Aromaticity of six-membered nitro energetic compounds through molecular electrostatic potential, magnetic, electronic delocalization and reactivity-based indices.

The electron density depletion associated with π-hole at the ring center typical of energetic compounds was clearly revealed by the molecular electrostatic potential (ESP). In addition, the spatial arrangement of NO2 groups appears to affect the ESP value in the ring center, and therefore sensitivity to detonation. Indeed, for monocyclic nitrobenzene compounds with the same number of NO2 groups, the ESP value in the ring center decreases as the NO2 groups are more closely spaced. As expected, the central rings become less aromatic as NO2 groups are added. The MCI, PDI, PLR, NICSzz(1), FLU indices are all strongly correlated with the ESP values observed in the ring center of the set of nitrobenzenes. Aromaticity indices based on electron delocalization criteria appear to be very sensitive to small variations in aromaticity. Among magnetic-based indices, only NICSzz(1) is capable to predict small changes in aromaticity. The PLR index derived from conceptual DFT is quite relevant for predicting small variations in aromaticity. According to our results, the most suitable aromaticity index is not based on a single criterion, and that selecting it is more subtle. Therefore, it is important to combine information from several criteria to obtain a more complete description of the aromaticity of the studied compounds.

The effect of {O,N}=X⋯M={Ti,Zr,Hf} interactions on the sensitivity of CNO2 trigger bonds in FOX-7: Approach based on the QTAIM/EDA-NOCV analysis.

The local chemical reactivity of FOX-7 (1,1-diamino-2,2-nitroethylene, also known as DADNE from DiAminoDiNitroEthylene) was elucidated through a quantitative study of the electrostatic potential on the molecular surface, topological analysis based on Bader's theory, and the EDA-NOCV method. Unlike (O2N)2CC(NH2)H2N⋯Cp2MCH3+ complexes, which exhibit both σ-donor and π-acceptor features, the situation is different concerning the (H2N)2CC(NO2)(O)NO⋯Cp2MCH3+ complexes, where both charge transfers correspond to the σ-donation. The two charge transfers reinforce each other, resulting in increased stability for (H2N)2CC(NO2)(O)NO⋯Cp2MCH3+. This seems to strengthen the (H2N)2CC(NO2)(O)NO⋯M={Ti,Zr,Hf} bond, which may explain the high stability of (H2N)2CC(NO2)(O)NO⋯Cp2MCH3+ compared to (O2N)2CC(NH2)-H2N⋯Cp2MCH3+. Results from topological analysis revealed that the decreased sensitivity to decomposition of CNO2 bonds depends on the chemical nature of the interacting metal, and the best achievements are obtained for the Hf-based complex. Our results demonstrate that the interaction of M={Ti,Zr,Hf} with CNO2 is more favourable than that with CNH2, this specific action on the trigger bond may support the use of Metallocene Methyl Cations (MMC) as possible neutralisers.

Theoretical investigation of the effect of O⋯M={Ti,Zr,Hf} interactions on the sensitivity of energetic N-nitro compounds.

This paper outlines the role of intermolecular interactions involving group 4 transition metals in stabilising the N-NO2 trigger bonds. Minimising sensitivity is the foremost priority in designing energetic compounds. A quantitative analysis with Molecular Electrostatic Potential (MEP) evidenced anomalies arising from the marked depletion of negative charge distribution of RDX and HMX. The Energy Decomposition Analysis with Natural Orbitals for Chemical Valence (EDA-NOCV) results reveal that the electrostatic and orbital contributions are the dominant factors driving the assembly of the M={Ti,Zr,Hf}-based complexes. Sensitivity of the N-NO2 trigger bonds is investigated by using the Quantum Theory of Atoms in Molecules (QTAIM). The QTAIM topological analysis showed that the O⋯M={Ti,Zr,Hf} interaction strengthens these trigger bonds, revealing an increased stability to decomposition. This effect is more marked in the Hf- and Zr-based complexes. Finally, the results based on Interaction Indicator Region (IRI) are fully consistent with those generated from QTAIM analysis.

