This research focuses on the development and validation of a capillary electrophoresis (CE) method for the chiral separation of three H1-antihistamine drugs chlorcyclizine, norchlorcyclizine, and neobenodine using sulfated β-cyclodextrin (S-β-CD) as the chiral selector. The study explores various factors influencing the separation efficiency, including CD concentration, organic modifier content, voltage application, and buffer pH. Optimal conditions were identified as a 100 mM phosphate buffer (pH 6.0) with 34 mg mL-1 S-β-CD and 40% (v/v) methanol. The method demonstrated excellent linearity in calibration curves, with coefficients of determination exceeding 0.99 for each enantiomer. Precision studies revealed good intra- and inter-day precision for migration times and peak areas. The limits of detection and quantification for the analytes were within the ranges of 5.9-11.4 and 18-34.6 µmol L-1, respectively. Overall, the developed CE method offers a robust and precise approach for the chiral separation of H1-antihistamine drugs, holding promise for pharmaceutical applications.

• Klíčová slova
• capillary electrophoresis, chiral separation, methanol, piperazine derivatives, sulfated β‐cyclodextrin,
• MeSH
• beta-cyklodextriny * chemie   MeSH
• elektroforéza kapilární * metody   MeSH
• koncentrace vodíkových iontů MeSH
• limita detekce * MeSH
• lineární modely MeSH
• piperaziny chemie   analýza   MeSH
• reprodukovatelnost výsledků MeSH
• sírany chemie   analýza   MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny * MeSH
• piperaziny MeSH
• sírany MeSH

The incorporation of phosphorothioate linkages has recently been extensively employed in therapeutic oligonucleotides. For their separation and quality control, new high-efficient and high-sensitive analytical methods are needed. In this work, a new affinity capillary electrophoresis method has been developed and applied for the separation of a potential anticancer drug, 2',3'-cyclic diadenosine diphosphorothioate (Rp, Rp) (ADU-S100), and three recently newly synthesized diastereomers of its difluorinated derivative, 3',3'-cyclic di(2'-fluoro, 2'-deoxyadenosine phosphorothioate). The separation was performed in the various background electrolytes (BGEs) within a pH range 5-9 using several native and derivatized cyclodextrins (CDs) as chiral additives of the BGE. Relatively good separations were obtained with β-, γ-, and 2-hydroxypropyl-γ-CDs in some of the BGEs tested. However, the best separation was achieved using the 2-hydroxypropyl-β-CD chiral selector at 43.5 mM average concentration in the BGE composed of 40 mM Tris, 40 mM tricine, pH 8.1. Under these conditions, all the previous four cyclic dinucleotides (CDNs) were baseline separated within 4 min. Additionally, the average apparent binding constants and the average actual ionic mobilities of the complexes of all four CDNs with 2-hydroxypropyl-β-CD in the above BGE were determined. The formed complexes were found to be relatively weak, with the average apparent binding constants in the range of 12.2-94.1 L mol-1 and with the actual ionic mobilities spanning the interval (-7.8 to -12.7) × 10-9 m2 V-1 s-1. The developed method can be applied for the separation, analysis, and characterization of the above and similar CDNs.

• Klíčová slova
• affinity capillary electrophoresis, binding constant, chiral analysis, cyclic dinucleotides, cyclodextrins,
• MeSH
• beta-cyklodextriny * chemie   MeSH
• dinukleosidfosfáty chemie   izolace a purifikace   analýza   MeSH
• elektroforéza kapilární * metody   MeSH
• hydroxypropyl beta cyklodextrin * chemie   MeSH
• koncentrace vodíkových iontů MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny * MeSH
• dinukleosidfosfáty MeSH
• hydroxypropyl beta cyklodextrin * MeSH

