Document Type

Theses, Ph.D

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Disciplines

1.4 CHEMICAL SCIENCES

Publication Details

Successfully submitted for the award of Doctor of Philosophy (Ph.D) to the Technological University Dublin, 2011.

Abstract

Almost half of commercial pharmaceuticals are chiral and therefore effective analytical techniques to detect and quantify enantiomers are important in the pharmaceutical sector to ensure drug safety and efficacy. In this work copper(II) complexes of aminoalkane derivatives of β-cyclodextrin (CDEn, CDPn and CDBn) were investigated to determine if they provide a versatile solution for the direct separation of the enantiomers of DOPA, benserazide and carbidopa using capillary electrophoresis. Tyrosine was used as a model compound. Electronic spectroscopy was used in order to determine if copper(II) coordinates to the amino-CDs and to determine if further coordination to the guest species occurs. Decreases in λmax for the d-d transitions on coordination of the metal ion suggest the formation of a CuCDAm binary complex with CDEn and CDPn acting as bidentate ligands and CDBn acting as a monodentate ligand. A further blue shift on the introduction of a guest species suggests further coordination of copper(II) and formation of ternary complexes of tyrosine and DOPA with all three metallo-complexes of the aminoalkane derivatives. A ternary complex also formed between CuCDEn and Lcarbidopa. No coordination was evident with benserazide. These results suggest that the use of these metallo-cyclodextrin derivatives for enantioselection may be guest specific if ternary complex formation is required for separation. Cicular dichroism (c.d.) can show the differential inclusion of enantiomers in cyclodextrin cavities and therefore was used here to determine if the metallocyclodextrins can differentiate between enantiomers. Increases in intensity of the bands in the spectra indicate deeper inclusion of a guest in the CD cavity. From the results obtained in this study it can be shown that the binary complex CuCDEn is the most ii enantioselective material of those studied towards both tyrosine and DOPA. CuCDPn and CuCDBn showed no enantioselection. The stoichiometry of all complexes was determined using electronic spectroscopy and Job’s method of continuous variation. A 1:1 binary complex formed between Cu(II) and CDEn. It was also shown that CuCDEn formed a 1:1 ternary complex with tyrosine and a 2:1 complex with DOPA. Results also suggested that both 1:1 and 2:1 complexes of CuCDEn and L-carbidopa were formed. Using CE in normal polarity mode and a background electrolyte (BGE) at pH 6.8, separation of the enantiomers of DOPA was not achieved using CuCDEn as a chiral selector. The stability of the binary complex is limited by pH and therefore CDEn alone was used as the chiral selector. Separation of L-DOPA from L-carbidopa was achieved using CDEn in a BGE at pH 2.5 and a resolution of 2.36 was obtained. However it was still not possible to separate the isomers of DOPA. An alternative charged CD derivative, sulfated-β-cyclodextrin was investigated and was found to successfully separate the enantiomers of D,L-DOPA in a BGE of pH 2.5 and a resolution of 3.62 was obtained. These results suggest that amino-cyclodextrin derivatives are guest specific for chiral separations in capillary electrophoresis and do not represent a universal method for separations required for regulatory compliance. Since separations were obtained using the anionic sulfated derivatives it is suggested that host molecules with a permanent charge are more useful and therefore inclusion is not the only factor needed for separation to be successful.

DOI

https://doi.org/10.21427/D74887

Creative Commons License

Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.

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