Search

α-Synuclein is an intrinsically disordered protein whose aggregation is related to Parkinson's disease and other neurodegenerative disorders. Metal cations are one of the main factors affecting the propensity of α-synuclein to aggregate, either by directly binding to it or by catalyzing the production of reactive oxygen species that oxidize it. His50, Asp121 and several additional C-terminal α-synuclein residues are binding sites for numerous metal cations, while methionine sulfoxidation occurs readily on this protein under oxidative stress conditions. Molecular dynamics simulations are an excellent tool to obtain a microscopic picture of how metal binding or methionine sulfoxidation alter the conformational preferences of α-synuclein and, hence, its aggregation propensity. In this work, we report the first coarse-grained molecular dynamics study comparing the conformational ensembles of the native protein, the protein bound to either Cu2+ or Ca2+ at its main binding sites, and the methionine-sulfoxidized protein. Our results suggest that these events alter the transient α-synuclein intramolecular contacts, inducing a greater solvent exposure of its hydrophobic, aggregation-prone NAC domain, in full agreement with a recent experimental study on Ca2+ binding. Moreover, metal-binding residues directly participate in the long-range contacts that shield this domain and regulate α-synuclein aggregation. These results provide a molecular-level rationalization of the enhanced fibrillation experimentally observed in the presence of Cu2+ or Ca2+ and the oligomerization induced by methionine sulfoxidation. [ABSTRACT FROM AUTHOR]

Coordination polymers (CPs) in recent times have emerged as active constituents in many semiconductor devices like light emitting diodes (LED), field effect transistors (FET), photovoltaic devices and Schottky barrier diodes. An intelligent choice of linkers, careful selection of metal ions and post synthetic modification (PSM) can provide a better pathway for charge transportation. However, a proper understanding of the charge transport mechanism in CPs is still inadequate due to the lack of considerable experimental and theoretical work. In this paper, we address the theoretical elucidation of semiconducting properties and a probable pathway for charge transportation in three of our previously published CPs using density functional theory (DFT). These results help us to recognize the orbitals that have major contributions in the formation of the valence band and also provide the most likely pathway for optimum electronic communication. In this regard, the role of hydrogen bonding and unpaired electrons of metal d-orbitals is also established. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Comprehensive and systematic study of two halide perovskites by using density functional theory (DFT) calculations. • Comparison of twenty-four exchange-correlation functionals to test their accuracy for the prediction of band gaps. • Some DFT methods are able to reproduce the experimental data at low computational cost. Abstract We report a comprehensive and systematic study of two halide perovskites by using density functional theory calculations. Two structurally different perovskites have been studied, which are cubic CH 3 NH 3 PbI 3 (MAPI) and HC(NH 2) 2 PbI 3 (FAPI). We have used twenty-four exchange-correlation functionals, ranging from three LDA functionals, ten GGA functionals, seven MGGA and four hybrids among others have been tested, in order to determine the accuracy of these methods for the prediction of band gaps. Moreover, we have studied several possibilities to tackle the calculations of perovskites. That is, we have tested Numerical Atomic Orbitals with All Electron Relativistic calculations and compared to Plane Wave framework with pseudopotentials and relativistic corrections. Moreover, we have studied different k-points set, pseudopotentials types, with and without cell optimizations, with and without dispersion corrections and with and without Spin Orbit coupling. The results show that PBE and RPBE exhibit a good compromise between the accuracy of the results and computational demands. [ABSTRACT FROM AUTHOR]

The interactions between the protein α-synuclein and the Zn(II) and Al(III) cations at different sites were studied at the M06/6-311+G(d,p)/SMD and the ωB97X-D/6-311+G(d,p)/SMD levels of theory. For Zn(II), previous experimental studies determined the presence of a high affinity site at Asp121 and a lower affinity one at His50. As for Al(III), an in vitro study showed it to be the most effective cation to induce structural changes in α-synuclein and to accelerate its aggregation. Besides Zn(II) and Al(III), Cu(II) also binds α-synuclein (in fact, its complexes are the most studied and the best characterized ones) forming square planar complexes, and several binding sites are known for it, involving Met1-Asp2 (only in nonacetylated α-synuclein), His50, and Asp121. Herein, we applied a simple theoretical methodology, which satisfactorily reproduces experimental geometries and energies for complexes of N-terminally acetylated α-synuclein with Cu(II), to study Zn(II) and Al(III) complexes at those same sites, as well as at some structurally analogous alternative sites. We found binding geometries for Zn(II) and Al(III) that differ from the ones for Cu(II). These results can help to understand the interactions between α-synuclein and metals, one of the factors leading to the formation of potentially neurotoxic α-synuclein aggregates. [ABSTRACT FROM AUTHOR]

The interactions between N-terminally acetylated α-synuclein and Cu(II) at several binding sites have been studied with DFT calculations, specifically with the M06 hybrid functional and the ωB97X-D DFT-D functional. In previous experimental studies, Cu(II) was shown to bind several α-synuclein residues, including Met1-Asp2 and His50, forming square planar coordination complexes. Also, it was determined that a low-affinity binding site exists in the C-terminal domain, centered on Asp121. However, in the N-terminally acetylated protein, present in vivo, the Met1 site is blocked. In this work, we simplify the representation of the protein by modeling each experimentally found binding site as a complex between an N-terminally acetylated α-synuclein dipeptide (or several independent residues) and a Cu(II) cation, and compare the results with a number of additional, structurally analogous sites not experimentally found. This way of representing the binding sites, although extremely simple, allows us to reproduce experimental results and to provide a theoretical rationale to explain the preference of Cu(II) for certain sites, as well as explicit geometrical structures for the complexes formed. These results are important to understand the interactions between α-synuclein and Cu(II), one of the factors inducing structural changes in the protein and leading to aggregated forms of it which may play a role in neurodegeneration. [ABSTRACT FROM AUTHOR]

