Alkylation of cyclomaltohexaose (α-cyclodextrin, α-CD) with allyl or cinnamyl bromide, followed by peracetylation of remaining hydroxyl groups and separation of isomers, resulted in the set of peracetylated 2(I)-O-, 3(I)-O- and 6(I)-O-alkylated α-CDs in up to 27% yields. Ozonolysis or oxidative cleavage of peracetylated allyl or cinnamyl derivatives resulted in a complete set of peracetylated 2(I)-O-, 3(I)-O- and 6(I)-O-formylmethyl or carboxymethyl derivatives that are useful precursors for preparation of regioselectively monosubstituted derivatives of α-CD. Moreover, a quick method to recognize single 2(I)-O-, 3(I)-O- and 6(I)-O-monosubstituted peracetylated CDs from one another using only their (1)H NMR spectra has been proposed.
- MeSH
- acetylace MeSH
- aldehydy chemická syntéza MeSH
- alfa-cyklodextriny chemická syntéza chemie izolace a purifikace MeSH
- alkylace MeSH
- katalýza MeSH
- kyseliny karboxylové chemická syntéza MeSH
- magnetická rezonanční spektroskopie MeSH
- oxidace-redukce MeSH
- síran měďnatý chemie MeSH
- sloučeniny ruthenia chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The acylation of prednisolone 20-hydrazone with star poly(ethylene glycol) tetracarboxylic acid (M = 20,000) has been used to prepare the corresponding pH-sensitive conjugate. With α-cyclodextrin, this conjugate forms a polypseudorotaxane, which was characterised by means of (1)H NMR spectra, powder X-ray diffraction patterns and STM microscopy. The rate of acid-catalysed hydrolysis of the conjugate was studied under in vitro conditions in model media of hydrochloric acid solutions, phosphate and acetate buffers (pH 2-5.8). The acid-catalysed hydrolysis (at pH 2) of the polypseudorotaxane was ca 3.5 times slower than that of the original conjugate. After 1h in this medium, 86% of the covalently attached prednisolone remained unchanged. The prepared polypseudorotaxane represents a promising peroral transport system of prednisolone with a pH-sensitive linker with delayed acid-catalysed hydrolysis thanks to protection at the molecular level using α-cyclodextrin.
- MeSH
- alfa-cyklodextriny chemická syntéza chemie farmakokinetika MeSH
- gely MeSH
- glukokortikoidy chemie MeSH
- hydrazony chemie MeSH
- koncentrace vodíkových iontů MeSH
- lékové transportní systémy MeSH
- polyethylenglykoly chemická syntéza chemie farmakokinetika MeSH
- pomocné látky MeSH
- prednisolon analogy a deriváty chemická syntéza chemie farmakokinetika MeSH
- příprava léků metody MeSH
- rotaxany chemie MeSH
- stabilita léku MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The reaction of α-amino-ω-methoxypoly(ethylene glycol) [M = 5000] or star α-amino-poly(ethylene glycol) [M = 20 000] with hemiesters of prednisolone dicarboxylic acids (succinic, glutaric, adipic, phthalic acid) has been used to prepare the corresponding conjugates. The rate of esterase catalyzed hydrolysis of the conjugates is controlled by the molecular mass of poly(ethylene glycol) and the length of the linker between prednisolone and poly(ethylene glycol) (τ(1/2)∼ 5-0.5 h). The enzymatic hydrolysis proceeds most rapidly at conjugates with linkers derived from adipic and phthalic acids. The synthesized conjugates form polypseudorotaxanes with α-cyclodextrin which were characterized by 2D NOESY NMR spectra, powder X-ray diffraction patterns and in one case also by STM microscopy. In the case of the polypseudorotaxane having the linker derived from adipic acid, the enzymatic release proceeds ca. five times slower in comparison with the rate of prednisolone release from the corresponding conjugate. The rate of prednisolone release from the carrier can be controlled by three factors: character of the linker between the polymeric carrier and prednisolone, the molecular mass of poly(ethylene glycol) and complex formation with α-cyclodextrin. The synthesized polypseudorotaxanes represent new promising transport systems intended for targeted release of prednisolone in transplanted liver.
n background electrolyte (BGE) with the optimal methanol concentration of 30% (v/v), the ion with -NCS group bonded to a cluster boron atom exhibits the strongest interaction with alpha-cyclodextrin and the highest separation selectivity. Interaction of ions with alkyl or thioalkyl group weakens with the increasing substituent size. The ion with phenyl group exhibits the weakest interaction. Bonding of a group to boron atom weakens the ion interaction with alpha-cyclodextrin. Second substituent further weakens the interaction with alpha-cyclodextrin. Separation efficiency is lower at the presence of alpha-cyclodextrin than at its absence. This separation efficiency loss, amounts up to 90%.
Eight phenolic acids were analyzed by capillary zone electrophoresis. On-line analyte preconcentration was carried out by hydrodynamic injection of large volume of sample followed by removal of the bulk of the low conductivity sample matrix by polarity switching. The optimal electrolyte system consisted of 50mM sodium tetraborate of pH 9.0 (adjusted with 0.1 M phosphoric acid) containing 2% of alpha-cyclodextrin. The separations were carried out with a fused silica capillary (effective length 50 cm, i.d. 50 microm) and monitored at 200 nm. Under optimized preconcentration conditions (sample injection 99 s at 100 mbar and the polarity switching time 1.0 min) linear calibration ranges (0.1-2.0 microg/ml, R=0.9979-0.9995), favourable limits of detection (0.01-0.025 microg/ml) and good repeatability of the peak areas (R.S.D.: 2.76-5.69%, n=6) were achieved.
- MeSH
- alfa-cyklodextriny chemie MeSH
- aminokyseliny chemie MeSH
- chemické modely MeSH
- krystalografie rentgenová metody MeSH
- molekulární konformace MeSH
- molekulární modely MeSH
- nanotechnologie metody MeSH
- nanotrubičky chemie MeSH
- organická chemie metody MeSH
- peptidy chemie MeSH
- vodíková vazba MeSH
- Publikační typ
- práce podpořená grantem MeSH