Chiral CE methods were developed for the elucidation of l- or d-configuration of tyrosine residue in antimicrobial dipeptide β-alanyl-tyrosine (β-Ala-Tyr) isolated from the hemolymph of larvae of fleshfly Neobellieria bullata and for the evaluation of enantiopurity of its synthetic isomers (β-Ala-d-Tyr and β-Ala-l-Tyr), and enantiomers of their amidated and acetylated derivatives, β-Ala-d,l-Tyr-NH2 and N-Ac-β-Ala-d,l-Tyr, respectively. Baseline separations were achieved for all three pairs of enantiomers: (i) for β-Ala-d,l-Tyr in acidic background electrolyte composed of 32/50 mM tris(hydroxymethyl)aminomethane/H3 PO4 , pH 2.5, and 20 mg/mL 2-hydroxypropyl-β-cyclodextrin as chiral selector; (ii) for β-Ala-d,l-Tyr-NH2 enantiomers in acidic background electrolyte consisting of 48/50 mM tris(hydroxymethyl)aminomethane/H3 PO4 , pH 3.5, and 30 mg/mL 2-hydroxypropyl-β-cyclodextrin; and (iii) for enantiomers of N-Ac-β-Ala-d,l-Tyr in alkaline background electrolyte composed of 50/49 mM Na2 B4 O7 /NaOH, pH 10.5, and 60 mg/mL 2-hydroxypropyl-β-cyclodextrin. From CE analyses of mixed samples of isolated β-Ala-Tyr and synthetic standards β-Ala-l-Tyr and β-Ala-d-Tyr, it turned out that isolated β-Ala-Tyr was pure l-enantiomer. In addition, the average apparent binding constants, Kb , and average actual ionic mobilities of the complexes of β-Ala-d,l-Tyr and its above derivatives with 2-hydroxypropyl-β-cyclodextrin were determined. These complexes were weak, with Kb values ranging from 11.2 to 79.1 L/mol. Their cationic mobilities were equal to (5.6-9.2) × 10-9 m2 /V/s, and anionic mobilities to (-1.3-1.6) × 10-9 m2 /V/s.

• Klíčová slova
• 2-hydroxypropyl-β-cyclodextrin, Binding constant, capillary electrophoresis, chiral separation, enantioseparation, β-alanyl-tyrosine,
• MeSH
• beta-cyklodextriny * chemie   MeSH
• cyklodextriny * chemie   MeSH
• elektroforéza kapilární metody   MeSH
• elektrolyty MeSH
• hydroxypropyl beta cyklodextrin MeSH
• koncentrace vodíkových iontů MeSH
• stereoizomerie MeSH
• tromethamin MeSH
• tyrosin MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny * MeSH
• cyklodextriny * MeSH
• elektrolyty MeSH
• hydroxypropyl beta cyklodextrin MeSH
• tromethamin MeSH
• tyrosin MeSH

Cyclin-dependent kinases (CDKs) play an important role in the cell-division cycle. Synthetic inhibitors of CDKs are based on 2,6,9-trisubstituted purines and are developed as potential anticancer drugs; however, they have low solubility in water. In this study, we proved that the pharmaco-chemical properties of purine-based inhibitors can be improved by appropriate substitution with the adamantane moiety. We prepared ten new purine derivatives with adamantane skeletons that were linked at position 6 using phenylene spacers of variable geometry and polarity. We demonstrated that the adamantane skeleton does not compromise the biological activity, and some of the new purines displayed even higher inhibition activity towards CDK2/cyclin E than the parental compounds. These findings were supported by a docking study, which showed an adamantane scaffold inside the binding pocket participating in the complex stabilisation with non-polar interactions. In addition, we demonstrated that β-cyclodextrin (CD) increases the drug's solubility in water, although this is at the cost of reducing the biochemical and cellular effect. Most likely, the drug concentration, which is necessary for target engagement, was decreased by competitive drug binding within the complex with β-CD.

• Klíčová slova
• 2,6,9-trisubstituted purine, adamantane, cyclin-dependent kinase, cytotoxicity, molecular docking, β-cyclodextrin,
• MeSH
• adamantan chemie   MeSH
• beta-cyklodextriny chemie   MeSH
• buňky K562 MeSH
• cyklin-dependentní kinasa 2 antagonisté a inhibitory   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• protinádorové látky chemie   farmakologie   MeSH
• puriny chemie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adamantan MeSH
• beta-cyklodextriny MeSH
• CDK2 protein, human MeSH Prohlížeč
• cyklin-dependentní kinasa 2 MeSH
• inhibitory proteinkinas MeSH
• protinádorové látky MeSH
• puriny MeSH

A nanoliquid chromatographic method for the stereoisomer separation of some flavanone aglycones and 7-O-glycosides has been proposed employing a C18 capillary column and a chiral mobile-phase additive such as cyclodextrin. The chiral separation of eriodictyol, naringenin, and hesperitin was obtained by addition of carboxymethyl-β-cyclodextrin to the mobile phase, whereas eriocitrin, naringin, narirutin, and hesperidin diastereoisomers were resolved by using sulfobutyl ether-β-cyclodextrin. The influence of the composition of the mobile phase, the length of the capillary column, and the flow rate on the chiral recognition were investigated. At optimum conditions, baseline separation for the selected aglycones and glycosylated forms were achieved with a mobile phase consisting of 50 mM sodium acetate buffer pH 3 and 30% methanol containing 20 mM of carboxymethyl-β-cyclodextrin and 10 mM of sulfobutyl ether-β-cyclodextrin, respectively. Precision, linearity, and sensitivity of the method were tested. Limits of detection and quantification for the studied flavanone glycosides were in the range 1.3-2.5 and 7.5-12.5 µg/mL, respectively. The method was used for the determination of the diastereomeric composition of the flavanone-7-O-glycosides in Citrus juices after solid-phase extraction procedure.

