Synthesis and NMR characterization of PEGylated β-cyclodextrins

• Published in: Journal of inclusion phenomena and macrocyclic chemistry Vol. 103; no. 5-6; pp. 213 - 222
• Main Authors: Nguyen, Kim Trang Huu, Ba, Yong
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.06.2023; Springer Nature B.V
• Subjects: Biocompatibility; Chemical bonds; Chemical synthesis; Chemistry; Chemistry and Materials Science; Crystallography and Scattering Methods; Cyclodextrins; Food Science; Hydroxyl groups; Inclusion complexes; Industrial applications; Mass spectrometry; MPEG encoders; NMR; Nuclear magnetic resonance; Organic Chemistry; Original Article; Pharmaceuticals; Polyethylene glycol; Two dimensional analysis; Water solubility; PEGylation; 2D NMR; β-cyclodextrin; Inclusion complex; Poly(ethylene glycol)
• ISSN: 1388-3127; 1573-1111
• DOI: 10.1007/s10847-023-01188-z

Cyclodextrins (CDs) and their chemical derivatives are well-known as effective carriers for low-water-soluble molecules for pharmaceutical and other industrial applications. We have carried out the synthesis of PEGylated β-CDs through ether chemical bond linkage between β-CD and poly(ethylene glycol) methyl ether (MPEG). The combination of β-CD with poly(ethylene glycol) will benefit from PEG’s properties including high water solubility, nontoxicity, non-immunogenicity, biocompatibility, and biodegradability. The synthesis proceeded through three steps: (a) tosylation of MPEG; (b) deprotonation of hydroxyl groups of β-CD using NaH; and (c) the combination of the above two intermediates through the S N 2 mechanism to obtain the MPEG-β-CD compounds. The products were confirmed by MALDI-TOF mass spectrometry, and their structures were analyzed using 1 H 2D COSY and ROESY NMR methods. It was found that the site of PEGylation occurred on the (OH)6 site of β-CD. The inclusion property of the MPEG-β-CDs was demonstrated by forming inclusion complexes with 1-fluroroadamantane. We anticipate that the newly added properties of the MPEG to β-CD promote their pharmaceutical and other industrial applications.