Molecular solids, polymorphs

The properties of molecular solids are well known to depend not only on the structure of the molecule itself, but also on the three-dimensional architecture adopted during crystallization. Such is the variation in properties with crystal structure that the existence of different polymorphs can, for example, switch on and off photoinduced reactions as well as profoundly affect the pharmaceutical activity of drugs [1-3]. 

Even though molecular crystal polymorphs contain exactly the same molecules or ions, they usually possess different chemical and physical properties such as density, diffraction pattern, solid-state spectra, melting point, stability and reactivity. 

The problem of whether an amorphous material may or may not be considered a form of a solid substance has been discussed [18a]. Many compounds yield stable noncrystalline phases either as the exclusive product of a crystallization process, or in a mixture with crystals or as a consequence of the treatment of otherwise crystalline phases [18]. The fundamental drawback when dealing with amorphous phases is the dearth of techniques for the thorough characterization of an amorphous phase or for the discrimination between different amorphous phases. In general, diffraction techniques are of little help when dealing with amorphous materials and one has to rely mainly on spectroscopic means (see below). Clearly, if one takes the fulfilment of Bragg s law as the pre-condition for the existence of a crystalline phase, and hence for the existence of a molecular crystal polymorph, amorphous materials are not to be considered. 

A (molecular) crystal polymorph is a solid crystalline phase of a given compound resulting from the possibility of at least two different arrangements of the molecules of that compound in the solid state Conformational polymorphs are formed by molecules that can adopt different conformations in different crystal structures formed by coordination complexes where ligands bound in delocalized bonding modes adopt different relative orientations Concomitant polymorphs are polymorphic modifications of the same substance obtained from the same crystallisation process Pseudo-polymorphs are ... 

It has been argued above that molecular crystal polymorphism can be seen as a form of crystal isomerism, and that the change in crystal structure associated with polymorph interconversion, i.e. a solid-to-solid phase transition between ordered... 

In spite of the great interest in the phenomenon of polymorphism and of the increased research activity beyond the boundaries of organic solid-state chemistry, it is a fact that only a few molecular compounds possess several crystalline forms, whereas for many other tens of thousands of molecular compounds only one crystalline form is known. In other words, why are there so few molecular crystals polymorphs The often quoted association between number of known forms and the time and energy spent in searching for them put forward by McCrone probably contains the answer to this question. It is probable that if thorough (combinatorial ) crystallization experiments were carried out on any given molecular species or molecular salt, alternative crystalline forms would be found. It is probable but not certain. 

Winter, G. (1999). Polymorphs and solvates of molecular solids in the pharmaceutical industry. In Reactivity of molecular solids, the molecular solid state (ed. E. Boldyreva and V. Boldyrev), Vol. 3, pp. 241-70, John Wiley Sons, Ltd., Chichester. [240]... 

Another empirical rule is the Heat of Fusion Rule, which states that if the higher melting form has a lower heat of fusion relative to the lower melting form, then the two forms bear an enantiotropic relationship. Less well obeyed is the Density Rule, which states that the most dense form will be the most stable at absolute zero. Strictly speaking, the Density Rule is only properly applied to polymorphs of molecular solids where intramolecular hydrogen bonding is not a significant factor. 

Two examples of molecular mobility liberated near two different first-order transitions, namely a solid-solid polymorphic transition and melting, are described ... 

The differences between polymorphs and hydrates are significant. The basis for all these differences is that polymorphs are different crystal structures of the same molecules(s) while hydrates are crystals of the drug molecule with different numbers of water molecules. As discussed above, the hydration state (and therefore the structure) of a crystalline hydrate is a function of the water vapor pressure (water activity) above the solid. Polymorphs, however, are typically only affected by changes in water vapor pressure if water sorption allows molecular motion, which in turn allows a reorganization into a different polymorph (i.e., a solution mediated transformation). This distinction is particularly important in defining the relative free energy of hydrates. A simple (only one molecule) anhydrous crystalline form is a one component system, and the free energy is, practically, specified by temperature and pressure. A crystalline hydrate is a two-component system and is specified... 

The concept of the multi-component molecular solid covers co-crystals, mixed crystals, salts, clathrates, and complexes. As Yan and Evans have indicated,multi-component systems of luminescent dyes with a variety of co-assembled units offer a more flexible method for tuning the packing-directed luminescent properties of the dye than the formation of polymorphs of the pure material. An example has already been given above (16). ° Another example is the organic salts of anthracene-2,6-disulfonic acid (20) with amines (Scheme 6). ... 

Two underlying mechanisms of color change in a piezochromic material have been advanced (/). In a polymorphic crystalline solid diat has one phase at ambient pressure and another at hi pressme, the corresponding colors or optical properties of the two phases can be observed by pressme-induced phase transition. Alternatively, pressure induced changes in molecular geometry and intermolecular interactions of the molecular solid can cilitate die continuous variation of optical properties with pressure. The latter mechanism appears to... 

P—Oteraiinai bond distances are 160 and 140 pm. When the vapour is condensed rapidly, a volatile and extremely hygroscopic solid is obtained which also contains P4O10 molecules. If this solid is heated in a closed vessel for several hours and the melt maintained at a high temperature before being allowed to cool, the solid obtained is macro-molecular. Three polymorphic forms exist at ordinary pressure and temperature, with the basic building block being unit 15.59. In each polymorph, only three of the four... 

A soft mode is a lattice mode whose frequency becomes imaginary at some value of the density (or external pressure). See e.g. Dove, M. T. Rae, A. I. M. Structural phase transitions in malononitrile, Faraday Disc. 1980, 69, 98-106. The whole discussion, entitled Phase transitions in molecular solids , is extremely instructive reading for the theory, experiment, and simulation of second-order phase transitions, operatively defined as those transitions that occur without a major discontinuity in enthalpy and heat capacity the onset of molecular rotation is an example, as opposed to first-order transitions like polymorphic transitions or melting. 

The diffusion, location and interactions of guests in zeolite frameworks has been studied by in-situ Raman spectroscopy and Raman microscopy. For example, the location and orientation of crown ethers used as templates in the synthesis of faujasite polymorphs has been studied in the framework they helped to form [4.297]. Polarized Raman spectra of p-nitroaniline molecules adsorbed in the channels of AIPO4-5 molecular sieves revealed their physical state and orientation - molecules within the channels formed either a phase of head-to-tail chains similar to that in the solid crystalline substance, with a characteristic 0J3 band at 1282 cm , or a second phase, which is characterized by a similarly strong band around 1295 cm . This second phase consisted of weakly interacting molecules in a pseudo-quinonoid state similar to that of molten p-nitroaniline [4.298]. 

In the penultimate section, it is shown, with some examples, that other characterization technique (in particular FTIR and solid-state NMR), besides diffraction techniques, can be useful in the study of the polymorphism of polymers at the molecular level. 

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