An AAAA-DDDD quadruple hydrogen-bond array

Secondary electrostatic interactions between adjacent hydrogen bonds can have a significant effect on the stability of a supramolecular complex. In theory, the binding strength should be maximized if all the hydrogen-bond donors (D) are on one component and all the hydrogen-bond acceptors (A) are on the other. Here, we describe a readily accessible AAAA-DDDD quadruple hydrogen-bonding array that exhibits exceptionally strong binding for a small-molecule hydrogen-bonded complex in a range of different solvents (K-a > 3 x 10(12) M-1 in CH2Cl2, 1.5 x 10(6) M-1 in CH3CN and 3.4 x 10(5) M-1 in 10% v/v DMSO/CHCl3). The association constant in CH2Cl2 corresponds to a binding free energy (Delta G) in excess of -71 kJ mol(-1) (more than 20% of the thermodynamic stability of a carbon-carbon covalent bond), which is remarkable for a supramolecular complex held together by just four intercomponent hydrogen bonds.