Apolar Cavity Research Articles

Studies of cyclodextrin inclusion complexes. I. The salbutamol-cyclodextrin complex as studied by phase solubility and DSC

Cyclodextrins (CYDs) are cyclic non-reducing oligosaccharides built up from six, seven or eight glucopyranose units (α-, β- or γ-CYD, respectively). Many drugs are able to form an inclusion complex with CYDs, being trapped entirely or at least partially into their slightly apolar cavities. Complexes of CYDs and salbutamol were obtained in both the liquid and solid state. The influence of both temperature and CYD concentration on complex solubility was studied using the method of Higuchi and Connors ( Adv. Anal. Chem., 4 (1965) 117–212). This is based on monitoring changes in the solubility of substrate (salbutamol) on the addition of complexing agents (α-, β-, Me-β- and γ-CYD). The rate of increase in substrate solubility with CYD concentration varied with the type of CYD used (Me-β->β-⪢γ->α-CYD). As salbutamol is water soluble and an A L type diagram is obtained, the solid complex was prepared by freeze-drying (lyophilization). In order to confirm solid complex formation, differential scanning calorimetry (DSC) was used. When guest molecules are incorporated in the CYD cavity, their melting, boiling or sublimation points usually shift to a different temperature or disappear within the temperature range where the CYD is decomposed. The thermograms obtained showed an endothermic peak for the freeze-dried salbutamol and for the physical mixture (salbutamol and β-CYD both freeze-dried) which was eliminated for the inclusion complex.

2,2′,7,7′‐Tetrahydroxy‐1,1′‐Binaphthyl: A Versatile Chiral Spacer for Monotopic and Ditopic Cyclophane Hosts with Apolar Binding Sites

AbstractDerivatives of 2,2′,7,7′‐tetrahydroxy‐1,1′‐binaphthyl (5) are synthetically readily available chiral shapes with a major and a minor groove. Previous work by Cram et al. has shown that efficient chiral crown ether binding sites can be constructed at the binaphthyl minor groove. The major groove is almost twice as wide and possesses suitable dimensions to shape flat apolar binding sites in chiral cyclophane hosts. The eight‐step syntheses of the two novel cyclophanes 6 and 7 are described. The apolar cavities of these hosts are formed by bridging with two linear four‐carbon chains the 7,7′‐oxygens at the major groove of 5 to the two phenolic oxygens of a 4,4‐bis(4‐hydroxy‐3,5‐dimethylphenyl)piperidine unit. 1H NMR complexation studies show that 1:1 complexes of 6 and 7 with 6‐methoxy‐2‐naphthonitrile and other naphthalene derivatives in aqueous methanol are as stable as the previously reported complexes of bis(diphenylmethane)‐hosts. The different solvation characteristics of cation and apolar binding are demonstrated with the ditopic host 7. In addition to the apolar binding site at the major groove, 7 also possesses a crown ether binding site at the minor groove of the binaphthyl spacer. By changing the methanol content of a water‐methanol mixture, this host can be switched from an efficient binder of neutral naphthalene guests to a good host for potassium cations. The activities of the two binding sites in 7 are almost entirely independent of each other; consequently, the binding of a naphthalene guest in the 1:1:1 (host‐naphthalene‐K+) complex is nearly as strong as in the 1:1 complex. The methyl ester of (S)‐naproxen forms stable complexes with the racemic hosts 6 and 7. The 1H NMR spectra of these complexes show considerably different shifts for the aromatic resonances of the host enantiomers. These differences indicate the formation of diastereomeric complexes of different geometries or stabilities.

Crystal and molecular structure of a crown-bridgedp-t-butyl-calix[4]arene (1:1) pyridine complex. Host-guest interaction model based on molecular mechanics analysis [1

The crystal and molecular structure of a crownedp-t-butyl-calix[4]arene (1:1) pyridine complex is reported. Colourless transparent prismatic crystals (obtained from pyridine) C54H74O8·C5H5N,a=13.486(4),b=15.193(4),c=16.432(5) A, β=116.44(4)°, space groupP21,Z=2,D calc=1.02g cm−3, CuK α radiation λ=1.5418 A μ(CuK α)=4.99 cm−1. Refinement was carried out using 1702 reflections withI>3σ(I) toR 0.12. The macrocycle shows a distorted cone conformation which defines an intramolecular apolar cavity whose elliptical aperture is 11.5×8.6 A calculated as distances between the two opposite central C atoms of the Bu t groups. A molecule of pyridine is included in this cavity, whereas the intermolecular cavities of the host lattice remain empty. The influence of the guest molecule on the conformation of the calixarene-crown is discussed. Potential energy calculations are performed in order to understand the nature of the host-guest interactions responsible for the stabilisation of the complex. Evidence for stabilizing CH3-π interactions are obtained from the calculations.