Cyclodextrins thermodynamics

Koushik KN, Band N, Kompella UB, Interaction of [D-Trp6, Des-Glyl0]-LHRH ethylamide and hydroxypropyl-y -cyclodextrin thermodynamics of interaction and protection from degradation by alpha-chymotrypsin, Pharm. Dev. Technol. 2001 6 595-606. 

Cabral Marques, H. M. (1994b). Applications of cyclodextrins. Thermodynamic aspects of cyclodextrin complexes. Revista. Portuguesa de Farmdcia, XLIV, 85-96. 

R. Chadha, M. Bala, P. Arora, D.V.S. Jain, R.R.S. Pissurlenkar, and E.C. Coutinho, Valsartan inclusion by methyl-p-cyclodextrin Thermodynamics, molecular modelling. Tween 80 effect and evaluation, Carb. Pol., 103,300-309,2014. 

Although the chiral recognition mechanism of these cyclodexttin-based phases is not entirely understood, thermodynamic and column capacity studies indicate that the analytes may interact with the functionalized cyclodextrins by either associating with the outside or mouth of the cyclodextrin, or by forming a more traditional inclusion complex with the cyclodextrin (122). As in the case of the metal-complex chiral stationary phase, configuration assignment is generally not possible in the absence of pure chiral standards. 

The applications of quantitative structure-reactivity analysis to cyclodextrin com-plexation and cyclodextrin catalysis, mostly from our laboratories, as well as the experimental and theoretical backgrounds of these approaches, are reviewed. These approaches enable us to separate several intermolecular interactions, acting simultaneously, from one another in terms of physicochemical parameters, to evaluate the extent to which each interaction contributes, and to predict thermodynamic stabilities and/or kinetic rate constants experimentally undetermined. Conclusions obtained are mostly consistent with those deduced from experimental measurements. 

Water plays a crucial role in the inclusion process. Although cyclodextrin does form inclusion complexes in such nonaqueous solvents as dimethyl sulfoxide, the binding is very weak compared with that in water 13 Recently, it has been shown that the thermodynamic stabilities of some inclusion complexes in aqueous solutions decrease markedly with the addition of dimethyl sulfoxide to the solutions 14,15>. Kinetic parameters determined for inclusion reactions also revealed that the rate-determining step of the reactions is the breakdown of the water structure around a substrate molecule and/or within the cyclodextrin cavity 16,17). 

Table 1. Thermodynamic parameters for the association of cyclodextrin with alcohol in an aqueous solution at 25 °C...

Matsui and Mochida24) have determined the thermodynamic stabilities (log 1 /Kd) for a- and P-cyclodextrin complexes with a variety of alcohols (Table 2) and analyzed the results in connection with the physicochemical properties of the guest molecules by the multivariate technique. The log 1/Kd values were plotted against log Pe, where Pe is the partition coefficient of alcohol in a diethyl ether-water system. The plots for the a- and P-cyclodextrin complexes with eight 1-alkanols gave approximately straight lines with slopes of around one. 

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... 

Table 2 Thermodynamic parameters for the /1-cyclodextrin-catalysed decarboxylation of the 4-chlorophenylcyanoacetate anion."...

Tetrahedral intermediates, derived from carboxylic acids, spectroscopic detection and the investigation of their properties, 21, 37 Thermodynamic stabilities of carbocations, 37, 57 Topochemical phenomena in solid-state chemistry, 15, 63 Transition state analysis using multiple kinetic isotope effects, 37, 239 Transition state structure, crystallographic approaches to, 29, 87 Transition state structure, in solution, effective charge and, 27, 1 Transition state structure, secondary deuterium isotope effects and, 31, 143 Transition states, structure in solution, cross-interaction constants and, 27, 57 Transition states, the stabilization of by cyclodextrins and other catalysts, 29, 1... 

The most important property of cyclodextrins is in their ability to accommodate guest molecules within their cavity, which has a volume of 262 per molecule or 157 mL per mol of [3-CD (cavity diameter 6.0-6.5 A). In aqueous solution, this cavity is filled with molecules of water the displacement of which by a less polar guest leads to an overall decrease in free energy. Stability constants and thermodynamic parameters for complexation of a vast number of guest molecules can be found in ref. [3]. 

Part II starts with the possibilities of ACE for characterizing the relevant physicochemical properties of drugs such as lipophilicity/hydrophilicity as well as thermodynamic parameters such as enthalpy of solubilization. This part also characterizes interactions between pharmaceutical excipients such as amphiphilic substances (below CMC) and cyclodextrins, which are of interest for influencing the bioavailability of drugs from pharmaceutical formulations. The same holds for interactions of drugs with pharmaceutical vehicle systems such as micelles, microemulsions, and liposomes. 

SG Penn, ET Bergstrom, DM Goodall, JS Loran. Capillary electrophoresis with chiral selectors. Optimization of separation and determination of thermodynamic parameters for binding of ticonazole enantiomers to cyclodextrins. Anal Chem 66 2866-2873, 1994. 

Auletta T, de Jong MR, Mulder A, van Veggel FCJM, Huskens J, Reinhoudt DN, Zou S, Zapotoczny S, Schonherr H, Vancso GJ, Kuipers L. 3-Cyclodextrin host-guest complexes prohed under thermodynamic equilibrium thermodynamics and AFM force spectroscopy. J Am Chem Soc 2004 126 1577-1584. 

Determination of Thermodynamic Processes of the Cyclodextrin Inclusion Process 115... 

Zhang, X., Gramlich, G., Wang, X. and Nau, W.M. (2002) A joint structural, kinetic, and thermodynamic investigation of substituent effects on host-guest complexation of bicyclic azoalkanes by -cyclodextrin./. Am. Chem. Soc., 124 (2), 254-263. 

Redenti, E., L. Szente, and J. Szejtli (2001). Cyclodextrin complexes of salts of acidic drugs. Thermodynamic properties, structural features, and pharmaceutical applicatloFffearm. Sci., 90 979-986. 

Cramer, F., Saenger, W, and Spatz, H. C. 1967. Inclusion compounds. XIX. The formation of inclusion compounds ofc-cyclodextrin in aqueous solutions. Thermodynamics and kinelickm. Chem. Soc. 

The advantage of using antibiotics, cyclodextrins, maltodextrins and fullerenes as chiral selectors is that the enantioselectivity of the molecular interaction takes place in two places inside the cavity (internal enantioselectivity) and outside the cavity—due to the arrangement, size and type of the radicals, atoms or ions bound on the external chain of the chiral selector (external enantioselectivity) [10]. The thermodynamics of the reaction between the enantiomers and chiral selectors plays the main role in the enantioselectivity of molecular interaction. 

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