*3.4. Supramolecular Analysis*

Form I is centrosymmetric (*P*21*/c*) with a unit cell containing two pairs of molecules that are identical within the pair and inversely-related between pairs. Form II is noncentrosymmetric (*P*21), thus lacking an inversion center.

The extensive hydrogen bonding network in form I is highly visible along its packing pattern, which seems to follow zigzag lines when viewed along *c* (Figure 9a). This type of pattern allows the layers of molecules to be very close to one another, hence enabling the optimal use of space available [40]. While the molecular volume of form I is greater than that of form II, packing in the former is more compact as evidenced by the volume of its Hirshfeld surface, packing coefficient and density value (Table 1). Figure 9b shows where the purine backbones seem to be parallel to one another, while the side chains are "out of plane". Layering of the guanine rings creates an off-center parallel stacking, but distance and angular parameters of the guanine ring centroids are at the upper limits for effective π ... π interactions, suggested by the literature [41,42]. This property was also highlighted by a low percentage contribution of C . . . C contacts in the fingerprint plots.

**Figure 9.** Packing in (**a**) form I and (**b**) form II, with a central molecule (pink) each having the same back-bone orientation. Hanging contacts were removed for better visualization.



The packing arrangements in both forms were compared to other crystal structures with similar molecular arrangements. However, even though there were five more entries in the CSD which involved ganciclovir as a component, only the two hydrates (mono- and tri-), resulted in having one out of a cluster of 15 molecules, with a degree of similarity when compared to both anhydrates [32] demonstrating the uniqueness of the packing patterns of form I and II. This test also verified the significant differences between the way in which both anhydrous forms were arranged three-dimensionally resulting in an RMS of 1.017 (see Figure 8).
