Studying Crystal Packing Interactions

Once H CSs are resolved, correlation experiments and CST calculation can be used to prove cocrystal formation and examine the bond properties. The crystallization of methyl paraben and quinidine produced two new peaks at 9.39 and 13.45 ppm, suggesting cocrystal formation [62]. These two new peaks were assigned using H labeling to the hydroxyl protons of quinidine (H48) and methyl paraben (H67), 

FIGURE 12.13 H- C CP-HETCOR spectrum of the methyl paraben quinidine cocrystal acquired at850MHz using a commercially available 1.3 mm MAS probe at a MAS rate=50 kHz (left). X-ray crystal structure of methyl paraben quinidine cocrystal showing intermolecnlar contacts (right). Reprinted with permission from Ref. [62]. Copyright 2010, American Chemical Society. 

Other reports show that SSNMR methods were explored to prove cocrystal formation of the solids produced during solid form screening activities [54]. H ICS and H correlation experiments were found to be the fastest and most definite methods to prove molecular association. The authors first recommend screening solids by C and H spectra to assess phase purity, confirm the presence of new crystalline species, and identify strong H-bonding between conformers from the downfield H ICS. H- C CP-HETCOR and H- H DQ recoupling experiments can then provide dipolar connectivity to demonstrate molecular association between components. CST calculations can further confirm molecular association. This protocol was vetted with nine cocrystal systems to prove complexation. 

Uldry etal. on uracil and 4-cyano-4 -ethynylbiphenyl, andMafraetal. on ciprofloxacin polymorphs, GIPAW CST and NICS calculations on the piece-wise deconstructed crystalline lattice are used to deconvolute these effects [20, 59]. 

For the antibiotic ciprofloxacin, the packing interactions and and the impact of hydration on the H and C ICSs are examined for 

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Fabian and Kalman [5] retrieved 50 structures from the Cambridge Structural Database, including the polymorphs of 22 compounds, in order to evaluate the frequency of isostructurality among polymorphs. It was found that one-, two-, or three-dimensional isostructurality was exhibited by approximately one-half of the compounds studied. Three-dimensional isostructurality was connected to the gradual ordering of crystal structures, while one- and two-dimensional isostructurality could be related to specific packing interactions. Interestingly, conformational polymorphs were not found to exhibit isostructurality. 

Highlights in the chemistry of cyclopentadienyl compounds have been reviewed.65 Trends in the metallation energies of the gas-phase cyclopentadienyl and methyl compounds of the alkali metals have been studied by ab initio pseudopotential calculations. Whereas there is a smooth increase in polarity of M-(C5H5) bonds from Li to Cs, lithium appears to be less electronegative than sodium in methyl derivatives. The difference between C5H5 and CH3 derivatives is attributed to differences in covalent contributions to the M-C bonds. In solution or in the solid state these trends may be masked by the effects of solvation or crystal packing.66 The interaction between the alkali metal ions Li+-K+ and benzene has also been discussed.67... 

Investigation of environmental effects. As has been stressed in this chapter, homoaromaticity is just a matter of a few kcal mol-1 stabilization energy in most cases, and therefore environmental effects may have a large impact on structure, stability and other properties of a homoaromatic compound. Future work in theory (as well as in experiment) has to clarify how environmental effects can influence electron delocalization, through-space interactions and bonding in homoaromatic molecules. The theoretical methods are now available to calculate solvent and counter ion effects (for homoaromatic ions in solution) or to study intermolecular and crystal packing forces in the solid state. 

In another theoretical study on metal-metal interactions in indium(I) and thallium(I) cyclopentadienyls (178), the authors interpret the short M—M contacts in the above dimers as weak donor-acceptor interactions, similar to the Sn—Sn bond in dimeric stannylenes (12) (163,175). However, they also attribute the general structural arrangement as being determined by crystal packing forces. ... 

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