Active conformation spectroscopic studies

NMR spectroscopic studies of two rhodium complexes 18 and 19 also indicate that the binding of the C2F4 group to rhodium is better pictured as a conformationally locked metallacyclopropane (59). The activation barrier for rotation of the C2H4 ligands around the Rh-olefin (centroid) vector in 19 was determined to be 15.0 0.2 kcal/mol. In contrast, the rotational barrier for the C2H4 ligand in 18 was demonstrated to be 13.6 0.6 kcal/mol... 

Under these circumstances, it is inevitable to estimate the active conformation of a chemical by another approach. The quantitative structure-activity relationship (QSAR) O) is one of the important approaches, particularly when the target site of a biologically active compound is unknown. Although X-ray crystallography is also helpful to estimate the active conformation, it provides the conformational information in a solid phase. More important is the conformation of a chemical in solution, which can be assigned in part by spectroscopic studies. Nuclear magnetic resonance (NMR) spectroscopy has been utilized to estimate the relative orientation of each atom in a molecule (2-5). Infra-red ( IR) spectroscopy is sometimes a useful tool, especially when hydrogen bonds are present ( ). Recently,... 

However, these spectroscopic methods deal with various low energy conformations of molecules in solution or crystal state and it is difficult to seek the active conformation only from the spectroscopic studies. 

In recent years, much effort has been spent trying to determine the absolute configuration of the many polyene macrolide asymmetric centers, using well-established enantioselective organic transformations and advanced spectroscopic studies. This work is a necessary prelude to any accurate chemical modification, conformational analysis related to biological activity and, of course, attempt to totally synthesize a given antibiotic or analogue. 

The Ca " -binding characteristics of the products of Factor IX activation are similar to those of the native zymogen.A low a-helical content and a high level of /3-structure and random coil conformations were the main conformational features of all the products as shown by c.d. spectroscopic studies. 

The anomalous activity characteristics have been attributed to conformational changes of the solubilized enzyme [49], but more recent spectroscopic studies seem to indicate that this is not the main cause. Solubilization of an enzyme into microemulsion droplets does not normally lead to major conformational alterations, as indicated, e.g., by fluorescence and phosphorescence spectral investigations [28,50]. The situation is complex, however, and it has been shown by circular dichroism (CD) measurements that the influence of the oil/water interface on enzyme conformation may vary even between enzymes belonging to the same class [51]. In the case of human pancreatic lipase, the conformation of the polypeptide chain is hardly altered after the enzyme is transferred from a bulk aqueous solution to the microenvironment of reverse micelles. Conversely, the CD spectra of the lipases from... 

The pH of the reaction medium is another important factor for modulating both the activity and enantioselectivity of Lipase OF. The enzyme showed optimal hydrolysis activity at pH 4.0, while the enantioselectivity increased sharply with the decrease in medium pH from 4.0 to 2.2. Based on spectroscopic studies, the enhancement of the lipase activity and enantioselectivity at the lower pH could be attributed to the changes in the flexible and sensitive conformation of the lipase induced by tuning the biocatalyst microenvironment. Using a hybrid strategy by modulating pH and surfactant, enantiomer-enriched (5)-ketoprofen could be obtained with 95.5% ee and 39.1% yield from rac-ketoprofen chloroethyl ester (100 mM) at pH 2.5 in the presence of 0.5% (w/v) Tween-80 as a modulator. ... 

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