Table 2.

Experimental binding details for all host–guest systems

ID	Name	$K_a$ (M${}^{-1}$)	$\mathrm{\Delta }G$ (kcal/mol)	$\mathrm{\Delta }H$ (kcal/mol)	$T\mathrm{\Delta }S$ (kcal/mol)${}^{\text{b}}$	n
CB8–G1	Methamphetamine${}^{\text{a}}$ ${}^{\text{c}}$	1.5 × 105 ± 0.1 × 105	$-7.05\pm 0.04$	$-7.8\pm 0.3$	$-0.8\pm 0.3$	1.00
CB8–G2	Fentanyl${}^{\text{a}}$ ${}^{\text{c}}$	1.9 × 107 ± 0.1 × 107	$-9.93\pm 0.03$	$-10.8\pm 0.3$	$-0.9\pm 0.3$	1.00
CB8–G3	Morphine${}^{\text{a}}$ ${}^{\text{d}}$	3.4 × 108 ± 0.2 × 108	$-11.63\pm 0.03$	$-13.6\pm 0.4$	$-2.0\pm 0.4$	1.00
CB8–G4	Hydromorphone${}^{\text{a}}$ ${}^{\text{d}}$	1.7 × 108 ± 0.1 × 108	$-11.22\pm 0.04$	$-15.8\pm 0.5$	$-4.6\pm 0.5$	1.00
CB8–G5	Ketamine${}^{\text{a}}$ ${}^{\text{e}}$	10.9 × 108 ± 0.8 × 108	$-12.32\pm 0.04$	$-17.3\pm 0.5$	$-5.0\pm 0.5$	1.00
CB8–G6	Phenylcyclohexylpiperidine(PCP)${}^{\text{a}}$ ${}^{\text{e}}$	2.1 × 1010 ± 0.2 × 1010	$-14.07\pm 0.06$	$-14.9\pm 0.4$	$-0.8\pm 0.5$	1.00
CB8–G7	Cocaine${}^{\text{a}}$ ${}^{\text{c}}$	6.4 × 105 ± 0.5 × 105	$-7.92\pm 0.04$	$-8.3\pm 0.3$	$-0.3\pm 0.3$	1.00
TEMOA–G1	3-Hydroxy-2-naphthoic acid	1.3 × 105 ± 0.1 × 105	$-6.96\pm 0.05$	$-17.0\pm 1.0$	$10.0\pm 1.0$	1.00
TEMOA–G2	p-Bromophenol	14.8 × 105 ± 0.6 × 105	$-8.41\pm 0.02$	$-15.7\pm 0.2$	$7.2\pm 0.2$	1.00
TEMOA–G3	Cyclopentylacetic acid	17.4 × 103 ± 0.7 × 103	$-5.78\pm 0.02$	$-7.9\pm 0.2$	$2.2\pm 0.2$	1.00
TEMOA–G4	Piperonylic acid	4.6 × 105 ± 0.2 × 105	$-7.72\pm 0.02$	$-17.7\pm 0.3$	$10.0\pm 0.3$	1.00
TEMOA–G5	p-Toluic acid	7.8 × 104 ± 0.3 × 104	$-6.67\pm 0.02$	$-14.2\pm 0.8$	$7.6\pm 0.7$	1.00
TEETOA–G1	3-Hydroxy-2-napththoic acid	2.0 × 103 ± 0.2 × 103	$-4.49\pm 0.05$	$-13.6\pm 0.2$	$9.2\pm 0.1$	1.00
TEETOA–G2	p-Bromophenol	6.1 × 103 ± 0.2 × 103	$-5.16\pm 0.02$	$-11.6\pm 0.3$	$6.5\pm 0.3$	1.00
TEETOA–G3	Cyclopentylacetic acid${}^{\text{f}}$	ND ± ND	ND ± ND	ND ± ND	ND ± ND	1.00
TEETOA–G4	Piperonylic acid	1.9 × 103 ± 0.2 × 103	$-4.47\pm 0.05$	$-13.0\pm 0.9$	$8.5\pm 0.8$	1.00
TEETOA–G5	p-Toluic acid${}^{\text{g}}$	2.7 × 102 ± 0.1 × 102	$-3.32\pm 0.02$	ND ± ND	ND ± ND	1.00

All quantities are reported as point estimate ± statistical error from the ITC data fitting procedure. The upper bound ($1\%$) was used for errors reported to be $<1\%$. For the CB8 dataset, concentration error had not been factored in to the original error estimates, so we included a 3% relative uncertainty in the titrant concentration and we assumed the stoichiometry coefficient to be fitted to the ITC data [20]. For the TEMOA/TEETOA sets, provided uncertainties already include concentration error. $\mathrm{\Delta }G$ was obtained from $K_a$ via the standard thermodynamic equation. The average $\mathrm{\Delta }H$ and $\mathrm{\Delta }G$ values were then used to calculate an average $-T\mathrm{\Delta }S$, and the corresponding standard deviations calculated using the standard equation for the propagation of uncertainties for subtraction. The deviations in log$K_a$ and $\mathrm{\Delta }G$ were obtained by using the standard equation for the propagation of uncertainties for logarithms. Binding measurements not detected or not measured are labeled with ND.

${}^{\text{a}}$Statistical errors were propagated from the $K_a$ measurements

${}^{\text{b}}$All experiments were performed at 298 K

${}^{\text{c}}$Direct ITC titration

${}^{\text{d}}$Competitive ITC titration with C1

${}^{\text{e}}$Competitive ITC titration with C2

${}^{\text{f}}$Binding is too weak to be observed by ${}^1$H NMR or ITC

${}^{\text{g}}$Determined by ${}^1$H NMR spectroscopy