Table 1.

Chemical structures and physicochemical properties.

Compound	Structure	Log P	pKa	Log D (pH 7.4)	Ionization (mol%, pH 7.4)	Electrostatic potential (kcal/mol)
Mexiletine		2.21 ± 0.01	9.28 ± 0.01	0.53	98.7	−50.3
mHM		1.67 ± 0.01	9.04 ± 0.01	0.02	97.7	−48.0
pHM		1.53 ± 0.01	8.97 ± 0.01	−0.05	97.3	−50.4
HMM		1.15 ± 0.01	9.13 ± 0.01	−0.59	98.1	−64.9
bHMM		0.25 ± 0.05	9.21 ± 0.03	−0.85	98.5	−62.6
pHHMM		0.23 ± 0.02	8.89 ± 0.02	−1.27	96.8	−65.0

The Log P, pK_a, Log D, and electrostatic potential values were determined experimentally, as described in the Section “Materials and Methods.” Values of Log P and pK_a are given as mean ± SEM. Ionization of the amine group at pH 7.4 was calculated from Henderson–Hasselbalch equation, $\text{Ionization}=1-10^{\left(\text{pH}-\text{p}{K}_{\text{a}}\right)}.$