title: Determination of thermodynamic values of acidic dissociation constants and complexation constants of profens and their utilization for optimization of separation conditions by Simul 5 Complex.
abstract: In this paper we determine acid dissociation constants, limiting ionic mobilities, complexation constants with β-cyclodextrin or heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, and mobilities of resulting complexes of profens, using capillary zone electrophoresis and affinity capillary electrophoresis. Complexation parameters are determined for both neutral and fully charged forms of profens and further corrected for actual ionic strength and variable viscosity in order to obtain thermodynamic values of complexation constants. The accuracy of obtained complexation parameters is verified by multidimensional nonlinear regression of affinity capillary electrophoretic data, which provides the acid dissociation and complexation parameters within one set of measurements, and by NMR technique. A good agreement among all discussed methods was obtained. Determined complexation parameters were used as input parameters for simulations of electrophoretic separation of profens by Simul 5 Complex. An excellent agreement of experimental and simulated results was achieved in terms of positions, shapes, and amplitudes of analyte peaks, confirming the applicability of Simul 5 Complex to complex systems, and accuracy of obtained physical-chemical constants. Simultaneously, we were able to demonstrate the influence of electromigration dispersion on the separation efficiency, which is not possible using the common theoretical approaches, and predict the electromigration order reversals of profen peaks. We have shown that determined acid dissociation and complexation parameters in combination with tool Simul 5 Complex software can be used for optimization of separation conditions in capillary electrophoresis.
authors.affiliation: Charles University in Prague, Faculty of Science, Department of Physical and Macromolecular Chemistry, Prague, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Riesová
authors.affiliation: Charles University in Prague, Faculty of Science, Department of Physical and Macromolecular Chemistry, Prague, Czech Republic; Ruprecht-Karls-Universität Heidelberg, Organisch-Chemisches Institut, Heidelberg, Germany. Electronic address: svobod.j@natur.cuni.cz.
authors.forename: Jana
authors.initials: J
authors.lastname: Svobodová
authors.affiliation: Charles University in Prague, Faculty of Science, Department of Physical and Macromolecular Chemistry, Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Ušelová
authors.affiliation: NMR Laboratory, Charles University in Prague, Faculty of Science, Prague, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Tošner
authors.affiliation: Charles University in Prague, Faculty of Science, Department of Physical and Macromolecular Chemistry, Prague, Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Zusková
authors.affiliation: Charles University in Prague, Faculty of Science, Department of Physical and Macromolecular Chemistry, Prague, Czech Republic.
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Gaš
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003198:Computer Simulation; D019075:Electrophoresis, Capillary / Q000379:methods; D005480:Flurbiprofen / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry*; D007660:Ketoprofen / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009288:Naproxen / Q000737:chemistry*; D009994:Osmolar Concentration; D012984:Software; D013816:Thermodynamics; D014783:Viscosity; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047392:beta-Cyclodextrins; C000609658:heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin; D009288:Naproxen; D005480:Flurbiprofen; D007660:Ketoprofen; C031215:betadex; D007052:Ibuprofen
keywords: Acid dissociation constants; Affinity capillary electrophoresis; Complexation constants; Cyclodextrin; Profen; Simulations