Polymorphism conformational polymorphs

Conformational polymorphs conformational polymorphs are different pure crystal forms of the same snbstance that differ in one or mode bond rotations in the molecular structure. The implication is that these two or more conformers are in rapid equilibrinm under the conditions under which the crystal formed and hence usnally represent rotations about single bonds. If this were not the case the different conformers wonld be distinct isomers and would be formally different chemical substances and hence not polymorphs. Crystal packing interactions can stabilise particular conformers that are relatively unstable in solntion and hence crystals can contain sometimes surprising conformational isomers. A remarkable example is trans-l,4-diethynylcyclohexane-l,4-diol which has two forms (A and... 

Different crystalline structures of one substance (single- or multicomponent) are named polymorphs [9, 10]. Polymorphism, which exists as a result of different crystal packing of rigid molecules, is called a packing polymorphism. Conformational polymorphism is a more common phenomenon for typically flexible drug-like molecules and results from crystallization of different conformers of the same molecule. At a given enviromnental conditions (temperature, humidity, pressure, etc.) only one solid form is thermodynamically stable (lowest free energy), while all other forms are considered metastable. 

Unlike other synthetic polymers, PVDF has a wealth of polymorphs at least four chain conformations are known and a fifth has been suggested (119). The four known distinct forms or phases are alpha (II), beta (I), gamma (III), and delta (IV). The most common a-phase is the trans-gauche (tgtg ) chain conformation placing hydrogen and fluorine atoms alternately on each side of the chain (120,121). It forms during polymerization and crystallizes from the melt at all temperatures (122,123). The other forms have also been well characterized (124—128). The density of the a polymorph crystals is 1.92 g/cm and that of the P polymorph crystals 1.97 g/cm (129) the density of amorphous PVDF is 1.68 g/cm (130). 

In concluding this discussion, it is important to point out that crystalline polymers can be polymorphic because of slight differences in the conformation of the helical disposition of stereoregular polymer chains the polymorphism is attributable to differences in the weak intermolecular bonds. This abstruse phenomenon (which does not have the same centrality in polymer science as it does in inorganic materials science) is treated by Lotz and Wittmann (1993). 

Likewise for 4-aminopyrazoles 46 and 5-aminopyrazoles 47 (Scheme 28), the most stable tautomer possesses either the amino structure 46a [76AHC(S1), pp. 425, 445 98H(49)157]-or 47a [76AHC(S1), pp. 420, 444 84CHEC-I(5)167 96CHEC-II(3)1], X-Ray structural analysis revealed that the parent 4-aminopyrazole exists in the solid state in two polymorphic forms of amino tautomer 46a these forms differ only by the conformation of the NH2 group [98H(49)157j. 

Ikura M, Ames JB (2006) Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily two ways to promote multifunctionality. Proc Natl Acad Sci USA 103 1159-1164... 

Within the class of polymer crystals having, ideally, long-range positional order for all the atoms, different crystalline forms (polymorphs) may arise as a result of having different almost isoenergetic macromolecular conformations (of the main chain, in most known cases) or as a result of different, almost isoenergetic modes of packing of macromolecules with identical conformations [1-3]. 

Polymorphic forms characterized by widely different conformations are observed in several cases. 

A polymorphic behavior involving packing of chains having completely different conformations has been found also for isotactic polymers. For instance, isotactic polystyrene, under suitable experimental conditions, can produce crystalline gels in which the chains assume a nearly fully extended conformation [11,12], very close to a truns-planar, rather than the classical conformation of three-fold helix [13]. The two possible conformations proposed for the two crystalline forms of i-PS are shown in Fig. 2. 

In other cases, polymorphic forms are characterized by slightly different conformations. In other words, while the chain conformations packed in the different polymorphs are different, they correspond, however, to small variations in the sequences of the dihedral angles along the main chain. 

The different chain conformations observed in different polymorphic forms of a polymer are generally associated to nearly equivalent minima in the conformational energy maps, calculated for isolated chain models [2, 3],... 

An analogous case, of identical chain conformations as well as of similar unit cell dimensions, have been described for the two crystalline forms of poly-p-phenylene terephtalamide [33-36] (better known with the trade name of Kevlar). The projections along the c axis of the packing of the chains proposed for the two forms [36] has been sketched in Fig. 8, corresponding to the localization of the chain axes in (0,0, z) and (1/2,1/2, z) for the more common polymorph, in (0, 0, z) and (1/2,0, z) for the other polymorph. 

As usual, this can be due both to thermodynamic and kinetic reasons. In fact, the presence of comonomeric units increases, in general, the energy content of all the crystalline forms, but, since the extent of increase may be different, it may destabilize some chain conformation or some kind of packing more than other ones. On the other hand, the influence of the comonomeric units on the polymorphic behavior of a polymer can be due to a change in the crystallization rates of the various forms. 

Although the diffraction techniques are unique in providing detailed information on the structural organization at the molecular level in the different crystalline forms, there are other characterization techniques which are sensitive to the chain conformation and in some cases to the chain packing, which can be used advantageously (and in some case more efficiently than diffraction techniques) in the recognition and quantification of the different polymorphs in polymeric materials. 

Several bands of the FTIR spectra are conformationally sensitive. For this reason by this technique it is, in general, easy to distinguish between polymorphic forms presenting different chain conformations. 

It is hence easy to detect by this technique different polymorphic forms having different chain conformations. For instance, the a or p forms of s-PS (tram-planar chain conformations) present only a single methylene resonance at 48.1 ppm (vs.TMS), while the y form (helical conformation) presents two methylene resonances at 37.3 and 47.3 ppm (Fig. 20) [114]. 

