Physical properties of permeant and “impermeant” compounds
Compound | MM | Chemical formula | pKa and pKb | % neutral at pH 7.4 | log Kocta | Koct neutral | Koct * % neutral/100 | Pmeasuredb neutral | Pcellc at pH 7.4 | τd 16-µm diameter cell |
D | % | µm/s | µm/s | |||||||
Norepinephrine | 169.2 | C8H11NO3 | 8.6 | 6 | −1.11 | 0.078 | 0.005 | - | 0.0003 | 5.1 h |
Epinephrine | 183.2 | C9H13NO3 | 8.6 | 6 | −0.87 | 0.13 | 0.008 | - | 0.0006 | 2.9 h |
1,4-Butanediol | 90.1 | C4H10O2 | >15 | 100 | −0.70 | 0.20 | 0.20 | 3e | 0.014 | 7.2 min |
Nitric oxide | 30.0 | NO | −2.9 | 100 | −0.35 | 0.45 | 0.45 | - | 0.031 | 3.2 min |
5-HT | 276.2 | C10H12N2O | 9.7 | 0.50 | 0.50 | 3.2 | 0.016 | - | 0.0011 | 1.5 h |
Butyric acid | 88.1 | C4H8O2 | 4.7 | 0.2 | 0.70 | 5.0 | 0.01 | 1,000e | 0.3 | 17 s |
NAS | 218.3 | C12H14N2O2 | 10.1 | 99.8 | 0.68 | 4.8 | 4.8 | - | 0.3 | 18 s |
Nicotine | 162.2 | C10H14N2 | 8.0 | 20 | 1.10 | 12.6 | 2.5 | - | 0.2 | 34 s |
Codeine | 299.4 | C18H21NO3 | 9.7 | 0.50 | 1.24 | 17 | 0.09 | 1,400e | 0.006 | 16 min |
Melatonin | 232.3 | C13H16N2O2 | 16.3 | 100 | 1.39 | 25 | 25 | 1.7f | 1.7 | 3.5 s |
Indole-3-ethanolg | 161.2 | C10H11NO | 15.2 | 100 | 1.62 | 42 | 42 | 2.3h | 2.9 | 2.1 s |
Hexanoic acid | 116.2 | C6H12O2 | 4.8 | 100 | 1.71 | 51 | 51 | 11,000i | 3.6 | 1.7 |
Lidocaine | 234.3 | C14H22N2O | 7.9 | 24 | 2.15 | 141 | 33.9 | - | 2.4 | 2.5 s |
Compound | MM | Chemical formula | pKa and pKb | % neutral at pH 7.4 | log Kocta | Koct neutral | Koct * % neutral/100 | Pmeasuredb neutral | Pcellc at pH 7.4 | τd 16-µm diameter cell |
D | % | µm/s | µm/s | |||||||
Norepinephrine | 169.2 | C8H11NO3 | 8.6 | 6 | −1.11 | 0.078 | 0.005 | - | 0.0003 | 5.1 h |
Epinephrine | 183.2 | C9H13NO3 | 8.6 | 6 | −0.87 | 0.13 | 0.008 | - | 0.0006 | 2.9 h |
1,4-Butanediol | 90.1 | C4H10O2 | >15 | 100 | −0.70 | 0.20 | 0.20 | 3e | 0.014 | 7.2 min |
Nitric oxide | 30.0 | NO | −2.9 | 100 | −0.35 | 0.45 | 0.45 | - | 0.031 | 3.2 min |
5-HT | 276.2 | C10H12N2O | 9.7 | 0.50 | 0.50 | 3.2 | 0.016 | - | 0.0011 | 1.5 h |
Butyric acid | 88.1 | C4H8O2 | 4.7 | 0.2 | 0.70 | 5.0 | 0.01 | 1,000e | 0.3 | 17 s |
NAS | 218.3 | C12H14N2O2 | 10.1 | 99.8 | 0.68 | 4.8 | 4.8 | - | 0.3 | 18 s |
Nicotine | 162.2 | C10H14N2 | 8.0 | 20 | 1.10 | 12.6 | 2.5 | - | 0.2 | 34 s |
Codeine | 299.4 | C18H21NO3 | 9.7 | 0.50 | 1.24 | 17 | 0.09 | 1,400e | 0.006 | 16 min |
Melatonin | 232.3 | C13H16N2O2 | 16.3 | 100 | 1.39 | 25 | 25 | 1.7f | 1.7 | 3.5 s |
Indole-3-ethanolg | 161.2 | C10H11NO | 15.2 | 100 | 1.62 | 42 | 42 | 2.3h | 2.9 | 2.1 s |
Hexanoic acid | 116.2 | C6H12O2 | 4.8 | 100 | 1.71 | 51 | 51 | 11,000i | 3.6 | 1.7 |
Lidocaine | 234.3 | C14H22N2O | 7.9 | 24 | 2.15 | 141 | 33.9 | - | 2.4 | 2.5 s |
MM, molecular mass; pKa and pKb, acid or base equilibrium dissociation constant; log Koct, logarithm to base 10 of n-octanol/water partition coefficient of neutral form; Koct, partition coefficient of neutral form.
Each log Koct value is the mean of several calculated and experimental “logP” values reported in the DrugBank database (Law et al., 2014) and the SciFinder database of the American Chemical Society. Koct is computed from these mean values. See also discussion in Sangster (1989).
Pmeasured, experimental membrane permeabilities measured in planar lecithin bilayers or in tsA201 cells.
Pcell, predicted permeabilities for cell membranes at pH 7.4 calculated from Eq. 1b.
τ, predicted exponential equilibration time constant between inside of cell and bath at pH 7.4 calculated from Eq. 2 for a 16-µm diameter cell.
Three values of membrane permeability measured experimentally with egg lecithin/hexadecane painted planar lipid bilayers (Finkelstein, 1976; Orbach and Finkelstein, 1980).
Pm in tsA201 cells from this paper.
Also called tryptophol.
Membrane permeability measured experimentally with tocopherol/cholesterol/brain phospholipid/chloroform-methanol painted planar lipid bilayers (Bean et al., 1968).
Membrane permeability measured experimentally with egg phosphatidylcholine/decane painted planar lipid bilayers (Walter and Gutknecht, 1986).