Cyclodextrins association constants

Valko, I. E., Siren, H., and Riekkola, M. L. (1997). Determination of association constants of dansyl-amino acids and beta-cyclodextrin in N-methylformamide by capillary electrophoresis. Electrophoresis 18, 919-923. 

A Amini, N Merclin, S Bastami, D Westerlund. Determination of association constants between enantiomers of orciprenaline and me thy 1-/3-cyclodextrin as chiral selector by capillary zone electrophoresis using a partial filling technique. Electrophoresis 20 180-188, 1999. 

Figure 14.11 shows the separation of R and S isomers of a series of structurally related local anaesthetics. Wide separations were achieved for the compounds in this series where it was proposed that the fit of the hydrophobic portion of the analyte into the cyclodextrin was optimal when one of the substituents at the chiral centre was able to interact with the chiral hydroxyl groups on the rim of the cyclodextrin cavity. Table 14.3 shows the association constants calculated for the interaction of the enantiomeric pairs with the dimethylcyclodextrin. The larger the value of K, the... 

Table 14.3 Association constants of some enantiomers of some local anaesthetics with dimethyl P-cyclodextrin and their mobilities in free solution...

The hetero-dimerization behavior of dye-modified -cyclodextrins with native CDs was investigated by means of absorption and induced circular dichroism spectroscopy in aqueous solution [43], Three types of azo dye-modified /i-CDs show different association behavior, depending on the positional difference and the electronic character of substituent connected to the CD unit in the dye moiety. p-Methyl Red-modified fi-CD (1), which has a 4-(dimethylamino)azobenzene moiety connected to the CD unit at the 4 position by an amido linkage, forms an intramolecular self-complex, inserting the dye moiety in its / -CD cavity (Figure 13). 1 also associates with native a-CD by inserting the dye residue into the a-CD cavity. The association constants for such hetero-dimerization are 198 M"1 at pH 1.00 and 305 M 1 at pH 6.59, which are larger than the association constants of 1 for / -CD (43 M 1 at pH 1.00). 

A further contribution from this group, in collaboration with Pikramenou, deals with energy transfer processes in self-assembled structures of multin-uclear complexes. Each ligand of a Ru(bpy)32+ unit is connected to the rim of a /1-cyclodextrin receptor to form Ru(/J-CD-mbpy), which can complex in a polar medium the biphenyl (or adamathyl) tail of an Ir(III)-terpyridine complex, Fig. 24c [131]. In order to provide complexation of the Ir guest and because of the low association constant, a consistent excess of the Ru(/J-CD-mbpy) host is required, (80-90% of host relative to guest). Under these... 

With "bifunctional" guest, i.e. that interacts with two cyclodextrins the binding is much stronger (57). This is clearly seen in the values of association constants and on the solubility enhancing effect of 8-cyclodextrin and its soluble polymers (Table III). 

The terms in the denominator of the right side of Equation 1 include 0, the phase ratio A, stationary phase adsorption site and K, the association constant of a solute to the stationary phase binding site. The binding constant, K., can be evaluated graphically (by plotting 1/k versus [CD]) or by linear least squares. When complex equilibria are involved, Equation 1 deviates from linearity. In cases where two cyclodextrin molecules bind to a simple solute the correct pseudophase retention equation is (jl) ... 

The cyclodextrin-sandwiched porphyrin 18 of Kuroda [98] effectively recognizes hydrophobic quinones in water, with association constants ranging from A a = 7.4 X 10 M for 1,4-naphthoquinone to Ka > 5 x 10 M for an adamantyl-functionalized benzoquinone. In contrast, the association of p-benzoquinone is negligible. Molecular modeling predicts that the quinone approaches the porphyrin from an out-of-plane direction. Time-resolved fluorescence measurements give an estimate of the intramolecular electron transfer rate constant on the order of 10 s for all quinones studied. 

Until recently, cyclodextrins (CD s) were used mostly for complexation of amino acids, with partially contradictive results. In some cases unsubstituted cyclodextrins were used fluorescence titrations with tyrosine containing pentapeptides showed with a-cyclodextrin even a lower association constant (around K=25 M" )... 

Lantz AW, Rodriguez MA, Wetterer SM, Armstrong DW. 2006. Estimation of association constants between oral malodor components and various native and derivatized cyclodextrins. Analytica ChimicaActa 557(1-2) 184—190. 

In catalysis the excess of a phosphine ligand is often necessary because it preserves the active species in the medium [2a]. However, it retards to some extent the co-ordination of the alkene to the metal center. Recent studies, performed by Monflier and coworkers, have shown that the water-soluble TPPTS ligand could reduce the rate of the reaction by another effect. Indeed, TPPTS can be included partially in the cyclodextrin hydrophobic cavity [53,54] NMR measurements, observation by UV-visible spectroscopy and circular dichroism, as well as scanning tunneling microscopy are consistent with a 1 1 inclusion complex in which the phosphorus atom would be incorporated into the torus of the /S-CD. NMR investigations carried out on (m-sulfonatophenyl)diphenylphosphine have shown that a phenyl group is incorporated [55]. Thus, the phosphorus ligand could modify the association constant of the alkene with the cyclodextrin so that the mass transfer between the two phases could be decreased. 

The participation of the secondary alcoholic functions to the increase in association constant of the ketone recalls the basic catalysis of various esters in aqueous medium. Indeed, this hydrolysis is clearly assisted by j6-CD and Tee et al. present a mechanism in which an ionized hydroxy group of the cyclodextrin acts as a nucleophile towards the guest ester [56]. In several cases the kinetics studies are consistent with a hydrolysis process in which a complex formed from the ester and two molecules of cyclodextrin is involved [57]. 

The use of a chiral additive in the mobile phase has been exemplified by Roussel and Favrou who studied the separation of several N-aryl-thiazo-line-2-thione atropisomers on an achiral column with p or y cyclodextrin in the mobile phase. It is worth recalling that the association constants between each enantiomer and the chiral selector can be determined by varying the chiral additive concentration (93CHI471, 93JIP283). 

Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful and versatile methods for the elucidation of molecular structure and dynamics. It is also very well suited to study molecular complexes and their properties [1]. Therefore, it has been widely used for studying inclusion complexes formed by cyclodextrins (CyD) [2-4]. Some examples of the applications of NMR in conjunction with other techniques are presented in other chapters, in particular in Chapter 6. The success of NMR spectroscopy in this field is due to its ability to study complex chemical systems and to determine stoichiometry, association constants, and conformations of molecular complexes, as well as to provide information on their symmetry and dynamics. Furthermore, compared to other techniques, NMR spectroscopy provides a superior method to study complexation phenomena, because guest and host molecules are simultaneously observed at the atomic level. 

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