Dynamic HPLC on chiral stationary phases: A powerful tool for the investigation of stereomutation processes

D’Acquarica, Ilaria; Gasparrini, Francesco; Pierini, Marco; Villani, Claudio; Zappia, Giovanni

doi:10.1002/jssc.200600129

Cited by 103 publications

(75 citation statements)

References 34 publications

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“…[34][35][36][37][38] Enantioselective dynamic chromatography has been used for the determination of the kinetics of stereolabile compounds, e.g., atropisomers, drugs and drug-related compounds, compounds with stereogenic nitrogen and sulfur, and pheromones covering the range of interconversion barriers DG { between 75 and 170 kJ mol 21 . Depending on the physical properties of the analyte molecule and the expected interconversion barrier, different dynamic chromatographic or electrophoretic techniques (e.g., DGC, DSFC, DHPLC, DCE, DCEC, DMEKC) can be applied to determine interconversion barriers.…”

Section: Introductionmentioning

confidence: 99%

The stereodynamics of 1,2‐dipropyldiaziridines

et al. 2009

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N-alkylated trans-diaziridines are an intriguing class of compounds with two stereogenic nitrogen atoms which easily interconvert. In the course of our investigations of the nature of the interconversion process via nitrogen inversion or electrocyclic ring opening ring closure, we synthesized and characterized the three constitutionally isomeric diaziridines 1,2-di-n-propyldiaziridine 1, 1-isopropyl-2-n-propyldiaziridine 2, and 1,2-diisopropyldiaziridine 3 to study the influence of the substituents on the interconversion barriers. Enantiomer separation was achieved by enantioselective gas chromatography on the chiral stationary phase Chirasil-beta-Dex with high separation factors alpha (1-isopropyl-2-n-propyldiaziridine: 1.18; 1, 2-diisopropyldiaziridine: 1.24; 100 degrees C 50 kPa He) for the isopropyl substituted diaziridines. These compounds showed pronounced plateau formation between 100 and 150 degrees C, and peak coalescence at elevated temperatures. The enantiomerization barriers DeltaG(double dagger) and activation parameters DeltaH(double dagger) and DeltaS(double dagger) were determined by enantioselective dynamic gas chromatography (DGC) and direct evaluation of the elution profiles using the unified equation implemented in the software DCXplorer. Interestingly, 1-isopropyl-2-n-propyldiaziridine and 1,2-diisopropyldiaziridine exhibit similar high interconversion barriers DeltaG(double dagger) (100 degrees C) of 128.3 +/- 0.4 kJ mol(-1) and 129.8 +/- 0.4 kJ mol(-1), respectively, which indicates that two sterically demanding substituents do not substantially increase the barrier as expected for a distinct nitrogen inversion process.

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Section: Introductionmentioning

confidence: 99%

The stereodynamics of 1,2‐dipropyldiaziridines

et al. 2009

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“…26 In fact, the minor but consistently higher activation barriers for the M/P inversion of 1 in D-HPLC when being compared to off-column racemization data (DDG ] enant value of around 1.5 kJ/mol at 40 and 458C) may indicate a certain deactivating (stabilization) effect of the chiral selector of the CSP.…”

Section: The Slightly Higher Dgmentioning

confidence: 97%

“…[26][27][28] These models form the basis to extract kinetic data from experimental elution profiles for firstorder and pseudo-first order interconversion.…”

Section: On-column Enantiomerizationmentioning

confidence: 99%

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Determination of enantiomerization barriers of hypericin and pseudohypericin by dynamic high‐performance liquid chromatography on immobilized polysaccharide‐type chiral stationary phases and off‐column racemization experiments

