Derivates of 1,6-dihyadroazaazulenes as inhibitors of tyrosine kinases BCR-ABL1 wild type and mutant T315I: a molecular dynamics approach.

The protein tyrosine kinase (PTK) produced by the BCR-ABL1 gene has generated significant interest in the development of inhibitors since the presence of punctual mutations causes resistance to currently approved drugs, mainly the T315I mutation has been the most difficult to address. In this work, derivatives of 1,6-dihydroazaazulenes are studied as possible inhibitors of this PTK in its wild form and the mutant T315I. The recognition of the ligands was explored through molecular docking, and the stability of the complexes and their evolution over time was studied using molecular dynamics (MD) simulations. Our results show that complexes are energetically stable and reside on the ATP binding site in all cases during the MD experiments. Interestingly, a few of our proposed ligands presented greater affinity for T315I, finding more favorable binding free energies (ΔG) than the reference drug axitinib. Furthermore, they may act as inhibitors for both isoforms. Our findings are promising because mutation of T315I does not prevent ligand recognition, as detailed in this work, which is very important to conduct further experimental research.Communicated by Ramaswamy H. Sarma.

Biological Activities of Organic Extracts of the Genus Aristolochia: A Review from 2005 to 2021.

Different ethnomedicinal studies have investigated the relationship between various phytochemicals as well as organic extracts and their bioactive aspects. Studies on biological effects are attributed to secondary metabolites such as alkaloids, phenolic compounds, and terpenes. Since there have been no reviews in the literature on the traditional, phytochemical, and ethnomedicinal uses of the genus Aristolochia so far, this article systematically reviews 141 published studies that analyze the associations between secondary metabolites present in organic extracts and their beneficial effects. Most studies found associations between individual secondary metabolites and beneficial effects such as anticancer activity, antibacterial, antioxidant activity, snake anti-venom and anti-inflammatory activity. The aim of this review was to analyze studies carried out in the period 2005-2021 to update the existing knowledge on different species of the genus Aristolochia for ethnomedicinal uses, as well as pharmacological aspects and therapeutic uses.

Structural and electronic properties for Be-doped Ptn (n = 1-12) clusters obtained by DFT calculations.

In this work, we have performed a computational study on the structure and electronic properties for Be-doped Ptn (n = 1-12) clusters in the framework of density functional theory (DFT). The most stable structures of the clusters are obtained by a structure search procedure based in simulated annealing. The results show that the PtnBe clusters adopt compact structure motifs with Be situated at the edge sites while only in Pt11Be the Be atom occupies the center site. The energetic parameters showed that Pt5Be, Pt7Be and Pt10Be are the most stable ones. The PtnBe clusters with (n = 5-7) have similar vertical ionization potential (vIP) and vertical electron affinity (vEA) parameters compared to the unary Pt clusters, while Pt9Be and Pt11Be have the higher vEA values. In particular, the d-band center is slightly higher for the doped clusters, suggesting an enhanced reactivity. The σ-holes are found more remarkable for the doped clusters, which are situated in the Be dopant and low coordinated Pt sites. The data on the infrared spectra of the clusters is also provided and showed a significant blue shift due to the vibrational modes of the Be atom. These results are useful for understanding the fundamental properties of Be-doped Ptn clusters in the subnanometer region.

Electronic properties and reactivity of oxidized graphene nanoribbons and their interaction with phenol.

The effect of the oxidized functional groups on the structural, electronic, and reactivity properties of armchair graphene nanoribbons has been investigated in the framework of the density functional theory. The presence of functional groups near the edges stabilizes the oxidized graphene nanoribbons (OGNRs) more than substituting near the center. Overall, we found slight differences in the electronic properties of OGNRs concerning the pristine ones. The oxygen contribution of functional groups to the DOS is found in the conducting energy bands far from the Fermi level. Consequently, the semiconducting behavior is maintained after doping. Based on the reactivity of OGNRs, the most promising nanostructures were proposed as adsorbents studying the interaction and complexation with phenol, a critical pollutant removed mainly by hydrotreating processes (HDO) to produce bio-oil. Parallel and perpendicular phenol conformations were found towards the OGNRs in the optimized complexes driven by a physisorption process. These results provide significant insights for catalytic processes that use biomass derivatives containing phenolic compounds. The physisorption of streams containing pollutants on OGNRs could be adapted to new technological applications for the remotion of aromatic compounds under environmentally friendly operational conditions.

Iodine(III)-Mediated, Controlled Di- or Monoiodination of Phenols.

An oxidative procedure for the electrophilic iodination of phenols was developed by using iodosylbenzene as a nontoxic iodine(III)-based oxidant and ammonium iodide as a cheap iodine atom source. A totally controlled monoiodination was achieved by buffering the reaction medium with K3PO4. This protocol proceeds with short reaction times, at mild temperatures, in an open flask, and generally with high yields. Gram-scale reactions, as well as the scope of this protocol, were explored with electron-rich and electron-poor phenols as well as heterocycles. Quantum chemistry calculations revealed PhII(OH)·NH3 to be the most plausible iodinating active species as a reactive "I+" synthon. In light of the relevance of the iodoarene moiety, we present herein a practical, efficient, and simple procedure with a broad functional group scope that allows access to the iodoarene core unit.

