Crystalline mesophases

Some drug substances can form mesophases with or without a solvent [19-26]. In the absence of a solvent, an increase in temperature causes the transition from the solid state to the liquid crystalline state, called thermotropic mesomorphism. Lyotropic mesomorphism occurs in the presence of a solvent, usually water. A further change in temperature may cause additional transitions. Thermotropic and/or lyotropic liquid crystalline mesophases of drug substances may interact with meso-morphous vehicles as well as with liquid crystalline structures in the human organism. Table 1 presents drug substances for which thermotropic or lyotropic mesomorphism has been proved. 

The LC nature of diols la-lg was demonstrated by DSC (Fig. 1). Two first order transitions were observed. The lower transition temperature appeared to be the crystalline-mesophase transition (T, ), and the higher transition temperature the mesophase-isotropic transition (T ). Other transitions were not evident in the DSC. The thermal data revealed an odd-even spacer effect for Tj . 

Polymeric material that, under suitable conditions of temperature, pressure, and concentration, exists as a liquid-crystalline mesophase (Definition 6.1 in Chapter 7). 

The most common and easily applicable method of characterising liquid crystalline mesophases is polarisation microscopy. In this method, thin samples of the surfactant solution are viewed under a microscope between crossed polarisation filters. Due to optical anisotropy of liquid crystals they are birefringent. Hence, they give rise to a brightness in the microscope and show patterns that are very characteristic for the specific phases examples are shown in Figure 3.17. 

Cho et al. described the synthesis and polymerization of 4,8-cyclododeca-dien-l-yl-(4 -methoxy-4-biphenyl) terephthalate VIII [54,55]. Polymerization was carried out with WCl4(OAr)2/PbEt4. The double bonds in the polymer backbone were subsequently hydrogenated with H2/Pd(C), leading to a SCLCP with a fully saturated hydrocarbon backbone. This polymer system had a very flexible polymer backbone but a stiff connection between the main chain and the mesogenic unit. The distance between two adjacent side chains was about 12 methylene units. This very flexible main chain allowed the polymer to organize into a LC mesophase. Both polymers - the unsaturated and the saturated -showed smectic liquid crystalline mesophases with almost the same transition temperatures (see Table 5). 

Block copolymers consisting of a smectic SCLCP-block and a partially crystalline apolar block were synthesized via ROMP of IV-n with cyclooctene and initiator 1 or 2 [63]. The block copolymers also formed smectic liquid crystalline mesophases and showed lamellar phase-separation. 

More recently, a systematic study of the properties of side-chain LC dendrimers has been undertaken on these PPI dendrimers and also on PAMAM systems by Serrano et al. [211]. In these dendrimers, the mesogenic group is connected to the dendritic scaffold by an imine linkage. In all cases, it was found that the enthalpic gain of the mesogenic units arranged as in a classical liquid crystalline mesophase dominates over the entropic tendency of the dendrimer core to adopt a globular isotropic conformation. The flexibility of the dendritic PAMAM and PPI cores allows the macromolecule to adopt... 

The two algorithms already developed and used to reproduce ESR line-shapes of paramagnetic species in free diffusion are applied in this subsection to the case of spin probes dissolved in liquid crystalline mesophases. The main point of diffoence with the previously examined cases is due to the introduction of an orienting potential v ose nature is directly reflected in the structure of the Fokker-Planck opoator, whidi in the difiusional assumption is given by Eq. (2.6). The explicit form of the potential we use in this... 

Liquid crystalline compounds are remarkable because of their ability to show spontaneous anisotropy and readily induced orientation in the liquid crystalline state. When polymers are processed in the liquid crystalline state, this anisotropy may be maintained in the solid state and can readily lead to the formation of materials of great strength in the direction of orientation. A particularly important example of the use of this property for polymers is in the formation of fibers from aromatic polyamides which are spun from shear oriented liquid crystalline solutions Solutions of poly(benzyl glutamate) also show characteristics of liquid crystalline mesophases, and both of these types of polymers are examples of the lyotropic solution behaviour of rigid rod polymers which was predicted by Flory... 

