Assaying the Energies of Biological Halogen Bonds

Bromine halogen bonds (X-bonds) had previously been assayed using DNA junctions in which the X-bonds compete against hydrogen bonds (H-bonds) in defining the conformational form of the junction. Here, we show calorimetrically that the stabilizing effect of the X-bond in solution derives primarily from a negative enthalpy (-5 kcal/mol) but is opposed by a negative entropy (-8 cal/mol.K, equivalent to -2 kcal/mol for T Delta S at room temperature), resulting in an overall stabilizing free energy of -3 kcal/mol for the X- vs H-bond. Quantum chemical energies for this X-bond are nearly identical to energies derived from the crystallographic and solution assays, confirming that the stabilizing potentials are primarily reflected in the components of the X-bond. A study in which the bromine is replaced by a methyl group (substituents that are similar in size and hydrophobicity) showed that the solvent and steric effects of burying these substituents in the tight pocket of the junction Is nearly equivalent in energy to the competing H-bond.. Thus, the stabilization of DNA junctions by a bromine X-bond in crystals is reflected in the enthalpic stabilization in solution and that both energies are direct measures of the X-bonding potential of the bromine in a biomolecular system.