Interaction of benzene sulfonamies has been discussed with Zn-metal, Zn2+-ion and carbonic anhydrase (Zn2+-CA) in terms of metal ligand interaction energy (Eint), shift in charge (∆N) and lowering in energy (∆E). The structure of all the above compounds has been drawn and their geometries have been optimized with the help of CAChe software by applying semiempirical PM3 method. Interaction energy shows that the interactions between sulfonamides and carbonic anhydrase are dominant over Zn-metal and Zn2+-ion. Charge transfer phenomenon shows that the interactions between sulfonamides and Zn2+-ion are dominant over Zn-metal and Zn2+-CA. Energy lowering show that the interactions between sulfonamides and Zn2+-ion are dominant over Zn-metal and Zn2+-CA.