Abstract
The study of unsubstituted and disubstituted β-cyclodextrins (β-CDs) by ESI-mass spectrometry is reported, applying a cone-induced fragmentation in the presence of a twofold excess of sodium chloride, in order to gain information about the fragmentation of the different regioisomers. On the basis of the fragmentation pattern observed for the unsusbstituted β-CD, a statistical model shows that the fragments generated by every regioisomer of a disubstituted CD (AB, AC, and AD) are expected to differ in their relative intensity and, therefore, they can be used for correctly identifying the three different regioisomers. The model was tested on the three regioisomeric (AB, AC, and AD) diamino-β-CDs and ditosyl-β-CD and on the AC and AD regioisomers of dimesitylenesulphonyl-β-CD, allowing in every case through statistical analysis of the fragmentation pattern the correct assignment of every regioisomer on the basis of an ESI mass spectrum (single quadrupole analyzer, high cone voltage) of the pure compounds. The absolute intensities of the fragmentation peaks were voltage-dependent but their ratios was voltage-independent, indicating that no mass bias in peak ratios is introduced by the analyzer. Given the fast time of analysis and its general applicability, independently from the substituents, we propose our method as an easy way to identify the regioisomers of disubstituted β-CDs.
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Atwood, J. L.; Davies, J. E.; MacNicol, D.; Vogtle, F.; Lehn, J. M. Comprehensive Supramolecular Chemistry; Elsevier Science Ltd.: Oxford, 1996, Vol. III
Li, S.; Purdy, W. C. Circular Dichroism, Ultraviolet, and Proton Nuclear Magnetic Resonance Spectroscopic Studies of the Chiral Recognition Mechanism of β-Cyclodextrin. Anal. Chem. 1992, 64, 1405–1412.
Szejtli, J. Cyclodextrin Technology. Kluwer Academic: Dordrecht, 1988.
Lehn, J.-M. Supramolecular Chemistry. VCH: Weinheim, 1995, 109, 44–45.
Szejtli, J. Introduction and General Overview on Cyclodextrin Chemistry. Chem. Rev. 1998, 98, 1743–1753.
Wenz, G. Cyclodextrins as Building Blocks for Supramolecular Structures and Functional Units. Angew. Chem. Int. Ed. Engl. 1994, 33, 803–822.
Khan, A. R.; Forgo, P.; Stine, K. J. D.’; Souza, V. T. Methods for Selective Modifications of Cyclodextrins. Chem. Rev. 1998, 98, 1977–1996.
Fujita, K.; Matsunaga, A.; Imoto, T. 6A6B, 6A6C, and 6A6D-ditosylates of β-Cyclodextrin. Tetrahedron Lett 1984, 25, 5533–5536.
Fujita, K.; Yamamura, H.; Imoto, T. Unsymmetrically Disubstituted β-Cyclodextrins. 6A,6X-Dideoxy-6A-azido-6X-[(mesitylsulfonyl)oxy] Derivatives. J. Org. Chem. 1985, 50, 4393–4395.
Tabushi, I.; Yamamura, K.; Nabeshima, T. Characterization of Regiospecific A,C- and A,D-Disulfonate Capping of β-Cyclodextrin. Capping as an Efficient Production Technique. J. Am. Chem. Soc. 1984, 106, 5267–5270.
Tabushi, I.; Nabeshima, T.; Fujita, K.; Matsunaga, A.; Imoto, T. Regiospecific A,B Capping onto β-Cyclodextrin. Characteristic Remote Substituent Effect on 13C NMR Chemical Shift and Specific Taka-Amylase Hydrolysis. J. Org. Chem. 1985, 50, 2638–2643.
Breslow, R.; Canary, J. W.; Varney, M.; Waddell, S. T.; Yang, D. Artifical Transaminases Linking Pyridoxamine to Binding Cavities: Controlling the Geometry. J. Am. Chem. Soc. 1990, 112, 5212–5219.
Galaverna, G.; Paganuzzi, M. C.; Corradini, R.; Dossena, A.; Marchelli, R. Enantiomeric Separation of Hydroxy Acids and Carboxylic Acids by Diamino-β-Cyclodextrins (AB, AC, AD) in Capillary Electrophoresis. Electrophoresis 2001, 22, 3171–3177.
