2.2.3. <sup>13</sup>C{1H} CP-MAS NMR

The solid-state NMR spectra of efavirenz, γ-CD heptahydrate and the two freeze-dried products of γ-CD with EFV are depicted in Figure 5.

The spectrum of efavirenz presents a set of well-resolved resonances, with multiple signals observed for its carbons with the exception of C2. Signal multiplicity for EFV carbons was previously reported by Rodrigues de Sousa et al., having been attributed to the presence of more than one polymorphs of efavirenz and to different molecular conformations [26]. The host, γ-CD, exhibits multiple sharp resonances for each type of carbon atom, which is ascribed, for C<sup>1</sup> and C<sup>4</sup> carbons, to differences in the conformation about the α-1,4 bonds, and, for carbons located closer to the rims, as is the case of C6, to ambient changes in the hydrogen-bonding network and the varying number of hydration water molecules [27,28]. In the spectra of (γ-CD)3·(EFV)<sup>2</sup> and γ-CD·EFV, the host carbons appear as single broad resonances, thus indicating symmetrisation of the γ-CD as a result of inclusion of EFV and of the spatial organisation into channels. Regarding the guest signals, and as previously noted for FT-IR results, the 1:1 sample, γ-CD·EFV, shows contamination with pure efavirenz. In <sup>13</sup>C{1H} CP-MAS NMR, this is particularly evident when one observes the carbonyl region. The spectrum of γ-CD·EFV exhibits two resonances for the carbonyl (C1, see Figure 1) with chemical shift similar to those of pure efavirenz, thus indicating the presence of non-included guest. In turn, the spectrum of (γ-CD)3·(EFV)2, bears only one resonance for the carbonyl. This indicates the presence of the pure inclusion complex, in which inclusion into the cavity of γ-CD resulted in a more symmetrical chemical environment for the C=O.

**Figure 5.** <sup>13</sup>C{1H} CP-MAS NMR spectra of (**a**) EFV, (**b**) γ-CD, (**c**) (γ-CD)<sup>3</sup> ·(EFV)<sup>2</sup> , and (**d**) γ-CD·EFV (see labelling in Figure 1). Efavirenz carbons were assigned as in Rodrigues de Sousa et al. [26].