• Klíčová slova
• chiral mobile phase additive, citrus juices, cyclodextrins, nano-liquid chromatography, stereoisomer separation,
• MeSH
• beta-cyklodextriny chemie   MeSH
• flavanony chemie   izolace a purifikace   MeSH
• glykosidy chemie   izolace a purifikace   MeSH
• molekulární struktura MeSH
• nanotechnologie * MeSH
• stereoizomerie MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• flavanony MeSH
• glykosidy MeSH

The optimization of sustainable protocols for reductive amination has been a lingering challenge in green synthesis. In this context, a comparative study of different metal-loaded cross-linked cyclodextrins (CDs) were examined for the microwave (MW)-assisted reductive amination of aldehydes and ketones using either H2 or formic acid as a hydrogen source. The Pd/Cu heterogeneous nanocatalyst based on Pd (II) and Cu (I) salts embedded in a β-CD network was the most efficient in terms of yield and selectivity attained. In addition, the polymeric cross-linking avoided metal leaching, thus enhancing the process sustainability; good yields were realized using benzylamine under H2. These interesting findings were then applied to the MW-assisted one-pot synthesis of secondary amines via a tandem reductive amination of benzaldehyde with nitroaromatics under H2 pressure. The formation of a CuxPdy alloy under reaction conditions was discerned, and a synergic effect due to the cooperation between Cu and Pd has been hypothesized. During the reaction, the system worked as a bifunctional nanocatalyst wherein the Pd sites facilitate the reduction of nitro compounds, while the Cu species promote the subsequent imine hydrogenation affording structurally diverse secondary amines with high yields.

• Klíčová slova
• bimetallic nanocatalyst, heterogeneous catalysis, microwaves, one-pot reductive amination, sustainable protocols,
• MeSH
• aminace MeSH
• aminy chemie   MeSH
• benzaldehydy chemie   MeSH
• beta-cyklodextriny chemie   MeSH
• cyklodextriny chemie   MeSH
• katalýza MeSH
• kovy chemie   MeSH
• měď chemie   MeSH
• mikrovlny * MeSH
• nanočástice chemie   MeSH
• palladium chemie   MeSH
• reagencia zkříženě vázaná chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminy MeSH
• benzaldehyde MeSH Prohlížeč
• benzaldehydy MeSH
• beta-cyklodextriny MeSH
• betadex MeSH Prohlížeč
• cyklodextriny MeSH
• kovy MeSH
• měď MeSH
• palladium MeSH
• reagencia zkříženě vázaná MeSH

A new hyaluronan derivative modified with β-cyclodextrin units (CD-HA) was prepared via the click reaction between propargylated hyaluronan and monoazido-cyclodextrin (CD) to achieve a degree of substitution of 4%. The modified hyaluronan was characterized by 1H-nuclear magnetic resonance spectroscopy (NMR) and size exclusion chromatography. Subsequent 1H-NMR and isothermal calorimetric titration experiments revealed that the CD units on CD-HA can form virtual 1:1, 1:2, and 1:3 complexes with one-, two-, and three-site adamantane-based guests, respectively. These results imply that the CD-HA chains used the multitopic guests to form a supramolecular cross-linked network. The free CD-HA polymer was readily restored by the addition of a competing macrocycle, which entrapped the cross-linking guests. Thus, we demonstrated that the new CD-HA polymer is a promising component for the construction of chemical stimuli-responsive supramolecular architectures.

• Klíčová slova
• click reaction, cyclodextrin, host-guest systems, sodium hyaluronan, supramolecular network,
• MeSH
• beta-cyklodextriny chemická syntéza   chemie   MeSH
• click chemie MeSH
• kalorimetrie MeSH
• kyselina hyaluronová chemická syntéza   chemie   MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulární struktura * MeSH
• polymery chemická syntéza   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• betadex MeSH Prohlížeč
• kyselina hyaluronová MeSH
• polymery MeSH

Three chiral stationary phases were prepared by dynamic coating of sulfobutylether-β-cyclodextrin (SBE-β-CD) with different degrees of substitution, onto strong anion-exchange stationary phases. The enantioselective potential and stability of newly prepared chiral stationary phases were examined using a set of structurally different chiral analytes. Measurements were performed in RP-HPLC. Mobile phases consisted of methanol/formic acid, pH 2.10, and methanol/10 mM ammonium acetate buffer, pH 4.00, in various volume ratios. SBE-β-CDs with degrees of substitution (DS) 4, 6.3, and 10 proved suitable for the enantioseparation of 14, 11, and 8 analytes, respectively. The SBE-β-CD DS 4 based chiral stationary phase enabled the enantioseparation of the nearly all basic and neutral compounds. Chiral stationary phases with higher sulfobutylether-β-cyclodextrin substitution (especially DS 10) yielded higher enantioresolution values for acidic compounds.

