MALDI-MSn Analysis Method to Assign Regioisomeric Structures of Multi-Modified Cyclodextrins

Introduction

Cyclodextrins (hereafter, CyD) are cyclic oligosaccharides made up of D-glucose units linked α 1-4, and depending on the number of glucose units, are named α (6 glucose units), β (7 glucose units), or γ (8 glucose units)-CyD. CyD is shaped like a doughnut with a hollowed out center, endowing this molecule with the characteristic that allows hydrophobic substances (guest molecules) that do not usually dissolve in aqueous solution to be "hosted" in this hollow, and thereby dissolved. Owing to this characteristic, the commercial use of cyclodextrins has exploded; with applications in food, pharmaceutical, agricultural and chemical industries. However, molecules that can become "guests" and the solvents that can be dissolved are limited to only the naturally occurring CyDs. Accordingly, various types of modifications have been applied to CyDs, and on-going research is expanding their application range. A modern challenge is determining where among the multiple glucoses in the structure the modification should be targeted, and how to verify the modification site of an artificially synthesized modified CyD. For instance, in a β-CyD consisting of 7 glucoses, if a modification is to be made at any of the OH groups in position 6 of glucose, 1 - 7 different modified CyDs could exist based on the number of modification positions. Furthermore, if 2 - 5 modifications are introduced simultaneously, positional isomerism will occur, resulting in the existence of 19 types of modified CyD. The synthesis and purification of this type of modified CyD are difficult, but determining the positional isomer of the successfully synthesized molecule as well as its identification are also difficult tasks. Up to now, NMR has often been used to conduct structural analysis to determine the structures of these molecules, but this requires a high degree of refinement and a large quantity of synthesized molecules, making it unsuitable for small scale screening of synthesized molecules. In this article, we introduce a simple, fast technique for identifying positional isomers of modified CyDs even for small amounts of synthesized molecules.

October 30, 2009 GMT