The study of hydroxyapatite (HAP) crystal growth inhibitors has become an important field of research since HAP was identified as the main mineral component involved in pathological calcifications of soft tissues. In this work we performed a theoretical study of the deposition and the adsorption of a series of the most important HAP crystal inhibitors, such as pyrophosphate, etidronate, citrate and phytate, by means the Density Functional Theory. We showed that the adsorption energies of the inhibitors increased in the sequence: pyrophosphate < etidronate < citrate ⪡ phytate, which correlated with the increase of functional groups of the molecules that interact with the HAP surface, and the total molecular negative charge. The study highlights phytate as the best inhibitor of pathological calcifications of the series, but also opened the door to further structural modifications of citrate that will match the inhibition potency of phytate. [ABSTRACT FROM AUTHOR]

The effect of different side chain groups of bisphosphonates (BPs) on the adsorption on the hydroxyapatite (HAP) is still a controversial issue. In this work, we studied the deposition and adsorption of a set of 26 BPs on the HAP (001) surface by using density functional theory (DFT) in which has been shown that the charge, the length or the presence of different functional groups at R 2 side chain can modulate the adsorption energy of the BP. It was observed that negative charged groups at R 2 enhanced the favourable electrostatic interactions between the BP and the HAP surface, but also that the length of R 2 was important to enable the formation of the favorable electrostatic interactions between the functional group at R 2 and the surface. A crossover study between the HAP/BP model (3D-QSAR/DFT) and the inhibition of the human farnesyl pyrophosphate synthase (FPPS) (3D-QSAR) pointed out that the electrostatic character of the R 2 side chain provokes contrary effects in the inhibition of pathological crystallization and in the bone antiresorptive action of BPs. [ABSTRACT FROM AUTHOR]

We have studied the mechanism of the reaction between the most stable and the most represented in literature tautomers of metformin and methylglyoxal by density functional theory calculations. Designed models included 16 explicit water solvent, which forms hydrogen bond networks around the reactants and intermediates molecules, facilitating intramolecular proton transfer in some steps of the reaction mechanism. The reaction takes place in five steps, namely: (1) formation of a dimethylguanide–guanylhydrazone–acetylcarbinol adduct, (2) formation of a zwitterionic triazepine derivative by ring closure, (3) dehydration of this intermediate, (4) an imine–enamine tautomerism, (5) an enol–keto tautomerism. The first step was found as the rate-determining step for the reaction, having the reaction an overall activation energy value of 9.7 kcal mol−1. [ABSTRACT FROM AUTHOR]

We have studied the mechanism of the reaction between aminoguanidine (AG) and methylglyoxal (MG) by carrying out Dmol3/DFT calculations, obtaining intermediates, transition-state structures, and free-energy profiles for all of the elementary steps of the reaction. Designed models included explicit water solvent, which forms hydrogen-bond networks around the reactants and intermediate molecules, facilitating intramolecular proton transfer in some steps of the reaction mechanism. The reaction take place in four steps, namely: (1) formation of a guanylhydrazone-acetylcarbinol adduct by condensation of AG and MG; (2) dehydration of the adduct; (3) formation of an 1,2,4-triazine derivative by ring closure; and (4) dehydration with the formation of 5-methyl 3-amino-1,2,4-triazine as the final product. From a microkinetic point of view, the first dehydration step was found to be the rate-determining step for the reaction, with the reaction having an apparent activation energy of 12.65 kcal mol. Additionally, some analogous structures of intermediates and transition states for the reaction between AG and 2,3-dicarbonyl-phosphatidylethanolamine, a possible intermediate in Amadori-glycated phosphatidylethanolamine (Amadori-PE) autooxidation, were obtained to evaluate the reaction above a phosphatidylethanolamine (PE) surface. Our results are in agreement with experimental results obtaining by other authors, showing that AG is efficient at trapping dicarbonyl compounds such as methylglyoxal, and by extension these compounds joined to biomolecules such as PE in environments such as surfaces and their aqueous surroundings. [ABSTRACT FROM AUTHOR]

We report the results of a comparative molecular field analysis and comparative molecular similarity index analysis of the human farnesyl pyrophosphate synthase (FPPS) inhibition by nitrogen bisphosphonates (NBPs) taking into account their time-dependent inhibition efficacies. The 3D-QSAR models obtained provide steric, electrostatic and hydrophobic contour maps consistent with the interactions into the active site of human FPPS observed in available crystallographic structures. Furthermore, the 3D-QSAR models obtained provide accurately IC values of the NBPs of the training set. The predictive ability of these 3D-QSAR models was found to rely on the choice of biologically active conformations of the target molecules and on a careful examination of the protonation status of the NBPs in the training set. The best models obtained can be useful to predict biological values of a high number of NBPs that have been used for the treatment of different diseases as potential inhibitors of the activity of the FPPS enzyme. [ABSTRACT FROM AUTHOR]

Elastic properties are an important issue in explaining the behavior of seisms and to ascertain the mineralogical composition of the Earth's shells through which seismic waves pass. Computational methods can yield an additional, detailed, free-of-heterogeneity model knowledge of the mineral series of interest. Therefore, a computational study on the influence of the interlayer cation in the muscovite-paragonite (Ms-Pg) series on the crystal cell, internal geometry, and the elastic properties was made to shed light on the mineralogical, geophysical, and geochemical properties of the series. These properties have been calculated by means of Density Functional Theory (SIESTA2.0.2 code). The crystal structure and internal geometry agreed with the range of experimental values in the literature. In general, elastic stiffness constants (EC) agreed with the known experimental values. ECs of different interlayer cation configurations for the middle concentration sample showed very similar values, except for C33, The majority of ECs, with the exception of C33 and C66, decreased as a function of Na' [Na/(Na+K)], many of which showed ideal crystalline solution behavior, and some showed mixing terms. The polycrystalline bulk modulus registered similar values for the end-members of the series and a minimum at Na' = 0.5, although an estimate of the value at room temperature made the Pg stiffer than Ms; while the shear modulus showed a decreasing trend as a function of the Na'. Velocities of the sound waves lowered as a function of Na'. Local deformabilities were also studied, where the highest deformability was found for the interlayer space. The results are discussed in the framework of the mineralogical, geochemical, and geophysical knowledge of the series. [ABSTRACT FROM AUTHOR]

