Positive ionizable groups

A from the center of a positive ionizable group was identified. However, its predictive performance on a test set consisted of eight structurally similar compounds was relatively poor. To achieve a computational model with greater predictability, a descriptor-based QSPR model was also developed. Descriptors related to molecular hydrophobicity as well as hydrogen bond donor, shape and charge features contributed to explain hOCTl inhibitor properties of the analyzed compounds. 

Langer et al. [63] used a training set of propafenone-type MDR modulators tested with a daunorubicin competition assay and developed a pharmacophore for P-gp inhibition using Catalyst software. The pharmacophore features identified by this model were one hydrogen-bond acceptor, one hydrophobic area, two aromatic centers, and (iv) one positively ionizable group. 

PL of excitons bound to neutral group-II acceptors in germanium has been reported by Nakata and Otsuka [179], Thewalt et al. [247], and references therein. Such excitons can be seen as positively ionized group-II acceptors (A+ions) bound to an electron. These A+ ions, discussed in Sect. 7.5, are stable at very low temperature, and when they trap an electron, they can be considered as pseudo-donors. The far-IR absorption and magnetoabsorption at 1.6 and 4.2 K of these pseudo-donors, produced by the above-band-gap laser excitation of Be- and Zn-doped germanium samples, has for instance been reported by Natsaka and Otsuka [180], and references therein, [148], ([247], and references therein). This absorption is shown in Fig. 6.40. 

For many properties in the ADMET field, ligand-based approaches are appUed. Among them, 3D-pharmacophores are quite powerful as they identify molecular features which are responsible for undesired properties of a series. For example, pharmacophores have been developed for the Kvll.l potassium ion channel (hERG). Most hERG pharmacophores contain a spatial arranganent of one positively ionizable group surrounded by some Upophific features [35-39]. 

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