Table 2. Physicochemical Properties of Dimeric Pyridinium Bromides 1–4.
| physicochemical parameters | 1 | 2 | 3 | 4 |
|---|---|---|---|---|
| lipophilicity (XLOGP3) | 2.92 | 3.48 | 1.98 | 2.54 |
| size (MW; g/mol) | 314.47 | 348.48 | 258.36 | 292.38 |
| molar reactivity | 100.79 | 111.01 | 81.18 | 91.41 |
| polarity (TPSA; Å2) | 14.24 | 14.24 | 59.80 | 59.80 |
| solubility (LogS) | –3.49 | –4.31 | –2.76 | –3.59 |
| saturation (fraction; Csp3) | 0.47 | 0.27 | 0.33 | 0.11 |
| flexibility (number of rotatable bonds) | 8 | 6 | 6 | 4 |
| HBA(N + O) | 4 | 4 | 4 | 4 |
| HBD(NH + OH) | 0 | 0 | 4 | 4 |
| BBB permeant | yes | yes | yes | yes |
| log Kp (skin permeation; cm/s) | –6.15 | –5.95 | –6.47 | –6.28 |
| P-gp substrate | yes | yes | yes | yes |
| log Po/w | 2.26 | 2.49 | 1.31 | 1.54 |
| bioavailability score | 0.55 | 0.55 | 0.55 | 0.55 |
| CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4 | CYP2D6 (yes) | CYP2D6 (yes) | CYP2D6 (yes) |