Enantioseparation of ß-carboline, tetrahydroisoquinoline and benzazepine analogues of pharmaceuti... more Enantioseparation of ß-carboline, tetrahydroisoquinoline and benzazepine analogues of pharmaceutical importance: Utilization of chiral stationary phases based on polysaccharides and sulfonic acid modified Cinchona alkaloids in high-performance liquid and subcritical fluid chromatography
Enantioseparation of ß-carboline, tetrahydroisoquinoline and benzazepine analogues of pharmaceuti... more Enantioseparation of ß-carboline, tetrahydroisoquinoline and benzazepine analogues of pharmaceutical importance: Utilization of chiral stationary phases based on polysaccharides and sulfonic acid modified Cinchona alkaloids in high-performance liquid and subcritical fluid chromatography
The stereoisomers of five 1-(phenylethylamino)methyl-2-naphthol analogs or 1-(naphthylethylamino)... more The stereoisomers of five 1-(phenylethylamino)methyl-2-naphthol analogs or 1-(naphthylethylamino)methyl-2-naphthol analogs containing two chiral centers were directly separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenyl) carbamate (Lux Cellulose-1), cellulose tris-(3-chloro-4-methylphenyl) carbamate (Lux Cellulose-2) and amylose tris-(5-chloro-2-methylphenyl) carbamate (Lux Amylose-2). Experiments were performed in normal-phase mode in a wide temperature range -5 to 70°C. Thermodynamic parameters and T(iso) values were calculated from plots of lnk or lnα vs. 1/T. -Δ(ΔH°) ranged from 1.0 to 4.7 kJ mol(-1), -Δ(ΔS°) from 1.6 to 11.0 J mol(-1) K(-1) and -Δ(ΔG°) from 0.1 to 1.5 kJ mol(-1). The sequence of elution of the stereoisomers was determined in all cases and in one case a temperature-induced inversion of the elution sequence was observed.
The stereoisomers of five 1-(phenylethylamino)methyl-2-naphthol analogs or 1-(naphthylethylamino)... more The stereoisomers of five 1-(phenylethylamino)methyl-2-naphthol analogs or 1-(naphthylethylamino)methyl-2-naphthol analogs containing two chiral centers were directly separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenyl) carbamate (Lux Cellulose-1), cellulose tris-(3-chloro-4-methylphenyl) carbamate (Lux Cellulose-2) and amylose tris-(5-chloro-2-methylphenyl) carbamate (Lux Amylose-2). Experiments were performed in normal-phase mode in a wide temperature range -5 to 70°C. Thermodynamic parameters and T(iso) values were calculated from plots of lnk or lnα vs. 1/T. -Δ(ΔH°) ranged from 1.0 to 4.7 kJ mol(-1), -Δ(ΔS°) from 1.6 to 11.0 J mol(-1) K(-1) and -Δ(ΔG°) from 0.1 to 1.5 kJ mol(-1). The sequence of elution of the stereoisomers was determined in all cases and in one case a temperature-induced inversion of the elution sequence was observed.
Normal phase (NP) high-performance liquid and sub-and supercritical fluid chromatographic (both a... more Normal phase (NP) high-performance liquid and sub-and supercritical fluid chromatographic (both acronymed as SFC) methods have been developed for the enantiomer separation of three basic and three ampholytic structurally related C-3-substituted indole analogs on seven non-ionic (neutral) polysaccharide-based and two chemically entirely different zwitterionic Cinchona alkaloid-and sulfonic acid-based chiral stationary phases (CSPs). In a systematic fashion the effect of the composition of the mobile phase, the nature of the alcohol and amine additives on the retention characteristics and enantioselectivity of the ionizable analytes were investigated. On all studied polysaccharide-based CSPs the three ampholytes remained unretained in NP-LC mode, while they were nicely retained and resolved in SFC mode. These unexpected results underline a specific property of liquid CO 2 as bulk solvent in combination with alcohols as co-solvents and amine additives thus creating an environment around the chiral selector sites which support the retention of ampholytes. The zwitterionic CSPs worked equally well for the resolution of the basic and ampholytic analytes using a polar ionic mobile phase in both LC and SFC modes. Results acquired by studying the effect of temperature were used to calculate the changes in standard enthalpy (H •), entropy (S •), and free energy (G •) applying van't Hoff plots. The values of the thermodynamic parameters depended on the nature of selectors, the structure of analytes and the properties of the mobile phases. On polysaccharide-based CSPs and columns operated in NP-LC mode enthalpically-, whereas in SFC mode both enthalpically-and entropically-driven enantiomer separations were observed.