Explaining the High Catalytic Activity in Bis(indenyl)methyl Zirconium Cation Using Combined EDA-NOCV/QTAIM Approach.

The main purpose of this study is to elucidate some discrepancies already observed in the catalytic activity values of some zirconocene methyl cations. The EDA-NOCV scheme was employed for a theoretical description of the interactions between an ethylene molecule and five catalysts of zirconocene methyl cation. The nature of the chemical interactions has been elucidated through the QTAIM topological analysis. The steric hindrance due to the ligands was evaluated qualitatively by means of an IRI-based analysis and quantitively through Fisher information. The findings prove that the indenyl ligand seems to favor the orbital interaction between the ethylene molecule and the metal centre of zirconocene methyl cation. Both electrostatic and orbital contributions play a crucial role in stabilising the studied complexes. Based on the NOCV deformation density contributions, the strongest orbital interaction is reached with the bis(indenyl)methyl zirconium cation, which is the only one exhibiting covalent interactions. Especially, the strong contribution of π-back donation (occurring from the occupied orbitals of the zirconium atom to the π* anti-bonding orbital of ethylene) may be a key to understand why this catalyst has a higher polymerisation yield than the other studied catalysts. This work suggests a perspective for predicting values of catalytic activity when theoretically designing novel catalysts of zirconocene type.

Facial paralysis after intraoral anesthetic injection: A systematic review.

Many complications can occur after the injection of local intraoral anesthetics (ILIA) before dental intervention. Facial paralysis (FP) is one of these complications. The purpose of this study was to systematically analyze the association between ILIA and FP. A systematic review was carried out taking into account the methodology of the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA statement. The search strategy used "Palsy AND Facial" and "Paralysis AND Facial" as search terms. The ScienceDirect, PubMed and Scopus databases were searched using the "dentistry journal" filter. The inclusion criteria included studies describing FP after or during ILIA that were published in dental journals. The CAse REports (CARE) checklist was applied in evaluating the methodological quality of case reports. A total of 2,462 articles (algorithm) were identified. After reviewing titles and abstracts, 18 articles were deemed relevant taking into account the objectives of this study. Only 13 of them, after reading the full text, met the inclusion criteria and were analyzed. Case reports on 18 cases of FP were analyzed, 12 of which described the early development of FP (onset within 24 h) and 6 the late development (onset after 24 h). Acceptable compliance with CARE guidelines was observed in the included studies . Early FP CRs presented the effect of the administered anesthetic on the facial nerve, and the vascular effect of the vasoconstrictor included in the anesthetic formula, while more recent FP CRs focused on the reactivation of herpes simplex virus type 1 (HSV-1), human herpesvirus 6 (HHV-6) or varicella-zoster virus (VZV).

Trypanosoma cruzi pathogenicity involves virulence factor expression and upregulation of bioenergetic and biosynthetic pathways.

The molecular repertoire of Trypanosoma cruzi effects its virulence and impacts the clinical course of the resulting Chagas disease. This study aimed to determine the mechanism underlying the pathogenicity of T. cruzi. Two T. cruzi cell lines (C8C3hvir and C8C3lvir), obtained from the clone H510 C8C3 and exhibiting different virulence phenotypes, were used to evaluate the parasite's infectivity in mice. The organ parasite load was analysed by qPCR. The proteomes of both T. cruzi cell lines were compared using nLC-MS/MS. Cruzipain (Czp), complement regulatory protein (CRP), trans-sialidase (TS), Tc-85, and sialylated epitope expression levels were evaluated by immunoblotting. High-virulence C8C3hvir was highly infectious in mice and demonstrated three to five times higher infectivity in mouse myocardial cells than low-virulence C8C3lvir. qPCR revealed higher parasite loads in organs of acute as well as chronically C8C3hvir-infected mice than in those of C8C3lvir-infected mice. Comparative quantitative proteomics revealed that 390 of 1547 identified proteins were differentially regulated in C8C3hvir with respect to C8C3lvir. Amongst these, 174 proteins were upregulated in C8C3hvir and 216 were downregulated in C8C3lvir. The upregulated proteins in C8C3hvir were associated with the tricarboxylic acid cycle, ribosomal proteins, and redoxins. Higher levels of Czp, CRP, TS, Tc-85, and sialylated epitopes were expressed in C8C3hvir than in C8C3lvir. Thus, T. cruzi virulence may be related to virulence factor expression as well as upregulation of bioenergetic and biosynthetic pathways proteins.

