Molecular Mechanics Cyclodextrin Studies

Similarly, in spite of extensive experimental study of the complexes of styrene and methylstyrene with j8-CyD, the claim by Cao and coworkers [70] on the basis of PM3 calculations that only van der Waals attractions and dipole-dipole interactions influence the complexes geometry seems ill-founded. 

Once more it should be stressed that the use of quantum calculations to analyze chiral recognition by CyDs [47, 48, 49] is strongly discouraged in view of the very small energy differences involved and all the other arguments described earlier. 

As mentioned before, the situation with MM calculations for large and very flexible molecules and their inclusion complexes, especially those involving CyDs, is different from that of the calculations for small and medium organic molecules. As discussed in Section 1.3, the former systems are highly flexible, and in the majority of cases they are studied either in the solid state (discussed in Chapter 7) crystallized with, even more mobile, solvent molecules or in solution. Therefore, all the objections raised in Sections 11.1 and 11.2 concerning comparison of the calculated MM results with the corresponding experimental data are also valid. 

The pitfalls in MM calculations on CyD complexes can be illustrated by the study of the complexes of isomeric decalins 1 2 [25]. As mentioned in Section 11.1, early MM calculations suggested that, contrary to experimental findings [20], the complex with the trans-isomer la is more stable than those with the ds-isomers 

The colorful lipophilicity surfaces determined on the basis of the above MM calculations [2] aroused admiration and were awarded the Science Award of Sugar Processing Research Inc., New Orleans, LA, although the only reliable information they conveyed, namely that the narrower a-CyD base is less polar than the broader one, results from the presence of twelve OFI groups on the broader base as compared to six on the narrow base, information which is available without carrying out any computations. 

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CGTases (EC 2.4.1.19) are bacterial enzymes that facilitate the biosynthesis of cyclodextrins from starch through intramolecular transglucosylation. The primary structures of most of these enzymes have been published, and the three-dimensional structure of Bacillus circulans CGTase has been established. Studies of transglucosylation molecular mechanism have indicated that amino acids such as histidine and tryptophan are implicated in such mechanisms. Nitration of CGTase with TNM induces a loss of enzyme activity, a decrease in enzyme affinity towards the (i-CD copolymer, and a loss of tryptophan fluorescence (Villette etal. 1993). 

The computational studies described above are representative examples meant to illustrate the diversity of computational techniques used to assess chiral recognition by cyclodextrins in chiral chromatography. Other published examples include the use of molecular mechanics to describe shapes of aminoalkylphosphonic acids binding to a covalently linked acetylated cyclodextrin [72], the computation of free energies of atenolol binding to a perphenylcarbamate-p-cyclodextrin likewise covalently bound to silica gel [73], and studies of cyclodextrins used as chiral mobile phase additives in reverse-phase HPLC [74] and in capillary electrophoresis [75]. 

Four of the molecular mechanics studies of the inclusion compounds of cyclodextrins discussed in this section present, as necessary preliminary work, detailed pictures of calculated structures for cyclodextrins without guest molecules [6,11-13]. The resulting structures often show a high degree of (sometimes imposed) symmetry, and compare well with published X-ray structures of cyclodextrins (Figure 3). 

Quantum Mechanics and Molecular Mechanics Studies of Host-Guest Stabilization and Reactivity in Cyclodextrin Nanocavities... 

An understanding of the recognition of chirality at a molecular level has become of interest in many fields of chemistry and biology. In the past decade, many attempts to clarify the mechanism of chiral recognition on CSPs for liquid chromatography have been made by means of chromatography, NMR spectroscopy,199 202 X-ray analysis, and computational methods.203 - 206 The successful studies have been mostly carried out for the small-molecule CSPs, especially cyclodextrin-based CSPs and Pirkle-type (brush-type) CSPs. In contrast, only a few mechanistic studies on chiral discrimination at the molecular... 

The mechanism of chiral recognition in permethyl-p-cyclodextrin has been thoroughly studied by Lipkowitz et al. [269] employing a molecular modelling approach. Not surprisingly, the host s most enantiodiscriminating domain was found to be inside the macrocyclic cavity. 

C02Me) in the presence of 2,4,6-triphenylpyrylium tetrafluoroborate as sensitizer gives cyclopropenes together with 2H-pyrroles which arise by solvent addition to the 1,3-radical cation intermediate. Phenylmercaptotetrazole has been photo-catalytically oxidised on aerated Ti02 dispersions (Xjn- >330 nm) and a mechanism suggested which involves the formation of CO2, S04, NOa, and NH4. Photooxidation of phenothiazine in either benzene or cyclohexane in the presence of molecular oxygen has been shown by EPR experiments to give the phenothiazine nitroxyl radical rather than the radical cation. These observations are supported by the results of AMI calculations. The photooxidation of Azure A (81) as well as its fluorescence properties have been studied in the presence of P-cyclodextrin, and this has enabled an induced fluorimetric method to be developed for the determination of (81). ... 

Although the understanding of IPTC is still limited in comparison to that of normal PTC, it is clear that this method is apt to effect organic reactions in water. As discussed in the introduction simple pyridine derivatives were introduced mainly in connection to kinetic and mechanism studies, but more recently, it was shown that the use of host compounds such as cyclodextrins and water-soluble calix[n]arenas,offers the opportunity to combine IPTC, molecular recognition, and transition metal catalysis, with additional economic and environ-metal advantages deriving from the use of water as a bulk solvent. 

TTie CNDO/2 method [46] of Pople et al. was chosen for these types of studies because its computational simplicity allows the feasible consideration of large, complex, and conformationally mobile systems such as cyclodextrin host-guest systems. In contrast to ab initio methods, which seek to directly derive molecular properties from the basic principles of quantum mechanics, CNDO/2 is a semiempirical method, which means that not only are the expressions for wavefunctions simplified algebraically, but also that certain coefficients associated with the resulting approximate functions are arbitrarily assigned in order to duplicate experimental data. 

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