Normal phase (NP) high-performance liquid and sub-and supercritical fluid chromatographic (both a... more Normal phase (NP) high-performance liquid and sub-and supercritical fluid chromatographic (both acronymed as SFC) methods have been developed for the enantiomer separation of three basic and three ampholytic structurally related C-3-substituted indole analogs on seven non-ionic (neutral) polysaccharide-based and two chemically entirely different zwitterionic Cinchona alkaloid-and sulfonic acid-based chiral stationary phases (CSPs). In a systematic fashion the effect of the composition of the mobile phase, the nature of the alcohol and amine additives on the retention characteristics and enantioselectivity of the ionizable analytes were investigated. On all studied polysaccharide-based CSPs the three ampholytes remained unretained in NP-LC mode, while they were nicely retained and resolved in SFC mode. These unexpected results underline a specific property of liquid CO 2 as bulk solvent in combination with alcohols as co-solvents and amine additives thus creating an environment around the chiral selector sites which support the retention of ampholytes. The zwitterionic CSPs worked equally well for the resolution of the basic and ampholytic analytes using a polar ionic mobile phase in both LC and SFC modes. Results acquired by studying the effect of temperature were used to calculate the changes in standard enthalpy (H •), entropy (S •), and free energy (G •) applying van't Hoff plots. The values of the thermodynamic parameters depended on the nature of selectors, the structure of analytes and the properties of the mobile phases. On polysaccharide-based CSPs and columns operated in NP-LC mode enthalpically-, whereas in SFC mode both enthalpically-and entropically-driven enantiomer separations were observed.
High-performance liquid chromatographic and subcritical fluid chromatographic separation of α-ary... more High-performance liquid chromatographic and subcritical fluid chromatographic separation of α-arylated ß-carboline, N-alkylated tetrahydroisoquinolines and their bioisosteres on polysaccharide-based chiral stationary phases
High-performance liquid chromatographic and subcritical fluid chromatographic separation of α-ary... more High-performance liquid chromatographic and subcritical fluid chromatographic separation of α-arylated ß-carboline, N-alkylated tetrahydroisoquinolines and their bioisosteres on polysaccharide-based chiral stationary phases
The enantiomers of 1-(a-aminobenzyl)-2-naphthol and 2-(a-aminobenzyl)-1-naphthol analogs were sep... more The enantiomers of 1-(a-aminobenzyl)-2-naphthol and 2-(a-aminobenzyl)-1-naphthol analogs were separated isothermally on a 3,5-dimethylphenylcarbamoylated b-cyclodextrin-based chiral stationary phase (Cyclobond DMP), with an n-hexane/alcohol modifier as mobile phase. Optimization of the separation was achieved by variation of combinations of the polar mobile phase additives ethanol and methanol. The nature and position of the a-aminobenzyl substituent of the 1-and 2-naphthol analogs influenced the retention and the selectivity.
The enantiomers of 1-(a-aminobenzyl)-2-naphthol and 2-(a-aminobenzyl)-1-naphthol analogs were sep... more The enantiomers of 1-(a-aminobenzyl)-2-naphthol and 2-(a-aminobenzyl)-1-naphthol analogs were separated isothermally on a 3,5-dimethylphenylcarbamoylated b-cyclodextrin-based chiral stationary phase (Cyclobond DMP), with an n-hexane/alcohol modifier as mobile phase. Optimization of the separation was achieved by variation of combinations of the polar mobile phase additives ethanol and methanol. The nature and position of the a-aminobenzyl substituent of the 1-and 2-naphthol analogs influenced the retention and the selectivity.
Enantiomers of cationic compounds of pharmaceutical relevance, namely tetrahydro-ß-carboline and ... more Enantiomers of cationic compounds of pharmaceutical relevance, namely tetrahydro-ß-carboline and 1,2,3,4-tetrahydroisoquinoline analogs, were separated by high-performance liquid chromatography. Separations were performed on Cinchona-alkaloid-based zwitterionic ion exchanger type chiral stationary phases applied as cation exchangers using mixtures of methanol and acetonitrile or tetrahydrofuran as bulk solvent components containing triethylammonium acetate or ammonium acetate as organic salt additives. On the zwitterionic ZWIX(+) and ZWIX(−) columns investigated, retention and enantioseparation of the studied basic analytes were influenced by the nature and concentration of the organic components of the mobile phase. The effect of organic salt additives on the retention behavior of the studied analytes can be described by the stoichiometric displacement model related to the counterion concentration. Investigations on the structure-retention relationships were performed applying different mobile phase systems for the two types of cationic analytes. For the thermodynamic characterization, parameters such as changes in standard enthalpy (Δ(ΔH •)), entropy (Δ(ΔS •)), and free energy (Δ(ΔG •)) were calculated on the basis of van't Hoff plots derived from the ln α versus 1/T curves. In most cases, enthalpy-driven enantioseparations were observed, with a consistent dependence of the calculated thermodynamic parameters on the mobile phase composition. Elution sequences of the studied compounds were determined in all cases.
