ALBERT

Description: Quantitative Structure Activity Relationships (QSAR or SAR) have helped scientists to establish mathematical relationships between molecular structures and their biological activities. In the present article, SAR studies have been carried out on 89 tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepine (TIBO) derivatives using different classifiers, such as support vector machines, artificial neural networks, random forests, and decision trees. The goal is to propose classification models that will be able to classify TIBO compounds into two groups: high and low inhibitors of HIV-1 reverse transcriptase. Each molecular structure was encoded by 10 descriptors. To check the validity of the established models, all of them were subjected to various validation tests: internal validation, Y-randomization, and external validation. The established classification models have been successful. The correct classification rates reached 100% and 90% in the learning and test sets, respectively. Finally, molecular docking analysis was carried out to understand the interactions between reverse transcriptase enzyme and the TIBO compounds studied. Hydrophobic and hydrogen bond interactions led to the identification of active binding sites. The established models could help scientists to predict the inhibition activity of untested compounds or of novel molecules prior to their synthesis. Therefore, they could reduce the trial and error process in the design of human immunodeficiency virus (HIV) inhibitors.

Description: The number of scientific papers on the unique properties and the potential for various applications of compounds with a diradical character is growing constantly. The diradical character enhances and even engenders certain desired optical properties and its modulation is a modern molecular design strategy. Nowadays, molecules with a non-zero diradical character are regarded as promising materials for new-generation and highly efficient solar cells and photonics devices. What is the price, however, of the unique properties of open-shell compounds? Alongside all the benefits, the diradical character is usually associated with low stability and high reactivity—unwanted molecular qualities for practical purposes. Thus, from a fundamental and applied point of view, it is important to investigate the correlation between the diradical character and laboratory stability, which is the goal of the present paper. Here, we report a combined quantum–chemical study (conceptual DFT and spin-projected HF theory) and multivariate analysis of the diradical character of a series of o- and p-quinomethides, for the stability of which experimental data are available. Our results reveal that a compromise between the diradical character and laboratory stability of a molecule is feasible and that the relationship between these two quantities can be understood in the framework of Clar’s sextet theory.