Reactivity of Atomically Functionalized C-Doped Boron Nitride Nanoribbons and Their Interaction with Organosulfur Compounds.

The electronic and reactivity properties of carbon doped (C-doped) boron nitride nanoribbons (BNNRs) as a function of the carbon concentration were investigated in the framework of the density functional theory within the generalized gradient approximation. We found that the main routes to stabilize energetically the C-doped BNNRs involve substituting boron atoms near the edges. However, the effect of doping on the electronic properties depends of the sublattice where the C atoms are located; for instance, negative doping (partial occupations of electronic states) is found replacing B atoms, whereas positive doping (partial inoccupation of electronic states) is found when replacing N atoms with respect to the pristine BNNRs. Independently of the even or odd number of dopants of the C-doped BNNRs studied in this work, the solutions of the Kohn Sham equations suggest that the most stable solution is the magnetic one. The reactivity of the C-doped BNNRs is inferred from results of the dual descriptor, and it turns out that the main electrophilic sites are located near the dopants along the C-doped BNNRs. The reactivity of these nanostructures is tested by calculating the interaction energy between undesirable organosulfur compounds present in oil fuels on the C-doped BNNRs, finding that organosulfur compounds prefer to interact over nanosurfaces with dopants substituted on the B sublattice of the C-doped BNNRs. Most importantly, the selective C doping on the BNNRs offers the opportunity to tune the properties of the BNNRs to fit novel technological applications.

Oxidative amidation of benzaldehyde using a quinone/DMSO system as the oxidizing agent.

An efficient transition-metal-based heterogeneous catalyst free procedure for obtaining the oxidative amidation of benzaldehyde using quinones as oxidizing agents in low molar proportions is described here. Pyrrolylquinones (PQ) proved to be more suitable than DDQ and 2,5-dimethylbenzoquinone to conduct the oxidation process. Although the solvent itself acted as the oxidant with low to moderate yields, PQ/DMSO provided an efficient system for carrying out the reaction under operational simplicity, mild reaction conditions, short reaction times and high yields of the desired product. The scope of the method was evaluated with substituted benzaldehydes and secondary amines. Theoretical foundations are given to explain the participation of quinones as an oxidizing agent in the reaction.

Interfacial properties of the ionic liquid [bmim][triflate] over a wide range of temperatures.

We carried out molecular dynamics simulations of the liquid/vacuum equilibrium of the ionic liquid [bmim][triflate] in a wide range of temperatures (323.15 to 573.15 K). The results showed liquid phases with high densities even at temperatures close to the decomposition temperature of the liquid. The density and surface tension behaviors are linear across this wide range of temperatures, which is an extension of the behaviors of these systems at low temperatures, where these properties have been experimentally measured. The interfacial region shows peaks of adsorption of the ions; they are ordered, with the alkyl chains of the [bmim] cations pointing out of the liquid, and the tailing angle of the chains becomes 90° at higher temperatures. The alkyl chains are part of the outermost interfacial region, where intra- and intermolecular tangential forces are in equilibrium; thus, they do not contribute to the total surface tension. Unlike simpler organic liquids, the surface tension is composed of positive normal contributions of intermolecular interactions; these are almost in equilibrium with the negative normal contributions of intramolecular interactions, which are mainly vibrations of the distance and the angle of valence. The pressure profiles show that the molecules are in 'crushed' conformations internally in the bulk liquid and even more so in the normal direction at the interface. The total pressure profiles show values with physical meaning, where the tangential peaks show higher values than normal pressures and give rise to the surface tension. Short cutoff radii for the calculation of intermolecular forces (less than 16.5 Å) produce a system that is not mechanically stable in the region of the bulk liquid (confirmed by radial distribution function calculations); this produces a difference between the normal pressure and the average of the tangential pressures, which affects the calculation of the surface tension due to overestimation by up to 20% when using the global expression, which is extensively used for the calculation of surface tension. The use of a sufficiently long cutoff radius avoids these mechanical balance problems.

Molecular dynamics simulations of 2-(dimethylamino)ethanol (DMEA).

We develop a multipurpose force field to investigate the properties of the condensed phases of 2-(dimethylamino)ethanol (DMEA). We use ab initio computations at the HF/6-311++G(2d,2p) level to derive partial charges, obtain force constants, and compute the electrostatic potential of the DMEA. We find that the HF predictions for the dipole moment are in excellent agreement with the experimental result (2.6 D). The computations also show the strong preference of DMEA to form intramolecular hydrogen bonds between the hydrogen in the alcohol group and nitrogen. We have tested the accuracy of our force field by computing coexistence and interfacial properties as well as thermal conductivities in wide range of thermodynamic states. In all these instances we find excellent agreement with the available experimental data. We have further investigated the structure of the liquid by computing pair correlations. Our results indicate a clear preference for DMEA to form low-dimensional structures, such as linear and bifurcated chains, which are driven by the association of the DMEA molecules via the alcohol group. Overall, our force field provides a good basis to compute the bulk and interfacial properties of DMEA.