It is also well known that different polymorphic forms can present largely different crystallite moduli along the chain axis (both observed and calculated). These differences can be large if large variations in the chain conformations are involved, and can have a significant influence on the bulk properties... 

Since the discovery of the double hehcal structure of deoxyribonucleic acid (DNA) by Watson and Crick in 1953 [1], there has been considerable belief that the canonical right-handed B-DNA may adopt a wide range of different conformations depending on the nucleotide sequences and environmental conditions. This speculation turned out to be a reahty [2-10]. hi hving systems, the conformational flexibility of DNA resides primarily in the polymorphs of the DNA double hehx (including right-handed and left-handed double hehcal DNA) and occurs under various environmental conditions [4j. The main family of DNA forms identified, based on circular dichroic and... 

Table 1 Conformational parameters of different polymorphic forms of DNA...

Identification of proteins that bind to Z-DNA added one further step to the establishment of the presence of Z-DNA in vivo and its possible biological role. Herbert and Rich [22] demonstrated an in vitro assay system where one type of double-stranded RNA adenosine deaminase, called DRAD-binding Z-DNA. There are evidences that topoisomerase II from Drosophila, hiunan and calf thymus recognizes a number of DNA shapes, including Z-DNA [34,35]. Bloomfield and coworkers [36] have found that the condensation of plasmids is enhanced by Z-DNA conformation in d(CG)n repeats. The information related to B-Z transition [31], the effect of ligands on it [28,29] and X-ray crystal structure data [37,38] appear to suggest that the possible biological role of this polymorphic form of DNA will be soon established. 

Arakawa, H., Nakashiro, S., Maeda, M., and Tsuji, A., Analysis of single-strand DNA conformation polymorphism by capillary electrophoresis, /. Chromatogr. A, 722, 359, 1996. 

Applications The general applications of XRD comprise routine phase identification, quantitative analysis, compositional studies of crystalline solid compounds, texture and residual stress analysis, high-and low-temperature studies, low-angle analysis, films, etc. Single-crystal X-ray diffraction has been used for detailed structural analysis of many pure polymer additives (antioxidants, flame retardants, plasticisers, fillers, pigments and dyes, etc.) and for conformational analysis. A variety of analytical techniques are used to identify and classify different crystal polymorphs, notably XRD, microscopy, DSC, FTIR and NIRS. A comprehensive review of the analytical techniques employed for the analysis of polymorphs has been compiled [324]. The Rietveld method has been used to model a mineral-filled PPS compound [325]. 

Stereochemistry. - There has been a far infra-red spectroscopic study of ethyl phosphine,130 and in combination with X-ray fluorescence, further work completed on the conformational analysis of dialkylphenyl phosphines.131 The influence of water on the conformational equilibria of trimethyl phosphate has received attention.132 There has been a low temperature solid state and matrix isolation study of methyl phosphorodichi oridate,133 and a conformational study of polymorphic modifications of diphenyl-phosphinyl acetic acid hydrazide. 34... 

Progress in molecular biology has provided a new perspective. Techniques such as the polymerase chain reaction and single-strand conformation polymorphism analysis have greatly facilitated the molecular analysis of erythroenzymopathies. These studies have clarified the correlation between the functional and structural abnormalities of the variant enzymes. In general, the mutations that induce an alteration of substrate binding site and/or enzyme instability might result in markedly altered enzyme properties and severe clinical symptoms. 

H13. Hirono, A., Miwa, S., Fujii, H Ishida, F., Yamada, K., and Kubota, K., Molecular study of eight Japanese cases of glucose-6-phosphate dehydrogenase deficiency by non-radioisotopic singlestrand conformation polymorphism (SSCP) analysis. Blood 83,3363-3368 (1994). 

K11. Kanno, H Fujii, H., and Miwa, S Molecular heterogeneity of pyruvate kinase deficiency identified by single strand conformational polymorphism (SSCP) analysis. Blood 84 (Suppl. 1), 13a... 

M6. Maekawa, M., Sudo, K., Kitajima, M., Matsuura, Y Li, S. S.-L., and Kanno, T., Detection and characterization of new genetic mutations in individuals heterozygous for lactate dehydroge-nase-B (H) deficiency using DNA conformation polymorphism analysis and silver staining. Hum. Genet. 91, 163-168 (1993). 

The classic disilene 1 is unusual in that it exists in at least three crystalline modifications orange and yellow unsolvated forms and a yellow toluene solvate (Fig. 2). The orange polymorph has a helical conformation in which all of the mesityl substituents are twisted in the same direction thus molecules of 1 in this form are chiral.51 The toluene solvate has an unusual conformation in which two mesityl rings cis to each other are nearly coplanar with the Si=Si bond, while the other two cis mesityl groups are nearly orthogonal.41 The structure of the yellow unsolvated form is not yet known. Because of the flat potential surface for the Si=Si... 

Furthermore, it is often possible to extract from the structural analysis of solid solvates a significant information on solvation patterns and their relation to induced structural polymorphism. An interesting illustration has been provided by crystal structure determinations of solvated 2,4-dichloro-5-carboxy-benzsulfonimide (5)35). This compound contains a large number of polar functions and potential donors and acceptors of hydrogen bonds and appears to have only a few conformational degrees of freedom associated with soft modes of torsional isomerism. It co-crystallizes with a variety of solvents in different structural forms. The observed modes of crystallization and molecular conformation of the host compound were found to be primarily dependent on the nature of the solvent environment. Thus, from protic media such as water and wet acetic acid layered structures were formed which resemble intercalation type compounds. 

In addition to quantitative crystallinity data, IR and Raman have been proven valuable tools to extract information on chain conformation in the three major phases [112-114], local order in amorphous polymers [115,116] high throughput characterization [117] and structural and polymorphic changes on heating and cooling semi-crystalline polymers [118-120]. 

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