N-Cyclo­amino substituent effects on the packing architecture of ortho-sul­fan­il­amide mol­ecular crystals and their in silico carbonic anhydrase II and IX inhibitory activities

In the search for new ‘sulfa drugs’ with therapeutic properties, o-nitro­sul­fonamides and N-cyclo­amino-o-sul­fan­il­amides were synthesized and characterized using techniques including (1)H NMR, (13)C NMR and FT–IR spectroscopy, and single-crystal X-ray diffraction (SC-XRD). The calculated density functional theory (DFT)-optimized geometry of the mol­ecules showed similar conformations to those obtained by SC-XRD. Mol­ecular docking of N-piperidinyl-o-sul­fan­il­amide and N-indolinyl-o-sul­fan­il­amide supports the notion that o-sul­fan­il­amides are able to bind to human carbonic anhydrase II and IX inhibitors (hCA II and IX; PDB entries 4iwz and 5fl4). Hirshfeld surface analyses and DFT studies of three o-nitro­sul­fonamides {1-[(2-nitro­phen­yl)sul­fon­yl]pyrrolidine, C(10)H(12)N(2)O(4)S, 1, 1-[(2-nitro­phen­yl)sul­fon­yl]piperidine, C(11)H(14)N(2)O(4)S, 2, and 1-[(2-nitro­phen­yl)sul­fon­yl]-2,3-di­hydro-1H-indole, C(14)H(12)N(2)O(4)S, 3} and three N-cyclo­amino-o-sul­fan­il­amides [2-(pyrrolidine-1-sul­fon­yl)aniline, C(10)H(14)N(2)O(2)S, 4, 2-(piperidine-1-sul­fon­yl)aniline, C(11)H(16)N(2)O(2)S, 5, and 2-(2,3-di­hydro-1H-indole-1-sul­fon­yl)aniline, C(14)H(14)N(2)O(2)S, 6] suggested that forces such as hydro­gen bonding and π–π inter­actions hold mol­ecules together and further showed that charge transfer could promote bioactivity and the ability to form biological inter­actions at the piperidinyl and phenyl moieties.