Conformational and Structural Analysis

Conformational Analysis.— The major effort in this area has been directed towards empirical correlations of chemical shift and conformation. Tonelli and co-workers have examined the stereosequence dependence of C chemical shifts in polypropylene (PP) poly(vinyl chloride) (PVC), and polystyrene (PS) using the rotational isomeric-state scheme of polymer statistical mechanics. The structural variation of C shifts was shown to correlate well with the occurrence of three-bond gauche (y) interactions between carbon atoms together with y interactions between carbon and chlorine atoms in PVC and ring-current shifts in PS. It has been 

Schaefer and E. O. Stejskal, Top. Carbon-13 Nucl. Magn. Reson. Spectrosc., 1979.3, 283. 

Statistical Mechanics of Chain Molecules , Wiley-lnterscience, New York, 1969. 

Winnik et al. have suggested that the doublet structure of the H peak of long n-alkanes in certain solvents arises from solvation effects at the chain ends rather than conformational effects as first thought. 

---

Caminati, W., A. C. Fantoni, L. Schafer, K. Siam, and C. Van Alsenoy. 1986. Conformational and Structural Analysis of Methyl Hydrazinocarboxylate by Microwave Spectroscopy and Ab Initio Geometry Refinements. J. Am. Chem. Soc. 108,4364 1367. 

This Chapter is restricted to synthetic polymers and is divided as in Volume 1 into three main sections on conformational and structural analysis, the dynamics of polymers in solution, and the phase structure and dynamics of bulk polymers. However, the limited space available forbids mentioning the 400 or so papers that could have been included. Since the majority of these papers involve the relatively routine use of n.m.r. as an analytical tool, the section on structural analysis has been considerably abbreviated and now includes only a few papers of general theoretical or experimental interest. It is felt that in this Series it is more useful to maintain a reasonably comprehensive coverage of the remaining sections, rather than a sketchy coverage of the whole. 

Nuclear Overhauser enhancements are not just an experimental curiosity. They are independent relaxation parameters which can be used to investigate molecular motions in detail. Also, the technique of measuring specific H- H Overhauser enhancements by NOE difference spectroscopy detects spatial rather than chemical proximity and hence adds a powerful new tool to conformational and structural analysis. 

The thermodynamic analysis of conformational and structural transformations in the melt at high pressures34 showed that the free volume and free energy minimum required for hydrostatic compression is attained as a result of the transition of the molecules in the melt into a more extended conformation (gauche —> trans transitions) since the extended molecules ensure a more compact packing of the chains at compression. Chain uncoiling leads to a decrease in their flexibility parameter f with increasing pressure p ... 

Analysis of the conformational and structural stability of N-vinylnitrone CH2=CH—N(0)=CH2 and /V-(2,2-dichlorovinyl)nitrone CCl2=CH-N(0) = CH2 with DFT-B3LYP and MP2 methods revealed that they have a planar structure resulting from the apparent conjugation between C=C and N=C bonds. 

In addition, any rational approach to peptide hormone and neurotransmitter design must ultimately depend on the application of physical-chemical principles of conformation and structure, the use of various spectroscopic methods (especially nuclear magnetic resonance, circular dlchrolsm, and Raman spectroscopies. X-ray analysis where possible, etc.), and an understanding of the nature of a hormone-receptor Interaction In physical-chemical terms. Here again the use of conformatlonally restricted peptide structures Is critical (, 2. Recently we have... 

Raman and IR Conformational changes and structural analysis of the species 129,132)... 

The Boehringer Ingleheim HPV project was discontinued during lead optimization [140] nevertheless, this effort shows how in the absence of structural validation, a variety of assays can be used to identify and verify inhibitors. It also illustrates the importance of information gained through crystal structures and structural analysis, and the ability of small molecules to exploit the conformational mobility of hydrophobic hot spots. 