Mechanisms for the formation of the Schiff base from acetaldehyde and butylamine, glycine and phosphatidylethanolamine based on Dmol3/DFT calculations were realized. For the case of phosphatidylethanolamine, calculations were done under periodic boundary conditions, in an amine-phospholipid monolayer model with two molecules of phosphatidylethanolamine by cell. All models contained explicit aqueous solvent. In the three cases, a neutral amino group is used to model the nucleophilic attack on the carbonyl group of acetaldehyde, and water molecules form hydrogen bond networks. These networks were involved in the reactions by performing as proton-transfer carriers, important in some steps of reactions, and stabilizing reaction intermediates. In all the studied reactions, they take place in two steps, namely: (1) formation of a carbinolamine and (2) its dehydration to the Schiff base, being the dehydration the rate-determining step of the process, consistent with available experimental evidence for similar reactions. The main difference between the studied reactions is found in the value for relative free energy for the intermediates and transition states in the second step; these values are lower in the cases of glycine and phosphatidylethanolamine in comparison with butylamine, due the influence of their molecular environments. Based on the results, the aminophospholipid surface environment and carboxylic group of glycine may boost Schiff base formation via a neighboring catalyst effect. [ABSTRACT FROM AUTHOR]

A mechanism for the formation of the Schiff base between an acetaldehyde and an amine-phospholipid monolayer model based on Dmol3/density functional theory calculations under periodic boundary conditions was constructed. This is the first time such a system has been modeled to examine its chemical reactivity at this computation level. Each unit cell contains two phospholipid molecules, one acetaldehyde molecule, and nine water molecules. One of the amine-phospholipid molecules in the cell possesses a neutral amino group that is used to model the nucleophilic attack on the carboxyl group of acetaldehyde, whereas the other has a charged amino group acting as a proton donor. The nine water molecules form a hydrogen bond network along the polar heads of the phospholipids that facilitates very fast proton conduction at the interface. Using periodic boundary conditions afforded proton transfer between different cells. The reaction takes place in two steps, namely, (1) formation of a carbinolamine and (2) its dehydration to the Schiff base. The carbinolamine is the primary reaction intermediate, and dehydration is the rate-determining step of the process, consistent with available experimental evidence for similar reactions. On the basis of the results, the cell membrane surface environment may boost phospholipid glycation via a neighboring catalyst effect. [ABSTRACT FROM AUTHOR]

Abstract: A DFT study has been made for the 2×2×1 supercell of the crystal lattice of low-charge dioctahedral 2:1 phyllosilicates. Norm-conserving pseudopotentials of Al, Si, O, H, Na as well as the basis sets have been optimised. The generalized gradient approximation (GGA) was used with numerical atomic orbitals of the improved basis sets. Crystallographic and spectroscopical properties of some known samples with high charge have been calculated, being consistent with previous computational and experimental results. These results are useful to validate the pseudopotentials and basis set optimised to be applied to study the low-charge samples. Different low-charge dioctahedral 2:1 phyllosilicates have been calculated, revealing good agreement with experimental crystallographic properties. [Copyright &y& Elsevier]

The uncoordinated sulfur atom of the thiocyanato ligand of a 3D metallo-organic framework (MOF), [Ni(3-bpd)2(NCS)2]n (1), where 3-bpd is 1,4-bis(3-pyridyl)-2,3-diaza-1,3-butadiene, has been explored for selective visual detection and effective removal of Hg2+ in aqueous medium. [Ni(3-bpd)2(NCS)2]n has been synthesized under ambient conditions and characterized by elemental analysis, FT-IR spectroscopy, UV-vis spectroscopy, FE-SEM and EDX, XPS and X-ray single crystal diffraction analysis. 1 shows two thiocyanato moieties bound to the hexacoordinated metal center with N atoms whereas the sulfur end remains uncoordinated. The strategy for binding and removal of Hg2+ is very simple. Hg2+ is known for its affinity for strong bond formation with the soft center, S. The sulfur atoms form bonds with this heavy metal ion. The color of 1 changes from green to grey as Hg atoms form coordinate bonds with S atoms of the SCN− group. It has been found that Hg is present in grey materials in a 2 : 1 ratio (Hg/Ni). 1 is selective for Hg as other metals/metalloids, including heavy metal ions, present in water are unable to change the color of 1 as they do not form any bond with it. Binding of Hg with the S end of the thiocyanato moiety has been confirmed by a number of techniques, e.g. IR and UV-vis spectra, FESEM, EDX, and XPS. Simple filtration is done to separate grey materials for the removal of Hg2+ ion from the water medium. A theoretical calculation has been performed to rationalize the fact. [ABSTRACT FROM AUTHOR]

