Cyclodextrins in water

When p-nitrophenolate is incrementally added to a-cyclodextrin in water, the ultraviolet spectrum of this anion changes such that successive spectra give rise to two isobestic points (Figure 5.2). Such behaviour is in accord with the formation of a 1 1 species. The spectral changes may be used for the direct calculation of K, which in this case was found to be approximately 104 dm3 mol-1 (Cramer, Saenger Spatz, 1967). 

Table 3 Basic cleavage of w-t-butylphenyl acetate by /3-cyclodextrin in water and in 60% (v/v) aqueous DMSO."...

Chemical modification of cyclodextrins is achieved through reactions of their hydroxyl groups. Of the 21 hydroxyls ofP-CD, the seven primary ones (C-6) can easily be reacted. In addition, the C-2 secondary hydroxyl groups are also fairly reactive while the ones at C-3 resist modification (e.g. by methylation). Several CD derivatives are available commercially in large quantities including -among others- randomly methylated P-cylodextrin and hydroxypropyl-P-cylodextrin [2]. Chemical modifications substantially alter the solubility of cyclodextrins in water. For example, the solubility of P-CD... 

Krishnaveni NS, Surendra K, Reddy MA, Nageswar YVD, Rao KR (2003) Highly efficient deprotection of aromatic acetals under neutral conditions using beta-cyclodextrin in water. J Org Chem 68 2018-2019... 

It had been reported that fullerene Cgo forms a water-soluble complex with y-cyclodextrin by heating with an excess amount of y-cyclodextrin in water [10] or in a mixture of refluxing water and toluene for a long time, such as 30 h [ 11]. The isolated complex is considered to have the Cgo structure bicapped with y-cyclodextrin in a molar ratio of 1 2 [11], and the complex dissolved in water to give a solution of C o with a concentration of nearly 10 mol L 410,11 ]. Fullerene Qo was also solubilized in water by complexation with a sulfocalix[8] arene, i.e., calix-[8]aryloxy-49,50,51,52,53,54,55,56-octakis(propane-3-sulfonate). The concentration of this complex in water is estimated as 5x10 mol L [12]. Complex formation between fullerene and various calixarenes has also been reported [8]. 

Figure 6.22 Guests and their binding constants for a-cyclodextrin in water.

Figure 3. ITC-measurement of the complexation of (-)camphor by a-cyclodextrin in water. Left Primary heat pulse trace (CFB = cell feedback current) the saw-tooth shape arises from changing the aliquots of titrand solution. Right The time integral of the heat pulses furnishes the titration curve. The solid line represents the best fit to a 2 1 host-guest sequential binding model.

Mechanisms have been suggested for the N-bromosuccinimide (NBS) oxidation of cyclopentanol and cyclohexanol, catalysed by iridium(III) chloride,120 of ethanolamine, diethanolamine, and triethanolamine in alkaline medium,121 and for ruthenium(III)-catalysed and uncatalysed oxidation of ethylamine and benzylamine.122 A suitable mechanism has been suggested to explain the break in the Hammett plot observed in the oxidation of substituted acetophenone oximes by NBS in acidic solution.123 Oxidation of substituted benhydrols with NBS showed a C-H/C-D primary kinetic isotope effect and a linear correlation with er+ values with p = —0.69. A cyclic transition state in the absence of mineral acid and a non-cyclic transition state in the presence of the acid are proposed.124 Sulfides are selectively oxidized to sulfoxides with NBS, catalysed by ft-cyclodextrin, in water. This reaction proceeds without over-oxidation to sulfones under mild conditions.125... 

The other point that was discovered was that some reaction rates were accelerated by operating in a mixed solvent rather than in pure water. The one that was examined most carefully was the acetyl transfer from bound ra-f-butylphenyl acetate to /3-cyclodextrin with buffers that in water give a pH of 9.5. It was observed that the reaction was almost 50-fold accelerated in a 60% DMS0-H20 solvent compared with the reaction rate in pure water. Part of this acceleration came from an increase in the apparent basicity of the medium, since relative pK s are solvent dependent part of it was also a solvent effect on the reaction rate of the cyclodextrin anion with the substrate. Thus, in 60% DMSO-H20 the /3-cyclodextrin reaction with this substrate was 13,000-fold faster than was the rate of hydrolysis of the substrate in an aqueous buffer of the same composition. Of this approximately 50-fold acceleration over cyclodextrin in water, about 10-fold was caused by changes in the pK s in the system and about 5-fold was caused by a change in the reaction rate of the cyclodextrin. 

In biological structures, the conformational flip-flop disorder will occur in the carbohydrates, the cyclodextrins, in water, or generally, in all systems where hydroxyl groups are involved. 