A combined QTAIM/IRI topological analysis of the effect of axial/equatorial positions of NH2 and CN substituents in the [(PY5Me2)MoO]+ complex.

By means of the Interaction Region Indicator (IRI) and Quantum Theory of Atoms in Molecules (QTAIM), the influence exerted by NH2 (amino) and CN (cyano) as electron donor and electron acceptor substituent groups, respectively, located at para-positions of axial and equatorial pyridine rings of derivatized complexes coming from the [(PY5Me2)MoO]+ complex during the hydrogen molecular release in the gas phase was analyzed. In any case, a H-H covalent bond is forming at the transition state, with a strengthening of the electron density of 5.5% when the substituent group involved is NH2 at the para-position of the axial pyridine ring. However, there was no difference between NH2 and CN when these substituent groups are located at the para-positions of the equatorial pyridine rings. The topological properties of electron densities from the QTAIM are not perturbed by the electron donor and electron acceptor nature of the substituents, even when these substituent groups are located at the axial or equatorial pyridine rings of the Mo-based complex.

The Dual Descriptor Reveals the Janus-Faced Behaviour of Diiodine.

The Janus-faced ligand behavior of diiodine (I2) was evidenced after applying the dual descriptor (DD or second-order Fukui function), thus providing additional support to the work performed by Rogachev and Hoffmann in 2013. Along with its capacity to reveal sites susceptible to undergo attacks simultaneously of nucleophilic and electrophilic types, another advantage of DD lies in being an orbital-free descriptor. That means it is based only upon total electron densities when written in its most accurate operational formula. This quality is not exclusive of DD because when Fukui functions are written in terms of electron densities instead of densities of frontier molecular orbitals, they become orbital-free descriptors too. Furthermore, the present work is an application of the generalized operational formula of the dual descriptor published in 2016 that takes into account any possible degeneracy in frontier molecular orbitals. As a proof about capabilities of DD, the possible sites for a favorable interaction between I2 with two organometallic compounds [Rh2(O2CCF3)4] and [(C8H11N2)Pt (CH3)] were correctly revealed by overlapping the biggest lobe for receiving nucleophilic attacks of one molecule with the biggest lobe for receiving electrophilic attacks of the other molecule, so allowing to predict the same coordination modes as experimentally known: linear "end-on" for the [(C8H11N2)Pt (CH3)]…I2, and bent "end-on" for the [Rh2(O2CCF3)4]…I2 interactions.

Physicochemical and Theoretical Characterization of a New Small Non-Metal Schiff Base with a Differential Antimicrobial Effect against Gram-Positive Bacteria.

Searching for adequate and effective compounds displaying antimicrobial activities, especially against Gram-positive bacteria, is an important research area due to the high hospitalization and mortality rates of these bacterial infections in both the human and veterinary fields. In this work, we explored (E)-4-amino-3-((3,5-di-tert-butyl-2-hydroxybenzylidene)amino) benzoic acid (SB-1, harboring an intramolecular hydrogen bond) and (E)-2-((4-nitrobenzilidene)amino)aniline (SB-2), two Schiff bases derivatives. Results demonstrated that SB-1 showed an antibacterial activity determined by the minimal inhibitory concentration (MIC) against Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus (Gram-positive bacteria involved in human and animal diseases such as skin infections, pneumonia, diarrheal syndrome, and urinary tract infections, among others), which was similar to that shown by the classical antibiotic chloramphenicol. By contrast, this compound showed no effect against Gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, and Salmonella enterica). Furthermore, we provide a comprehensive physicochemical and theoretical characterization of SB-1 (as well as several analyses for SB-2), including elemental analysis, ESMS, 1H and 13C NMR (assigned by 1D and 2D techniques), DEPT, UV-Vis, FTIR, and cyclic voltammetry. We also performed a computational study through the DFT theory level, including geometry optimization, TD-DFT, NBO, and global and local reactivity analyses.

