Complexation
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A novel approach to inducing anion transport over the dialytic membrane was proposed and successfully tested using the dihydrogen phosphate anion. The anion receptor based on isophthalamide was anchored on a dendritic skeleton, resulting in a macromolecular structure with a limited possibility to cross the dialytic membrane. The dendritic receptor was placed in a compartment separated from a mother anion solution by a membrane. The resulting anion complexation reduced the actual concentration of the anion and induced the anion transfer across the membrane. The anion concentration in mother solution decreased, while it was found to be increased in the compartment with the dendritic receptor. This phenomenon was observed using dendritic receptors with four and eight complexation sites. A detailed analysis of a series of dialytic experiments by 1H NMR spectroscopy enabled an assessment of the complexation behavior of both receptors and an evaluation of the dendritic effect on the anion complexation.
- Publikační typ
- časopisecké články MeSH
Byla stanovena rozpustnost nového antileukotrienického léčiva quinlukast (kyselina 4-{[4-(2-chinolylmethoxy) fenyl]sulfanyl}benzoová) ve vodě a ve vodných roztocích α-cyklodextrinu (α-CD), ß-cyklodextrinu (ß-CD), hydroxypropyl-ß-cyklodextrinu (HP-ß-CD, průměrný stupeň substituce 0,8) a methyl-ß-cyklodextrinu (M-ß-CD, průměrný stupeň substituce 1,8). Stanovená rozpustnost quinlukastu ve vodě byla 0,081±0,008 mmol/l (3,12±0,30 mg/100ml) a v roztocích ß-CD se pozorovalo pouze nevýznamné zvýšení rozpustnosti quinlukastu. Tři dobře rozpustné cyklodextriny však byly solubilizačně účinné, ve vodných roztocích s nevelkou koncentrací cyklodextrinu 5 g/100 ml se pozorovalo 12násobné zvýšení rozpustnosti quinlukastu v případě M-ß-CD a 10násobné zvýšení rozpustnosti v případě HP-ß-CD a α-CD. Byly stanoveny fázové diagramy rozpustnosti quinlukastu ve vodných roztocích těchto cyklodextrinů (do 0,05 mol/l). V případě M-ß-CD a HP-ß-CD byly diagramy rozpustnosti lineární (AL) a odpovídaly tvorbě rozpustného inkluzního komplexu quinlukast–cyklodextrin 1:1, s vyhodnocenými konstantami stability K11 300±35 l/mol (M-ß-CD) resp. 260± 30 l/mol (HP-ß-CD). Fázový diagram rozpustnosti quinlukastu ve vodných roztocích α-CD se vyznačoval výraznou pozitivní odchylkou od linearity (AP), solubilizační účinnost zředěných roztoků α-CD byla poměrně nízká, avšak progresivně vzrůstala s koncentrací α-CD. Při celkovém hodnocení se cyklodextriny α-CD, HP-ß-CD a M-ß-CD ukázaly být vhodnými solubilizéry quinlukastu do vodného roztoku.
Solubility of the new antileukotrienic drug quinlukast (4-{[4-(2-quinolylmethoxy)phenyl]sulfanyl}benzoic acid) was determined in water and in aqueous solutions of α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), hydroxypropyl- β-cyclodextrin (HP-β-CD, average degree of substitution 0.8), and methyl-β-cyclodextrin (M-β-CD, average degree of substitution 1.8). The determined solubility of quinlukast in water was 0.081±0.008 mmol/l (3.12± 0.30 mg/100ml) and only an insignificant increase in quinlukast solubility was observed in aqueous solutions of β-CD. However, three well soluble cyclodextrins showed a marked solubilizing effect, in aqueous solutions with a moderate cyclodextrin concentration 5 g/100ml, a 12-fold increase in quinlukast solubility was observed in the case of M-β-CD, and a 10-fold increase in the case of both HP-β-CD and α-CD. Phase solubility diagrams of quinlukast in aqueous solutions of these cyclodextrins (up to 0.05 mol/l) were determined. In the cases of M-β-CD and HP-β-CD, the solubility diagrams were linear (AL) and they corresponded to the formation of a soluble inclusion complex quinlukast – cyclodextrin 1:1 with the evaluated stability constants K11 300±35 l/mol and 260±30 l/mol for M-β-CD and HP-β-CD, respectively. The phase solubility diagram of quinlukast in aqueous solutions of α-CD showed a marked positive deviation (AP) from linearity, the solubilization efficiency of dilute α-CD solutions was relatively low but it increased progressively with the increasing α-CD concentration. In the overall evaluation, the cyclodextrins α-CD, HP-β-CD and M-β-CD appeared to be suitable for the quinlukast solubilization into aqueous solutions.
The repetition of urea-based binding units within the receptor structure does not only lead to monomer properties multiplication. As confirmed by spectroscopic studies, UV-Vis and 1H-NMR in classical or competitive titration mode, the attachment to a carrier allocates the active moieties to mutual positions predetermining the function of the whole receptor molecule. Bivalent receptors form self-aggregates. Dendritic receptors with low dihydrogen phosphate loadings offer a cooperative complexation mode associated with a positive dendritic effect. In higher dihydrogen phosphate concentrations, the dendritic branches act independently and the binding mode changes to 1:1 anion: complexation site. Despite the anchoring, the dendritic receptors retain the superior efficiency and selectivity of a monomer, paving the way to recyclable receptors, desirable for economic and ecological reasons.
