The Role of Aromaticity in the Planarity of Lumiflavin

Ab initio MP2/6-31G(d,p) and density functional theory B3LYP/6-31G(d,p) calculations were performed to investigate the molecular structure of the active part of flavins in the oxidized and reduced forms, using lumiflavin as a model compound. The possible aromatic character of these systems was explored by using the following aromaticity indexes:  nucleus-independent chemical shifts, the anisotropy of the magnetic susceptibility, the Bird index, and natural bond orbital analysis. To provide further insight, calculations on the 2+ charged species were also carried out. Both the MP2 and B3LYP computations predict a planar conformation for the oxidized form and a bent structure for the reduced form, in agreement with previous experience. For both the oxidized and reduced states, ring A is found to be the most aromatic, as expected. The calculations suggest that the folding in the reduced form is mainly a result of electronic preferences rather than steric hindrance.