Mechanism for the Uncatalyzed Cyclic Acetone-Peroxide Formation Reaction: An Experimental and Computational Study

In this study, a mechanism for the uncatalyzed reaction between acetone and hydrogen peroxide is postulated. The reaction leads to the formation of the important homemade explosives collectively known as cyclic acetone peroxides (CAP). The proposed mechanistic scheme is based on Raman, GC-MS, and nuclear magnetic resonance measurements, and it is supported by <i>ab initio</i> density functional theory (DFT) calculations. The results demonstrate that the proposed mechanism for the uncatalyzed formation reaction of CAP occurs in three steps: monomer formation, polymerization of the 2-hydroperoxipropan-2-ol monomer, and cyclization. The temporal decay of the intensities of important assigned-bands is in excellent agreement with the proposed mechanism. Previous reports also confirm that the polymerization step is favored in comparison to other possible pathways

<i>Dry</i> selection and <i>wet</i> evaluation for the <i>rational</i> discovery of new anthelmintics

<p>Helminths infections remain a major problem in medical and public health. In this report, atom-based 2D bilinear indices, a <i>TOMOCOMD-</i><i>CARDD</i> (QuBiLs-MAS module) molecular descriptor family and linear discriminant analysis (LDA) were used to find models that differentiate among anthelmintic and non-anthelmintic compounds. Two classification models obtained by using non-stochastic and stochastic 2D bilinear indices, classified correctly 86.64% and 84.66%, respectively, in the training set. Equation 1(2) correctly classified 141(135) out of 165 [85.45%(81.82%)] compounds in external validation set. Another LDA models were performed in order to get the most likely mechanism of action of anthelmintics. The model shows an accuracy of 86.84% in the training set and 94.44% in the external prediction set. Finally, we carry out an experiment to predict the biological profile of our ‘in-house’ collections of indole, indazole, quinoxaline and cinnoline derivatives (∼200 compounds). Subsequently, we selected a group of nine of the theoretically most active structures. Then, these chemicals were tested in an <i>in</i> <i>vitro</i> assay and one good candidate (VA5-5c) as fasciolicide compound (100% of reduction at concentrations of 50 and 10 mg/L) was discovered.</p