Analysis in silico of chemical reactivity employing the local hyper-softness in some classic aromatic compounds, boron aromatic clusters and all-metal aromatic clusters.

In the current work, the authors analyzed and compared the chemical behavior of some (anti)aromatic compounds. The species selected are benzene and cyclobutadiene as the aromatic and antiaromatic classical examples, respectively. Next, the anion Al 4 2 - , which is the first all-metal molecule catalogued as aromatic and its non-metallic isoelectronic analog, B 4 2 - were also analyzed. The antiaromatic clusters Al 4 4 - and B 4 4 - were studied in form of lithium salts. And the end, the non-planar B 12 boron cluster and its isoelectronic analogs ( B 11 Be - and B 11 C + ) were considered for being analyzed under the same criterium. The analysis was realized employing the following descriptors: molecular electrostatic potential and local hyper-softness to get insights concerning local reactivity when facing reagents leading to ionic or covalent interactions. The results show that all the molecules analyzed presented some specific variations in their respective local reactivity despite being labeled as aromatic compounds. This analysis provides a notion that the local reactivity is more based on the nature of the atoms and the molecular geometry than the aromatic character by itself.

In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles.

Calcineurin (CaN) is present in all eukaryotic cells, including intracellular trypanosomatid parasites such as Trypanosoma cruzi (Tc) and Leishmania spp. (Lspp). In this study, we performed an in silico analysis of the CaN subunits, comparing them with the human (Hs) and looking their structure, post-translational mechanisms, subcellular distribution, interactors, and secretion potential. The differences in the structure of the domains suggest the existence of regulatory mechanisms and differential activity between these protozoa. Regulatory subunits are partially conserved, showing differences in their Ca2+-binding domains and myristoylation potential compared with human CaN. The subcellular distribution reveals that the catalytic subunits TcCaNA1, TcCaNA2, LsppCaNA1, LsppCaNA1_var, and LsppCaNA2 associate preferentially with the plasma membrane compared with the cytoplasmic location of HsCaNAα. For regulatory subunits, HsCaNB-1 and LsppCaNB associate preferentially with the nucleus and cytoplasm, and TcCaNB with chloroplast and cytoplasm. Calpain cleavage sites on CaNA suggest differential processing. CaNA and CaNB of these trypanosomatids have the potential to be secreted and could play a role in remote communication. Therefore, this background can be used to develop new drugs for protozoan pathogens that cause neglected disease.

Demodex folliculorum (Trombidiformes: Demodicidae) and Demodex brevis Prevalence in an Extreme Environment of Chile.

The prevalence of mites of the genus Demodex and their associations with host age, gender, workplace, and comorbid skin and ocular conditions were studied in participants in Antofagasta, Chile, which is in a region with an extreme environment. We examined 680 participants aged 18-88 yr using standardized surface skin biopsies. Among them, Demodex had a prevalence of 13.5 % (95% confidence interval, 10.88-16.17). A slightly higher prevalence was observed in males (51.1%; 95% confidence interval, 40.9-61.3; nonsignificant) and participants in the 69-88 yr age group (50.0%; 95% confidence interval, 23.8-76.2; P < 0.05). Regarding the species involved, Demodex folliculorum was found in 89.1% (CI 82.7-95.5) of cases, while D. brevis was found in the remaining 10.9% of cases. A higher prevalence (25.0% CI 16.1-33.91) was observed in participants who worked indoors in generally enclosed and dust-rich environments (such as theaters, libraries, and administrative offices). There was also a strong association between Demodex prevalence and conjunctival hyperemia, with 35.9% (95% confidence interval, 9.1-35; OR 17.9) of the Demodex positive participants having this pathology compared to 10.3% of the noninfested participants. In summary, the prevalence of Demodex in Antofagasta, Chile (13.5%) was toward the lower end of the range reported among other regions around the world. Environmental factors such as exposure to the sun (including ultraviolet rays) or environmental pollution may affect the mites. In addition, Demodex genetics (related to virulence) and the ocular or skin microbiota may positively or negatively influence infestation and pathology.

