Cyclodextrin complex structure

J. I. Seeman and H. V. Secor, Enantiomeric resolution and chiral recognition of racemic nicotine and nicotine analogues by P-cyclodextrins complexation. Structure-enantiomeric resolution relationship in host guest interaction, Anal. Chem. 60 (1988), 2120. 

J.I. Seeman, H.V Secor, D.W. Armstrong, K.D. Timmons and T.J. Ward, Enantiomeric Resolution and Chiral Recognition of Racemic Nicotine and Nicotine Analogues by P-Cyclodextrin Complexation. Structure-Enantiomeric Resolution Relationships in Host-Guest Interactions, Anal. Chem., 60(1988) 2120. 

It is known that several intermolecular interactions are responsible for cyclodextrin complexation, acting simultaneously. These interactions are separable from one another by quantitative structure-reactivity analysis. Furthermore, correlations obtained by the analysis can be discussed in direct connection with actual interactions already elucidated experimentally for the action site of cyclodextrin. Thus, the results must serve to make the background of the correlation analysis more concrete. 

The present review is concerned with the applications of the quantitative structure-reactivity analysis to cyclodextrin complexation and cyclodextrin catalysis, mostly from our laboratories, as well as the experimental and theoretical backgrounds of these approaches. 

Ihb = 1, whereas Ihb = 0 when it is inert to hydrogen bonding. Since —AG,° is proportional to log 1/Kd, where Kd is the dissociation constant of a cyclodextrin complex with a guest molecule, we can derive a quantitative structure-reactivity relationship as shown, for example, in Eq. 4 ... 

Quantitative Structure-Reactivity Analyses of the Inclusion Processes of Cyclodextrin Complexes... 

Nishioka and Fujita78) have also determined the Kd values fora- and (S-cyclodextrin complexes with p- and/or m-substituted phenyl acetates through kinetic investigations on the alkaline hydrolysis of the complexes. The Kd values obtained were analyzed in the same manner as those for cyclodextrin-phenol complexes to give the Kd(X) values (Table 5). The quantitative structure-activity relationships were formulated as Eqs. 30 to 32 ... 

The importance of the proximity effect in cyclodextrin catalysis has been discussed on the basis of the structural data. Harata et al. 31,35> have determined the crystal structures of a-cyclodextrin complexes with m- and p-nitrophenols by the X-ray method. Upon the assumption that m- and p-nitrophenyl acetates form inclusion complexes in the same manner as the corresponding nitrophenols, they estimated the distances between the carbonyl carbon atoms of the acetates and the adjacent second-... 

As shown above, quantitative structure-reactivity analysis is very useful in elucidating the mechanisms of cyclodextrin complexation and cyclodextrin catalysis. This method enables us to separate several intermolecular interactions, acting simultaneously,... 

Let us compare the methods applied by Pedersen for establishing the complex formation with a modern approach. Today tedious solubility studies are carried out almost exclusively with practical applications in mind, but they are not performed to prove the complex formation. For instance, one ofthe main reasons for the use of cyclodextrin complexes in the pharmaceutical industry is their solubilizing effect on drugs [8]. There, and almost only there, solubility studies are a must. As concerns spectroscopic methods, at present the NMR technique is one ofthe main tools enabling one to prove the formation of inclusion complex, carry out structural studies (for instance, making use of the NOE effect [9a]), determine the complex stability [9b, c] and mobility of its constituent parts [9d]. However, at the time when Pedersen performed his work, the NMR method was in the early stage of development, and thus inaccurate, and its results proved inconclusive. UV spectra retained their significance in supramolecular chemistry, whilst at present the IR method is used to prove the complex formation only in very special cases. 

In addition to 1 1 (host-guest) complexes with different structures, a number of complexes with different host-guest ratios exist in equilibrium when aromatic molecules are included into either a- or p-CD. For example, sodium 1-pyrenebutyrate (75)/a or /J-cyclodextrin complexes in solution form equilibrium mixtures of a 1 1 and 2 1 complexes and form 1 1 and 2 2 complexes with y-CD (Figure 39) [247]. 

Figure 39. Various modes of complexation of guests within cyclodextrin. Possible structures of 1 1, 1 2, and 2 2 complexes are shown.

A review with ca 500 references has appeared on the stability of cyclodextrin complexes in solution. The principal headings in it are nature of cyclodextrins (CDs) binding equilibria and kinetics strengths of CD complexes structures of CD complexes sources of CD complex stability and prediction of CD stability.168... 

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. 

Katritzky, A.R. Fara, D.C. Yang, H. Karelson, M. Suzuki, T. Solov ev, V.P. Varnek, A. Quantitative structure-property relationship modeling of beta-cyclodextrin complexation free energies. J. Chem. Inf. Comp. Sci. 2004, 44 (2), 529-541. 

Harata, K., Uekama, K., Otagiri, M., Hirayama, F., Ohtani, Y., The structure of the cyclodextrin complex. 18. Crystal-structure of beta-cyclodextrin benzyl alcohol (1-1) complex pentahydrate. Bull. Chem. Soc. Jpn. 1985, 58, 1234-1238. 

Harata K (1987) The structure of the cyclodextrin complex 20. Crystal-structure of uncom-plexed hydrated gamma-cyclodextrin. Bull Chem Soc Jpn 60 2763-2767. 

Armstrong et al. developed a chromatographic technique which could be used to evaluate the stoichiometry and all relevant binding constants for most substrate-CD systems (8). This method was not dependent on a solute s spectroscopic properties, conductivity, electrochemical behavior, or solubility. This work presented theory and chromatographic evidence for multiple cyclodextrin complex formation. Previous theoretical work considered only 1 1 complex formation (9-12). A two to one complexation equation was derived by expanding on the equation first used in 1981 to describe the 1 1 complexation behavior of a solute in a pseudophase system (13.14). Using this method, it was demonstrated that closely related compounds such as structural isomers of nitroaniline could exhibit different binding behaviors (8). 

Lindner, K. Saenger, W. Topography of cyclodextrin complexes. Part XVII. Crystal and molecular structure of cycloheptaamylose dodecahydrate. Carbohydr. Res. 1982, 99(2), 103-115. 

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