This study reports the synthesis and characterization of two closely related semicarbazone/thiosemicarbazone-based organic compounds: N-(2-hydroxy-3-methoxy-5-methylbenzylidene)semicarbazide (1) and N-(2-hydroxy-3-methoxy-5-methylbenzylidene)thiosemicarbazide (2). Structural studies revealed the conformational diversity in these systems as compound 1 crystallized as only one conformer, while compound 2 crystallized as a mixture of two conformers. DFT calculations in combination with the quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses revealed that the energy difference between the two conformers was larger in compound 1, while the difference between both conformers was very small in the thiosemicarbazide derivative (2), in line with the X-ray crystallographic characterizations. The synthesized compounds were tested for their electrical conductivity behaviour via current density–voltage measurements, as well as impedance spectroscopy, which revealed that both compounds were semiconducting in nature, arising from the charge transport through space via π⋯π contacts, and could be useful for the fabrication of electrical devices, particularly 1, in which the conductivity fell by a higher order of magnitude than observed in similar organic semiconductors tested earlier. Moreover, the combined experimental and theoretical studies showed the importance of the non-covalent interactions on the stability of the different conformers, thereby guiding the possible isolations of different polymorphic forms of such conformationally diverse semicarbazone/thiosemicarbazone systems through the selective stabilization of a particular conformer by varying the reaction conditions. [ABSTRACT FROM AUTHOR]

Cladosporium spp. have been reported for their great diversity of secondary metabolites which represent as a prominent base material for verifying the biological activities. Several bioactive compounds which have antimicrobial, cytotoxic, quorum sensing inhibitory and phytotoxic activities have been isolated from Cladosporium species. Most of them are still needed to be explored for their anticancer properties. Therefore, the present study is focused on screening and identifying the bioactive compounds of Cladosporium spp. for their anticancer activity via the integrated approaches of Molecular Docking (MD), Molecular Dynamics Simulation (MDS) and Density Functional Theory (DFT) studies. A total of 123 bioactive compounds of Cladosporium spp. were explored for their binding affinity with the selected breast cancer drug target receptor such as estrogen receptor alpha (PDB:6CBZ). The Molecular Docking studies revealed that amongst the bioactive compounds screened, Altertoxin X and Cladosporol H showed a good binding affinity of − 10.5 kcal/mol and − 10.3 kcal/mol, respectively, with the estrogen receptor alpha when compared to the reference compound (17 β -Estradiol: − 10.2 kcal/mol). The MDS study indicated the stable binding patterns and conformation of the estrogen receptor alpha-Altertoxin X complex in a stimulating environment. In addition, in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) study suggested that Altertoxin X has a good oral bioavailability with a high LD 50 value of 2.375 mol/kg and did not cause any hepatotoxicity and skin sensitization. In summary, the integrated approaches revealed that Altertoxin X possesses a promising anticancer activity and could serve as a new therapeutic drug for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than −8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of −10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (−10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski's rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study. [ABSTRACT FROM AUTHOR]

Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide. [ABSTRACT FROM AUTHOR]

Outdoor air pollution is a mixture of multiple atmospheric pollutants, among which nitrogen oxide (NOx) stands out due to its association with several diseases. NOx reactivity can conduct to DNA damage as severe as interstrand crosslinks (ICL) formation, that in turn is able to block DNA replication and transcription. Experimental studies have suggested that the ICL formation due to NOx is realized through a diazonium intermediate (DI). In this work, we have modeled the DI structure, including a DNA double-strand composed of two base pairs GC/CG, being diazotized as one of the guanine nucleotides. The structural stability of DNA with DI lesion was essayed through 500 ns molecular dynamics simulations. It was found that the DNA structure of the oligonucleotide is stable when the DI is present since the loss of a Guanine–Cytosine hydrogen bond is replaced by the presence of two cation-π interactions. Additionally, we have studied the mechanism of formation of a crosslink between the two guanine nucleobases from the modeled DI by carrying out DFT calculations at the M06-L/DNP+ level of theory. Our results show that the mechanism is thermodynamically favored by a strong stabilization of the ICL product, and the process is kinetically viable since its limiting stage is accessible. [ABSTRACT FROM AUTHOR]

CBS-QB3, two simplified and less computationally demanding versions of CBS-QB3, DFT-B3LYP, and HF quantum chemistry methods have been used in conjunction with the CPCM continuum solvent model to calculate the free energies of proton exchange reactions in water solution following an isodesmic reaction approach. According to our results, the precision of the predicted p K values when compared to experiment is equivalent to that of the thermodynamic cycles that combine gas-phase and solution-phase calculations. However, in the aqueous isodesmic reaction schema, the accuracy of the results is less sensitive to the presence of explicit water molecules and to the global charges of the involved species since the free energies of solvation are not required. In addition, this procedure makes easier the prediction of p K values for molecules that undergo large conformational changes in solvation process and makes possible the p K prediction of unstable species in gas-phase such as some zwitterionic tautomers. The successive p K values of few amino acids corresponding to the ionization of the α-carboxylic acid and α-amine groups, which is one of the problematic cases for thermodynamic cycles, were successfully calculated by employing the aqueous isodesmic reaction yielding mean absolute deviations of 0.22 and 0.19 p K units for the first and second ionization processes, respectively. [ABSTRACT FROM AUTHOR]

Simplified versions of CBS-QB3 model chemistry were used to calculate the free energies of 36 deprotonation reactions in the gas phase. The best such version, S9, excluded coupled cluster calculation [CCSD(T)], and empirical (ΔEemp) and spin-orbit (ΔEint) correction terms. The mean absolute deviation and root mean square thus obtained (viz. 1.24 and 1.56 kcal/mol, respectively) were very-close to those provided by the original CBS-QB3 method (1.19 and 1.52 kcal/mol, respectively). The high-accuracy of the proposed simplification and its computational expeditiousness make it an excellent choice for energy calculations on gas-phase deprotonation reactions in complex systems. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [ABSTRACT FROM AUTHOR]

