## 3 Biotransformation of Viniferins
### Prediction of Some Parameters That Describe Drug-Likeness
#### 5.2.1 General Overview
The lowest \(V_{\text{vdW}}\) = 344.10 A\({}^{3}\) was assigned to the compound (**29**; Table S2) that contained a properly substituted condensed bicyclic core and two aromatic rings, which were hydroxylated at 4-positions (Figure 12). The highest value of a given parameter (\(V_{\text{vdW}}\) = 550.09 A\({}^{3}\)) was generated for the derivative (**27**; Table S2) with a suitably substituted condensed bicyclic scaffold and three aromatic rings at which _Cl_-atoms, OCH\({}_{3}\)-groups, and OH-moieties were introduced. Sterically bulky substituents were attached to the proper positions of aromatic systems in the structure of the miniseries (**25**)-(**27**) increasing the relevant \(V_{\rm vdW}\)s, as expected (Figure 10, Table S2). Such predictions could be very useful because \(V_{\rm vdW}\) of molecules generally described the impact of nondirectional forces and was notably related to their activity in vitro against some Gram-positive bacteria, including several strains of _S. aureus_ and _L. monocytogenes_[167, 168, 169]. The investigated compounds contained \(n_{\rm het}=4\) (**29**)-8 (**27**), and their flexibility parameter (Table S3) ranged from 0.069 (**23**) to 0.207 (derivatives (**25**), (**26**) and (**27**), respectively). The current calculations confirmed the conclusions published in [162, 164]. The mentioned research stated that a limitation of the aromatic ring count, especially the moieties containing no heteroatoms, could be beneficial for oral drugs and, in a broader sense, contribute to the developability of the compounds that could become drug candidates or drugs. * Hydrogen bonding and lipohydrophilic properties  
Recent analysis [117] suggested that hydrogen bonding and lipohydrophilic properties appear to be the factors that contribute more significantly to a drug-like profile of pharmacologically effective compounds or drug candidates, which were biologically available after administration per os, than their \(MW\) parameters. The compounds (**16**)-(**29**) contained \(n_{\rm OHNH}=3\)-5 and \(n_{\rm ON}=4\)-6 (Table S3). Subseries (**16**)-(**24**) characterized with \(n_{\rm OHNH}>4\) was very slightly outside of the calculated 90 th percentile \(n_{\rm OHNH}\) value (90 th percentile \(n_{\rm OHNH}=4\)) observed for drugs, which FDA approved during 1998-2017 [164]. The hydrogen bonding and lipophilicity contributed in different ways to the efficiency in vitro of molecules against Gram-positive bacteria [170]. The \(n_{\rm OHNH}\) parameter was a rather conservative structural index for highly lipophilic compounds and suitably indicated the extent of passive permeability via biological membranes [171]. The derivative (**29**), to which attention was drawn in the previous paragraphs, was defined with \(MW<414.00\) Da, \(n_{\rm OHNH}=3\), \(tPSA=73.83\) A\({}^{2}\), and log \(D_{7,4}=3.86\) (Tables S2-S4). If molecules are characterized with \(n_{\rm OHNH}>n_{\rm ON}\), the probability that they can form a large portion of hydrate structures is higher and their free forms are in the minority [172]. The opposite situation was observed for all molecules (**16**)-(**29**), that is, their \(n_{\rm ON}>n_{\rm OHNH}\) (Table S3), indicating that they can be found in free forms. Proper spatial arrangement of particular functional groups within the structure of currently discussed compounds together with balance in lipohydrophilic properties determined their activity in vitro against Gram-positive foodborne pathogens [138]. The cell wall of Gram-positive bacteria contains, among others, lipophilic compartments [173], which facilitate the permeation of lipophilic compounds, and, in addition, they can be suitable biological targets for numerous antimicrobial effective molecules [174]. The lipophilicity log \(P\) descriptor was generated for (**16**)-(**29**) using a [PERSON]'s method (MLOGP) [92] integrated in SwissADME [66], fragmental CLOGP 4.0 approach (CLOGP 4.0) [93] implemented within a ChemDraw ver.