Structures of crystalline hydrates

Water [579] is present in the structure of true crystalline hydrates [580] either as ligands co-ordinated with the cation (e.g. [Cu(OH2)4]2+ in CuS04 5 H20) or accommodated outside this co-ordination sphere within voids left in anion packing, further stabilized by hydrogen bonding (e.g. the remaining water molecule in CuS04 5 H20). 

Every water molecule in a crystalline hydrate has, as its nearest neighbours [579], two proton acceptors and at least one electron acceptor. Where only a single electron acceptor is present, co-ordination of the H20 molecule is approximately planar trigonal, and, when two are present, tetrahedral co-ordination is adopted. Large deviations from these configurations seldom occur. Classification [579—582] of the water molecules in hydrates, on the basis of co-ordination of the lone pair orbitals, has been discussed further [579,581] and modified [580] (see Fig. 9 and Table 9). For example, the water in CuS04 5 H20 is located in three different environments two H20 molecules are in Class 1, type D two are in Class 1, type J, and the remaining one is in Class 2, type E. 

Makatun and Shchegrov [583] have considered the kinetics of water evolution in terms of retention of vibrational individuality of the H20 

Classification of water molecules in crystalline hydrates on the basis of co-ordination environment 

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Hydrates of this type contain metal ion coordinated water, and the major concern with these is the effect of the metal-water interaction on the structure of crystalline hydrates. The metal-water interaction can be quite strong relative to the other bonding in a molecular crystal, so that dehydration takes place only at very high temperatures [13], Drugs with solubility, dissolution, or handling problems are most often recrystallized as Na(I), K(I), Ca(II), or Mg(II) salts and are often hygroscopic to some degree [16],... 

Depending on the pH, the cation present, and the temperature, a variety of hydrated polyborates can appear as saturating solid phases [10], In fact, many hydrated polyborates occur naturally [10]. The structures of polyborate anions in solution appear to conform to a list of rules formulated by Edwards and Ross [182] by analogy to the structures of crystalline hydrated polyborates ... 

Biochemistry and chemistry takes place mostly in solution or in the presence of large quantities of solvent, as in enzymes. As the necessary super-computing becomes available, molecular dynamics must surely be the method of choice for modeling structure and for interpreting biological interactions. Several attempts have been made to test the capability of molecular dynamics to predict the known water structure in crystalline hydrates. In one of these, three amino acid hydrates were used serine monohydrate, arginine dihydrate and homoproline monohydrate. The first two analyses were by neutron diffraction, and in the latter X-ray analysis was chosen because there were four molecules and four waters in the asymmetric unit. The results were partially successful, but the final comments of the authors were "this may imply that methods used currently to extract potential function parameters are insufficient to allow us to handle the molecular-level subtleties that are found in aqueous solutions" (39). 

Both X-ray and neutron diffraction methods are applied to determine the structure of crystalline solid hydrates. Because of the very small scattering cross-section of hydrogen atoms for X-rays it is much desirable to solve the crystal structure by means of neutron diffraction techniques. 

Hydrogen bonds play an important part in determining the structures of crystalline compounds containing N, 0, or F in addition to H. We deal here with the hydrides of these elements, and with certain fluorides, oxy-acids, and acid salts. Ice and water, together with hydrates, are considered in Chapter 15, and hydroxy-acids are grouped with hydroxides in Chapter 14. 

Many metal carboxylates are prepared in the form of hydrates and water is lost in a lower temperature range than that required for the onset of anion decomposition [86]. The removal of water from the structure must be accompanied by substantial bond redistribution within the anhydrous phase so formed, and this can sometimes lead to structural reorganization within the solid [142]. Nickel salts, prepared in the form of crystalline hydrates, however, show a low degree of lattice order after water removal [116,118,121]. The crystal structures of few dehydrated metal carboxylates are known in any detail, an omission that must be remembered in formulating reaction mechanisms. 

A second consequence of the tetrahedral structure of the water molecule is that these molecules may also occur in a crystal structure in a different capacity, without any cation neighbours i.e. they may be bound only to other water molecules (as is, of course, the case in ice) or to some water molecules and to some anions, provided that such an arrangement can be achieved in a way which satisfies the characteristic charge distribution. These distinctive roles of water provide a convenient basis for the classification of crystalline hydrates into two groups, as we now explain. 

With the exception of cellulose and chitin, plant polysaccharides are usually hydrated. Hydration often occurs in the crystalline regions as well as in the amorphous areas. When water of hydration is found in the crystallites, it may or may not affect the conformation of the polysaccharide backbone and in most cases, it affects the unit-cell dimensions, while in a few cases, the water appears to have no effect on unit-cell dimensions. The structures of six hydrated neutral polysaccharides will be examined with regards to the state of water of hydration in the structure. It wi 11 be seen that water may occur as columns or as sheets in these structures. The structures that will be discussed are (1 4)-3-p-xylan, nigeran, amylose, galactomannan, (1 3)-3-p-gTucan and (1 3)-s-P-xy1 an. The chemical structures of these polysaccharides are shown in Figure 1. 