Enantiomers of cationic compounds of pharmaceutical relevance, namely tetrahydro-ß-carboline and ... more Enantiomers of cationic compounds of pharmaceutical relevance, namely tetrahydro-ß-carboline and 1,2,3,4-tetrahydroisoquinoline analogs, were separated by high-performance liquid chromatography. Separations were performed on Cinchona-alkaloid-based zwitterionic ion exchanger type chiral stationary phases applied as cation exchangers using mixtures of methanol and acetonitrile or tetrahydrofuran as bulk solvent components containing triethylammonium acetate or ammonium acetate as organic salt additives. On the zwitterionic ZWIX(+) and ZWIX(−) columns investigated, retention and enantioseparation of the studied basic analytes were influenced by the nature and concentration of the organic components of the mobile phase. The effect of organic salt additives on the retention behavior of the studied analytes can be described by the stoichiometric displacement model related to the counterion concentration. Investigations on the structure-retention relationships were performed applying different mobile phase systems for the two types of cationic analytes. For the thermodynamic characterization, parameters such as changes in standard enthalpy (Δ(ΔH •)), entropy (Δ(ΔS •)), and free energy (Δ(ΔG •)) were calculated on the basis of van't Hoff plots derived from the ln α versus 1/T curves. In most cases, enthalpy-driven enantioseparations were observed, with a consistent dependence of the calculated thermodynamic parameters on the mobile phase composition. Elution sequences of the studied compounds were determined in all cases.
The direct separation of the enantiomers of 1-(α-aminoarylmethyl)-2-naphthol, 1-(αaminoalkyl)-2-n... more The direct separation of the enantiomers of 1-(α-aminoarylmethyl)-2-naphthol, 1-(αaminoalkyl)-2-naphthol, 2-(α-aminoarylmethyl)-1-naphthol analogs and 2-(1-amino-2methylpropyl)-1-naphthol) was performed on a newly developed chiral stationary phase containing isopropyl carbamate-cyclofructan6 as chiral selector, with n-heptane/alcohol/TFA as mobile phase. The effects of the mobile phase composition, the nature and concentration of the alcoholic and acidic modifiers, and the structures of the analytes on the retention and resolution were investigated. In some cases separations were carried out at constant mobile phase compositions in the temperature range 5-40 °C. Thermodynamic parameters and T iso values were calculated from plots of ln k' or ln α versus 1/T.-Δ(ΔH°) ranged from 2.8. to 3.2 kJ mol −1 ,-Δ(ΔS°) from 7.7 to 10.1 J mol −1 K −1 and-Δ(ΔG°) from 0.2 to 0.5 kJ mol −1. It was found that the enantioseparations were enthalpy driven. The sequence of elution of the stereoisomers determined in some cases was (R)<(S).
The direct separation of the enantiomers of 1-(α-aminoarylmethyl)-2-naphthol, 1-(αaminoalkyl)-2-n... more The direct separation of the enantiomers of 1-(α-aminoarylmethyl)-2-naphthol, 1-(αaminoalkyl)-2-naphthol, 2-(α-aminoarylmethyl)-1-naphthol analogs and 2-(1-amino-2methylpropyl)-1-naphthol) was performed on a newly developed chiral stationary phase containing isopropyl carbamate-cyclofructan6 as chiral selector, with n-heptane/alcohol/TFA as mobile phase. The effects of the mobile phase composition, the nature and concentration of the alcoholic and acidic modifiers, and the structures of the analytes on the retention and resolution were investigated. In some cases separations were carried out at constant mobile phase compositions in the temperature range 5-40 °C. Thermodynamic parameters and T iso values were calculated from plots of ln k' or ln α versus 1/T.-Δ(ΔH°) ranged from 2.8. to 3.2 kJ mol −1 ,-Δ(ΔS°) from 7.7 to 10.1 J mol −1 K −1 and-Δ(ΔG°) from 0.2 to 0.5 kJ mol −1. It was found that the enantioseparations were enthalpy driven. The sequence of elution of the stereoisomers determined in some cases was (R)<(S).
The focus of this contribution is a comparative investigation of enantioseparations of 19 N α-Fmo... more The focus of this contribution is a comparative investigation of enantioseparations of 19 N α-Fmoc proteinogenic amino acids on Quinine-based zwitterionic and anion-exchanger type chiral stationary phases employing hydro-organic and polar-ionic liquid and subcritical fluid chromatographic conditions. Effects of mobile phase composition (including additives, e.g., water, basis and acids) and nature of chiral selectors on the chromatographic performances were studied at different chromatographic modes. Thermodynamic parameters of the temperature dependent enantioseparation results were calculated in the temperature range 5-50 • C applying plots of lnα versus 1/T. The differences in standard enthalpy and standard entropy for a given pair of enantiomers were calculated and served as a basis for comparisons. Elution sequence in all cases was determined, where a general rule could be observed, both in liquid and subcritical fluid chromatographic mode the D-enantiomers eluted before the L ones. In both modes, the principles of ion exchange chromatography apply.