Terpyridinium salts of hydracids [PTPH3](Br)3·H2O (1), [PTPH3](Cl)3·2H2O (2) and oxoacid [PTPH3](ClO4)3·H2O (3) (PTP = 4′-(3-pyridyl)-4,2′:6′,4′′-terpyridine) were synthesized and characterized using single crystal X-ray diffraction analyses. The crystallographic analysis reveals that the π+⋯π, π+⋯π+, anion⋯π and anion⋯π+ interactions play a crucial role in the stabilization of the self-assembled structure, which in turn is responsible for enhancing the dimensionality of all the compounds. All the compounds confirm their usefulness as optoelectronic devices owing to the pronounced electrical conductivity and photosensitivity. Experimental and theoretical observations clarify an increase in the electrical conductivity on irradiation compared to dark conditions, especially in 3. [ABSTRACT FROM AUTHOR]

In this manuscript we report the preparation of three N6-aminoacid-adenine-derivatives: N-(7H-purin-6-yl)glycine·0.5H 2 O (N6-GlyAde), N-(7H-purin-6-yl)-β-alanine·1.5H 2 O (N6-β-AlaAde) and N-(7H-purin-6-yl)-γ-aminobutyric·2H 2 O (N6-GabaAde) and the synthesis and X-ray characterization of three Ir(III) NAMI-A derivatives (NAMI-A is [imidazoleH][ trans -RuIIICl 4 (DMSO- κ S)(imidazole)]) [ trans -IrIIICl 4 (DMSO- κ S)(N3-H)-(7H-purin-6-yl)glycine- κ N9] (1), [ trans -IrIIICl 4 (DMSO- κ S)(N3-H)-(7H-purin-6-yl)-β-alanine- κ N9] hydrate (2) and [ trans -IrIIICl 4 (DMSO- κ S)(N3-H)-(7H-purin-6-yl)-γ-aminobutyryl- κ N9] (3). In all complexes the metal center shows octahedral geometry with coordination to four chlorido ligands and one S coordinated dimethylsulfoxide (DMSO- κ S). The coordination sphere of the metal is completed by the modified adenine molecule which is bound via N(9) and protonated at N(3). In two complexes the importance of lone pair (lp)–π interactions involving the adenine ring have been studied using density functional theory (DFT) calculations and the Bader's theory of atoms in molecules. Furthermore, the ability of complexes (1 – 3) to affect the cell viability was evaluated against three different cancer cell lines: human lung carcinoma cells (A549), human cervical carcinoma cells (HeLa) and human breast cancer cells (MCF7). We have also analyzed their ability to cleave the DNA experimentally and their affinity for two models of DNA has been studied using molecular docking simulations. Three Ir(III) complexes with modified adenine ligands have been characterized by X-ray diffraction, density functional theory and the Bader's theory of atoms in molecules. The ability of these complexes to affect the cell viability is reported. The ability to cleave DNA in combination with docking studies are also reported. Unlabelled Image • The Ir(III) complex with (purin-6-yl)glycine, (Ir-N6-GlyAde) was prepared. • The Ir(III) complex with (purin-6-yl)β-alanine (Ir-N6-β-AlaAde) was prepared. • The Ir(III) complex with (purin-6-yl)γ-aminobutyric (Ir-N6-GabaAde) was prepared. • The compounds were characterized by X-ray diffraction and density functional theory. • The Ir(III) complexes don't show cytotoxic activity in 3 cancer cell lines. [ABSTRACT FROM AUTHOR]

This manuscript reports the improved synthesis of the α,α,α,α isomer of tetra-p-iodophenyl tetra-methyl calix[4]pyrrole and the X-ray characterization of two solvate polymorphs. In the solid state, the calix[4]pyrrole receptor adopts the cone conformation, including one acetonitrile molecule in its aromatic cavity by establishing four convergent hydrogen bonds between its nitrogen atom and the four pyrrole NHs of the former. The inclusion complexes pack into rods, displaying a unidirectional orientation. In turn, the rods form flat 2D-layers by alternating the orientation of their p-iodo substituents. The 2D layers stack on top of another, resulting in a head-to-head and tail-to-tail orientation of the complexes or their exclusive arrangement in a head-to-tail geometry. The dissimilar stacking of the layers yields two solvate polymorphs that are simultaneously present in the structures of the single crystals. The ratio of the two polymorph phases is regulated by the amount of acetonitrile added to the chloroform solutions from which the crystals grow. Halogen bonding interactions are highly relevant in the crystal lattices of the two polymorphs. We analyzed and characterized these interactions by means of density functional theory (DFT) calculations and several computational tools. Remarkably, single crystals of a solvate containing two acetonitrile molecules per calix[4]pyrrole were obtained from pure acetonitrile solution. [ABSTRACT FROM AUTHOR]

Here, we report the preferential CO2 adsorption on a new zinc-based porous 3D framework compound, [Zn2(H2O)(nic)(pyrz)]n·nH2O, which has solvent accessible void space. Upon dehydration the porosity of the framework compound was enhanced significantly. At 298 K, the as-synthesized and dehydrated compound showed an uptake of carbon-dioxide of 2.2 and 5.7 wt% at 0.15 bar and 5.3 and 12.2 wt% at 1 bar, respectively, which increased to 5.6 and 11.7 wt% at 0.15 bar and 10.2 and 23.6 wt% at 1 bar, respectively, upon cooling to 273 K. The selectivity of CO2 with respect to CH4 at 273 K is calculated to be 22.4. The framework compound and its dehydrated product show very selective CO2 adsorption with respect to other small gas molecules like H2, N2, and CH4 at low partial pressure. The low pressure selective CO2 adsorption is quite impressive with respect to other reported framework systems where selectivity was found particularly over one or two small gas molecules amongst H2, N2, and CH4etc. [Zn2(H2O)(nic)(pyrz)]n·nH2O exhibits fairly strong CO2–framework interactions as evidenced from the measured heat of adsorption, ∼50 kJ mol−1 at low loading. Molecular dynamics and Monte Carlo simulations explain the selective CO2 adsorption over other small gas molecules (H2, N2 and CH4) in the framework compound. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Satish Anandan and Hittanahallikoppal Gajendramurthy Gowtham. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-22038-x, published online 27 December 2022 The original version of the Article contained an error in the Author Information section. [Extracted from the article]

