Electrolysis: processes – compositions used therein – and methods – Electrolytic analysis or testing – For organic compound
Reexamination Certificate
2002-06-13
2004-12-07
Noguerola, Alex (Department: 1753)
Electrolysis: processes, compositions used therein, and methods
Electrolytic analysis or testing
For organic compound
C205S775000
Reexamination Certificate
active
06827840
ABSTRACT:
§1. BACKGROUND
§1.1 Field of the Invention
The present invention concerns detecting an enantiomer or enantiomers in general, and detecting or and distinguishing enantiomeric compounds by chiral ligand exchange potentiometry (CLEP) in particular.
§1.2 Related Art
Distinguishing enantiomers, such as amino acids has important applications to analytical chemistry, biotechnology, and medical sciences. For example, a simple monitoring system for distinguishing enantiomers would be extremely useful in biotechnological processes and medical diagnosis. The importance of chiral drugs that express different biological activities, and therefore often different therapeutic properties, for different enantiomers has been recognized by both pharmacologists and regulatory authorities.
Known techniques for detecting enantiomers include high-performance liquid chromatography (“HPLC”), capillary zone electrophoresis (“CZE”), and chiral ligand-exchange chromatography (“CLEC”). CLEC, which has been the most widely used of these techniques, accomplishes enantiomer separation by forming transient ternary copper complexes with an optically active amino acid derivative. See, e.g., the article V. A. Davankov, et al.,
Ligand Exchange Chromatography,
47 (1988) (hereafter referred to as “the Davankov article I”). With CLEC, an optically active bidentate ligand that functions as the chiral selector is grafted onto the support surface of the stationary phase. Ternary complexes are formed with amino acid analytes loaded with Cu(II) ions, which are a component of the mobile phase. See, e.g., the articles: S. Ahuja, J.
Amer. Chem. Soc.,
(1996); and the Davankov article I. (These articles are incorporated herein by reference.) Separation occurs if the free energies of formation for the diastereoisomeric complexes are sufficiently different.
Unfortunately, the CLEC, HPLC and CZE techniques for enantiomeric resolution of compounds do not have a detection system that can distinguish different enantiomers. Instead, the enantiomers must be separated before detection.
A known technique for distinguishing enantiomers is the electrochemical enzyme biosensor method. Electrochemical enzyme biosensors are amperometric detection systems that couple the enantioselectivity of the enzyme and the sensitivity of the amperometry. Unfortunately, however, the biological components in these biosensors limit their effectiveness. In particular, problems arise concerning long-time stability, irreversible deactivation at high temperatures or under harsh chemical environments, and operation in organic phases. See, e.g., the article F. Scheller, et al.,
Biosensors,
(1992).
The drawbacks of techniques such as HPLC, CZE, CLEC, and the electrochemical enzyme biosensor method limit their potential applications. For example, HPLC, CZE, and CLEC do not have detection systems that can distinguish enantiomers. The electrochemical enzyme biosensor's biological components limit its use. A method with a detection system that can distinguish enantiomers and that is not limited by biological components would overcome these drawbacks.
In view of the shortcomings of previous techniques, a better way to detect and distinguish enantiomers is needed.
§2. SUMMARY OF THE INVENTION
The present invention provides novel electrochemical methods for distinguishing or detecting enantiomers.
The present invention provides a novel electrochemical enantiodiscrimination method, referred to as “chiral ligand exchange potentiometry” (CLEP), which combines an electrochemical technique with ligand exchange. In a first embodiment, chiral ligand exchange potentiometry (CLEP) involves an electrode in contact with a solution of chiral selector ligands and enantiomers complexed with metal ions (labile coordination complexes). Ligand exchange occurs between the labile coordination complexes and the chiral selector ligands to form complexes of metal ions, chiral selector ligands, and enantiomers which are diastereoisomeric complexes. Diastereoisomeric complexes with different enantiomers have different net charges (Nernst factors). It is this difference in net charges that allows the potentiometric electrode to distinguish them.
In another embodiment, the present invention achieves enantiomer identification using a modified electrode (chiral sensor). Chiral selector ligands are incorporated into the modified electrode, thereby enabling the electrode to act as molecular sensors that recognize one enantiomer and preferentially immobilize that type of enantiomer on the surface of the electrode. In this embodiment, the solution needn't include the chiral selector ligand. Again, the net charge of the diastereoisomeric complex formed between the chiral selector ligand on the modified electrode and the enantiomer identifies the enantiomer.
REFERENCES:
patent: 6033630 (2000-03-01), Hinton et al.
Kataky et al. (“Functionalized alpha-Cyclodextrins as Potentiometric Chiral Sensors,” Analyst, Aug. 1992, vol. 117), pp. 1113-1117.*
Ng et al. (“Chiral discrimination of enantiomers with a self-assembled monolayer of functionalized beta-cyclodextrins on Au surfaces,” Tetrahedron Letters 43 (2002) 2863-2866).*
Troughton et al. (“Monolayer Films Prepared by the Spontaneous Self-Assmbly of Symmetrical and Unsymmetrical Dialkyl Sulfides from Solution onto Gold Substrates: Structure, properties, and Reactivity of Constituent Functional Groups,” Langmuir 1988, 4, 365-385).
Levon Kalle
Yu Bin
Zhou Yanxiu
Noguerola Alex
Pokotylo John C.
Polytechnic University
Straub & Pokotylo
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