The geometries of substituted sulfonamides [sulfonamide (1) sulfamic acid (11), sulfamide (111), methane sulfonamide (IV), 1,1,1-trifluoromethanesulfonamide (V), 4-aminobenzenesulfonamide (VI), 1,2-benzisothiazol-3-(2H)-one-1, 1-dioxide (saccharin) (VII), N-(5-sulfamoyl-1,3,4-thiadiazol-2yl)acetamide (acetazolamide) (VIII), 4-(aminosulfonyl)-N-[(4-fluorophenyl)methyl]-benzamide (119L) (IX), (R)-(+)-4-(ethylamino)2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,-dioxide (brinzolamide) (X), and (4S-trans)-(+)-4-(ethylamino)-5,6-dihydro-6-methyl-4H-thieno-[2,3-b]thiopyran-2-sulfonamide 7,7dioxide (dorzolamide) (XI)] in both neutral and deprotonated forms, were optimized using CBS-QB3 theory (compounds I-IV), the Becke3LyP/6-311+G(d,p) method (compounds I-VIII), and the two-layered ONIOM-(B3LYP 6-311+G(d,p): MNDO) method (compounds VIII - XI). Sulfamic acid behaves in the gas phase as O-acid. The investigated acids are weak acids with calculated acidity of about 1320-1420 kJ mol(-1). Of the N-acids studied, saccharin possesses the highest gas-phase acidity (1324 kJ mol-1). The acidities of phenyl-substituted derivatives computed using the hybrid ONIOM (B3LYP/6-311+G(d,p): MNDO) method are in good agreement with the full DFT ones, and this method can be adopted to model large substituted sulfonamides.