The density polarization reveals directions of electron displacements due to the substituent effect: Analysis performed on a metal-organic Mo-Oxo catalyst.

Some Mo-oxo complexes bearing pyridine rings have the capability for dihydrogen production from water. However, energy barrier and overall energy vary depending on the effect exerted by several substituent groups located at different positions around one or more pyridine rings which are ligands of these compounds. Based on the Karunadasa and coworkers investigation where the para-position was experimentally tested in compounds derivatised from the 2,6-bis[1,1-bis(2-pyridil)ethyl]-pyridine oxo-molybdenum complex synthesized (Karunadasa et al., Nature, 2010, 464, 1329), we tested the combined effect of electron-withdrawing and electron-donating groups simulated as perturbations represented by point-charges. Then, we used the density polarization concept, δρ(r), a local reactivity descriptor corresponding to the partially integrated linear response function, χ(r, r') (a non-local reactivity descriptor), which is able to reveal different displacements of π-electrons on molecular structures. We perturbed the para-positions in the pentadentate ligand 2,6-bis[1,1-bis(2-pyridil)ethyl]-pyridine in the Mo-based complex by means of point-charges. They were located in three different configurations of the organic ligand (trans, geminal, and cis) which could help to explain energy barriers and overall energy of reactions catalyzed by this type of Mo-complexes. Our results indicate that the trans configuration of point-charges induces the most amount of fraction of electron shifted on the complex. A Mo-based complex bearing the same trans configuration for electron-withdrawing and electron-donating substituent groups (cyano and amino, respectively), leads to a kinetically more favorable H2 release than the cis or geminal configuration of the substituent groups aforementioned.

1,3-Dipolar Cycloadditions by a Unified Perspective Based on Conceptual and Thermodynamics Models of Chemical Reactivity.

The main aim in the present report is to gain a deeper understanding of typical 1,3-dipolar cycloadditions by means of three chemical reactivity models in a unified perspective: conceptual density functional theory, distortion/interaction, and reaction force analysis. The focus is to explore the information provided by each reactivity model and how they complement or reinforce each other. Our results showed that the Bell-Evans-Polanyi (BEP) relationship is fulfilled, which is consistent with the Hammond-Leffler postulate. The electronic chemical potential based analysis classifies the reactions as HOMO-, HOMO/LUMO-, and LUMO-controlled reactions as the activation energy increases. It seems likely that HOMO-controlled reaction shifts into LUMO-controlled one as the transition state (TS) position does from early into late. Therefore, the transition from HOMO- (and early TS) into LUMO-controlled (and late TS) is paid by shifting the overall energy change into an endothermic direction, thus supporting the fulfillment of the BEP principle. While thermodynamic models unveil that the distortion or structural rearrangements mainly drive the activation barriers rather than interaction or electronic rearrangements in accord with the distortion/interaction and reaction force analysis, respectively. It is also found that both models are consistent when energy associated with structural and electronic reordering from reaction force analysis is respectively confronted with destabilizing (distortion and Pauli repulsion) and stabilizing (electrostatic and orbital interactions) contributions from the distortion/interaction model, which, on the other hand, increases as low activation barrier and high exothermicity are converted into the high barrier and low exothermicity along with the BEP relation. Finally, the reaction force constant reveals that all 1,3-dipolar cycloaddition reactions proceed by a synchronous single-step mechanism, unveiling that the degree of synchronicity is quite the same in all reactions, confirming the statement that BEP is fulfilled for similar reactions proceeding by a quite alike degree of synchronicity.

