Characterization of inclusion complexes

A variety of techniques are used to analyze complexes. Only NMR proves that a complex is formed. A shift in peaks can be observed for both the CD and the guest. As the environment around the hydrogen atoms in the cavity changes with association with the guest, a shift in the peaks for the CD can be observed. Similarly, shifts can be observed for peaks corresponding to the atoms of the guest which penetrate into the cavity of the CD [11]. 

Most users of complexes do not have access to an NMR and use other means to characterize the complex. While these methods do not prove that a complex has 

Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy have also been used for analyses of complexes. Upon complexation of the guest, shifts or changes in the spectrum occur. There are interferences in the spectra from the CD, and some of the changes are very subtle, requiring careful interpretation of 

Several other techniques have also been used to characterize complexes, such as ORD, circular dichroism, mass spectroscopy, fluorescence and X-ray crystallography. Selection of some of these specialized techniques frequently depends on equipment available and properties of the guest which make the particular technique most sensitive or reliable for the particular complex [11]. 

Some functional assays can also be used. For labile guests, accelerated stability tests can be done to determine if decomposition of the guest is prevented or is within the expected range for a complex. Since most guests complexed by CDs are hydrophobic, their interaction with water is altered so that tests measuring wet ability, dissolution rate or even rate of release of guest from some complexes can be used [11,12]. 

---

R705 C. M. Fernandes and F. J. B. Veiga, The Cyclodextrins in Pharmaceutical Technology. III. Preparation and Characterization of Inclusion Complexes in the Solid State , Rev. Cienc. Farm. (Sao Paulo), 1999, 20, 375... 

A. Ribeiro, A. Eigueiras, D. Santos, and E. Veiga, Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl- -cyclodextrin, AAPS PharmSciTech, 9 (4), 1102-1109, 2008. 

Okumura, H., Kawaguchi, Y., and Harada, A. (2001) Preparation and characterization of inclusion complexes of poly (dimethylsiloxane)s with cyclodextiins. Macmmolecules, 34,6338 343. 

Ferro, S., Jori, G., Sortino, S., Stancanelli, R., Nikolov, P., Tongon, G., Ricchelli, F., and Mazzaglia, A. (2009). Inclusion of 5-[4-(l-dodecanoylpyridinium)-10,15,20-triphenylpor-phine in supramolecular aggregates of cationic amphiphilic cyclodextrines Physic-chemical characterization of the complexes and strengthening of the antimicrobial photosensitizing activity. Biomacromolecules 10(9), 2592-2600. 

While the magnitudes of NQR frequencies are for the most part a consequence of the nature and the electronic structure of the molecules that are under study, they are modified by the fact that these molecules are present in the solid state. The nuclear quadrupole coupling tensor for an isolated molecule is accessible from the study of its pure rotational spectrum but when the molecule is incorporated in a crystalline solid its observed NQR frequencies are slightly different from those that would have been expected from its quadrupole coupling tensor, even if the forces that retain the molecule in the solid are weak van der Waals forces or even the physical entrapment that characterizes many inclusion complexes. Furthermore the resonance frequencies are temperature-dependent. As will be shown below, it is in these solid state effects and in the temperature-dependence of the resonance frequencies that resides the utility of the NQR technique for the study of inclusion complexes. 

A large number of inclusion complexes of polymers in a wide variety of host molecules have been prepared and characterized. Direct preparation of inclusion complexes of polymers with these hosts by crystallization have been employed. Inclusion polymerization has also been used for preparation of inclusion complexes. These polymeric inclusion complexes have unique structures and properties. They are considered to be one of the molecular composites made by an engineering-up procedure. 

In calculation the authors of the model assume that the cube material possesses the complex modulus EX and mechanical loss tangent tg dA which are functions of temperature T. The layer of thickness d is composed of material characterized by a complex modulus Eg = f(T + AT) and tg <5B = f(T + AT). The temperature dependences of Eg and tg SB are similar to those of EX and tg <5A, but are shifted towards higher or lower temperatures by a preset value AT which is equivalent to the change of the glass transition point. By prescibing the structural parameters a and d one simulates the dimensions of the inclusions and the interlayers, and by varying AT one can imitate the relationship between their respective mechanical parameters. 

In contrast to the reactions of the cycloamyloses with esters of carboxylic acids and organophosphorus compounds, the rate of an organic reaction may, in some cases, be modified simply by inclusion of the reactant within the cycloamylose cavity. Noncovalent catalysis may be attributed to either (1) a microsolvent effect derived from the relatively apolar properties of the microscopic cycloamylose cavity or (2) a conformational effect derived from the geometrical requirements of the inclusion process. Kinetically, noncovalent catalysis may be characterized in the same way as covalent catalysis that is, /c2 once again represents the rate of all productive processes that occur within the inclusion complex, and Kd represents the equilibrium constant for dissociation of the complex. 

Ventura CA, Giannone I, Musumeci T, Pignatello R, Ragni L, Landolfi C, Milanese C, Paolino D, Puglisi G (2006) Physico-chemical characterization of disoxaril-dimethyl-beta-cyclodextrin inclusion complex and in vitro permeation studies. Eur J Med Chem 41 233-240. 

The majority of reported studies of formation of cyclodextrin inclusion complexes in solution have been mainly concerned with determination of the stability constants by using equilibrium spectroscopic techniques, and the measurement of the enthalpy and entropy changes characterizing the complexation reaction. The aim of much of this work has been to determine the driving force of complex-formation. Despite the amount of research in this area, however, no general agreement has been reached, and... 

---