In 1981, the macrocyclic methylene-bridged glycoluril hexamer (CB[6]) was dubbed "cucurbituril" by Mock and co-workers because of its resemblance to the most prominent member of the cucurbitaceae family of plants--the pumpkin. In the intervening years, the fundamental binding properties of CB[6]-high affinity, highly selective, and constrictive binding interactions--have been delineated by the pioneering work of the research groups of Mock, Kim, and Buschmann, and has led to their applications in waste-water remediation, as artificial enzymes, and as molecular switches. More recently, the cucurbit[n]uril family has grown to include homologues (CB[5]-CB[10]), derivatives, congeners, and analogues whose sizes span and exceed the range available with the alpha-, beta-, and gamma-cyclodextrins. Their shapes, solubility, and chemical functionality may now be tailored by synthetic chemistry to play a central role in molecular recognition, self-assembly, and nanotechnology. This Review focuses on the synthesis, recognition properties, and applications of these unique macrocycles.

The cucurbit[n]uril family

The Stability of Cyclodextrin Complexes in Solution.

The synthesis of 4-dialkylaminopyridines can be accomplished in two steps starting from pyridine. Compared to pyridine, these derivatives are approximately 104 times more active when used as acylation catalysts. Dialkylaminopyridines are being used with ever-increasing frequency for acylation reactions which proceed either incompletely or not at all in pyridine. This article reviews the various possible applications of 4-dialkylaminopyridines in terpene, steroid, carbohydrate and nucleoside chemistry as well as in the transformation of amino acids into α-acyl aminoketones and polymerization of isocyanates. In addition, N-substituted 4-dialkylaminopyridinium salts can be used for the transfer of sensitive groups to nucleophiles in aqueous medium. The exceptional catalytic effect of these derivatives, even in non-polar solvents, is due, in part, to the formation of high concentrations of N-acylpyridinium salts which are present in solution as loosely-bound, highly reactive ion pairs.

4-Dialkylaminopyridines as Highly Active Acylation Catalysts. [New synthetic method (25)]

Determination of Association Constants (Ka) from Solution NMR Data

The driving forces leading to the inclusion complexation of cyclodextrins were reviewed, which included the electrostatic interaction, van der Waalsinteraction, hydrophobic interaction, hydrogen bonding, release of conformational strain,exclusion of cavity-bound high-energy water, and charge–transferinteraction. It was shown that except for the release of conformation strain and exclusion of cavity-bound water, the otherinteractions were indeed contributive to the complex formation. However, it was concludedthat the enthalpy and entropy changes of the complexation were not good criteria to be used injudging whether a particular driving force was present or important, mainly because of theoccurrence of enthalpy-entropy compensation. On the other hand, the multivariate quantitativestructure-activity relationship analyses usually could illustrate which driving forces wereimportant in certain inclusion complexation systems.

The Driving Forces in the Inclusion Complexation of Cyclodextrins

Acutumine and acutumidine, chlorine containing alkaloids with a novel skeleton (1): X-ray analysis of acutumine.

The inclusion complex formation of α-cyclodextrin(α-CD) with various alcohols has been studied by means of titration calorimetry. The titration curve was analyzed successfully by the formation of a 1:1 hostguest complex, and the thermodynamic parameters were determined. The entropies of reaction are estimated from the statistical thermodynamics of molecules. However, the estimated values are found to deviate by an order of magnitude from the experimental ones. To resolve such a discrepancy, α-CD in solution is assumed to include a definite number(n) of water molecules which are replaced by a guest molecule with the progress of reaction. The entropies thus estimated depend extensively on the value of n, and a value of n is determined for each alcohol so that it reproduces just the experimental entropy. The resulting n values are nearly constant for various alcohols studied and are within a reasonable range expected from the data reported in crystal, supporting the model of interpretation.

Entropy Changes in the Inclusion Complex Formation of α-Cyclodextrin with Alcohols as Studied by the Titration Calorimetry

Circular dichroism (CD) and visible spectra of inclusion compounds between Methyl Orange (MO) analogues and α-, β-, γ-cyclodextrin (cdx), 2,6-dimethyl-and 2,3,6-trimethyl- β-cdx, water soluble α-, β-, γ-cdx polymer products were investigated. In the CD-spectroscopic investigation, the complex with α-cdx epichlorohydrin condensate showed a large amplitude and splitting of the induced π→π*band. Fractions of glyceryl ether of less than 2000 and polymer of more than 10000 dalton molecular mass were separated. Complexes of above two fractions and MO showed the same splitting spectral pattern. Job’s plots from visible spectra showed the formation of the 1:1 complex and CD-data suggested the co-existence of the 2:1 MO-cdx complex. This splitting pattern showed the reversal of the signs when α-cdx-ethyleneglycol-bis(epoxypropyl) ether was used and disappeared when larger host molecules and azo dyes were used. The splitting was explained by exciton interaction.

Spectroscopic Investigation of Cyclodextrin Monomers, Derivatives, Polymers and Azo Dyes (1)

The complex formation molar ratio of methyl orange and cyclodextrin, position and freedom of motion after inclusion were examined by nuclear magnetic resonance (NMR). 1) Methyl orange forms 1 : 1 complexes with α- and β-cyclodextrin. 2) Methyl orange is included predominantly from the N, N-dimethylamino group side. α-Cyclodextrin includes firmly methyl orange at the N, N-dimethylaniline side and β-cyclodextrin includes methyl orange at the benzenesulfonate side with little perturbation. 3) The data of 1H NMR showed that α- and β-cyclodextrin include methyl orange in the whole of the cavity and the results of 13C NMR showed that deformation at the linkage positions of glucose is detectable.

Inclusion Compound of Cyclodextrin and Azo Dye. I. Methyl Orange

Carbon-13 Nuclear Magnetic Resonance Spectroscopy. VI. Studies on Carbon-13 Magnetic Resonance Spectra in Aromatic and Heteroaromatic Systems.(2). On the Chemical Shifts of Substituted Pyridine Derivatives

Yoshio Sasaki

Papers

Acutumine and acutumidine, chlorine containing alkaloids with a novel skeleton (1): X-ray analysis of acutumine.

Entropy Changes in the Inclusion Complex Formation of α-Cyclodextrin with Alcohols as Studied by the Titration Calorimetry

Spectroscopic Investigation of Cyclodextrin Monomers, Derivatives, Polymers and Azo Dyes (1)

Inclusion Compound of Cyclodextrin and Azo Dye. I. Methyl Orange

Carbon-13 Nuclear Magnetic Resonance Spectroscopy. VI. Studies on Carbon-13 Magnetic Resonance Spectra in Aromatic and Heteroaromatic Systems.(2). On the Chemical Shifts of Substituted Pyridine Derivatives