Abstract The understanding of the effect of non-enzymatic post-translational modifications on the protein structure is essential to unveil the molecular mechanisms underlying their related pathological processes. Among those modifications, protein glycation emerges as one of the main responsible for the development of diabetes-related diseases. While some reports suggest that glycation has a chaotropic effect, others indicate that it does not modify the protein structure. Here we aim to better clarify this effect and therefore, we have studied the effect of glycation mediated by ribose and methylglyoxal on a fifteen-residue model peptide, which readily undergoes a pH-induced coil-helix transition. Neither ribose nor methylglyoxal were able to induce the structuration of the peptide at physiological pH. Moreover, neither ribose nor methylglyoxal severely modified the α-helical structure acquired by the peptide at pH ~ 3. Among the different glycation products experimentally detected (i.e. the ribose-derived Schiff base; the Amadori compound; N ε -(carboxyethyl)lysine; N ε -(carboxymethyl)lysine; and MOLD), the Amadori compound was the one with the greatest impact on the α-helicity. Our data contribute to clarify the effect of glycation on the structure of proteins by proving that the glycation products do not necessarily affect the α-helical structure of a peptide stretch. [ABSTRACT FROM AUTHOR]

Graphical abstract Two new 1D coordination polymers were assembled and fully characterized; their structural, spectroscopic, magnetic, theoretical and antimicrobial features are discussed in detail. Highlights • Base assisted tuning of coordination polymer. • Structures and C/H-Ni(II) Agostic interaction. • Disaggregation of polymeric structures in solution. • Zero-field splitting effect on Ni(II)-magnetism. • Potential pyocyanin production inhibitor. Abstract A new azo-ligand, 1,3-dimethyl-5-(p -carboxy-phenylazo)-6-aminouracil (H 3 L) containing 6-aminouracil (a biomolecule) and a carboxylic function (a potential linker) was synthesized. This ligand was then employed for complexation with Ni(II), resulting in the Ni(II)/Na(I) heterometallic {[NiNa 2 (μ-HL) 2 (μ-H 2 O) 2 (H 2 O) 6 ]·6H 2 O} n (1) and Ni(II) homometallic {[Ni 2 (μ-HL) 2 (H 2 O) 4 ]·5·.5H 2 O} n (2) 1D coordination polymers. These were obtained from similar reaction mixtures and conditions, except the type of the base (NaOH for 1 or KOH/Et 3 N for 2). Compounds 1 and 2 were characterized by single-crystal X-ray diffraction, UV-vis, NMR, and IR spectroscopy. Both the coordination polymers 1 and 2 show resembling zigzag chains that are topologically classified as 2-connected underlying nets with the 2C1 topology. In 1 , the 1D metal-organic chains are further extended by intermolecular H-bonds, giving rise to a 3D H-bonded net; it is topologically described as a uninodal 6-connected net with the pcu topology. In solution, the 1D polymeric structures of both compounds disaggregate into monomeric Ni(II)-square-planar complex units [Ni(HL) 2 ]2−, as evidenced by NMR and UV-vis spectroscopy studies. The magnetic properties of 2 were also investigated, indicating a dominant zero field splitting parameter D of the Ni(II) center. The type of the base is important for tuning the selective formation of the desired product 1 or 2. Density functional theory (DFT) study justifies the experimental findings for a base-assisted selectivity between the compounds 1 or 2 by optimizing their structures at the PBE-D/DNP level of theory. The existence of agostic interactions between the C H bonds of the methyl groups of the coordinated HL2− moieties and the Ni centers in both structures is suggested by natural bond orbital (NBO) calculations at the M06-2X/6-31 + G∗ level of theory. The compound 1 proves to be a potential inhibitor of a bacterial virulence factor, pyocyanin. [ABSTRACT FROM AUTHOR]

Azo based organic semiconductor molecules are mostly used as write once, read-many-times (WORM) memory systems. Therefore, a large scope still remains in the fabrication of photoconducting azo compounds, which can be used under acute conditions for advanced applications. In this context we have designed a very simple, small azo based organic molecule, viz. [1,4-phenylenebis(azanylylidene)bis(methanylylidene)bis(2-methoxy-4-(phenyldiazenyl)phenol)] (compound 1). The device fabricated using compound 1 showed Schottky barrier behavior. The value of the rectification ratio is 6.22 and 18.27 under dark and photoirradiated conditions, respectively. Thermally stable and low cost compound 1 can be used in the area of optoelectronic devices probably being the first azo-organic material showing such properties. Experimentally measured optical conductivity is again correlated theoretically using DFT computation. It has been observed that the change in the dihedral angle produces a decrease in the energy for the allowed electronic transition. [ABSTRACT FROM AUTHOR]

A novel 1D Cd(ii) based coordination polymer (complex 1) has been synthesized involving an 8-aminoquinoline based Schiff base ligand and cyanate ion. It has been characterized by elemental analysis, different spectroscopy methods and X-ray single crystal diffraction technique. Most interestingly it exhibits unique properties like electrical conductivity and photosensitivity which shows its potential in optoelectronic device application. We prove both experimentally and theoretically that electrical conduction under irradiation of visible light increases many fold in comparison with that under dark condition. Our synthesized material based device shows some paramount behaviour under irradiance of light which is obvious in light sensing Schottky devices. The rectification ratio of our complex based device was found to be 12.44 and 27.74 under dark and photoirradiation conditions respectively. The discovery of such type of coordination polymer advances the area of optoelectronic devices. [ABSTRACT FROM AUTHOR]

