In silico toxicity evaluation for transformation products of antimicrobials, from aqueous photolysis degradation.

This study investigates degradation processes of three antimicrobials in water (norfloxacin, ciprofloxacin, and sulfamethoxazole) by photolysis, focusing on the prediction of toxicity endpoints via in silico quantitative structure-activity relationship (QSAR) of their transformation products (TPs). Photolysis experiments were conducted in distilled water with individual solutions at 10 mg L-1 for each compound. Identification of TPs was performed by means of LC-TOF-MS, employing a method based on retention time, exact mass fragmentation pattern, and peak intensity. Ten main compounds were identified for sulfamethoxazole, fifteen for ciprofloxacin, and fifteen for norfloxacin. Out of 40 identified TPs, 6 have not been reported in the literature. Based on new data found in this work, and TPs already reported in the literature, we have proposed degradation pathways for all three antimicrobials, providing reasoning for the identified TPs. QSAR risk assessment was carried out for 74 structures of possible isomers. QSAR predictions showed that all 19 possible structures of sulfamethoxazole TPs are non-mutagenic, whereas 16 are toxicant, 18 carcinogenic, and 14 non-readily biodegradable. For ciprofloxacin, 28 out of the 30 possible structures for the TPs are mutagenic and non-readily biodegradable, and all structures are toxicant and carcinogenic. All 25 possible norfloxacin TPs were predicted mutagenic, toxicant, carcinogenic, and non-readily biodegradable. Results obtained from in silico QSAR models evince the need of performing risk assessment for TPs as well as for the parent antimicrobial. An expert analysis of QSAR predictions using different models and degradation pathways is imperative, for a large variety of structures was found for the TPs.

Neutral 4-phenyl-1-[phenyl(pyridin-2-yl)methylidene]semicarbazide and its salt forms with inorganic anions.

Semicarbazones can exist in two tautomeric forms. In the solid state, they are found in the keto form. This work presents the synthesis, structures and spectroscopic characterization (IR and NMR spectroscopy) of four such compounds, namely the neutral molecule 4-phenyl-1-[phenyl(pyridin-2-yl)methylidene]semicarbazide, C19H16N4O, (I), abbreviated as HBzPyS, and three different hydrated salts, namely the chloride dihydrate, C19H17N4O+·Cl-·2H2O, (II), the nitrate dihydrate, C19H17N4O+·NO3-·2H2O, (III), and the thiocyanate 2.5-hydrate, C19H17N4O+·SCN-·2.5H2O, (IV), of 2-[phenyl({[(phenylcarbamoyl)amino]imino})methyl]pyridinium, abbreviated as [H2BzPyS]+·X-·nH2O, with X = Cl- and n = 2 for (II), X = NO3- and n = 2 for (III), and X = SCN- and n = 2.5 for (IV), showing the influence of the anionic form in the intermolecular interactions. Water molecules and counter-ions (chloride or nitrate) are involved in the formation of a two-dimensional arrangement by the establishment of hydrogen bonds with the N-H groups of the cation, stabilizing the E isomers in the solid state. The neutral HBzPyS molecule crystallized as the E isomer due to the existence of weak π-π interactions between pairs of molecules. The calculated IR spectrum of the hydrated [H2BzPyS]+ cation is in good agreement with the experimental results.

Valence and diffuse-bound anions of noble-gas complexes with uracil.

Valence-bound (VB) and diffuse-bound (DB) anions of noble-gas (Ar, Kr, and Xe) complexes with uracil have been studied with ab initio methods. MP2 optimizations revealed minima corresponding to anions of both kinds in each case. Coupled-cluster singles and doubles with perturbative triples, CCSD(T), and electron propagator single-point calculations were performed in order to assess vertical and adiabatic electron detachment energies of these complexes. Ab initio electron propagator calculations employed the outer valence Green's function and partial third-order approximations, and the algebraic diagrammatic construction in third order. Basis set effects have been systematically examined. DB anions of all three complexes were adiabatically bound, with calculated adiabatic electron attachment energies below 0.06 eV. Corresponding vertical electron detachment energies were below 0.1 eV. As to VB anions, only the Xe complex had a positive adiabatic electron detachment energy, of 0.01 eV, with a corresponding vertical electron detachment energy of 0.6 eV. These computational findings are consistent with the interpretation of results previously obtained experimentally by Hendricks et al.