Journal of Pharmaceutical and Biomedical Analysis, Mar 1, 2013
The stereoisomers of ten unusual amino acid analogs, 1- and 2-naphthol-substituted glycine and it... more The stereoisomers of ten unusual amino acid analogs, 1- and 2-naphthol-substituted glycine and its ester derivatives, were separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenylcarbamate) (Cellulose-1), cellulose tris-(3-chloro-4-methylphenylcarbamate) (Cellulose-2), cellulose tris-(4-methylbenzoate) (Cellulose-3), cellulose tris-(4-chloro-3-methylphenylcarbamate) (Cellulose-4) and amylose tris-(5-chloro-2-methylphenylcarbamate) (Amylose-2). Experiments were performed in normal-phase mode with n-heptane/alcohol/diethylamine mobile phases in a wide temperature range: 5-50°C. Thermodynamic parameters were calculated from plots of lnk or lnα vs. 1/T. Δ(ΔH°) ranged from -10.1 to 6.2kJmol(-1), Δ(ΔS°) from -31.5 to 22.5Jmol(-1)K(-1) and -Δ(ΔG°) from 0.4 to 1.4kJmol(-1), and both enthalpy and entropy-controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature. The sequence of elution of the stereoisomers was determined in some cases.
The focus of this contribution is a comparative investigation of enantioseparations of 19 N α-Fmo... more The focus of this contribution is a comparative investigation of enantioseparations of 19 N α-Fmoc proteinogenic amino acids on Quinine-based zwitterionic and anion-exchanger type chiral stationary phases employing hydro-organic and polar-ionic liquid and subcritical fluid chromatographic conditions. Effects of mobile phase composition (including additives, e.g., water, basis and acids) and nature of chiral selectors on the chromatographic performances were studied at different chromatographic modes. Thermodynamic parameters of the temperature dependent enantioseparation results were calculated in the temperature range 5-50 • C applying plots of lnα versus 1/T. The differences in standard enthalpy and standard entropy for a given pair of enantiomers were calculated and served as a basis for comparisons. Elution sequence in all cases was determined, where a general rule could be observed, both in liquid and subcritical fluid chromatographic mode the D-enantiomers eluted before the L ones. In both modes, the principles of ion exchange chromatography apply.
Normal phase (NP) high-performance liquid and sub- and supercritical fluid chromatographic (both ... more Normal phase (NP) high-performance liquid and sub- and supercritical fluid chromatographic (both acronymed as SFC) methods have been developed for the enantiomer separation of three basic and three ampholytic structurally related C-3-substituted indole analogs on seven non-ionic (neutral) polysaccharide-based and two chemically entirely different zwitterionic Cinchona alkaloid- and sulfonic acid-based chiral stationary phases (CSPs). In a systematic fashion the effect of the composition of the mobile phase, the nature of the alcohol and amine additives on the retention characteristics and enantioselectivity of the ionizable analytes were investigated. On all studied polysaccharide-based CSPs the three ampholytes remained unretained in NP-LC mode, while they were nicely retained and resolved in SFC mode. These unexpected results underline a specific property of liquid CO as bulk solvent in combination with alcohols as co-solvents and amine additives thus creating an environment aroun...
Journal of Pharmaceutical and Biomedical Analysis, Mar 1, 2013
The stereoisomers of ten unusual amino acid analogs, 1- and 2-naphthol-substituted glycine and it... more The stereoisomers of ten unusual amino acid analogs, 1- and 2-naphthol-substituted glycine and its ester derivatives, were separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenylcarbamate) (Cellulose-1), cellulose tris-(3-chloro-4-methylphenylcarbamate) (Cellulose-2), cellulose tris-(4-methylbenzoate) (Cellulose-3), cellulose tris-(4-chloro-3-methylphenylcarbamate) (Cellulose-4) and amylose tris-(5-chloro-2-methylphenylcarbamate) (Amylose-2). Experiments were performed in normal-phase mode with n-heptane/alcohol/diethylamine mobile phases in a wide temperature range: 5-50°C. Thermodynamic parameters were calculated from plots of lnk or lnα vs. 1/T. Δ(ΔH°) ranged from -10.1 to 6.2kJmol(-1), Δ(ΔS°) from -31.5 to 22.5Jmol(-1)K(-1) and -Δ(ΔG°) from 0.4 to 1.4kJmol(-1), and both enthalpy and entropy-controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature. The sequence of elution of the stereoisomers was determined in some cases.
The enantiomeric pairs of cis and trans stereoisomers of cyclic β-aminohydroxamic acids and their... more The enantiomeric pairs of cis and trans stereoisomers of cyclic β-aminohydroxamic acids and their related cis and trans cyclic β-amino acids containing two chiral centers were directly separated on four structurally related chiral stationary phases derived from quinine and quinidine modified with (R,R)- and (S,S)-aminocyclohexanesulfonic acids. Applying these zwitterionic ion-exchangers as chiral selectors, the effects of the composition of the bulk solvent, the acid and base additives, the structures of the analytes, and temperature on the enantioresolution were investigated. To study the effects of temperature and obtain thermodynamic parameters, experiments were carried out at constant mobile phase compositions in the temperature range 5-50°C. The differences in the changes in standard enthalpy Δ(ΔH°), entropy Δ(ΔS°), and free energy Δ(ΔG°) were calculated from the linear van't Hoff plots derived from the ln α versus 1/T curves in the studied temperature range. Results thus o...
