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Protonated methane, CH5, is a key reactive intermediate in hydrocarbon chemistry and a borderline case for chemical structure theory, being the simplest example of hypercoordinated carbon. Early quantum mechanical calculations predicted that the properties of this species could not be associated with only one structure, because it presents serious limitations of the Born−Oppenheimer approximation. However, ab initio molecular dynamics and diffusion Monte Carlo calculations showed that the most populated structure could be pictured as a CH3tripod linked to a H2moiety. Despite this controversy, a model for the chemical bonds involved in this ion still lacks. Here we present a modern valence bond model for the electronic structure of CH5. The chemical bond scheme derived directly from our calculations pictures this ion as H3C···H2. The fluxionality can be seen as the result of a proton transfer between C−H bonds. A new insight on the vibrational bands at ∼2400 and ∼2700 cm-1is suggested. Our results show that the chemical bond model can be profitably applied to such intriguing systems. [ABSTRACT FROM AUTHOR]

American Trypanosomiasis, also known as Chagas disease, is caused by the protozoan Trypanosoma cruzi and exhibits limited options for treatment. Natural products offer various structurally complex metabolites with biological activities, including those with anti- T. cruzi potential. The discovery and development of prototypes based on natural products frequently display multiple phases that could be facilitated by machine learning techniques to provide a fast and efficient method for selecting new hit candidates. Using Random Forest and k-Nearest Neighbors, two models were constructed to predict the biological activity of natural products from plants against intracellular amastigotes of T. cruzi . The diterpenoid andrographolide was identified from a virtual screening as a promising hit compound. Hereafter, it was isolated from Cymbopogon schoenanthus and chemically characterized by spectral data analysis. Andrographolide was evaluated against trypomastigote and amastigote forms of T. cruzi , showing IC 50 values of 29.4 and 2.9 μM, respectively, while the standard drug benznidazole displayed IC 50 values of 17.7 and 5.0 μM, respectively. Additionally, the isolated compound exhibited a reduced cytotoxicity (CC 50 = 92.8 μM) against mammalian cells and afforded a selectivity index (SI) of 32, similar to that of benznidazole (SI = 39). From the in silico analyses, we can conclude that andrographolide fulfills many requirements implemented by DND i to be a hit compound. Therefore, this work successfully obtained machine learning models capable of predicting the activity of compounds against intracellular forms of T. cruzi .