Synthesis and NMR characterization of PEGylated β-cyclodextrins

Abstract

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_N2 mechanism to obtain the MPEG-β-CD compounds. The products were confirmed by MALDI-TOF mass spectrometry, and their structures were analyzed using ¹H 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.