Enantioseparation of ß-carboline, tetrahydroisoquinoline and benzazepine analogues of pharmaceuti... more Enantioseparation of ß-carboline, tetrahydroisoquinoline and benzazepine analogues of pharmaceutical importance: Utilization of chiral stationary phases based on polysaccharides and sulfonic acid modified Cinchona alkaloids in high-performance liquid and subcritical fluid chromatography
Enantioseparation of ß-carboline, tetrahydroisoquinoline and benzazepine analogues of pharmaceuti... more Enantioseparation of ß-carboline, tetrahydroisoquinoline and benzazepine analogues of pharmaceutical importance: Utilization of chiral stationary phases based on polysaccharides and sulfonic acid modified Cinchona alkaloids in high-performance liquid and subcritical fluid chromatography
The stereoisomers of five 1-(phenylethylamino)methyl-2-naphthol analogs or 1-(naphthylethylamino)... more The stereoisomers of five 1-(phenylethylamino)methyl-2-naphthol analogs or 1-(naphthylethylamino)methyl-2-naphthol analogs containing two chiral centers were directly separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenyl) carbamate (Lux Cellulose-1), cellulose tris-(3-chloro-4-methylphenyl) carbamate (Lux Cellulose-2) and amylose tris-(5-chloro-2-methylphenyl) carbamate (Lux Amylose-2). Experiments were performed in normal-phase mode in a wide temperature range -5 to 70°C. Thermodynamic parameters and T(iso) values were calculated from plots of lnk or lnα vs. 1/T. -Δ(ΔH°) ranged from 1.0 to 4.7 kJ mol(-1), -Δ(ΔS°) from 1.6 to 11.0 J mol(-1) K(-1) and -Δ(ΔG°) from 0.1 to 1.5 kJ mol(-1). The sequence of elution of the stereoisomers was determined in all cases and in one case a temperature-induced inversion of the elution sequence was observed.
The stereoisomers of five 1-(phenylethylamino)methyl-2-naphthol analogs or 1-(naphthylethylamino)... more The stereoisomers of five 1-(phenylethylamino)methyl-2-naphthol analogs or 1-(naphthylethylamino)methyl-2-naphthol analogs containing two chiral centers were directly separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenyl) carbamate (Lux Cellulose-1), cellulose tris-(3-chloro-4-methylphenyl) carbamate (Lux Cellulose-2) and amylose tris-(5-chloro-2-methylphenyl) carbamate (Lux Amylose-2). Experiments were performed in normal-phase mode in a wide temperature range -5 to 70°C. Thermodynamic parameters and T(iso) values were calculated from plots of lnk or lnα vs. 1/T. -Δ(ΔH°) ranged from 1.0 to 4.7 kJ mol(-1), -Δ(ΔS°) from 1.6 to 11.0 J mol(-1) K(-1) and -Δ(ΔG°) from 0.1 to 1.5 kJ mol(-1). The sequence of elution of the stereoisomers was determined in all cases and in one case a temperature-induced inversion of the elution sequence was observed.
Normal phase (NP) high-performance liquid and sub-and supercritical fluid chromatographic (both a... more Normal phase (NP) high-performance liquid and sub-and supercritical fluid chromatographic (both acronymed as SFC) methods have been developed for the enantiomer separation of three basic and three ampholytic structurally related C-3-substituted indole analogs on seven non-ionic (neutral) polysaccharide-based and two chemically entirely different zwitterionic Cinchona alkaloid-and sulfonic acid-based chiral stationary phases (CSPs). In a systematic fashion the effect of the composition of the mobile phase, the nature of the alcohol and amine additives on the retention characteristics and enantioselectivity of the ionizable analytes were investigated. On all studied polysaccharide-based CSPs the three ampholytes remained unretained in NP-LC mode, while they were nicely retained and resolved in SFC mode. These unexpected results underline a specific property of liquid CO 2 as bulk solvent in combination with alcohols as co-solvents and amine additives thus creating an environment around the chiral selector sites which support the retention of ampholytes. The zwitterionic CSPs worked equally well for the resolution of the basic and ampholytic analytes using a polar ionic mobile phase in both LC and SFC modes. Results acquired by studying the effect of temperature were used to calculate the changes in standard enthalpy (H •), entropy (S •), and free energy (G •) applying van't Hoff plots. The values of the thermodynamic parameters depended on the nature of selectors, the structure of analytes and the properties of the mobile phases. On polysaccharide-based CSPs and columns operated in NP-LC mode enthalpically-, whereas in SFC mode both enthalpically-and entropically-driven enantiomer separations were observed.
