## 3 Biotransformation of Viniferins
### Prediction of Some Parameters That Describe Drug-Likeness
#### 5.2.1 General Overview
A more detailed view on the relationships between (i) in silico structural and physicochemical properties (Tables S2-S4), (ii) chosen in silico structural as well as physicochemical properties (Tables S2-S4) and ability to permeate via selected biological barriers (Table S4), (iii) chosen in silico structural as well as physicochemical properties (Tables S2-S4) and 'virtual' impact on selected CYP isoenzymes (Tables S5 and S6), (iv) chosen in silico structural as well as physicochemical descriptors and possible toxicological issues (Table S7) of the analyzed compounds (**16**)-(**29**) was provided using a chemometric principal component analysis (PCA) method [157]. The details are offered in the following paragraphs. The chemometric PCA technique (Table S6) was performed using a trial version of an XLSTAT ver. 2019 2.2 statistical software add-in (Addinsoft, New York, NY, USA) working in the Microsoft Excel environment. Regarding PCA that considered 'only' structural and physicochemical descriptors, all relevant parameters listed in Tables S2-S4 were included in that analysis. The calculated acid-base dissociation constants (p\(K_{\text{a}}\)) were excluded from the evaluation because all the investigated derivatives (**16**)-(**29**) were weak acids with pK\({}_{\text{a}}\)s \(\geq\) 8.1 and, in addition, contained a variable count of groups, which theoretically could be deprotonated (Figures S2-S15). The details connected with this evaluation are provided in Section 5.2.2. The \(n_{\text{sc}}\), Fsp\({}^{3}\), \(n_{\text{rotb}}\), \(n_{\text{rigb}}\), \(n_{\text{r}}\), \(n_{\text{c}}\), \(n_{\text{het}}\), \(n_{\text{OHNHH}}\), and \(n_{\text{OH}}\) parameters were not included in PCAs focusing on the exploration of the relationships between structural as well as physicochemical descriptors of the compounds (**16**)-(**29**), their ability to permeate via various biological barriers, and the impact on the chosen CYP isoenzymes (Tables S5 and S6), respectively. The reason was the minimum variance of the calculated values. For example, only five different Fsp\({}^{3}\) values could be utilized if a given parameter would be implemented (Table S2). Furthermore, the log \(S_{\text{ESOL}}\), log \(S_{\text{ALL}}\), and log \(S_{\text{S-IT}}\) solubility descriptors were not included as well because almost all of these outputs indicated poor aqueous solubility of (**16**)-(**29**). Finally, the calculated pK\({}_{\text{a}}\) parameters were not considered. The linearity of the inspected relationships was described with positive or negative \(r\) values (Table S6). The PCA technique was also used to adequately interpret the relationships between the chosen structural as well as physicochemical descriptors and possible toxicological issues (Table S7). The \(n_{\text{sc}}\), Fsp\({}^{3}\), \(n_{\text{rotb}}\), \(n_{\text{rigb}}\), \(n_{\text{r}}\), \(n_{\text{c}}\), \(n_{\text{het}}\), \(n_{\text{OHNHH}}\), \(n_{\text{OH}}\), log \(S_{\text{ESOL}}\), log \(S_{\text{ALL}}\), log \(S_{\text{S-IT}}\), and pK\({}_{\text{a}}\) parameters were excluded from this chemometric evaluation. 2.2 Predicted Structural and Physicochemical Properties of Chosen Viniferins and Viniferin-Based Compounds  
The preliminary view on eventual similarities or differences in the in silico structural and physicochemical descriptors, i.e., \(MW\), \(n_{\text{sc}}\), Fsp\({}^{3}\), \(MR\), \(V_{\text{vdW}}\), \(n_{\text{rotb}}\), \(n_{\text{rigb}}\), \(n_{\text{r}}\), \(n_{\text{C}}\), \(n_{\text{het}}\), flexibility, \(n_{\text{OHNHH}}\), \(n_{\text{ON}}\), MLOGP, CLOGP 4.0, WLOGP, ALOGPS, XLOGP3, miLogP 2.2, log \(D_{7A}\), \(tPSA\), log \(S_{\text{ESOL}}\), and log \(S_{\text{ALI}}\) (Tables S2-S4), of the evaluated compounds (**16**)-(**29**) was provided through PCA (Figure 13). The entire set of these molecules was visualized in the constructed coordinate system of Principal Component 1 (PC 1) \(\times\) PC 2. The analyzed derivatives (**16**)-(**29**) were grouped or visually 'isolated' following similarities or differences in given properties.