The IR and VCD spectra of a molecule are exquisitely sensitive to its three-dimensional structure, i.e., its stereochemistry. In addition, enantiomers exhibit mirror image VCD spectra. Consequently, IR and VCD spectra can be used to elucidate the conformational structure(s) of a molecule and VCD can, in addition, be used to determine its absolute configuration (AQ. In this section, we discuss the protocol by which conformational and configurational analysis is carried out, using the ab initio DFT calculational methodology described in the previous section. 

In the next section, the determination of the structure of (l->3)-B-D-glucan wi 11 be described in detail since it represents a complex structure solved with the help of x-ray diffraction and computer-based conformational and packing analysis. 

Vibrational circular dichroism (VCD) was developed as a supplementary technique in the 1970s, and is the IR counterpart of CD [398]. VCD measures the differential absorption of left and right circularly polarized IR light by chiral molecules. Since there are more spectral lines in the IR region than in the UV and each can have a chiral response, a more elaborate stereochemical and structural analysis is possible than on the basis of CD. Researchers have started to use VCD for conformational studies of all classes of chiral molecules, especially carbohydrates [399]. 

The crystal and molecular structure of a tri-O-ethylamylose polymorph, TEA-3, has been solved by stereochemical conformation and packing analysis, combined with X-ray fibre diffraction analysis. The unit cell is orthorhombic, space group jP2i2i2i, with a = 15.36 ( 0.03)A, Z> = 12.18 ( 0.05)A, and c (fibre repeat) = 15.48 ( 0.01) A. The actual chain conformation is a 43 helix with the 6-ethoxy-group in the tg position, as was previously found for the polymorph TEA-1. 

Proton ( H) NMR, initially, was used for structural characterization, and use of the Karplus equation has allowed conformational and configurational analysis to be carried out on a wide range of polymers in solution (42). The advent of... 

A novel approach based on the application of solid-state NMR spectroscopy has been reported that permits the rapid determination of 3D molecular structure with a single uniformly isotope labelled sample. Analogy with the solution NMR spectroscopic investigations is used, which rely on the detection of short distances between hydrogen atoms providing the principal source of information about the 3D fold of the protein. Since the 2D H, H-correlation methods are of limited use for solid-state NMR spectroscopy due to the restricted spectral resolution, the indirect detection and structural analysis of interactions via C, C-correlation spectroscopy is proposed. It has been shown that combined with dihedral-angle constraints, which can be derived from conformation-dependent chemical shifts, the characterisation of the 3D molecular structure from a single protein sample becomes possible. The new approach has been demonstrated on kaliotoxin, a 38-residue peptide. 

Taken together, LMSD developed by the Lipid MAPS consortium contains a large body of lipid information and a suite of tools in providing vital conformity in lipid nomenclature and structural analysis. LMSD should play an important role in advancement of lipidomics research. 

The most fundamental problem in evaluating the structure of polymer gels is the structural analysis on the molecular level, in particular, the determination of molecular conformation and quantitative analysis. 

Widmalm in a short review based mostly on the results of his laboratory has presented a perspective on structures of carbohydrates. He has underlined the central position of the solution state NMR spectroscopy in these studies starting with analysis of the primary structure of glycans (components and sequence), followed by conformational and dynamics analysis to the study of interaction with proteins. He has also anticipated that among other NMR parameters DFT calculated vicinal proton-proton, proton-carbon and carbon-carbon scalar couplings will aid these investigations. 

In previous papers a method was proposed to overcome the difficulties in evaluating structural models for liquid crystalline phases. If the crystalline phase of the side-chain polymer is available and the changes between the crystalline and liquid crystalline phases are known, the packing of the liquid crystalline phase may be determined. The accessibility of the polymer crystal structure by x-ray methods combined with conformation and packing analysis has become a standard method in polymer science. " ... 

A R, D P Dolata and K Prout 1990. Automated Conformational Analysis and Structure Generation Algorithms for Molecular Perception. Journal of Chemical Information and Computer Science 30 316-324. 

MJ McGregor, SA Islam, MJE Sternberg. Analysis of the relationship between side-chain conformation and secondary structure m globular proteins. J Mol Biol 198 295-310, 1987. 

---