Some examples of conformational polymorphism

Because of its sensitivity to differences in molecular conformation and molecular environment, solid state NMR can be a particularly useful technique to recognize conformational polymorphs. Often, detail can be extracted to structurally characterize the polymorphs which may be useful in the absence of crystal structure analyses (Smith et al. 1998 McGeorge et al. 1996). 

In general, the very extensively studied family of steroids (Duax and Norton 1975 Duax et al. 1 %2b) have exhibited a remarkable degree of conformational consistency (Duax etal.l 982a). Quite a few of them do exhibit polymorphism, however (Kuhnert-Brandstatter 1971) and as has been pointed out elsewhere (Duax et al. 1982a), any variety observed in the conformations of these molecules can provide useful information on the range of conformations accessible, and even on the mode of physiological action of a particular molecule or family of molecules. For instance, cortisone acetate 5-V is known to crystallize in at least three unsolvated forms (Kanters et al. 1985) 

The very rich structural chemistry of organometallic compounds also provides many examples of conformational polymorphism. For instance, cyclic ligands often have low barriers to rotation so that conformational variations between polymorphs might not be unexpected. Riley and Davis (1976) reported the structures of the dimorphic sandwich compound 5-VII, a system in which the molecular geometry is determined by the crystallographic site symmetry for both polymorphs (Fig. 5.8). In the triclinic form, the molecular site symmetry is C, requiring the trans orientation 

Some other notable examples of conformational polymorphism in organometallic complexes have been given by Foxman et al. (1981) (discussed in some detail in Bernstein 1987), Braga et al. (1992) and Wagner and Englert (1997), all of which exhibit some conformational variations in the orientation or conformation of the ligands. 

In a more recent example, Kelly et al. (1997, 1999) showed that 5-IX exists in two forms. Crystallization from hot acetonitrile yields blue crystals with square-planar coordination about the metal. Slow evaporation from methylene chloride/petroleum ether yields green needles with pseudo-tetragonal coordination about the metal. 

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In some cases molecules adopt more than one conformation in a single crystalline arrangement. When this occurs, each conformer is part of the regular array from which the crystal is built. An interesting example of this phenomenon is the reverse transcriptase inhibitor lamivudine (Fig. 27). Two crystal forms of this material are known (39). Polymorphic form II is unspectacular, characterized by a highly symmetrical tetragonal lattice containing only one conformer of lami-... 

Looking further at Figure 15-12, it would be useful to have some idea of other low-energy regions that are not populated by observed structures, and the barriers between a particular isolated structure and the majority conformation. Finally, computerized models are an important aide to thinking about why observed structures occur. For example, is the twofold conformation found in all of the pure cellulose polymorphs an intrinsically ideal form, or is it the result of intermolecular forces resulting from crystallization ... 

Finally, a few comments about the uniqueness of polymer crystal structures and phase space localization are warranted. Almost all crystallizable polymers exhibit polymorphism, the ability to form different crystal structures as a result of changes in thermodynamic conditions (e.g., temperature or pressure) or process history (e.g., crystallization conditions) [12]. Two or more polymorphs of a given polymer result when their crystal structures are nearly iso-energetic, such that small changes in thermodynamic conditions or kinetic factors cause one or another, or both, to form. Polymorphism may arise as a result of competitive conformations of the chain, as in the case of syndiotactic polystyrene, or as a result of competitive packing modes of molecules with similar conformations, as in the case of isotactic polypropylene. In some instances, the conformational change may be quite subtle isotactic polybutene, for example, exhibits... 

For some polymers, one does not observe a unique helical form but two or three different ones which possess very similar energies. Poly(oxymethylene) actually gives an example for such polymorphism . Here one can also find the helix shown in Fig. 2.4b. It also represents an a/Z- auc/ie -conformation, but the torsion angle, which was near to 60° for the first modification, now has increased to 77°. Which of the two helices is formed depends on the crystallization conditions. In principle, at a given temperature, only one of the modifications can be stable, the other one being metastable. Annealing can induce a transformation to the stable state, but often this transformation is kinetically hindered, and then it may become difficult to identify the stable modification. 

A study example concerning the solid structure of a-amino acid, polypeptide and a protein is given to introduce the basis of the chemical shift of proton NMR precisely, and studies to do this have only recently been undertaken. Some interesting work has been done, including the discrimination of amino acid crystal polymorphism, conformational analysis of polypeptides and fibrous proteins, and the determination of the N—H bond length in polypeptides. 

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