The Aromaticity of Rings in Some Pterin-Based Inhibitors of Dihydropteroate Synthase

Dihydropteroate synthase (DHPS) is a key enzyme in bacterial folate synthesis and the targetof sulfonamide class of antibacterials. Several pterin-based inhibitors (PBI) of DHPS witharomatic ringshave been identified. The estimation of aromaticity of rings (pyrimidine (1) andpyrazine (2)) of these inhibitors (see Fig. 1) is important in the prediction of inhibitory activity[1]. In this work, the aromaticity of some inhibitors have been estimated using the aromaticfluctuation index (FLU). The geometries of compounds were optimized at the B3LYP/6-31G(d,p) level of theory using the Gaussian 09 program [2]. The FLU index which is basedon the ρ values was calculated using the AIM analysis on the wave functions obtained at theB3LYP/6-31G(d,p) level of theory. With respect to the FLU values, the ring 2 is more aromaticthan 1. The largest aromaticitiy of rings 1 and 2 is corresponded to the cases in whichone C=O functional group changes to NH2 (in ring 1) or H (in ring 2).