Mannitol crystal structure

Fig. 12. Superposition of the X-ray structure of D-mannitol with its refinement from C NMR chemical shifts. Only the proton positions are refined (left), and their 50% probability spheres from the X-ray investigation are shown for comparison. The refined P-D-mannitol crystal structure (left) illustrates the hydrogen bond system.

Crystal structures of two hexitols, galactitol and D-mannitol, have been published. Galactitol is meso, but the permissible intramolecular center of symmetry is not utilized in the crystal.28 The molecules crystallize as enantiomorphic pairs that, in conformation, are almost centrosymmetric molecules the difference therefrom is of the same order of magnitude as the thermal motion of the atoms. The carbon atoms and terminal oxygen atoms form an approximately planar chain. All of the oxygen atoms are both donors and acceptors for an intricate network of hydrogen bonding. 

Another approach is to compare polymorphic forms of the same compound. This allows the comparison of molecules with the same constitution and configuration in different crystal fields. Do these different potential environments lead to different conformations There are few comparative crystal structural studies of organic polymorphs. For d-mannitol the molecules had the same conformation in all three polymorphic forms studied with differences in torsion angles for the two that were studied in detail of only a few degrees (see Table I). 

Finally, Samuelsson and co-workers designed a new C2-symmetric HIV-PR inhibitor, on the basis of X-ray crystal structures, which indicated that the HIV protease existed as a C2-symmetric dimer. The peptidomimetic scaffold of this new class of inhibitors was based on D-mannitol and duplication of the C-terminus. Compounds 21 and 22 were rapidly synthesized and displayed comparable enzyme-inhibitory and antiviral potencies to Indinavir (Figure 24.4, Table 24.1).29-32... 

The remedy to this situation is to perform a thermal treatment of the frozen solution. This treatment consists of a controlled rewarming of the solution until devitrification and recrystallization of the excipient occurs, followed by a last freezing step below the solidification temperature. A typical excipient justifiable of such a treatment on thermodynamic grounds is mannitol. In the absence of proteins that maintain the structural integrity of the pellet, mannitol solutions often yield cakes of poor appearance. The induction of mannitol crystallization by rewarming around -25°C evades this problem and allows one to obtain elegant pellets that are easy to lyophilize and do not shrink. 

Figure 4.2.2 Top Fischer projections of a few common glycitols and glyconic acids. Note the symmetrical structure of D-mannitol. Bottom Molecular structures of (a) linear D-mannitol, (b) bent D-glucitol, (c) D-glucaric acid, and (d) crystal structure of water-in-soluble D-galactaric acid. In the latter structure the intermolecular hydrogen band pattern is indicated.

IR Spectroscopy. - The FT IR spectra of galactaric acid and its K, NH4", Ca ", Ba " and La salts have been recorded and interpreted. The mid-lR spectra of some trivalent lanthanide complexes of inositols, e.g. PrCh myoinositol 9H2O, were consistent with their crystal structures. The FT IR spectra for the 2 1 1-0-a-D-glucopyranosyl-D-mannitol/ethanol adduct supported the X-ray crystallographic results referred to in Part 3.1 below. ... 

Fig. 3.17 I ce crystal structures on vertical cross-sections (10% mannitol) (a) upper position, nucleated at -2.04°C, (b) lower position, nucleated at -2.04°C, (c) upper position, nucleated at -8.17°C, (d) lower position, nucleated at —8.17°C according to Nakagawa etal. (2006).

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