Table 2.

EC₅₀ and cation-π binding ability for various Trp mutants at position α149

Side chain*	Cation–π binding,† kcal/mol	EC50,‡§ μM	Corrected EC50,§¶ μM
Trp	32.6	1.2	50
5-F-Trp	27.5	4.7	200
5,7-F2-Trp	23.3	13	(550)‖
5,6,7-F3-Trp	18.9	34	(1400)‖
4,5,6,7-F4-Trp	14.4	65	(2700)‖
5-Br-Trp	27.8	2.0	88
5-CN-Trp	21.5	114	(4750)‖
5-Me-Trp	33.4	—	49
4-F-Trp	27.9	—	56
6-F-Trp	27.4	—	48
1-Np-Ala	28.9	—	51
2-Np-Ala	28.9	—	82
7-aza-Trp	26.0	—	130
Bta	26.9	—	174
N-Me-Trp	33.7	—	95
5-NH2-Trp	36.4		280

^*See Fig. 2 for side-chain structures. 

^†The cation-π binding is defined as the negative of the binding energy (kcal/mol) of a generic probe cation (Na⁺) to the appropriate aromatic ring using ab initio HF 6-31G** calculations with full geometry optimization, as described previously (12). Since the 6-31G** basis set is not available for Br, the 6-311G** basis set was used for 5-Br-Trp, and then the value was corrected based on a linear correlation (r = 0.997) between binding energies for a collection of ten aromatics determined with the two different basis sets. Calculations were performed with gaussian 94 (34) or spartan (35). 

^‡For receptors with a βLeu-9′ → Ser mutation, see text. 

^§Hill coefficients are generally in the range 1.3–1.8, but for the relatively insensitive structures (5-CN-Trp and 4,5,6,7-F₄-Trp with βLeu-9′ → Ser mutations), values as low as 1.0 are observed. 

^¶For receptors that are otherwise wild type. 

^‖Obtained by multiplying the entries of the adjacent column by a constant factor of 42, to compensate for the βLeu-9′ → Ser mutation; see text.