• Klíčová slova
• Chromatography, Degree of substitution, Dynamic coating, Enantioseparation, Sulfobutylether-β-cyclodextrin,
• MeSH
• beta-cyklodextriny chemie   MeSH
• chemické modely MeSH
• chromatografie s reverzní fází MeSH
• stereoizomerie MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• SBE4-beta-cyclodextrin MeSH Prohlížeč

Chiral ITP of the weak base methadone using inverse cationic configurations with H+ as leading component and multiple isomer sulfated β-CD (S-β-CD) as leading electrolyte (LE) additive, has been studied utilizing dynamic computer simulation, a calculation model based on steady-state values of the ITP zones, and capillary ITP. By varying the amount of acidic S-β-CD in the LE composed of 3-morpholino-2-hydroxypropanesulfonic acid and the chiral selector, and employing glycylglycine as terminating electrolyte (TE), inverse cationic ITP provides systems in which either both enantiomers, only the enantiomer with weaker complexation, or none of the two enantiomers form cationic ITP zones. For the configuration studied, the data reveal that only S-methadone migrates isotachophoretically when the S-β-CD concentration in the LE is between about 0.484 and 1.113 mM. Under these conditions, R-methadone migrates zone electrophoretically in the TE. An S-β-CD concentration between about 0.070 and 0.484 mM results in both S- and R-methadone forming ITP zones. With >1.113 mM and < about 0.050 mM of S-β-CD in the LE both enantiomers are migrating within the TE and LE, respectively. Chiral inverse cationic ITP with acidic S-β-CD in the LE is demonstrated to permit selective ITP trapping and concentration of the less interacting enantiomer of a weak base.

• Klíčová slova
• Capillary electrophoresis, Chiral separation, Computer simulation, Isotachophoresis, Sulfated cyclodextrin,
• MeSH
• beta-cyklodextriny chemie   MeSH
• inosintrifosfát chemie   MeSH
• izotachoforéza metody   MeSH
• kationty MeSH
• methadon * chemie   izolace a purifikace   MeSH
• počítačová simulace MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• inosintrifosfát MeSH
• kationty MeSH
• methadon * MeSH

For the first time, capillary electrophoresis has been successfully employed for the fast and highly efficient separations of a novel type of stereoisomers - planar rotamers (planamers) of four newly synthesized 5-nitrosopyrimidine derivatives. These derivatives can form two rotamers differing in the orientation of nitroso group due to strong intramolecular hydrogen bonds. Partial separation of rotamers of two 5-nitrosopyrimidines was achieved in alkaline 50 mM sodium tetraborate, pH 9.3, and in acidic 18.5/42 mM Tris/phosphate, pH 2.3, background electrolytes (BGEs) free of stereoselectors. To improve the separation of these rotamers and to attain the baseline or better separation of rotamers of other two 5-nitrosopyrimidines, various BGEs and different cyclodextrins-based stereoselectors were tested. The most effective, i.e. the fastest and baseline or better separations of rotamers of all analyzed 5-nitrosopyrimidines were achieved within a short time, 3.7-9.3 min, in the above alkaline or acidic BGEs using β-cyclodextrin (β-CD) or carboxymethyl-β-CD as stereoselectors. Moreover, since the experiments with β-CD resulted in good separations of rotamers of all the investigated 5-nitrosopyrimidines, the apparent binding constants of their complexes with this selector were determined from the dependence of their effective mobilities on the β-CD concentration in the BGEs. The examined complexes were found to be relatively weak, with the apparent binding constants in the range 11.3-153.0 L/mol.

• Klíčová slova
• 5-Nitrosopyrimidines, Affinity capillary electrophoresis, Binding constant, Capillary electrophoresis, Cyclodextrins, Planar rotamers,
• MeSH
• beta-cyklodextriny chemie   MeSH
• elektroforéza kapilární metody   MeSH
• elektrolyty MeSH
• koncentrace vodíkových iontů MeSH
• nitrososloučeniny analýza   chemie   izolace a purifikace   MeSH
• pyrimidiny analýza   chemie   izolace a purifikace   MeSH
• stereoizomerie MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• elektrolyty MeSH
• nitrososloučeniny MeSH
• pyrimidiny MeSH