Molecular orbitals are critical in the rationalization of several chemical reactions. Thus, the frontier molecular orbital theory, proposed by Fukui's group, postulated the importance of the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) for chemical reactions. It should be kept in mind, however, that there are limitations of this theory and new perspectives about the chemical reactivity have recently been arisen based on composition and location of other frontier molecular orbitals. In this review, we have reported the development and the most recent applications of the Frontier Effective-for-Reaction Molecular Orbital (FERMO) concept, which describes the breaking and formation of new chemical bonds and can in turn, provide important clues that modulate chemical reactivity of atoms and molecules.

The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g., neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the patients’ quality of life and even causing death. In spite of their clinical diversity, these NDDs share common characteristics, such as the accumulation of specific proteins in the cells, the compromise of the metal ion homeostasis in the brain, among others. Despite considerable advances in understanding the mechanisms of these diseases and advances in the development of treatments, these disorders remain uncured. Considering the diversity of mechanisms that act in NDDs, a wide range of compounds have been developed to act by different means. Thus, promising compounds with contrasting properties, such as chelating agents and metal-based drugs have been proposed to act on different molecular targets as well as to contribute to the same goal, which is the treatment of NDDs. This review seeks to discuss the different roles and recent developments of metal-based drugs, such as metal complexes and metal chelating agents as a proposal for the treatment of NDDs.

Organophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. The diisopropyl fluorophosphatase (DFPase) enzyme has been considered as a potent biocatalyst for the hydrolysis of toxic OP and has potential for bioremediation of this kind of intoxication. In order to investigate the degradation process of the nerve agents Tabun, Cyclosarin and Soman through the wild-type DFPase, and taking into account their stereochemistry, theoretical studies were carried out. The intermolecular interaction energy and other parameters obtained from the molecular docking calculations were used to construct a data matrix, which were posteriorly treated by statistical analyzes of chemometrics, using the PCA (Principal Components Analysis) multivariate analysis. The analyzed parameters seem to be quite important for the reaction mechanisms simulation (QM/MM). Our findings showed that the wild-type DFPase enzyme is stereoselective in hydrolysis, showing promising results for the catalytic degradation of the neurotoxic agents under study, with the degradation mechanism performed through two proposed pathways.

Introduction: Alzheimer's disease is known to be a chronic disease, with an estimated prevalence of about 10-30%, considering the population over 60 years of age. Most patients with this disorder (> 95%) present the sporadic form, being characterized by a late onset (80-90 years of age), and it is the consequence of the failure to clear the amyloid-β (Aβ) peptide from the interstices of the brain. Significant numbers of genetic risk factors for the sporadic disease have been researched. Some existing drugs for Alzheimer's disease provide symptomatic benefit for up to 12 months, but there are no approved disease- modifying therapies. In this line, a complementary strategy based on repositioning drugs which are approved for the treatment of other disorders could be interesting. It is noteworthy the fact that some clinical trials indicate that several classes of drugs own potent and beneficial effects on the Alzheimer's disease treatment. In this present work, we present the details and evaluation of these alternative treatments. It has highlighted several compounds with relevant evidence for this purpose, which deserves further investigation to clarify optimal treatment conditions in the clinical trials of patients with Alzheimer's disease.