Five new coordination polymers (CPs) with the formula [Ln (hip) (adip) 0.5 (H 2 O) 2 ] n · n H 2 O [Ln = La ( 1 ), Ce ( 2 ), Sm ( 3 ) and Gd ( 4 )] and [Ln 2 (hip) 2 (adip)(H 2 O) 4 ] n ·2 n H 2 O [Ln = Eu ( 5 )] were synthesized by self-assembly of lanthanide salts with rigid [5-hydroxyisophthalic acid (H 2 hip)] and flexible [adipic acid (H 2 adip)] linkers under solvothermal condition. The CPs 1 – 4 crystallizes in monoclinic C 2/ c space group, whereas CP 5 has triclinic P 1 ¯ space groups respectively. The CPs 1 – 4 exhibit 1D linear ladder shaped extension with the linkage of lanthanide carboxylate chains having the backbone of H 2 hip and H 2 adip ligands, whereas CP 5 shows linear orthogonally twisted ladder shaped chains. The 1D linear ladder chains are grafted into three dimensional (3D) supramolecular frameworks via significant π–π and hydrogen bonding interactions. The DFT calculations support structures adopted by polymers. The CPs 3 (Sm) and 5 (Eu) emit strong ligand sensitized characteristic f – f luminescence emission. The CP 4 exhibit weak ferromagnetic interactions at low temperatures. [ABSTRACT FROM AUTHOR]

A Cd(ii) based 2D metal–organic framework (MOF), [Cd(4-bpd)(SCN)2]n (1) where 4-bpd = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene, has been synthesized and characterized by standard methods including single crystal X-ray diffraction analysis. When it is sandwiched between ITO coated glass and Al, 1 shows interesting conduction properties. The I–V characteristics of the ITO/1/Al configuration measured in the dark and under illumination of incident light exhibit a highly non-linear rectifying behavior, which signifies its Schottky diode character. The conductivity of the configuration is 2.90 × 10−4 S m−1 and 7.16 × 10−4 S m−1 under dark and photoirradiation conditions, respectively. Different parameters have been analyzed and these indicate that 1 can be a promising candidate for light sensing electronic devices. This material has good sensitivity to the light source when switched on/off. Theoretical calculations have been performed to understand the reason for the enhancement of conductivity under illumination of incident light. It has been found that upon irradiation, slight changes in the bond distances of 4-bpd in 1 occur. These changes are related to the considerable decrease in the energy needed for the allowed electronic transition. This may influence the increase of conductivity along with other factors. [ABSTRACT FROM AUTHOR]

This article reviews the use of Monte Carlo methods with cation-exchange potentials and effective Hamiltonians, based on empirical potentials and quantum-mechanical calculations, for the study of cation ordering in phyllosilicates. The basic methodology is described, and the application of the methods is illustrated with a number of key example case studies. These include Al-Si ordering in muscovite, Al-Fe-Mg ordering (both binary and ternary compositions) in the octahedral illite/smectite sheet, examination of the ordering behavior of phengite, in which the octahedral sites are occupied by Al and Mg and the tetrahedral sites by Al and Si, and Al-Si ordering in the tetrahedral phyllosilicate sheet with variable Al:Si ratio. In several cases, complex ordering processes were found. The essential conclusion from this work is that computer simulation studies of this nature can be a valuable tool in ordering studies of many nanomaterials. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Researchers are interested in Schiff bases and their metal complexes because they offer a wide range of applications. The chemistry of Schiff bases of heterocompounds has got a lot of attention because of the metal's ability to coordinate with Schiff base ligands. In the current study, a new bidentate Schiff base ligand, N-((1H-pyrrol-2-yl)methylene)-6-methoxypyridin-3-amine (MPM) has been synthesized by condensing 6-methoxypyridine-3-amine with pyrrole-2-carbaldehyde. Further, MPM is used to prepare Cu(II) and Co(II) metal complexes. Analytical and spectroscopic techniques are used for the structural elucidation of the synthesized compounds. Both MPM and its metal complexes were screened against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Klebsiella pneumoniae species for antimicrobial studies. Furthermore, these compounds were subjected to in silico studies against bacterial proteins to comprehend their best non-bonded interactions. The results confirmed that the Schiff base ligand show considerably higher binding affinity with good hydrogen bonding and hydrophobic interactions against various tested microbial species. These results were complemented with a report of the Conceptual DFT global reactivity descriptors of the studied compounds together with their biological scores and their ADMET computed parameters. [ABSTRACT FROM AUTHOR]

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of −8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1. [ABSTRACT FROM AUTHOR]

