Binding of Cyclodextrins to Alicyclic and Aromatic Substrates: Complex Formation of α-, β-, and γ-Cyclodextrins with Substituted Cyclohexanecarboxylic Acids and Phenylalkanoic Acids

Abstract

0 Complex binding constants of the three native cyclodextrins with seven cyclohexane derivatives (all possessing the carboxylic acid group) and with the series C 6 H 5 (CH 2 ) n COOH (n ) 0 to 4) were measured in aqueous solution at 25°C by potentiometry and the solubility method. These results, combined with literature data, indicate that R-and γ-cyclodextrins bind with comparable strength to both the cyclohexyl and phenyl moieties, with -cyclodextrin binding significantly more strongly. These acid series are compared with several series CH 3 (CH 2 ) n X, where X is CH 3 , COOH, COO -, OH, SO 3 -, etc., and it is concluded that the X group (for X other than methyl) contributes appreciably to complex stability, perhaps by means of an extracavity interaction. The COOH group provides a further augmentation of complex stability. NMR CIS and ROESY results indicate the presence of isomeric complexes in both the cyclohexyl and phenylalkanoic series, and clearly demonstrate the existence of intracavity inclusion. An NOE study of the R-cyclodextrin: cyclohexanecarboxylate system provides evidence for inclusion combined with interaction outside (that is, at the rim of) the cavity.Intense interest in cyclodextrin chemistry in recent years has resulted in the measurement of hundreds of binding constants for complexes comprised of cyclodextrins and aromatic guest molecules. Few systematic investigations into the cyclodextrin binding properties of alicyclic compounds have been made (though some useful results are available 1-12 ). In the present paper we augment these relatively few examples of alicyclic guest systems by examining the binding of the three "native" cyclodextrins (R-, -, and γ-cyclodextrin) with some alicyclic carboxylic acids and, for comparison purposes, some phenylalkanoic acids. These binding studies are supported by nuclear magnetic resonance (NMR) investigations of some of these systems. Experimental SectionMaterialssR-Cyclodextrin, -cyclodextrin, and γ-cyclodextrin (American Maize Products Company) were dried at 95°C for 48 h. Benzoic acid (Aldrich) was recrystallized from water; and phenylalkanoic acids (Aldrich) were recrystallized from water-methanol, their melting points being in good agreement with literature values. 3-Cyclohexenecarboxylic acid (Alfa) and the cyclohexane carboxylic acids (Aldrich) were purified by distillation under reduced pressure. House reverse-osmosis water was further treated with a Sybron/ Barnstead PCS ion-exchange purification system.ApparatussPotentiometric measurements were made with an Orion model 701A pH meter and a Corning semi-micro combination electrode. Spectrophotometric measurements were made with a Hitachi model U-3000 spectrophotometer. The solutions were thermostatted during potentiometric and spectrophotometric measurements at 25°C by means of an external, constant-temperature water bath.NMR experiments were carried out at 500 MHz with a Bruker DRX-500 spectrometer at 303 K with D2O as solvent.ProceduressPotentiometrysThe experimental operation consists of mea...

Influence of neutral cyclodextrin concentration on plate numbers in capillary electrophoresis

“…The benzoate K 0 was reported as 18.9 + 0.8 [46], 23 [54], and 42 + 1 [55]; our determination of 40 + 2 agrees well with the latter. The K 0 -values of DANS LLeu and DANS L-Asp were reported as 200 and 140, respectively [56]; our determinations of 201 + 3 and 132 + 3, respectively, closely agree with them.…”

Supramolecular Complex Formation: A Study of the Interactions between β‐Cyclodextrin and Some Different Classes of Organic Compounds by ESI‐MS, Surface Tension Measurements, and UV/Vis and 1H NMR Spectroscopy

“…All solutions were pre-pared in a 0.1 mol·L Ϫ1 Na 2 CO 3 buffer adjusted to pH 10.6. To determine the binding constants the concentration of phenolphthalein was 2 ϫ 10 Ϫ5 mol·L Ϫ1 in all experiments; the concentration of β-CD was kept constant at 3 ϫ 10 Ϫ4 mol·L Ϫ1 and the concentrations of surfactants [SDS, C n PNa 2 (n ϭ 8, 12,14) and C 18 P∆C 9Ϫ10 Na 2 ] were changed within a significant range (0Ϫ1 ϫ 10 Ϫ2 mol·L Ϫ1 ). The concentration of surfactant was always kept below the critical micellar concentration (see CMC values in the presence of β-CD in Table 2).…”

“…[10,11] Despite the great amount of work about the inclusion phenomena, relatively few data on the properties of such complexes are available. It should be remarked that it is possible, through changing the structures of the host and of the guest molecules in a systematic manner, to correlate the chemical structure of the species involved with their binding affinities [12,13] and general properties. [4] We now present some results on the interactions between β-CD and a series of linear alcohols [saturated (1) and unsaturated (2), such as oleyl alcohol as a typical (Z) isomer], the corresponding phosphate esters (alkylmonophosphoric acids 3 and 4) and their sodium salts (5 and 6), as well as some commercial surfactants with very different chemical structures [tetradecyldimethylamine oxide (7, C 14 DMAO, zwitterionic), sodium dodecylsulfate (8, SDS, anionic) and cetyltrimethylammonium bromide (9, CTABr, cationic)] characterized by hydrophobic appendices of different lengths and degree of unsaturation, with both charged and uncharged head groups, in order to evaluate the influence of the structure of the head group on the complexation (Figure 1).…”

Molecular Modelling and 1H-NMR: Ultimate Tools for the Investigation of Tolbutamide: .BETA.-Cyclodextrin and Tolbutamide: Hydroxypropyl-.BETA.-Cyclodextrin Complexes.

“…These techniques have been used as important tools for investigating the conformation of the most favored complexes and to obtain a better knowledge of the geometry of the system and the topology of the interactions between guest and CDs. [13][14][15][16][17] Therefore in the present study we coupled these techniques, which allowed us to compare and to integrate the theoretical findings obtained in a vacuum (molecular modelling) with the experimental data ( 1 H-NMR) to gain insight into the mode of inclusion and to clarify the most probable conformation of the TBM : CD complexes in aqueous medium. …”