As a result of their low Tg values and lack of crystallinity, many of these polymers showed liquid crystallinity at room temperature. The liquid crystalline mesophases of the monomers were identified as nematic but the polymeric mesophases were not identified, although they possessed a very broad thermal stability between their Tg and their clearing transitions. A mesophase temperature stability of up to 170 °C was observed for the polymers with bicyclohexane central mesogenic units. These polymers showed decreases in Tg and Tj with increased spacer lengths. 

A central issue in the field of surfactant self-assembly is the structure of the liquid crystalline mesophases denoted bicontinuous cubic, and "intermediate" phases (i.e. rhombohedral, monoclinic and tetragonal phases). Cubic phases were detected by Luzzati et al. and Fontell in the 1960 s, although they were believed to be rare in comparison with the classical lamellar, hexagonal and micellar mesophases. It is now clear that these phases are ubiquitous in surfactant and Upid systems. Further, a number of cubic phases can occur within the same system, as the temperature or concentration is varied. Luzzati s group also discovered a number of crystalline mesophases in soaps and lipids, of tetragonal and rhombohedral symmetries (the so-called "T" and "R" phases). More recently, Tiddy et al. have detected systematic replacement of cubic mesophases by "intermediate" T and R phases as the surfactant architecture is varied [22-24]. The most detailed mesophase study to date has revealed the presence of monoclinic. 

The most common definition of a microemulsion characterises it as a thermodynamically stable, transparent, optically isotropic, freely flowing surfactant mixture, often containing co-surfactants (e.g. alcohol) and added salts [37]. We restrict the definition further to non-crystalline (disordered) aggregates, since crystalline isotropic phases are better considered as liquid crystalline mesophases. Indeed, the most succinct description of a microemulsion would involve its microstructure. However, this has proven to be a very equivocal issue. So much so that until very recently it was widely believed that microemulsions were devoid of microstructure hence the thermod)mamic definition. 

Figure 4.31 (Left) Schematic view of the relative arrangement of chiral molecules (extended lozenges) in the cholesteric liquid crystalline mesophase (after [59]. The twist between layers is greatly exaggerated. In reality approximately 10 layers lie between equally inclined layers. (Right ) Helical arrangement of molecules, with a relative twist between molecules along one direction only the axis of the helical ribbon.

In this context, some comments on protein crystallisation can be made. The process of crystallisation can be viewed as one of self-assembly of the quaternary structure, although the constituent units now have a well-defined arrangement in space, in contrast to their less rigid shape in liquid crystalline mesophases. Indeed, twisted structures are very commonly found in globular protein crystals, which are reminiscent of the hyperbolic forms of micro- and mesoporous zeolites, described in Chapter 2. 

The phase transition of lipid bilayers which comprise phospholipid mixtures, or phospholipids with different lengths of acyl chains, are of great importance due to their similarities with biomembranes or with lipid drug carriers such as liposomes, it is important to study the phase transitions and to detennine the exact crystalline mesophases of the mixed system. Thermal analysis studies indicated that the mi.xed lipids provide higher melting temperatures compared to those of pure lipids. This phenomenon occurrs w hen the lengths of the acyl chains are substantially different. 

EQA/1.6-Hexanediol/1.4-Butanediol Oopolvesters. Figure 2 shows the effect of BD content cm the Tin and Ti values of BDA/HD/BD copolyesters. Modification of the BDA/HD hemopolyester with BD introduced disorder in the crystalline polymer and, consequently, the Tin s decreased until sufficient BD was present to start increasing the order as the BDA/BD hemopolyester composition was approached. The Ti values, on the other hand, increased continuously because the liquid crystalline mesophase became more stable as the six-cartoon HD component of the BDA/HD homopolyester was replaced by the less flexible four-carbon BD component. 

Poly(2,5-di-n-dodecyl-l,4-phenylene) of 73000-94000 show a single anisotropic liquid crystalline mesophase in the molten state and macromolecules with Mw 44000—73000 gave coexisting isotropic/anisotropic phases [17]. 

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