ORIGIN OF THE STRONG BINDING OF ADENINE TO A MOLECULAR TWEEZER

Monte Carlo statistical mechanics simulations and analyses of intrinsic interaction energies have been used to elucidate the observed strong binding of adenine derivatives to Zimmerman's molecular tweezer 3 in chloroform. Hydrogen bonding and π-stacking are found to contribute about equally to the remarkably strong interaction of the acid tweezer 6 and 9-methyladenine. The binding in chloroform is not enhanced by the existence of a naked binding cleft. Though 9-methyladenine easily wins the competition with chloroform for the binding site in 6, the interaction between the ester tweezer 7 and 9-methyladenine is not adequate to displace the one or two chloroform molecules in the cleft. The absolute free energy of binding for the acid 6 and 9-methyladenine in chloroform was computed with the double-annihilation technique. The accord with the experimental data for acid 3 provides support for the validity of the theoretical analyses. © 1990, American Chemical Society. All rights reserved.