Solid-state cyclodextrin inclusion complexes

Braun T, Buvari-Barcza A, Barcza L, Konkoly-Thege I, Fodor M, Migali B (1994) Mechanochemistry a novel approach to the synthesis of fullerene compounds. Water soluble Buckminster fullerene - gamma- cyclodextrin inclusion complexes via solid-solid reaction. Solid State Chem. 74 47-51. 

JR Moyano, MJ Arias-Bianco, JM Gines, F Giordano. Solid-state characterization and dissolution characteristics of gliclazide- 3-cyclodextrin inclusion complexes. Int J Pharm 148 211-217, 1997. 

Polyaniline/p-cyclodextrin inclusion complex (PANT/p-CD IC) and its relation with optical properties were investigated using solid-state NMR. Dynamics were interpreted in terms of chain motion. 

High resolution C-13 NMR spectroscopy is one of the most useful methods in the analysis of the structure and molecular dynamics of cyclodextrin inclusion-complexes both in aqueous solution[1,2] and in the solid state[3]. Earlier C-13 NMR studies of a-CD inclusion... 

W. Marie, and A. Maggie, Solid state studies of drug-cyclodextrin inclusion complexes in PEG 6000 prepared by a new method, Ear. J. Pharm. Scl, 8 (4), 269-281,1999. 

Inoue, Y, Kosaka, S., Matsumoto, K., Tsuneishi, H., Hakushi, T, Tai, A., Nakagawa, K., and Tong, L-H., Vacuum UV photochemistry in cyclodextrin cavities. Solid state Z-E photoisomerization of a cyclooctene-P-cyclodextrin inclusion complex,/. Photochem. Photobiol. A Chem., 71, 61-64,1993. 

Inclusion Complexes in the Solid State Cyclodextrin Hosts Zeolites 73-10... 

An important advantage of the inclusion complexes of the cyclodextrins over those of other host compounds, particularly in regard to their use as models of enzyme-substrate complexes, is their ability to be formed in aqueous solution. In the case of clathrates, gas hydrates, and the inclusion complexes of such hosts as urea and deoxycholic acid, the cavity in which the guest molecule is situated is formed by the crystal lattice of the host. Thus, these inclusion complexes disintegrate when the crystal is dissolved. The cavity of the cyclodextrins, however, is a property of the size and shape of the molecule and hence it persists in solution. In fact, there is evidence that suggests that the ability of the cyclodextrins to form inclusion complexes is dependent on the presence of water. Once an inclusion complex has formed in solution, it can be crystallized however, in the solid state, additional cavities appear in the lattice, as in the case of the hosts previously mentioned, which enable the inclusion of further guest molecules. ... 

The cyclodextrins are not the only molecules capable of forming inclusion complexes ( Einschlussverbindungen ). In contrast to the inclusion complexes of many other host molecules, however, those of the cyclodextrins are able to form in solution as well as in the solid state, a fact which was first recognized by Cramer, " after he had observed that... 

Although Freudenberg s hypothesis that complex-formation occurred by inclusion within the cavity was generally accepted, there was no direct evidence for this, either in solution or in the solid state. Broser and Lautsch had found by spectrophotometric titration that the complexes of a series of dyes with the cyclodextrins in solution obeyed the mass action law with a stoichiometry of 1 1. They suggested that association on the outside of the ring might not have a defined stoichiometric composition, and they thus interpreted their results as being consistent with inclusion by cyclodextrin. Their results were not conclusive, however. 

The first direct evidence for molecular inclusion came from X-ray crystallography. Hybl and coworkers determined the structure of the alpha cyclodextrin-potassium acetate complex by using three-dimensional X-ray diffraction data. They found that, in the solid state, the acetate anions are included by the alpha cyclodextrin. In the process, they also found that every D-glucosyl residue of the alpha cyclodextrin is in the C conformation. 

Rao et al. [100] for the first time report the biomimetic approach for the synthesis of a single enantiomer of p-aminoalcohol. In this approach p-cyclodextrin formed by the inclusion of complex 77 with racemic aryloxyepoxide which reacted enantioselectively with amines imder solid state condition to give the product in 100% ee and 70-79% isolated yield. The yield which was above 50% was explained in terms of continuous racemization of the... 

Ramamoorthy et al. (444) found that a-phenyl-A-(4-methylphenyl)nitrone can be the guest molecule in inclusion complexes with a p-cyclodextrin host in 1 1 and 1 2 ratios (guest/host), and that the latter undergoes a 1,3-dipolar cycloaddition reaction with electron-deficient alkenes. In more recent work, they have formed 1 1 inclusion complexes of the bowl-shaped p-cyclodextrin 383 with (3-nitrostyrene 381 or 1-nitrocyclohexene 382, which leave the alkene moiety exposed (Fig. 1.9) (445). Complexes 381 and 382 undergo cycloaddition reaction with ot-phenyl-A-(4-methylphenyl)nitrone in the solid state after thorough homogenization (60 °C, 3 h) to give the 4-substituted products exclusively in 80 and 85% yield, respectively. 

Oguchi and coworkers examined the decarboxylation behavior of -aminosalicylic acid (PAS) as a freeze-dried solid under thermal stress conditions (80°C) in the presence of the excipients pullulan (a linear polysaccharide which can not form inclusion complexes with PAS) and a-cyclodextrin (39). The solid-state stability was shown to correlate with the fraction of amorphous PAS. Increasing relative amounts of pullulan resulted in higher fractions of amorphous PAS. Rapid freezing (liquid nitrogen) was shown to result in a greater relative amount of amorphous drug, as expected. 

Bayomi B, Abanumay KA, Al-Angary AA. Effect of inclusion complexation with cyclodextrins on photostability of Nifedipine in solid state. Int J Pharm... 

The work reported here has shown that inclusion complexation of organic and organometallic chromophores by thiourea, TOT and cyclodextrins can induce second harmonic generation capability in the polar crystals which result, even when the original bulk materials are themselves incapable of SHG. Structural evidence has been presented to show tht the solid state inclusion structures are acentric, and a simple electronic picture t0 the polarization response of these materials within the two-state modeP ° has been discussed. In an earlier section we remarked that of the many complexes we have made, only one has NOT been acentric. This result was not anticipated. We postulate that it is a natural tendancy in such materials, rather that an exception. If we consider a dipolar molecule in isotropic solution, we can imagine that if it were to aggregate, it would do so in a head to tail fashion in order to minimize electrostatic repulsion. The situation is illustrated in Scheme 3. The arrangement that would result is centrosymmetric. 

Mielcarek, J. Photochemical stability of the inclusion complexes of nicardipine with a-, y-cyclodextrin, methyl-P-cyclodextrin, and hydroxypropyl-P-cyclodextrin in the solid state and in solution. Pharmazie 1996, 51 (7), 477-479. 

Cwiertnia, B. Hladon, T. Stobiecki, M. Stability of diclofenac sodium in the inclusion complex with P-cyclodextrin in the solid state. J. Pharm. Pharmacol. 1999, 51 (11), 1213-1218. 

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