Rockefeller University Press

Table 2.

Physical properties of permeant and “impermeant” compounds

Compound	MM	Chemical formula	pK_a and pK_b	% neutral at pH 7.4	log K_oct^a	K_oct neutral	K_oct * % neutral/100	P_measured^b neutral	P_cell^c at pH 7.4	τ^d 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	3^e	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	1,000^e	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	1,400^e	0.006	16 min
Melatonin	232.3	C₁₃H₁₆N₂O₂	16.3	100	1.39	25	25	1.7^f	1.7	3.5 s
Indole-3-ethanol^g	161.2	C₁₀H₁₁NO	15.2	100	1.62	42	42	2.3^h	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	pK_a and pK_b	% neutral at pH 7.4	log K_oct^a	K_oct neutral	K_oct * % neutral/100	P_measured^b neutral	P_cell^c at pH 7.4	τ^d 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	3^e	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	1,000^e	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	1,400^e	0.006	16 min
Melatonin	232.3	C₁₃H₁₆N₂O₂	16.3	100	1.39	25	25	1.7^f	1.7	3.5 s
Indole-3-ethanol^g	161.2	C₁₀H₁₁NO	15.2	100	1.62	42	42	2.3^h	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; pK_a and pK_b, acid or base equilibrium dissociation constant; log K_oct, logarithm to base 10 of n-octanol/water partition coefficient of neutral form; K_oct, partition coefficient of neutral form.

Each log K_oct 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. K_oct is computed from these mean values. See also discussion in Sangster (1989).

P_measured, experimental membrane permeabilities measured in planar lecithin bilayers or in tsA201 cells.

P_cell, 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).

P_m 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).

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