Aqueous Oxidation of Sulfonamide Antibiotics: Aromatic Nucleophilic Substitution of an Aniline Radical Cation

Abstract

Sulfonamide antibiotics are an important class of organic micropollutants in the aquatic environment. For several, sulfur dioxide extrusion products have been previously reported upon photochemical or dark oxidation. Using quantum chemical modeling calculations and transient absorption spectroscopy, it is shown that single‐electron oxidation from sulfadiazine produces the corresponding aniline radical cation. Density functional theory calculations indicate that this intermediate can exist in four protonation states. One species exhibits a low barrier for an intramolecular nucleophilic attack at the para position of the oxidized aniline ring, in which a pyrimidine nitrogen acts as a nucleophile. This attack can lead to a rearranged structure, which exhibits the same connectivity as the SO2‐extruded oxidation product that was previously observed in the aquatic environment and characterized by NMR spectroscopy. We report a detailed reaction mechanism for this intramolecular aromatic nucleophilic substitution, and we discuss the possibility of this reaction pathway for other sulfonamide drugs.

Kinetic and mechanistic investigations of the degradation of sulfamethazine in heat-activated persulfate oxidation process

“…It was reported that the para-position of aniliny radical cation of sulfadiazine could be subjected to intermolecular nucleophilic attack in which a pyrimidine nitrogen acted as a nucleophile [10,36]. This attack could lead to the intermolecular rearrangement (Smiles-type), resulting in SO 2 extrusion [10,36]. In the present study, the ␣-carbon adjacent to the sulfonamide group possessed strong positive charge in the resulting SMZ radical cation, which facilitated the nucleophilic attack of pyrimidine nitrogen.…”

“…4), and reaction between SO 4 • − and aniline could generate an aniliny radical cation [35]. Formation of aniliny radical cation has been confirmed by quantum chemical modeling calculation and transient absorption spectroscopy studies on single-electron oxidation of sulfonamides [36]. It was reported that the para-position of aniliny radical cation of sulfadiazine could be subjected to intermolecular nucleophilic attack in which a pyrimidine nitrogen acted as a nucleophile [10,36].…”

“…Formation of aniliny radical cation has been confirmed by quantum chemical modeling calculation and transient absorption spectroscopy studies on single-electron oxidation of sulfonamides [36]. It was reported that the para-position of aniliny radical cation of sulfadiazine could be subjected to intermolecular nucleophilic attack in which a pyrimidine nitrogen acted as a nucleophile [10,36]. This attack could lead to the intermolecular rearrangement (Smiles-type), resulting in SO 2 extrusion [10,36].…”

Carbon Stable Isotope Fractionation of Sulfamethoxazole during Biodegradation by Microbacterium sp. Strain BR1 and upon Direct Photolysis

“…The rate of degradation of the neutral species may outcompete the deprotonation, as supported by our higher degradation rates at lower pH. 49 Implications for the Environmental Applications of CSIA for SMX. In this study, we assessed for the first time the applicability of CSIA to monitor the biodegradation and photolysis of the antibiotic SMX.…”

DFT predictions of the oxidation potential of organic dyes for opto-electronic devices

“…[49,50,11,51]; that choice was dictated by the fact that electron densities and optimum geometries of some of the investigated dyes exhibit a large dependence on the dielectric environment [30]. For the same reason we have not tested the SMD solvation model [48], a method designed to compute absolute solvation energies starting from gas-phase optimization/Hessian calculations, although there is evidence that SMD is capable of very accurate predictions of redox free energy for small molecules [9,10].…”