Diverse associations in the ternary systems of ß-cyclodextrin, simple carbohydrates and phenyl derivatives of inorganic oxoacids.

Complex formation reactions of phenylboronic, phenylphosphonic, phenylarsonic and 4-aminophenyl arsonic acids with ß-cyclodextrin (cycloheptaamylose, ß-CD) and some simple carbohydrates (mannitol, sorbitol, glucose) have been studied using spectrophotometric, potentiometric methods and solubility measurements, supplemented with HPLC and IR analyses of the solid samples. Equilibrium constants have been determined at ionic strength of 0.2M (NaCl) and 25°C. ß-CD forms the most stable complexes with the neutral, undissociated forms of the acids, the stability constants are as follows: phenylboronic acid: 320 ± 36, phenylphosphonic acid: 108 ± 25, phenylarsonic acid: 97 ± 4 and 4-aminophenyl arsonic acid: 107 ± 10. The stability constants for the ß-CD-complexes of the ionic forms are much lower. Ternary complexes of low stability could be detected in the case of phenylphosphonic acid and sorbitol with the undissociated form and with glucose and the dianion. In more concentrated solutions phenylboronic acid forms insoluble complexes with mannitol, sorbitol and ß-CD. The solid phases obtained in the ternary systems are predominantly mixtures of ester type 3:1 complexes with the carbohydrate and 1:1 inclusion complex with the ß-CD. No significant interaction has been found with glucose. The phenomena can be explained by the differences in the structures of the components and by the changes in the H-bonding network of ß-CD on the complex formation.

Cyclodextrin/imatinib complexation: binding mode and charge dependent stabilities.

Host-guest interactions in various protonation forms of the anticancer drug imatinib with beta-cyclodextrin (CD) and randomly methylated beta-CD (RAMEB) have been investigated using techniques of proton magnetic resonance spectroscopy ((1)H NMR), phase solubility, pH-potentiometry and electrospray ionization mass spectrometry (ESI-MS). Phase-solubility analysis showed A(L)-type diagram with beta-CD, which suggested the formation of 1:1 inclusion complexes. The 1:1 stoichiometry was confirmed by potentiometry in aqueous solution and by ESI-MS in the gas phase. Charge-specific stability constants of the neutral, mono-, di-, and tricationic forms of imatinib were determined for both the beta-CD and RAMEB. Stability of the beta-CD complexes shows an unexpected minimum at the monoprotonated form, while a stepwise decrease with increasing guest charge was observed for RAMEB. The 1:1 complex stoichiometry and stability constants of selected imatinib protonation species were verified by (1)H NMR titrations. Two-dimensional rotating frame nuclear Overhauser effect spectroscopy (ROESY) experiments were carried out to identify the interacting host-guest moieties. The observed ROESY cross-peaks indicated spatial proximities between several aromatic hydrogens of imatinib and beta-CD protons, revealing that the inclusion occurs by accommodation of the benzamide ring of imatinib.

Cyclodextrin assisted nanophase determination of alkaloid salts.

The poor water solubility of the free base and the high dissociation constant (K(a)) hinder mainly the assay of alkaloid salts. We have elaborated an environment friendly method that can be carried out in aqueous media. The stability difference of the cyclodextrin (CD) complexes of free and protonated bases were used for this purpose. The base is included into the hydrophobic cavity of the CD (which serves as an apolar solvent phase on molecular level) and its solubility in water is increased. Since the base forms more stable inclusion complex than its protonated species, the pK(a) is decreased and the potentiometric titration is promoted by this way, too. Six different hydrohalide alkaloid salts have been investigated and the most appropriate CDs were chosen (depending on the size of the molecules and/or substituents). The results of the assays agree well with those obtained by the direct nonaqueous titrations. The stability constants of the inclusion complexes have been also computed.

[The background of acid-base interactions in nonaqueous solvents--an analytical approach]. / A nemvizes közegú reakciók elvi háttere az analitikai kémia szemszögéból.

The acid-base determination of different substances by non-aqueous titrations is highly preferred in pharmaceutical analyses since the method is quantitative, exact and well reproducible. The modern interpretation of the reactions in nonaqueous solvents started in the past century, but several inconsistencies and unsolved problems can still be found in the literature. The acid-base theories of Brönsted-Lowry and Lewis as well as the so-called solvent theory are outlined first, then the promoting (and levelling) and the differentiating effects are discussed on the basis of the hydrogen bond concept.