Arsenic trioxide-increased MDCK cells proliferation requires activator protein 1-mediated increase of the sodium/proton exchanger 1 activity.

The release of protons (H+) occurs via the Na+/H+ exchanger isoform 1 (NHE1) leading to a stable intracellular pH (pHi) in MDCK cells. Chronic intake of arsenic trioxide (ATO), in the drinking water, associated with higher morbidity and mortality in neoplastic tissues. ATO increased NHE1 expression and activity, resulting in intracellular alkalization and higher MDCK cells proliferation. Since the pro-proliferative transcription factor activator protein 1 (AP-1) gets activated by al alkaline intracellular pH, a phenomenon paralleled by higher NHEs activity, we asked whether ATO-increased MDCK cells proliferation involves AP-1-dependent NHE1 activation. Cells were exposed (48 h) to ATO (0.05 µmol/L), SR11302 (1 µmol/L, AP-1 inhibitor), HOE-694 (100 nmol/L, NHE1 inhibitor) and EIPA (50 µmol/L, NHE1/NHE3 inhibitor) in the presence of S3226 (10 µmol/L, NHE3 inhibitor), concanamycin A (0.1 µmol/L, V-ATPases inhibitor), and Schering (10 µmol/L, H+/K+-ATPase inhibitor). [3H]Thymidine incorporation, cell counting, wound healing assay, and AP-1 activity were determined. The pHi was measured in cells pre-loaded (10 min) with 2,7-bicarboxyethyl-5,6-carboxyfluorescein acetoxymethyl ester (12 mmol/L) and exposed to NH4Cl (20 mmol/L). Basal pHi and recovery rate (dpHi/dt), intracellular buffer capacity (ßi) and H+ flux (JH+) were determined. NHE1 protein abundance was measured by Western blotting and immunofluorescence. ATO increased the cell growth (1.5 fold), basal pHi (0.4 pHi units), dpHi/dt (1.8 fold), JH+ (1.4 fold), AP-1 activity and NHE1 protein abundance (1.3 fold). ATO also increased (1.5 fold) the nuclear/perinuclear NHE1 immunosignal. SR11302 and HOE-694 blocked ATO effects. Thus, ATO-increased proliferation resulted from AP-1-dependent NHE1 activation in MDCK cells.

KID Procedure Applied on the [(PY5Me2)MoO]+ Complex.

The KID (Koopmans in DFT) protocol usually applies in organic molecules of the closed-shell type. We used the KID procedure on an open-shell Mo-based system for the first time to choose the most suitable density functional to compute global and local reactivity descriptors obtained from the conceptual density-functional theory (DFT). From a set of 18 density functionals, spread from the second until the fourth rung of Jacob's ladder: BLYP, BP86, B97-D, MN12-L, MN15-L, M06-L, M11-L, CAM-B3LYP, PBE0, B3LYP, N12-SX, M06-2X, MN15, MN12-SX, ωB97X-D, M11, LC-ωHPBE, and APFD, we concluded that CAM-B3LYP provides the best outcome, and in the second place, M06-2X. Because the vertical first ionization potential and vertical first electron affinity in the ground state (gs) are defined as follows I = E gs(N - 1) - E gs(N) and A = E gs(N) - E gs(N + 1), where E gs(N - 1), E gs(N), and E gs(N + 1) correspond to energies of the system bearing N, N + 1, and N - 1 electrons, along with Koopmans' theorem (KT) given by I ≈ -εHOMO (εHOMO, highest occupied molecular orbital energy) and A ≈ -εLUMO (εLUMO, lowest unoccupied molecular orbital energy), the deviation from the KT was performed by the use of the index, such that J I = |E gs(N - 1) - E gs(N) + εHOMO| and J A = |E gs(N) - E gs(N + 1) + εLUMO|, which are absolute deviations from the perspective of I and A, respectively. Furthermore, the εSOMO (SOMO: singly-occupied molecular orbital energy) leads us to another index given by |ΔSL| = |εSOMO - εLUMO|. Therefore, J HL and |ΔSL| are indexes defined to evaluate the quality of the KT when employed within the context of quantum chemical calculations based on DFT and not the Hartree-Fock theory. We propose the index that could be more suitable to choose the most proper density functional because the J HL and |ΔSL| are independent indexes.