- MeSH
- magnetická rezonanční spektroskopie * MeSH
- molekulární modely MeSH
- sulfonamidy * MeSH
- Publikační typ
- časopisecké články MeSH
Electrospray ionization was used as a technique for the characterization of the interactions between cadmium(II) ions and malic acid (1) in aqueous solution. Particular attention was paid to the nature of the species formed, which generally correspond to complexes of CdX(+) cations with neutral malic acid, where X either is the counterion of the metal salt used as a precursor (i.e. X=Cl, I) or corresponds to singly deprotonated malic acid. In pure water solutions, also highly coordinated complexes [Cd(1-H)(1)(2)](+) and [CdCl(1)(2)](+) were detected, whereas the most abundant complexes detected in a sample of soil solution were: [Cd(1-H)(1)](+) and [CdCl(1)](+). With respect to possible application in environmental analysis, the effects of (i) metal salts present in solution, (ii) modest mineralization, and (iii) the matrices of real soil solutions were probed. While the presence of other metals leads to additional complexes, the characteristic species containing both cadmium(II) and malic acid can still be detected with good sensitivity.
Electrospray ionization mass spectrometry (ESI-MS) is used to probe the complex formation between tebuconazole (1) and copper(II) salts, which both are commonly used fungicides in agriculture. Experiments with model solutions containing 1 and CuCl(2) reveal the initial formation of the copper(II) species [(1)CuCl](+) and [(1)(2)CuCl](+) which undergo reduction to the corresponding copper(I) ions [(1)Cu](+) and [(1)(2)Cu](+) under more drastic ionization conditions in the ESI source. In additional experiments, copper/tebuconazole complexes were also detected in samples made from soil solutions of various origin and different amount of mineralization. The direct sampling of such solutions via ESI-MS is thus potentially useful for understanding of the interactions between copper(II) salts and tebuconazole in environmental samples.
Long-term delivery of growth factors and immunomodulatory agents is highly required to support the integrity of tissue in engineering constructs, e.g., formation of vasculature, and to minimize immune response in a recipient. However, for proteins with a net positive charge at the physiological pH, controlled delivery from negatively charged alginate (Alg) platforms is challenging due to electrostatic interactions that can hamper the protein release. In order to regulate such interactions between proteins and the Alg matrix, we propose to complex proteins of interest in this study - CXCL12, FGF-2, VEGF - with polyanionic heparin prior to their encapsulation into Alg microbeads of high content of α-L-guluronic acid units (high-G). This strategy effectively reduced protein interactions with Alg (as shown by model ITC and SPR experiments) and, depending on the protein type, afforded control over the protein release for at least one month. The released proteins retained their in vitro bioactivity: CXCL12 stimulated the migration of Jurkat cells, and FGF-2 and VEGF induced proliferation and maturation of HUVECs. The presence of heparin also intensified protein biological efficiency. The proposed approach for encapsulation of proteins with a positive net charge into high-G Alg hydrogels is promising for controlled long-term protein delivery under in vivo conditions.
- MeSH
- algináty chemie MeSH
- chemokin CXCL12 chemie MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- fibroblastový růstový faktor 2 chemie MeSH
- heparin chemie MeSH
- lidé MeSH
- mikrosféry MeSH
- nádorové buněčné linie MeSH
- tkáňové inženýrství MeSH
- vaskulární endoteliální růstový faktor A chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- MeSH
- chelátory chemie MeSH
- diabetes mellitus farmakoterapie MeSH
- EDTA analogy a deriváty chemie MeSH
- finanční podpora výzkumu jako téma MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
- magnetická rezonanční spektroskopie MeSH
- molybden chemie MeSH
- potenciometrie MeSH
- pyridony chemie MeSH
- spektrofotometrie MeSH
- Publikační typ
- srovnávací studie MeSH
Two novel methods for determination of binding constants in the systems with borate and cyclodextrin complexation were developed. The methods enable to determine all binding parameters in these systems and even the binding constants of interaction of a neutral analyte with a neutral cyclodextrin. The first method is based on nonlinear fitting of experimental data and further evaluation of fitting parameters. The second method requires a multiple regression. The methods provide identical results with low experimental error. Only one set of measurements is required for both methods. Thus the binding parameters can be mutually compared. The binding parameters for neutral analytes ((R,R)-(+)-hydrobenzoin and (S,S)-(-)-hydrobenzoin) and neutral cyclodextrin (heptakis(2,6-di-O-methyl)-β-cyclodextrin) were evaluated and the effect of individual types of interaction was revealed. The interaction of the analytes with cyclodextrin governs the chiral recognition, while the complexation of analyte with borate is responsible for electromigration. Very low values of the binding constants of mixed analyte-cyclodextrin-borate complexes indicate that this type of complexation has negligible effect on enantioseparation.
