Molecular structure conformation Conformations Diastereomers

Nuclear Magnetic Resonance (NMR) spectroscopy is one of the most powerful analytical techniques in organic chemistry for elucidating the molecular structures of chemicals (1,2). Moreover, an NMR spectrum may be used like a fingerprint to identify a chemical by comparing it with its reference spectrum recorded from the authentic chemical under comparable conditions. The spectrum also reveals information on molecular conformation, isomerism, molecular dynamics, and diastereomers (3 6). 

For each case in Figure 6.14, we have stereoisomers—structures with the same connectivities but differing arrangements of the atoms in space. They are not enantiomers, so they must be diastereomers. The novelty lies in the fact that these stereoisomers interconvert by a translation or reorientation of one component relative to the other. In some ways these structures resemble conformers or atropisomers, which involve stereoisomers that interconvert by rotation about a bond. For the supramolecular stereoisomers, however, interconversion involves rotation or translation of an entire molecular unit, rather than rotation around a bond. Note that for none of the situations of Figure 6.14 do we have topological stereoisomers. In each case we can interconvert stereoisomers without breaking and reforming bonds. 

This latter behavior differs from fhaf observed in fhe crystalline diastereomers of mandelic acid wifh 1-phenylefhylamine [63]. Here the n-salt crystallized in the triclinic PI space group, while the p-salt crystallized in the monoclinic P2i space group. The crystallographic structures of the two diastereomers revealed the existence of fairly equivalent hydrogen-bonding patterns, but at the same time substantially different conformations for fhe two molecular ions making up fhe donor-acceptor complex were noted. These structural differences became manifest in the relative solubilities of fhe two diastereomers, where the aqueous solubility of fhe p-salf was much less fhan fhaf of fhe n-salt. 

The term meso is commonly used to designate an achiral structure that is a diastereomer of one or more chiral structures. A meso compound contains chiral substructures but is not itself chiral because of overall molecular symmetry. Such structures often— but not always— have a plane of symmetry in at least one conformation, as is illustrated for 73 and 74. These structures are said to be internally compensated An example of a meso structure that does not have a plane of symmetry is the l,4-dichloro-2,5-difluorocyclohexane 75, which is achiral because it has a center of symmetry. Structure 75 is a diastereomer of the enantiomeric pair 76 and 77. 

Molecular modeling stndies have suggested that when proline is in the Xaa position of a (Pro-Pro-Gly)io helical strand, it adopts a Ci -endo pucker but when in the Yaa position a O-exo conformation is preferred, consistent with the observations noted above that (Pro-4-(/ )-F-Pro-Gly)io, (Pro-Hyp-Gly),o and (Pro-Pro-Gly)io form stable helical complexes [39, 49]. When a substituted proline is installed at the Xaa position, the conformational preference for the Ci -endo conformation would suggest that 4-(5)-F-Pro would function to form a collagen-like helix structure but the 4-(/ )-F-Pro diastereomer would not based on their conformational bias [39, 43]. This has been observed experimentally with both... 

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