Origin of the high basicity of 2,7-dimethoxy-1,8-bis-(dimethylamino)naphthalene: Implications for enzyme catalysis

Density functional calculations on model systems are performed to understand the origin of the large increase of basicity from 1,8-bis(dimethylamino)naphthalene (1) to 2,7-dimethoxy-1,8-bis(dimethylamino)naphthalene (2). It is found that the increase of the gas-phase proton affinity (PA) on going from 1 to 2 mainly comes from the relief of steric repulsions of the methoxy groups with their neighboring amino groups as a result of protonation. It is suggested that this relief of the steric repulsions along with favorable electrostatic interactions involving the methoxy groups in 2H(+) makes a major contribution to the enhanced basicity. (C) 2001 Elsevier Science B.V. All rights reserved.