Phenol, cyclodextrin inclusion complexes

Cyclodextrins have had valuable industrial uses for a considerable time, particularly as agents to bind or release volatile molecules. Accurate predictions concerning the selectivity and stability of cyclodextrin-guest complexes are therefore of considerable interest both academically and practically." MD was used to simulate cyclodextrin hydrates" as a test of the applicability of the GROMOS program package to systems beyond proteins and nucleic acids. Other early MD simulations focused on interactions with guests such as enantiomers of methyl-2-chloropropionate. Comparisons between calculated thermodynamic properties for complexes formed by O -cyclodextrin with para-substituted phenols and the results of MM simulations led to improvements in force fields that described the interactions. MM2 simulations were used to support NMR data for the -cyclodextrin inclusion complex with benzoic acid. " The well-known catalytic effect of cyclodextrins has been modeled. For example, the relative rate increase of hydrolysis of S over R phenyl ester stereoisomers in the presence of -cyclodextrin... 

The results were simple and clear-cut Only the two terms ofa° and Emin were involved for the a-cyclodextrin systems, and the two terms of k and Emin, for (S-cyclodextrin systems. This means that the stabilities of the inclusion complexes are mainly governed by the electronic and steric interactions in a-cyclodextrin systems and by the hydro-phobic and steric interactions in (i-cyclodextrin systems, regardless of the position of the substituents in the phenols. These observations agree well with those by Harata23), who showed that there is no appreciable difference in thermodynamic parameters between cyclodextrin complexes of m- and p-di substituted benzenes and that the contribution of the enthalpy term to the complexation is more significant in a-cyclodextrin systems than in P-cyclodextrin systems, where the inhibitory effect... 

Only the hydrophobic and steric terms were involved in these equations. There are a few differences between these equations and the corresponding equations for cyclo-dextrin-substituted phenol systems. However, it is not necessarily required that the mechanism for complexation between cyclodextrin and phenyl acetates be the same as that for cyclodextrin-phenol systems. The kinetically determined Kj values are concerned only with productive forms of inclusion complexes. The productive forms may be similar in structure to the tetrahedral intermediates of the reactions. To attain such geometry, the penetration of substituents of phenyl acetates into the cyclodextrin cavity must be shallow, compared with the cases of the corresponding phenol systems, so that the hydrogen bonding between the substituents of phenyl acetates and the C-6 hydroxyl groups of cyclodextrin may be impossible. 

Certain fundamental characteristics of MECC that influence retention have been investigated (5). The technique has been used in the analysis of a variety of samples including phenolic compounds (1), phenylthiohydantoin—amino acids (6), and metabolites of vitamin Bg (7). In related electrokinetic separation techniques, substituted benzene compounds have been separated based on the formation of inclusion complexes with an ionic cyclodextrin derivative in the mobile phase (8) and polyaromatic hydrocarbons have been separated based on solvophobic interactions with a tetraakyl— ammonium ion in the mobile phase (9). The effects of injection procedures on efficiency have also been studied (10). 

FIGURE 1 Molecular structures of I, II, and a-cyclodextrin (a-CD) alkoxide. Schematic representation of the inclusion complexes and reaction intermediates involved in the hydrolysis of I affording acetic acid and m-ferf-butyl phenol. The inset shows the CAChe-minimized structure of the ternary catalytic complex I C a-CD alkoxide-ll proposed by Bender et al. (7S). The putative hydrogen bond between the alkoxide of a-CD and II is indicated by a solid line. a-CD alkoxide is shown in stick representation, and only polar hydrogen atoms are specified. I is shown in CPK representation and II in ball and stick. (See Color Insert in the back of this book.)... 

Phenolic compounds form inclusion complexes with a-cyclodextrin (85), enhancing the fluorescent properties of the aromatic analytes. For example, p-hydroxybenzoic acid (86a),... 

Cyclodextrins. Cyclodextrins (CD s) form inclusion complexes with various aromatic compounds (58), including cinnamic acid (59). Complexation of the phenolic substrates of PPO by CD s might... 

Recent work indicates that the anion of the 3-hydroxyl group rather than the anion of the 2-hydroxyl group is the nucleophile. NMR studies of phenol-inclusion complexes [46] and the determination that the tosylation reaction of cyclodextrin takes place under basic conditions [47] lead to the conclusion that substitution occurs exclusively at the 3-position. 

Nevertheless, using the 1,8-ANS (5) method, with ANS as a guest, fluorescence increases with 10 and 11 and therefrom complex formation constants have been obtained, which are remarkably higher than that of the cyclodextrins and of open chained reference host compounds. The complex constants of 10 towards the hydroxy-naphthalene carboxylates 13 and 14 as guests have also been determined The authors suppose the intermediate formation of inclusion complexes also because of the capability of 10 and especially 12 to accelerate the hydrolysis of chloroacetic acid phenolates in water solution. The increase of the hydrolysis rate is explained by the activation of the complexed esters. 

The structure of the ternary inclusion complex composed of 3-cyclodextrin, phenol, and, chloroform or carbon tetrachloride, formed in the reaction mixture, is determined by NMR spectroscopy. The selective catalysis by cyclodextrin was attributed to the regulation of molecular conformation of substrates with respect to dichlorocarbene, to trichloromethy1 cation, or to allyl cation in the ternary molecular complex. 

Formylations of phenol, resorcinol and indole, dichloromethylations of 4-methylphenol and 5,6,7,8-tetrahydro-2-naphthol, carboxylation of phenol, and allylation of 2,4,6-trimethylphenol proceed site-selec-tively in high yields by using 3-cyclodextrin as catalyst. The formation of ternary inclusion complex composed of cyclodextrin, substrate, and dichlorocarbene, trichloromethyl cation or allyl cation in the reaction mixture is an important factor of the site-selective reactions. The cyclodextrin is also effective by limiting the molecular size of the reaction intermediate. 

Lignin-related polymers were synthesised. Coniferyl alcohol (4-hydroxy-3-methoxycinnamyl alcohol, CoA), a phenolic lignin monomer (monolignol) contained in plant cell walls, was polymerised in the presence of a-cyclodextrin (a-CD) in a HRP/H2O2 system. The presence of a-CD led to the product polymer containing 8-0-4 -richer linkages, compared with the no-additive case. This is probably due to the inclusion complex formation between CoA and a-CD, which suppresses other linkages such as 8-5 and 8-8, due to the steric hindrance of the complex [179]. 

Nishioka and Fujita 78> have determined the Kd values for a- and P-cyclodextrin complexes with m- and p-substituted phenols at pH 7.0. Taking into account the directionality in inclusion of a guest molecule, they assumed three and two probable orientational isomers for the cyclodextrin complexes with m- and p-substituted phenols respectively (Fig. 6). Then the observed Kd values were divided into two or three terms corresponding to the dissociation of the orientational isomers involved (Eqs. 16, 17) ... 

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