Biindolyl-based molecular clefts that bind anions by hydrogen-bonding interactions

Molecular clefts were synthesized from 2,2'-biindolyl scaffold that contains good hydrogen bond donors of two indole NHs. The molecular clefts were systematically modified in two different manners to increase binding affinities toward chloride. The association constant dramatically increased when additional hydrogen-bonding sites of two benzamide units were incorporated to the biindolyl scaffold. For example, the association constants of 1a and 1b are 5.1 x 10(3) and 1.4 x 10(4) M-1 in CH3CN at 22 +/- 1 degrees C, while reference molecule 10 having only two indole NHs showed the association constant of 340 M-1 under the same conditions. When the biindolyl backbone was structurally preorganized, the binding affinities toward anions were further increased with additional stabilization energy (-Delta Delta G) of 2.0 +/- 0.2 kcal/mol). (c) 2006 Elsevier Ltd. All rights reserved.