*2.1. Stoichiometry in a Water–Methanol Solution*

Inclusion stoichiometry in solution was first assessed as a means to understand the preferences of this host–guest system. For this, <sup>1</sup>H spectra were collected for series of solutions of EFV and γ-CD, prepared by the continuous variation method (see Section 3.3 for details).

The plot of χ(γ-CD) × ∆δ against the χ(γ-CD), for the two protons of γ-CD located at the inner cavity (H3 and H5), is represented in the Figure 2. The maximum of the experimental points, indicative of the host-to-guest proportion in the inclusion complex, is found at the χ(γ-CD) value of 0.6, thus indicating that the preferred stoichiometry is 3:2, that is, the most abundant species in this liquid medium is (γ-CD)3·(EFV)2. Note that

the presence of other species, namely the 1:1 complex, i.e., (γ-CD)·(EFV), albeit in lower abundance, cannot be excluded [21–23].

**Figure 2.** Job plot of the host protons H3 and H5 for the inclusion of efavirenz into γ-CD, measured in a mixed solution of D2O and CD3OD (1:1).
