| Abstract [eng] |
Various sulfonamides are used in medicine as drug components. Depending on the properties of these compounds, they can be used as antibacterial agents, drug carriers, etc. Acidity constant pK_a provides information concerning the strength of an acid, which in times often dictates its other properties related to, for example, solubility, adsorption, distribution and other important parameters. Synthesis of sulfonamides and their research can be a hard and time-consuming process so scientists are looking for alternative ways for more efficient and more accurate assessment of pK_a values. One of them is based on quantum chemical calculations using the thermodynamic cycles to evaluate the acid dissociation constants. The MAIN AIM of this work is to calculate pK_a values of 3-sulfanilamidopyrimidine, sulfapyridine, 2-sulfanilamidopyrazine, 3-sulfanilamidopyridazine, sulfadiazine, 5-sulfaniamido-pyrimidine, 4-sulfaniamido-pyrimidine, 2-sulfaniamido-4-methylpyrimidine, 2-sulfaniamido-4-aminopyrimidine, 2-sulfaniamido-4,6-dimethylpyrimidine, 5-sulfanilamido-2-chloropyrimidine, 2-sulfanilamidoӧxazole, 5-sulfanilamido-3-metilisoӧxazole, sulfanilylcyanamide, N1-acetylsulfanilamide, N1-benzoylsulfanilamide, N1-chloroacetylsulfanilamide by using direct and proton exchange thermodynamic cycles and various density functional theoretical methods, and compare results with the experimental values to evaluate reliability of used theoretical methods. Conformational analysis has revealed that secondary benzenesulfonamides had different lowest-energy conformations in vapor phase and in solution phase. In most cases small basis set 6-31G* was sufficient for conformational analysis and allowed to find the most stable conformations I a reliable manner. However, there were cases when large basis set cc-pVTZ gave more accurately results by providing some changes in the lowest energy conformations or even by finding new conformations. It was found that direct thermodynamic cycle is not suitable for calculation of acid dissociation constants pK_a of these secondary benzenesulfonamides because of the considerable deviations from the experimental values (MAD 1,49 – 11,92 pK_a units). On the other hand, reliability of proton exchange cycle depends on finding right reference species (MAD 0,37 – 8,83 pK_a vnt.). We have also observed that computed gas-phase free energy changes, ∆G_gas^0, were much more sensitive to the used electronic structure method as compared to the differences in solution energies. |