Tabushi, I.; Nabeshima, T.; Yamamura, K.; Fujita, K. 400 MHz Two-Dimensional NMR Studies of Cyclodextrin Derivatives for 1H and 13C Chemical Shift Determination. Bull. Chem. Soc. Japan. 1987, 60, 3705–3712.
Yamamura, H.; Nagaoka, H.; Saito, K.; Kawai, M.; Butsugan, Y.; Nakajima, T.; Fujita, K. Determination of the Structure of Tris(6-O-mesitylenesulfonyl)-α-Cyclodextrin Regioiomers by 1H NMR Analyses of the Corresponding 3,6-Anhydrocyclodextrin Derivatives. J. Org. Chem. 1993, 58, 2936–2937.
Yuan, D. Q.; Koga, K.; Yamagushi, M.; Fujita, K. Synthesis and Unique NMR Behavior of a Novel Capped α-Cyclodextrin. J. Chem. Soc. Chem. Commun. 1996, 16, 1943–1944.
Cucinotta, V. D.’; Alessandro, F.; Impellizzeri, G.; Pappalardo, G.; Rizzarelli, E.; Vecchio, G. Cyclopeptide Functionalized β-Cyclodextrin. A New Class of Potentially Enzyme Mimicking Compounds with Two Recognition Sites. J. Chem. Soc. Chem. Commun. 1991, 5, 293–294.
Bonomo, P. R.; Impellizzeri, G.; Pappalardo, G.; Rizzarelli, E.; Vecchio, G. Cyclo-L-Histidyl-L-Histidyl Capped β-Cyclodextrin. A New Potentially Enzyme-Mimicking Compound or Artificial Receptor with Two Recognition Sites. Gaz. Chim. Ital. 1993, 123, 593–595.
Tabushi, I.; Nabeshima, T. Regiospecific A,B Capping onto β-Cyclodextrin. Characteristic Remote Substituent Effect on 13C NMR Chemical Shift and Specific Taka-Amylase Hydrolysis. J. Org. Chem. 1985, 50, 2638–2643.
Tabushi, I.; Kuroda, Y.; Yokota, K.; Yuan, L. C. Regiospecific A,C- and A,D-Disulfonate Capping of β-Cyclodextrin. J. Am. Chem. Soc. 1981, 103, 711–712.
Fujita, K.; Yamamura, H.; Matsunaga, A.; Imoto, T.; Mihashi, K.; Fujioka, T. 6-Polysubstituted α-Cyclodextrins. Application of Koerner’s Absolute Method of Isomer Determination. J. Am. Chem. Soc. 1986, 108, 4509–4513.
Atsumi, M.; Izumida, M.; Yuan, D.-Q.; Fujita, K. Selective Synthesis and Structure Determination of 6A,6C,6E-Tri(O-sulfonyl)-β-Cyclodextrins. Tetrahedron Lett 2000, 41, 8117–8120.
Yamamura, H.; Iida, D.; Araki, S.; Kobayashi, K.; Katakai, R.; Kano, K.; Kawai, M. Polysulfonylated Cyclodextrins. Part II. Preparation and Structural Validation of Three Isomeric Pentakis(6-O-mesitylsulfonyl)cyclomaltoheptaoses. J. Chem. Soc. Perkin Trans. 1 1999, 21, 3111–3115.
Pearce, A. J.; Sinay, P. Diisobutylaluminum-Promoted Regioselective De-O-benzylation of Perbenzylated Cyclodextrins: A Powerful New Strategy for the Preparation of Selectively Modified Cyclodextrins. Angew. Chem. Int. Ed. Engl. 2000, 39, 3610–3612.
Hanessian, S.; Benalil, A.; Laferriere, C. The Synthesis of Functionalized Cyclodextrins as Scaffolds and Templates for Molecular Diversity, Catalysis, and Inclusion Phenomena. J. Org. Chem. 1995, 60, 4786–4797.
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Published online January 6, 2003
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Sforza, S., Galaverna, G., Corradini, R. et al. ESI-mass spectrometry analysis of unsubstituted and disubstituted β-cyclodextrins: fragmentation mode and identification of the AB, AC, AD regioisomers. J Am Soc Mass Spectrom 14, 124–135 (2003). https://doi.org/10.1016/S1044-0305(02)00853-X
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DOI: https://doi.org/10.1016/S1044-0305(02)00853-X