Normal phase (NP) high-performance liquid and sub-and supercritical fluid chromatographic (both a... more Normal phase (NP) high-performance liquid and sub-and supercritical fluid chromatographic (both acronymed as SFC) methods have been developed for the enantiomer separation of three basic and three ampholytic structurally related C-3-substituted indole analogs on seven non-ionic (neutral) polysaccharide-based and two chemically entirely different zwitterionic Cinchona alkaloid-and sulfonic acid-based chiral stationary phases (CSPs). In a systematic fashion the effect of the composition of the mobile phase, the nature of the alcohol and amine additives on the retention characteristics and enantioselectivity of the ionizable analytes were investigated. On all studied polysaccharide-based CSPs the three ampholytes remained unretained in NP-LC mode, while they were nicely retained and resolved in SFC mode. These unexpected results underline a specific property of liquid CO 2 as bulk solvent in combination with alcohols as co-solvents and amine additives thus creating an environment around the chiral selector sites which support the retention of ampholytes. The zwitterionic CSPs worked equally well for the resolution of the basic and ampholytic analytes using a polar ionic mobile phase in both LC and SFC modes. Results acquired by studying the effect of temperature were used to calculate the changes in standard enthalpy (H •), entropy (S •), and free energy (G •) applying van't Hoff plots. The values of the thermodynamic parameters depended on the nature of selectors, the structure of analytes and the properties of the mobile phases. On polysaccharide-based CSPs and columns operated in NP-LC mode enthalpically-, whereas in SFC mode both enthalpically-and entropically-driven enantiomer separations were observed.
High-performance liquid chromatographic and subcritical fluid chromatographic separation of α-ary... more High-performance liquid chromatographic and subcritical fluid chromatographic separation of α-arylated ß-carboline, N-alkylated tetrahydroisoquinolines and their bioisosteres on polysaccharide-based chiral stationary phases
High-performance liquid chromatographic and subcritical fluid chromatographic separation of α-ary... more High-performance liquid chromatographic and subcritical fluid chromatographic separation of α-arylated ß-carboline, N-alkylated tetrahydroisoquinolines and their bioisosteres on polysaccharide-based chiral stationary phases
The enantiomers of 1-(a-aminobenzyl)-2-naphthol and 2-(a-aminobenzyl)-1-naphthol analogs were sep... more The enantiomers of 1-(a-aminobenzyl)-2-naphthol and 2-(a-aminobenzyl)-1-naphthol analogs were separated isothermally on a 3,5-dimethylphenylcarbamoylated b-cyclodextrin-based chiral stationary phase (Cyclobond DMP), with an n-hexane/alcohol modifier as mobile phase. Optimization of the separation was achieved by variation of combinations of the polar mobile phase additives ethanol and methanol. The nature and position of the a-aminobenzyl substituent of the 1-and 2-naphthol analogs influenced the retention and the selectivity.
The enantiomers of 1-(a-aminobenzyl)-2-naphthol and 2-(a-aminobenzyl)-1-naphthol analogs were sep... more The enantiomers of 1-(a-aminobenzyl)-2-naphthol and 2-(a-aminobenzyl)-1-naphthol analogs were separated isothermally on a 3,5-dimethylphenylcarbamoylated b-cyclodextrin-based chiral stationary phase (Cyclobond DMP), with an n-hexane/alcohol modifier as mobile phase. Optimization of the separation was achieved by variation of combinations of the polar mobile phase additives ethanol and methanol. The nature and position of the a-aminobenzyl substituent of the 1-and 2-naphthol analogs influenced the retention and the selectivity.
Enantiomers of cationic compounds of pharmaceutical relevance, namely tetrahydro-ß-carboline and ... more Enantiomers of cationic compounds of pharmaceutical relevance, namely tetrahydro-ß-carboline and 1,2,3,4-tetrahydroisoquinoline analogs, were separated by high-performance liquid chromatography. Separations were performed on Cinchona-alkaloid-based zwitterionic ion exchanger type chiral stationary phases applied as cation exchangers using mixtures of methanol and acetonitrile or tetrahydrofuran as bulk solvent components containing triethylammonium acetate or ammonium acetate as organic salt additives. On the zwitterionic ZWIX(+) and ZWIX(−) columns investigated, retention and enantioseparation of the studied basic analytes were influenced by the nature and concentration of the organic components of the mobile phase. The effect of organic salt additives on the retention behavior of the studied analytes can be described by the stoichiometric displacement model related to the counterion concentration. Investigations on the structure-retention relationships were performed applying different mobile phase systems for the two types of cationic analytes. For the thermodynamic characterization, parameters such as changes in standard enthalpy (Δ(ΔH •)), entropy (Δ(ΔS •)), and free energy (Δ(ΔG •)) were calculated on the basis of van't Hoff plots derived from the ln α versus 1/T curves. In most cases, enthalpy-driven enantioseparations were observed, with a consistent dependence of the calculated thermodynamic parameters on the mobile phase composition. Elution sequences of the studied compounds were determined in all cases.
