## 3 Results and Discussion
### Computational Calculations
#### 3.4.2 The Complex of [Cu\({}^{\rm II}\)(\(\beta\)-CD)(EZM)]\({}^{2+}\)
The \(RSR\)-EZM partially enters the inner cavity of the \(\beta\)-CD and forms a Cu-O coordinate bond with a length of 2.05 A. The rest of the Cu-O bond lengths were 2.29 A and 2.12 A, respectively. The H-bond length between the hydrogen atom nearby and the oxygen atom on the \(\beta\)-CD was 1.66 A. Another H-bond forms at the large rim side, similar to the situation in Figure 6A with the same bond length. The binding energy for this pattern (Figure 6B) is 7.42 kcal/mol higher than the former optimized cluster (Figure 6A). In the \(SR\)-EZM case, we observed a similar binding mode with that shown in Figure 6B; that is, at least one part of the drug molecule entered the cavity and coordinated with the copper ion. The optimized structure of \(SR\)-EZM allows the drug molecule completely penetrating to the cavity of \(\beta\)-CD (Figure 6C). The phenyl ring moved to a position where it can act with the copper ion, possibly through \(\pi\)-\(\pi\) conjugation. In this complex, there are two oxygen atoms on the \(\beta\)-CD which interacting with the Cu(II) ion. With 2.10 and 2.04 A Cu-O bond lengths, making the whole complex more stable. Besides, the OH group near this phenyl also form two H-bonds with the \(\beta\)-CD. The bond lengths are 1.67 A and 1.65 A, respectively. In this optimized conformation, the coordinate bond between the copper ion and the drug molecule contributes significantly. We also observe another energy-favorable form (Figure 6D) that is same as the one shown in Figure 6B, where the EZM partially enters the inner cavity of the \(\beta\)-CD and forms a Cu-O coordinate bond with a length of 2.12 A. The other part which possesses a hydroxyl group acts with the H atom on the rim formed a H-bond with a length of 1.76 A. The Cu-O distances are 2.12 A, 2.13 A, and 2.17 A respectively. The energy is 2.02 kcal/mol higher than the optimized structure (Figure 6C), but 2.33 kcal/mol lower than the similar form for \(RSR\)-EZM (Figure 6B). As it is described previously, both the \(RSR\)-EZM and \(SR\)-EZM are observed to be stabilized with one OH group coordinating with the Cu and the other forming H-bond with the oxygen on the \(\beta\)-CD (Figure 6B,D). However, the \(SR\)-EZM tend to pass through the \(\beta\)-CD cavity and stretch to other side (Figure 6C) while the \(RSR\)-EZM is more likely to drop down from the cavity (Figure 6A). This may result from the difference of their conformation. Taking Figure 6C as an example, assuming that the \(SR\)-EZM are replaced with \(RSR\)-EZM, the hydroxyphenyl and the 3-(4-fluorophenyl) in the drug molecule would both tilt to the \(\beta\)-CD and even insert into its skeleton (Figure 6E). Compared with the \(SR\)-EZM, the \(RSR\)-EZM cannot form coordinate bonds with the copper ion. Besides, the angle between the two 4-fluorophenyls enlarges to almost 180\({}^{\circ}\), causing the steric geometry conformation of the drug molecule to become greatly distorted. During our optimization, when the \(RSR\)-EZM is put completely penetrating the whole \(\beta\)-CD cavity manually for the initial structure, the optimized procedure always turns out to be a failure, which is corresponding to the assumption.