An alternative is the solubilization with the help of cyclodextrins because these are soluble in water and can incorporate organic molecules inside their hydrophobic cavity [11-13]. P-cyclodextrin is the most useful regarding the typical size of molecules to be solubilized. Griseofulvin forms inclusion complexes of 1 1 stoichiometry with P-cyclodextrin [14, 15]. One possible problem is the moderate solubility of P-cyclodextrin in water (18.5 g/L) and the even lower solubility of most inclusion complexes. A more dramatic problem is the preparation of inclusion complexes of water-soluble cyclodextrins and organic molecules that are not soluble in water. The complexation takes place by means of hydrophobic interactions inside the cavity, which require the presence of water as a solvent. 

Oxidation of terminal alkenes may be carried out in benzene-water in the presence of cetyltrimethy-lammonium bromide at 80 C ° although cyclodextrins are better phase-transfer agents. In the presence of a catalytic amount of -cyclodextrin, 1-decene and cis-2-butene were oxidized at 65 C to 2-decanone (61%) and 2-butanone (76%) respectively. Selective oxidation of linear Cg-Cio terminal alkenes took place at 75 C in the presence of a-cyclodextrin in water, but a low yield was obtained with 1-do-decene. 

A. K. Chatjigakis, I. Clarot, P. J. P. Cardot, R. Nowakowski, and A. Coleman, Reversed phase chromatographic study of the inclusion selectivity of terpene derivatives with P-cyclodextrines in water/cosolvent mixtures, J. Liq. Chrom Rel. Technol. 22 (1999), 1267. 

Mulski, M.J. Connors, K.A. Solvent effects on chemical processes. 9. Energetic contributions to the complexation of 4-nitroaniline with a-cyclodextrin in water and inbinary aqueous-organic solvents. Supramol. Chem. 1995, 4 (4), 271-278. 

Michels JJ, Baars MWPL, Meijer EW, Huskens J, Reinhoudt DN (2000) Well-defined assemblies of adamantyl-terminated poly(propyleneimine) dendrimers and P-cyclodextrin in water. J Chem Soc Perkin Trans 2 1914—1918... 

Polymerization of phenyl or cyclohexyl methacrylate in 2,6-dimethyl-/3-cyclodextrin in water using a potassium persulfate-potassium bisulfite initiator gave better yields and higher molecular weights than obtained with an azo initiator in tetrahydrofuran.234... 

The modular NESI-chip system was used (i) to qualitatively as well as quantitatively study two well-known supramolecular systems, i.e. the Zn-porphyrin complexation with nitrogen-containing ligands in acetonitrile and the inclusion of small organic molecules into the cavity of (5-cyclodextrin in water,41 and (ii) to study the kinetics of the reaction of 4-nitro-7-piperazino-2,l,3-benzoxadiazole (NBDPZ) with isocyanates as a model system.42... 

The anri-selective aldol reaction between cyclohexanone and ArCHO reaches >99% ee if it is conducted in the presence of trawi -4-(4-t-butylphenoxy)-L-piDline and sulfated P-cyclodextrin in water at room temperature. Another catalyst is cw-A-fl-adamantane-carboxamido)-(5)-proline (1) in conjunction with P-cyclodextrin. ... 

Not all potential substrates can easily have nicotinate groups attached to both ends. Thus we set out to use hydrophobic binding into cyclodextrins in water as the mechanism for inducing formation of a complex between catalyst and substrate with geometric control and catalytic turnover. In the earliest work we have nonetheless attached groups to the substrates to solubilize them and promote their binding into cyclodextrins. 

Myron Bender had reported that a meta-f-butylphenyl acetate (4) acetylated 8-cyclodextrin in water with a rate 250 times as fast as that for hydrolysis of that same substrate at the same pH. We had shown that the same reaction was even faster in a mixed DMSO/ water solvent, but still the acceleration was not what one would have hoped for. Model-building suggested that in the acylation reaction the tetrahedral intermediate is partly pulled out of the cavity, so cyclodextrin binding is to some extent fighting against the reaction rate. Thus we made a new substrate, the p-nitrophenyl ester of ferrocene-acrylic acid (5), and saw that it acylated jS-cyclodextrin with a rate acceleration of 51,000 compared with the hydrolysis rate in free solution. With this substrate there... 

K. Surendra, N. S. Krishnaveni, K. R. Rao, Direct Barbier-type allylation of aromatic acetals and dioxolanes in the presence of )S-cyclodextrin in water. Tetrahedron Lett, 2006, 47, 2133-2136. 

M. A. Reddy, N. Bhanumathi, K. Rama Rao, A mild and efficient biomimetic synthesis of a-hydroxymethylarylketones from oxiranes in the presence of j8-cyclodextrin in water. Tetrahedron Lett., 2002, 43, 3237-3238. 

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