Enantiomers of cationic compounds of pharmaceutical relevance, namely tetrahydro-ß-carboline and ... more Enantiomers of cationic compounds of pharmaceutical relevance, namely tetrahydro-ß-carboline and 1,2,3,4-tetrahydroisoquinoline analogs, were separated by high-performance liquid chromatography. Separations were performed on Cinchona-alkaloid-based zwitterionic ion exchanger type chiral stationary phases applied as cation exchangers using mixtures of methanol and acetonitrile or tetrahydrofuran as bulk solvent components containing triethylammonium acetate or ammonium acetate as organic salt additives. On the zwitterionic ZWIX(+) and ZWIX(−) columns investigated, retention and enantioseparation of the studied basic analytes were influenced by the nature and concentration of the organic components of the mobile phase. The effect of organic salt additives on the retention behavior of the studied analytes can be described by the stoichiometric displacement model related to the counterion concentration. Investigations on the structure-retention relationships were performed applying different mobile phase systems for the two types of cationic analytes. For the thermodynamic characterization, parameters such as changes in standard enthalpy (Δ(ΔH •)), entropy (Δ(ΔS •)), and free energy (Δ(ΔG •)) were calculated on the basis of van't Hoff plots derived from the ln α versus 1/T curves. In most cases, enthalpy-driven enantioseparations were observed, with a consistent dependence of the calculated thermodynamic parameters on the mobile phase composition. Elution sequences of the studied compounds were determined in all cases.
The direct separation of the enantiomers of 1-(α-aminoarylmethyl)-2-naphthol, 1-(αaminoalkyl)-2-n... more The direct separation of the enantiomers of 1-(α-aminoarylmethyl)-2-naphthol, 1-(αaminoalkyl)-2-naphthol, 2-(α-aminoarylmethyl)-1-naphthol analogs and 2-(1-amino-2methylpropyl)-1-naphthol) was performed on a newly developed chiral stationary phase containing isopropyl carbamate-cyclofructan6 as chiral selector, with n-heptane/alcohol/TFA as mobile phase. The effects of the mobile phase composition, the nature and concentration of the alcoholic and acidic modifiers, and the structures of the analytes on the retention and resolution were investigated. In some cases separations were carried out at constant mobile phase compositions in the temperature range 5-40 °C. Thermodynamic parameters and T iso values were calculated from plots of ln k' or ln α versus 1/T.-Δ(ΔH°) ranged from 2.8. to 3.2 kJ mol −1 ,-Δ(ΔS°) from 7.7 to 10.1 J mol −1 K −1 and-Δ(ΔG°) from 0.2 to 0.5 kJ mol −1. It was found that the enantioseparations were enthalpy driven. The sequence of elution of the stereoisomers determined in some cases was (R)<(S).
The direct separation of the enantiomers of 1-(α-aminoarylmethyl)-2-naphthol, 1-(αaminoalkyl)-2-n... more The direct separation of the enantiomers of 1-(α-aminoarylmethyl)-2-naphthol, 1-(αaminoalkyl)-2-naphthol, 2-(α-aminoarylmethyl)-1-naphthol analogs and 2-(1-amino-2methylpropyl)-1-naphthol) was performed on a newly developed chiral stationary phase containing isopropyl carbamate-cyclofructan6 as chiral selector, with n-heptane/alcohol/TFA as mobile phase. The effects of the mobile phase composition, the nature and concentration of the alcoholic and acidic modifiers, and the structures of the analytes on the retention and resolution were investigated. In some cases separations were carried out at constant mobile phase compositions in the temperature range 5-40 °C. Thermodynamic parameters and T iso values were calculated from plots of ln k' or ln α versus 1/T.-Δ(ΔH°) ranged from 2.8. to 3.2 kJ mol −1 ,-Δ(ΔS°) from 7.7 to 10.1 J mol −1 K −1 and-Δ(ΔG°) from 0.2 to 0.5 kJ mol −1. It was found that the enantioseparations were enthalpy driven. The sequence of elution of the stereoisomers determined in some cases was (R)<(S).
The focus of this contribution is a comparative investigation of enantioseparations of 19 N α-Fmo... more The focus of this contribution is a comparative investigation of enantioseparations of 19 N α-Fmoc proteinogenic amino acids on Quinine-based zwitterionic and anion-exchanger type chiral stationary phases employing hydro-organic and polar-ionic liquid and subcritical fluid chromatographic conditions. Effects of mobile phase composition (including additives, e.g., water, basis and acids) and nature of chiral selectors on the chromatographic performances were studied at different chromatographic modes. Thermodynamic parameters of the temperature dependent enantioseparation results were calculated in the temperature range 5-50 • C applying plots of lnα versus 1/T. The differences in standard enthalpy and standard entropy for a given pair of enantiomers were calculated and served as a basis for comparisons. Elution sequence in all cases was determined, where a general rule could be observed, both in liquid and subcritical fluid chromatographic mode the D-enantiomers eluted before the L ones. In both modes, the principles of ion exchange chromatography apply.
