The electronic effects in supramolecular systems are a great challenge for computational chemistry, and the understanding of ligand-protein interactions driven by halogen bonds can be limited by molecular mechanics point of view. In fact, the variations of the halogen bond acceptors, such as an aromatic ring and electrons lone pairs, restrict the classical approximations even more. Our work enhances the statement that halogen bonds are led mainly by orbital interactions via σ*. Nonetheless, we have pointed a straight relationship between the maximum ESP value on the σ-hole and the LUMO energy levels of the halogen bond donor. In line with this scenario, the current work introduces a new promising empirical potential based on quantum parametrizations able to describe general halogen bonded systems. The new parameters allow force fields to detect variations on the molecular electronic structure of halogenated organic compounds to improve the description of fluorine, chlorine, and bromine in halogen bonds.

Alzheimer’s disease (AD) is a neurodegenerative disease that is usually accompanied by aging, increasingly being the most common cause of dementia in the elderly. This disorder is characterized by the accumulation of beta amyloid plaques (Aβ) resulting from impaired amyloid precursor protein (APP) metabolism, together with the formation of neurofibrillary tangles and tau protein hyperphosphorylation. The exacerbated production of reactive oxygen species (ROS) triggers the process called oxidative stress, which increases neuronal cell abnormalities, most often followed by apoptosis, leading to cognitive dysfunction and dementia. In this context, the development of new therapies for the AD treatment is necessary. Antioxidants, for instance, are promising species for prevention and treatment because they are capable of disrupting the radical chain reaction, reducing the production of ROS. These species have also proven to be adjunctive to conventional treatments making them more effective. In this sense, several recently published works have focused their attention on oxidative stress and antioxidant species. Therefore, this review seeks to show the most relevant findings of these studies.

Glyphosate is the active component of one of the top‐selling herbicides, which is also a potent EPSP synthase inhibitor. The herbicide is absorbed by living tissue and translocated via the phloem, to plant roots and rhizomes. When applied directly into the soil it has low activity, due to the high adsorption by soil constituents. Understanding the specific interactions between metals in the soil and glyphosate is the main step in understanding the low activity of the herbicide when applied directly into the ground and not pulverized. We can observe there is a stability order for both tetrahedral and octahedral complexes between glyphosate and metals: Zn>Cu>Co>Fe>Cr>Al>Ca>Mg. © 2012 Wiley Periodicals, Inc.

Elastase B (lasB) is a multifunctional metalloenzyme secreted by the gram-negative pathogen Pseudomonas aeruginosa , and this enzyme orchestrates several physiopathological events during bacteria-host interplays. LasB is considered to be a potential target for the development of an innovative chemotherapeutic approach, especially against multidrug-resistant strains. Recently, our group showed that 1,10-phenanthroline-5,6-dione (phendione), [Ag(phendione) 2 ]ClO 4 (Ag-phendione) and [Cu(phendione) 3 ](ClO 4 ) 2 .4H 2 O (Cu-phendione) had anti- P. aeruginosa action against both planktonic- and biofilm-growing cells. In the present work, we have evaluated the effects of these compounds on the (i) interaction with the lasB active site using in silico approaches, (ii) lasB proteolytic activity by using a specific fluorogenic peptide substrate, (iii) lasB gene expression by real time-polymerase chain reaction, (iv) lasB protein secretion by immunoblotting, (v) ability to block the damages induced by lasB on a monolayer of lung epithelial cells, and (vi) survivability of Galleria mellonella larvae after being challenged with purified lasB and lasB-rich bacterial secretions. Molecular docking analyses revealed that phendione and its Ag + and Cu 2+ complexes were able to interact with the amino acids forming the active site of lasB, particularly Cu-phendione which exhibited the most favorable interaction energy parameters. Additionally, the test compounds were effective inhibitors of lasB activity, blocking the in vitro cleavage of the peptide substrate, aminobenzyl-Ala-Gly-Leu-Ala- p -nitrobenzylamide, with Cu-phendione having the best inhibitory action (K i = 90 nM). Treating living bacteria with a sub-inhibitory concentration (½ × MIC value) of the test compounds caused a significant reduction in the expression of the lasB gene as well as its mature protein production/secretion. Further, Ag-phendione and Cu-phendione offered protective action for lung epithelial cells, reducing the A549 monolayer damage by approximately 32 and 42%, respectively. Interestingly, Cu-phendione mitigated the toxic effect of both purified lasB molecules and lasB-containing bacterial secretions in the in vivo model, increasing the survival time of G. mellonella larvae. Collectively, these data reinforce the concept of lasB being a veritable therapeutic target and phendione-based compounds (mainly Cu-phendione) being prospective anti-virulence drugs against P. aeruginosa .

No abstract