The Case of Large Molecules

In the present section, we consider molecules of usual size, i.e. of molecular weights (MW) of the order of 10. In Section 2.3 we shall consider emergence in macromolecules (MW of the order of 10 -10 ). Between these two levels, however, we believe that there exists an intermediate level of large molecules (MW of the order of KP) which may display emergent properties not seen in smaller molecules. What we have in mind here as an example is a property labelled chameleonic behaviour , whereby a large molecule is able to display large variations in polarity and lipophilicity due to very marked conformational changes as a function of solvent. 

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In contrast to the 1D experiment, where steady-state NOEs may be obtained, only the less intense transient NOE.s are measured in the NOESY experiment. ROEs can only be obtained as transient effects in both the ID and the 2D experiment. Furthermore the intensities of the NOESY and ROESY cross peaks depend upon the molecular size as well as the length of the mixing period. In the case of large molecules, e.g. polypeptides, rather short mixing times are usually chosen to avoid spin diffusion. 

The rotational correlation time can be directly obtained from 13C or deuterium relaxation measurements on a diamagnetic analogue (Y(III), La(III) or Lu(III)) of the Gd(III) complex [38,70-72]. One disadvantage is low sensitivity of 13C or 2D at natural abundance. Moreover, these methods do not measure the rotation of the metal - coordinated water vector, important from the practical point of view, and this may cause problems mainly in the case of large molecules. 

The surface forces technique measures the force between molecules (eg. surfactants, polymers) adsorbed on mica sheets. In the case of large molecules such as polymers, the measurement is most sensitive to the regions closest to the solution and provides little direct information about the region adjacent to the surface. As it is a measurement between macroscopic surfaces, it is unable to provide information on microscopic chemical differences at the interface. Infrared spectroscopy could provide additional information about the quantity of adsorbed material on the mica surface, the identity and orientation of the adsorbed species, and possibly the nature of the surface linkage. 

In the case of large molecules with apolar helices, such as peptides [89], shape selection—that is, bulges fitting into grooves—appears to be the dominating factor in determining the packing. 

The effects of diffusion are determined by the species that is being mixed, which can be characterized as a function of the Schmidt number ( ) defined as the ratio of momentum and mass diffiisivities. Although the characteristic lengths associated with LOC devices are very small - t q)ically on the order of 100 pm - diffusion alone in the case of large molecules does not allow... 

Especially in the case of large molecules like proteins this can lead to severe problems. For instance, the real time for a protein to fold from its denaturated into its globular state lies between a second and several minutes. To simulate this process within a molecular dynamics simulation would take about 108 s, a time interval that exceeds the estimated age of the universe. Still, what can be done is to use cases where the solid-state structure of the protein is known in order to validate the corresponding force field. If the force field is adequate it should reproduce the experimentally observed protein structure as an energetic minimum of the corresponding energy... 

In the case of large molecules, instead of the detailed quantum state characterization implied in the cross sections and rate coefficients of the master equation (A3.13.24). one derives more coarse grained... 

This statement of the theorem of Hohenberg and Kohn is the justification of many of the modern density functional approaches to chemistry. Here we shall outline the generalized and very concise constrained search proof as described by Levy [45-48]. This proof, as we shall see, lends itself to further generalizations that are of special advantage in the case of large molecules, such as proteins. 

On the other hand, it was reported that either several reactions could not be reproduced or no asymmetric effect was found Negative results in several works were explained by the large steps of the helix in the structure of cholesteric liquid crystals (300-400 nm) and by the absence of chirodiastaltic interaetion with the small molecules of the substrates. In the case of large molecules of complicated stereostmctures it was possible to wait for the appearance of such interactions as revealed by the appearance of induced circular dichroism (ICD) in the absorption bands of chromophors of components and products of the reaction. 

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