Journal of Pharmaceutical and Biomedical Analysis, Mar 1, 2013
The stereoisomers of ten unusual amino acid analogs, 1- and 2-naphthol-substituted glycine and it... more The stereoisomers of ten unusual amino acid analogs, 1- and 2-naphthol-substituted glycine and its ester derivatives, were separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenylcarbamate) (Cellulose-1), cellulose tris-(3-chloro-4-methylphenylcarbamate) (Cellulose-2), cellulose tris-(4-methylbenzoate) (Cellulose-3), cellulose tris-(4-chloro-3-methylphenylcarbamate) (Cellulose-4) and amylose tris-(5-chloro-2-methylphenylcarbamate) (Amylose-2). Experiments were performed in normal-phase mode with n-heptane/alcohol/diethylamine mobile phases in a wide temperature range: 5-50°C. Thermodynamic parameters were calculated from plots of lnk or lnα vs. 1/T. Δ(ΔH°) ranged from -10.1 to 6.2kJmol(-1), Δ(ΔS°) from -31.5 to 22.5Jmol(-1)K(-1) and -Δ(ΔG°) from 0.4 to 1.4kJmol(-1), and both enthalpy and entropy-controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature. The sequence of elution of the stereoisomers was determined in some cases.
The focus of this contribution is a comparative investigation of enantioseparations of 19 N α-Fmo... more The focus of this contribution is a comparative investigation of enantioseparations of 19 N α-Fmoc proteinogenic amino acids on Quinine-based zwitterionic and anion-exchanger type chiral stationary phases employing hydro-organic and polar-ionic liquid and subcritical fluid chromatographic conditions. Effects of mobile phase composition (including additives, e.g., water, basis and acids) and nature of chiral selectors on the chromatographic performances were studied at different chromatographic modes. Thermodynamic parameters of the temperature dependent enantioseparation results were calculated in the temperature range 5-50 • C applying plots of lnα versus 1/T. The differences in standard enthalpy and standard entropy for a given pair of enantiomers were calculated and served as a basis for comparisons. Elution sequence in all cases was determined, where a general rule could be observed, both in liquid and subcritical fluid chromatographic mode the D-enantiomers eluted before the L ones. In both modes, the principles of ion exchange chromatography apply.
Normal phase (NP) high-performance liquid and sub- and supercritical fluid chromatographic (both ... more Normal phase (NP) high-performance liquid and sub- and supercritical fluid chromatographic (both acronymed as SFC) methods have been developed for the enantiomer separation of three basic and three ampholytic structurally related C-3-substituted indole analogs on seven non-ionic (neutral) polysaccharide-based and two chemically entirely different zwitterionic Cinchona alkaloid- and sulfonic acid-based chiral stationary phases (CSPs). In a systematic fashion the effect of the composition of the mobile phase, the nature of the alcohol and amine additives on the retention characteristics and enantioselectivity of the ionizable analytes were investigated. On all studied polysaccharide-based CSPs the three ampholytes remained unretained in NP-LC mode, while they were nicely retained and resolved in SFC mode. These unexpected results underline a specific property of liquid CO as bulk solvent in combination with alcohols as co-solvents and amine additives thus creating an environment aroun...
Journal of Pharmaceutical and Biomedical Analysis, Mar 1, 2013
The stereoisomers of ten unusual amino acid analogs, 1- and 2-naphthol-substituted glycine and it... more The stereoisomers of ten unusual amino acid analogs, 1- and 2-naphthol-substituted glycine and its ester derivatives, were separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenylcarbamate) (Cellulose-1), cellulose tris-(3-chloro-4-methylphenylcarbamate) (Cellulose-2), cellulose tris-(4-methylbenzoate) (Cellulose-3), cellulose tris-(4-chloro-3-methylphenylcarbamate) (Cellulose-4) and amylose tris-(5-chloro-2-methylphenylcarbamate) (Amylose-2). Experiments were performed in normal-phase mode with n-heptane/alcohol/diethylamine mobile phases in a wide temperature range: 5-50°C. Thermodynamic parameters were calculated from plots of lnk or lnα vs. 1/T. Δ(ΔH°) ranged from -10.1 to 6.2kJmol(-1), Δ(ΔS°) from -31.5 to 22.5Jmol(-1)K(-1) and -Δ(ΔG°) from 0.4 to 1.4kJmol(-1), and both enthalpy and entropy-controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature. The sequence of elution of the stereoisomers was determined in some cases.
The enantiomeric pairs of cis and trans stereoisomers of cyclic β-aminohydroxamic acids and their... more The enantiomeric pairs of cis and trans stereoisomers of cyclic β-aminohydroxamic acids and their related cis and trans cyclic β-amino acids containing two chiral centers were directly separated on four structurally related chiral stationary phases derived from quinine and quinidine modified with (R,R)- and (S,S)-aminocyclohexanesulfonic acids. Applying these zwitterionic ion-exchangers as chiral selectors, the effects of the composition of the bulk solvent, the acid and base additives, the structures of the analytes, and temperature on the enantioresolution were investigated. To study the effects of temperature and obtain thermodynamic parameters, experiments were carried out at constant mobile phase compositions in the temperature range 5-50°C. The differences in the changes in standard enthalpy Δ(ΔH°), entropy Δ(ΔS°), and free energy Δ(ΔG°) were calculated from the linear van't Hoff plots derived from the ln α versus 1/T curves in the studied temperature range. Results thus o...
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