Effect of DODAB Nano-Sized Cationic Bilayer Fragments against Leishmania amazonensis.

The dioctadecyldimethylammonium bromide (DODAB) is a double-chained cationic lipid with potent bactericide and fungistatic activities; however, its toxicity on protozoan parasites is still unknown. Here, we show the antileishmanial activity of DODAB nano-sized cationic bilayer fragments on stationary-phase promastigotes and amastigotes of Leishmania amazonensis, the causative agent of cutaneous leishmaniasis. Upon treatment with DODAB, we analyzed the parasite surface zeta-potential, parasite viability, cellular structural modifications, and intracellular proliferation. The DODAB cytotoxic effect was dose-dependent, with a median effective concentration (EC50) of 25 µM for both life-cycle stages, comparable to the reported data for bacteria and fungi. The treatment with DODAB changed the membrane zeta-potential from negative to positive, compromised the parasite's morphology, affected the cell size regulation, caused a loss of intracellular organelles, and probably dysregulated the plasma membrane permeability without membrane disruption. Moreover, the parasites that survived after treatment induced small parasitophorous vacuoles and failed to proliferate inside macrophages. In conclusion, DODAB displayed antileishmanial activity, and it remains to be elucidated how DODAB acts on the protozoan membrane. Understanding this mechanism can provide insights into the development of new parasite-control strategies.

Toxicological Characterization and Phospholipase D Activity of the Venom of the Spider Sicarius thomisoides.

Envenomation by Loxosceles spiders (Sicariidae family) has been thoroughly documented. However, little is known about the potential toxicity of members from the Sicarius genus. Only the venom of the Brazilian Sicarius ornatus spider has been toxicologically characterized. In Chile, the Sicarius thomisoides species is widely distributed in desert and semidesert environments, and it is not considered a dangerous spider for humans. This study aimed to characterize the potential toxicity of the Chilean S. thomisoides spider. To do so, specimens of S. thomisoides were captured in the Atacama Desert, the venom was extracted, and the protein concentration was determined. Additionally, the venoms were analyzed by electrophoresis and Western blotting using anti-recombinant L. laeta PLD1 serum. Phospholipase D enzymatic activity was assessed, and the hemolytic and cytotoxic effects were evaluated and compared with those of the L. laeta venom. The S. thomisoides venom was able to hydrolyze sphingomyelin as well as induce complement-dependent hemolysis and the loss of viability of skin fibroblasts with a dermonecrotic effect of the venom in rabbits. The venom of S. thomisoides showed intraspecific variations, with a similar protein pattern as that of L. laeta venom at 32-35 kDa, recognized by serum anti-LlPLD1. In this context, we can conclude that the venom of Sicarius thomisoides is similar to Loxosceles laeta in many aspects, and the dermonecrotic toxin present in their venom could cause severe harm to humans; thus, precautions are necessary to avoid exposure to their bite.

A statistical thermodynamics view of electron density polarisation: application to chemical selectivity.

A fundamental link between conceptual density functional theory and statistical thermodynamics is herein drawn, showing that intermolecular electrostatic interactions can be understood in terms of effective work and heat exchange. From a more detailed analysis of the heat exchange in a perturbation theory framework, an associated entropy can be subsequently derived, which appears to be a suitable descriptor for the local polarisability of the electron density. A general rule of thumb is evidenced: the more the perturbation can be spread, both through space and among the excited states, the larger the heat exchange and entropy.