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Synthesis and NMR characterization of PEGylated β-cyclodextrins

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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 SN2 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.

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Acknowledgements

Funded by the NSF grant 1011836, and the Provost’s Faculty Fellow Award of California State University, Los Angeles.

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  1. Department of Chemistry and Biochemistry, California State University, Los Angeles, 5151 State University Drive, Los Angeles, CA, 91016, USA

    Kim Trang Huu Nguyen & Yong Ba

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  1. Kim Trang Huu Nguyen
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YB designed the chemical synthesis procedure and acquired research funding for carrying out this project. KN designed the chemical synthesis procedure and carried out the experiments. YB wrote the main manuscript text. KN prepared the Figures. All authors reviewed the manuscript.

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Correspondence to Yong Ba.

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Nguyen, K.T.H., Ba, Y. Synthesis and NMR characterization of PEGylated β-cyclodextrins. J Incl Phenom Macrocycl Chem 103, 213–222 (2023). https://doi.org/10.1007/s10847-023-01188-z

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