Application of capillary electrophoresis technique for the enantioseparation of bioactive ferrocene‐based compounds versus DFT calculated data

Abstract

Herein, a series of bioactive ferrocene‐modified N‐heterocycles with alkyl linkers was prepared in good to quantitative yields starting from easy accessible ferrocene alcohols and heterocycles under acidic or neutral (for imidazole) conditions in racemic forms. The analytical resolution of a number of bioactive racemic ferrocene azoles 1–6 (where azole = imidazole, pyrazole, and benzotriazole derivatives) into enantiomers was first carried out by CE using sulfobuthylether‐β‐CD (captisol) as a chiral selector. The analytical approaches to highly enantiomeric‐enriched ferrocene derivatives are based on the formation of their inclusion complexes. The best chiral separation was achieved using zone CE in a quartz capillary. The ACE was used to evaluate the stability constants of captisol complexes with enantiomeric forms of two ferrocene derivatives 1, FcCHMe‐imidazole, and 6, FcCHMe‐benzotriazole. The optimal conditions for the resolution of the studied (R, S)‐ferrocene compounds 1, 2, and 6 were predicted on the basis of the performed quantum chemical calculations and then implemented by the electrophoretic method. A high correlation between density functional theory calculation results and experimental electrophoresis data were obtained. Successful enantioseparation of racemic mixtures is of great importance for the characterization and further applications of drug candidates in enantiopure forms and in the development of clinical treatment. The advantages of the CE procedure make it possible to have important practical value and significance for determining the purity and enantiomeric excess of other ferrocene‐containing compounds.

Recent Advances in Separation and Analysis of Chiral Compounds

“…The method enabled direct determination of the enantiomers of tetrahydropalmatine and canadine in the complex samples of Corydalis Rhizoma with low LOD of 0.017 μg g –1 and good recovery of 89.1%–110.0% . Sulfated-β-CD (S-β-CD) and sulfobuthylether-β-CD sodium (SBE-β-CD) were used in chiral CE separation of racemic bioactive ferrocene-modified azoles and chiral fluoroquinolones, respectively. , Ionic liquid modified SBE-β-CD was also prepared to give a superior CE enantio-separation for racemic drugs to original SBE-β-CD . Sulfated-γ-CD (HS-γ-CD) was employed as CE chiral selector to investigate the enantioselective biodegradation of citalopram and verapamil .…”

Enantioseparation of organometallic compounds by electromigration techniques

“…Despite this, these metallocenes were not comprehensively explored in enantioseparation science, and very few systematic analytical and mechanistic studies about the function of the (η 5 -C 5 H 5 )Fe(η 5 -C 5 H 5 ) core in chromatographic and electromigration processes were reported so far. Coherently to this statement, only two recent studies about the enantioseparation of chiral ferrocenes by CE are available in the literature [16,51], even if in the past CE had found application in the analytical separation of mixtures of ferrocene derivatives [52,53].…”

Ferrocene derivatives with planar chirality and their enantioseparation by liquid‐phase techniques

“…Later, other CD-based CSPs were used for the enantioseparation of ferrocenes featured by central chirality exclusively [51,[173][174][175]. Recently, sulfobutylether-β-CD was used as a chiral selector for the CE enantioseparation of chiral ferrocenes exclusively containing a chiral centre, as a chiral element [176].…”