Physicochemical and structural properties of bacteriostatic sulfonamides: Theoretical study

Abstract

ABSTRACT:A theoretical study at the Hartree-Fock and density functional theory levels is performed on sulfonamide-type bacteriostatic compounds with the aim to provide an insight into their structure-activity relationship. The basicity of the p-amino group is analyzed by means of the proton affinities and the protonation energies, showing that molecules presenting bacteriostatic activity are less basic, i.e., they are characterized by larger protonation energies and smaller proton affinities. The acidity of the amide group is analyzed through the deprotonation energy. The results reveal that the more acidic molecules present a larger bacteriostatic activity. This result is also confirmed from a study of bond orders. A bond order analysis of the amide group suggests that the electron attracting group in these molecules is responsible for the increase in acidity. The charge of the SO 2 group is also shown to be affected by the presence of the electron attracting group and consequently related to the acidity of the molecules. A geometric analysis shows that structures in which the amino group is more coplanar with respect to the benzenic ring possess larger bacteriostatic activity. A conformational analysis of these molecules illustrates that active molecules have relatively larger torsion energy barriers.

Prediction of Physico-chemical Properties of Bacteriostatic N1-Substituted Sulfonamides: Theoretical and Experimental Studies

“…It has been found that this planarity in the SA drugs is a necessary condition for a pharmaceutical activity. 23 The dihedral angle between the SO 2 group and the phenyl ring, D ph-SO2 , was also close to 180° in all SAs (Table 1, column 3). However, for the SAA, SDZ, and SQX species, the C-S-N 1 bond angle (A CSN1 ) displayed a value of nearby 105°, although it was found to be 100 o for the STZ molecule.…”

“…Depending on the substituent type, the calculated charge at the SO 2 group shows a large variation. In both the experimental and theoretical works carried out by Bell et al 17 and Soriano-Correa et al, 23 respectively, the increase in the acidity of SAs (which is equivalent to an increase in the bacteriostatic activity) was found to be related to a reduction in the negative charge of the SO 2 group. In other words, the substituent electronegativity is an important parameter that controls the bacteriostatic activity in sulfa drug.…”

“…It is interesting that the H-L gaps for the R substituted species are lower with respect to the reference SA molecule, which is in good agreement with the less bacteriostatic reactivity of the original SA. 23 Among the compounds studied, SDZ and SQX have the lower H-L gaps, indicating that they can be show the higher reactivity. The results obtained revealed that the HO-MO-LUMO electronic transitions could be attributed to the tendency of the considered R groups to contribute the π-electrons with the molecular system.…”

“…It is interesting that the ph-S and S-N 1 bond lengths were not varied considerably by the R groups, where the distance between the S atom and R group changed due to the substituent steric hindrance. It has been established 23 that the sulfonamide activity is accompanied by a small distance between the N 1 atom and R group corresponding to the large bond order for d N1-R . According to Table 2 (column 5), the SDZ molecule with a shorter N 1 -R distance possesses a more bacteriostatic activity with respect to the other substituted SAs.…”

“…[23][24][25][26] In this way, sulfadiazine is one of the substantial sulfonamide antibiotics that are listed as WHO crucial medications in the cure of basic health system. 15 In comparison to the SA derivatives, it has been found that the original SA is at the lowest end of the activity spectrum.…”