Crystalline hydrates have been classified by either structure or energetics [6]. The idea of the structural classification scheme presented here is to divide the hydrates into three classes that are discernible by the commonly available analytical techniques. The classification of crystalline hydrates of pharmaceutical interest by their structural characteristics is the most common, intuitive, and useful approach. A good classification system should direct the preformulation/formulation scientist to the characteristics of the particular class that will help in identifying a new sample, in selecting the proper form of the substance, and in estimating boundary conditions for safe handling (Table 3). 

This subclass of crystalline hydrates has its water localized in a two- dimensional order, or plane. Figure 18 shows the packing diagram for sodium ibuprofen, where the waters of hydration are associated with the sodium ions localized in the a-c plane of the lattice. A similar structure has been reported for nedocromil zinc [23]. In both cases the water is ion associated, but there is no obvious reason that such structures require this to be the case. In the case of nedocromil zinc, the long axis of the crystal is perpendicular to the hydration plane, and under crossed polarizing microscopic optics was observed to dehydrate... 

Based on their structural characteristics, crystalline hydrates were broken into three main classes. These were (1) isolated lattice site water types, (2) channel hydrates, and (3) ion associated water types. Class 2 hydrates were further subdivided into expanded channel (nonstoichiometric) types, planar hydrates, and dehydrated hydrates. The classification of the forms together with a suitable phase diagram provides a rationale for anticipating the direction and likelihood of a transition, including transitions that may be solution mediated. 

Lehmann drew attention to some features in solid-state reactions, including the curious observations described in 1834 by Faraday, which are now considered as pioneering experimental studies of the structural sensitivity of the dehydration rate of crystalline hydrates. Crystals of easily eroding sodium salts (carbonates, phosphates, and sulphates), stored by Faraday for a few years, did not exhibit any visible deterioration. A fresh scratch on the crystal surface (birth of mechanochemistry) initiated, however, the onset of intense dehydration with a gradual expansion of the erosion zone until it covered the crystal s entire surface. 

Product Structure A feature frequently observed in the decomposition of crystalline hydrates, which has not yet been given a convincing interpretation in the framework of universally accepted ideas, is the formation of solid products in either an amorphous or a crystalline state, depending on the actual water vapour pressure in the reactor. This phenomenon was observed by Kohlschiitter and Nitschmann in 1931 [35] and has been the subject of numerous publications, including the study of Volmer and Seydel [36], who used it as a basis for explaining the Topley-Smith (T-S) effect, and a series of articles by Frost et al. [37-39]. Dehydration of many crystalline hydrates in vacuum entails formation of an X-ray amorphous (finely dispersed) residue and, in the presence of water vapour, formation of a crystalline product. The highest H2O pressure at which an amorphous product can still form varies for different hydrates from a few tenths to a few Torr (Table 2.4). As the decomposition temperature increases, the boundary of formation of the crystalline product shifts towards higher H2O pressures. 

The presence of hydrogen bonds also causes formation of crystalline hydrates such as NH3 H2O, SO2 H2O hydrocarbon hydrates (e.g. with natural gas components) as well as the zig-zag structure of the (HF) polymer. 

Leekumjom S, Sum AK (2007) Molecular characterization of gel and liquid-crystalline structures of hilly hydrated POPC and POPE bilayers. J Phys Chem Bill 6026... 

Phosphotungstic acid (1 12) is very soluble in water, in which it is completely dissociated. The pen-tahydrate has been shown to contain complex cations and should be formulated as 3(Hj05) PWjjO s. Decomposition to oxides occurs at 420°C. The crystalline 29 hydrate is built from PWjjO anions as in Figure 5.47a, and (H3 29H20) + units. This latter salt is an exceptionally good proton conductor and this is connected with the high freedom of movement of within the cavity structure of the hydrated cation units. 

Few if any of these various disilicic acids, which are highly polymerized in two dimensions, are identical. The relation of these to the previously discussed hydrated crystalline silicas obtained from hydrated sodium polysilicates is not known. It is evident that a large number of crystalline hydrated silicas may exist, some more stable than others, but all obtained from crystalline silicates by ion exchange. No crystalline hydrate silica is likely to be formed directly in the silica-water system in the absence of cations to bring about the organization of a regular polysilicate structure. 

Mootz, D. and Wunderlich, H., Crystalline structure of acid hydrates and oxonium salts. IV Dioxonium-1,2-ethane disulfonate, Acta Crystallogr. B26,1820-1825 (1970). 

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