2009

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Direct enantiomer separation of hypericin, pseudohypericin, and protohypericin was accomplished by high-performance liquid chromatography (HPLC) using immobilized polysaccharide-type chiral stationary phases (CSPs). Enantioselectivities up to 1.30 were obtained in the polar-organic elution mode whereby for hypericin and pseudohypericin Chiralpak IC [chiral selector being cellulose tris(3,5-dichlorophenylcarbamate)] and for protohypericin Chiralpak IA (chiral selector being the 3,5-dimethylphenylcarbamate of amylose) gave favorable results. Enantiomers were distinguished by on-line electronic circular dichroism detection. Optimized enantioselective chromatographic conditions were the basis for determining stereodynamic parameters of the enantiomer interconversion process of hypericin and pseudohypericin. Rate constants delivered by computational simulation of dynamic HPLC elution profiles (stochastic model, consideration of peak tailing) were used to calculate averaged enantiomerization barriers (DeltaG(enant)(#)) of 97.6-99.6 kJ/mol for both compounds (investigated temperature range 25-45 degrees C). Complementary variable temperature off-column (i.e., in solution) racemization experiments delivered DeltaG(enant)(#) = 97.1-98.0 kJ/mol (27-45 degrees C) for hypericin and DeltaG(enant)(#) = 98.9-101.4 kJ/mol (25-55 degrees C) for pseudohypericin. An activation enthalpy of DeltaH(#) = 86.0 kJ/mol and an activation entropy of DeltaS(#) = -37.7 J/(K mol) were calculated from hypericin racemization kinetics in solution, whereas for pseudohypericin these figures amounted to 74.1 kJ/mol and -82.6 J/(K mol), respectively. Although the natural phenanthroperylene quinone pigments hypericin and pseudohypericin as well as their biological precursor protohypericin are chiral and can be separated by enantioselective HPLC low enantiomerization barriers seem to prevent the occurrence of an excess of one enantiomer under typical physiological conditions--at least as long as stereoselective intermolecular interactions with other chiral entities are absent.

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“…In these cases, through suitable algorithm-based computer simulation of the acquired experimental traces, the rate constants relevant to the involved isomerization mechanism can be determined. [15][16][17][18][19][20][21][22][23] In principle, a quite wide range of temperatures …”

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confidence: 99%

Stereolability of Chiral Ruthenium Catalysts With Frozen NHC Ligand Conformations Investigated by Dynamic‐HPLC

et al. 2015

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The stereolability of chiral Hoveyda-Grubbs II type ruthenium complexes bearing N-heterocyclic carbene (NHC) ligands with Syn-phenyl groups on the backbone and Syn- or Anti-oriented o-tolyl N-substituents was studied by resorting to dynamic high-performance liquid chromatography (D-HPLC). A complete chromatographic picture of the involved stereoisomers (four for Anti- and two for Syn-complexes) was achieved at very low temperatures (-53°C and -40°C respectively), at which the NHC-Ru bond rotations were frozen out. Inspection of the chromatographic profiles recorded at higher temperatures revealed the presence of plateau zones between the couples of either Syn or Anti stereoisomers, attesting to the active interconversion between the eluted species. Such dynamic chromatograms were successfully simulated through procedures based on both theoretical plate and classical stochastic models. The good superimposition achieved between experimental and simulated chromatographic profiles allowed determination of the related isomerization energy barriers (ΔGisom (#) ), all derived by rotation around the NHC-Ru bond. The obtained diastereomerization barriers between the Anti isomers were found in very good agreement with those previously measured by experimental nuclear magnetic resonance (NMR) and assessed through Density Functional Theory (DFT) calculations. With the same approach, for the first time we also determined the enantiomerization barrier of the Syn isomer. Focused changes to the structure of complex Syn, studied by a molecular modeling approach, were found suitable to strongly reduce the stereolability arising from rotation around the NHC-Ru bond.

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Dynamic HPLC on chiral stationary phases: A powerful tool for the investigation of stereomutation processes

Cited by 103 publications

References 34 publications

The stereodynamics of 1,2‐dipropyldiaziridines

The stereodynamics of 1,2‐dipropyldiaziridines

Determination of enantiomerization barriers of hypericin and pseudohypericin by dynamic high‐performance liquid chromatography on immobilized polysaccharide‐type chiral stationary phases and off‐column racemization experiments

Stereolability of Chiral Ruthenium Catalysts With Frozen NHC Ligand Conformations Investigated by Dynamic‐HPLC

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