Carbonic anhydrase inhibitors: A quantum mechanical study of interaction between some antiepileptic drugs with active center of carbonic anhydrase enzyme

Density functional theory (DFT) using B3LYP and split-valance 6-31G* basis set have been employed to calculate the details of electronic structure and electronic energy of carbonic anhydrase enzyme active center (CA), six inhibitors of this enzyme including topiramate and its derivatives and its analogue, and complex between these inhibitors and active center of carbonic anhydrase. Also thermodynamic functions such as deprotonation enthalpy of inhibitors, standard enthalpies of formation ( Δ H f ∘ ) , standard entropy of formation ( Δ S f ∘ ) and standard Gibbs free energy of formation ( Δ G f ∘ ) for six CA–inhibitor complexes are evaluated. The calculated results indicate that deprotonated inhibitors are coordinated to the Zn2+ ion and all the complexes have tetrahedral geometry. According to the calculated thermodynamic functions substitution of sulfonamide group with hydroxyl reduces the tendency of inhibitor to bind to the active center of carbonic anhydrase. In all calculations solvent effects have been considered in water using SCRF method.