Correlation between molecular orbital distributions in drug-receptor interaction: Diels-Alder reaction systems and dihydrofolate reductase system.

An index which corresponds to charge transfer interaction is presented as a tool to study the correlation of molecular orbital (MO) distributions. The MO distribution correlation (MODIC) index was applied to Diels-Alder reaction systems (1-methoxy-1,3-butadiene—acrolein system and cyclopentadiene—maleic acid anhydride system), and the dihydrofolate reductase (DHFR) system. In the Diels-Alder reaction systems, the positions of reaction centers and orientations of substitutional groups predicted by the index were consistent with experimental findings. In the DHFR system, the reactivities of different ligands were explained by the index. Frontier electron theory provides some indexes to predict reactivities, based on the molecular orbital coefficients of the isolated molecule in its ground state. The MODIC index has the advantage that it contains information on the three-dimensional distribution of MO's. It can predict the MO's in the transition state of a reaction.