223.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Chemistry
dc.publisher.facultyFaculty of Science
dc.sourceBeilstein Journal of Organic Chemistry
dc.source.journalissue1
dc.source.journalvolume11
dc.source.pagination2616 - 2630
dc.source.urihttps://dx.doi.org/10.3762/bjoc.11.281
dc.subject.othercomplexation
dc.subject.othercyclodextrin
dc.subject.other2-methoxyestradiol
dc.subject.othersolubility
dc.subject.otherX-ray diffraction
dc.titleInclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin-steroid interaction
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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