• Co (II), Cu (II), Ni (II) and Zn (II) derivatives of Schiff base ligand were synthesized. • Structures of ligand and complexes were studied using FT-IR, UV-Visible, MS, 1H-NMR, 13C-NMR and thermogravimetric methods. • Antibacterial and antioxidant properties were evaluated through different in vitro assays. • Molecular Docking studies were carried out on the prepared ligand and receptor molecules using AutoDock 4.2. • Chemical reactivity of ligand and complexes was asserted considering Conceptual Density Functional Theory (CDFT) by means of the 'Koopmans in DFT' (KID) approximation. In the present work we have synthesized a Schiff base ligand, (HL) derived from 5-amino-4H-1,2,4-triazole-3-thiol and 4-hydroxy-3-methoxybenzaldehyde and its Co(II), Cu(II), Ni(II) and Zn(II) which are assigned as 1, 2, 3 and 4, respectively, in 2:1 stoichiometric ratio (2HL:M). The structures of the ligand and its metal complexes were evaluated using Fourier Transform Infrared Spectroscopy (FT-IR), Ultraviolet–visible spectroscopy (UV-Vis), Mass spectroscopy (MS), Nuclear magnetic resonance (1H and 13C-NMR) and Thermogravimetric (TGA) methods. The Schiff base ligand and its metal complexes were tested for in vitro antibacterial activities by using disc diffusion method and minimum inhibitory concentration (MIC) method by using Amoxicillin (1 mg/ml) and Dimethylsulfoxide (DMSO) as positive and negative control, respectively. The free radical scavenging ability of compounds was assessed by employing a series of in vitro assays viz., 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and Superoxide whereas Butylated hydroxyanisole (BHA) was used as a positive control. In vitro α-glucosidase inhibitory studies revealed that metal complexes had significant inhibitory potential than the ligand. The molecular docking studies were carried out on the prepared ligand and receptor molecules using AutoDock 4.2. The research was complemented by performing computational Density Functional Theory (DFT) studies on the chemical reactivity of the ligand and the three complexes by means of Conceptual Density Functional Theory (CDFT) through the "Koopmans in DFT" (KID) approximation. [Display omitted] [ABSTRACT FROM AUTHOR]

A novel thiocyanate bridged 2D MOF, [CdL(μ-1,3-SCN)2]n, [HL = 2-(2-(ethylamino)ethyliminomethyl)-6-ethoxyphenol] has been synthesized and characterized by X-ray crystallography. The band gap of the synthesized material in the solid state has been determined by experimental measurements and compared with the theoretical value obtained from DFT calculations. For the first time, the single crystal X-ray crystallography of a MOF has been reported along with its applicability in photosensitive devices. [ABSTRACT FROM AUTHOR]

Candida albicans, an opportunistic fungal pathogen, frequently colonizes immune-compromised patients and causes mild to severe systemic reactions. Only few antifungal drugs are currently in use for therapeutic treatment. However, evolution of a drug-resistant C. albicans fungal pathogen is of major concern in the treatment of patients, hence the clinical need for novel drug design and development. In this study, in vitro screening of novel putative pyrrolo[1,2-a]quinoline derivatives as the lead drug targets and in silico prediction of the binding potential of these lead molecules against C. albicans pathogenic proteins, such as secreted aspartic protease 3 (SAP3; 2H6T), surface protein β-glucanase (3N9K) and sterol 14-alpha demethylase (5TZ1), were carried out by molecular docking analyses. Further, biological activity-based QSAR and theoretical pharmacokinetic analysis were analyzed. Here, in vitro screening of novel analogue derivatives as drug targets against C. albicans showed inhibitory potential in the concentration of 0.4 µg for BQ-06, 07 and 08, 0.8 µg for BQ-01, 03, and 05, 1.6 µg for BQ-04 and 12.5 µg for BQ-02 in comparison to the standard antifungal drug fluconazole in the concentration of 30 µg. Further, in silico analysis of BQ-01, 03, 05 and 07 analogues docked on chimeric 2H6T, 3N9K and 5TZ1 revealed that these analogues show potential binding affinity, which is different from the therapeutic antifungal drug fluconazole. In addition, these molecules possess good drug-like properties based on the determination of conceptual Density Functional Theory (DFT)-based descriptors, QSAR and pharmacokinetics. Thus, the study offers significant insight into employing pyrrolo[1,2-a]quinoline analogues as novel antifungal agents against C. albicans that warrants further investigation. [ABSTRACT FROM AUTHOR]

Herein, we report the synthesis and characterization of a new Schiff base ligand 3-[[(E)-(3-hydroxyphenyl)-methylidene]amino]-2-methyl-quinazolin-4(3H)-one (HAMQ) and its Cd(II), Ni(II), Zn(II), and Cu(II) complexes (C1–C4). The ligand HAMQ was synthesized by reacting 3-hydroxybenzaldehyde and 3-amino-2-methyl-4(3H)-quinazolinone in a 1:1 molar ratio. The structure of the ligand and its complexes (C1–C4) were evaluated using ultraviolet (UV)–visible (Vis) light spectroscopy, 1H-NMR, Fourier-transform infrared (FT-IR) spectroscopy, MS, elemental analysis, conductance data, and thermogravimetric analysis (TGA). The characterization results suggested that the bidentate ligand, HAMQ, coordinated to the metal center through the lactum oxygen and the azomethine nitrogen. Moreover, all the metal complexes were analyzed using powder X-ray diffraction studies, which revealed that all of them belong to a triclinic crystal system. The research was supplemented by density functional theory (DFT) studies on the IR and UV–Vis spectra, as well as the chemical reactivity of the HAMQ and its four metallic derivatives making use of conceptual density functional theory (CDFT) by means of KID (Koopmans in DFT) methodology. The synthesized complexes displayed significant in vitro anticancer activity against human cancer cell lines (HeLa and HCT-115). [ABSTRACT FROM AUTHOR]

According to ISO 17402:2008 more knowledge is needed on processes controlling bioavailability of organic species so as to close the still existing gap between chemical measurements and biological effects. The bioavailability concept encompasses the investigation of the degree of penetration of target species across biological membranes. In addition, REACH (Registration, Evaluation, Authorisation and restriction of Chemicals) guidelines promote the use of in-vitro methods against conventional ecotoxicological tests because of the ethical controversy of in-vivo tests. This work is aimed at filling the gap by proposing a multidisciplinary approach based on high-resolution and low-resolution empirical techniques, and theoretical quantum mechanics for the in-vitro investigation of the bioavailability and membranotropic effects of organic emerging contaminants, including bioaccumulation, via passive diffusion across lipid bilayers. Phosphatidylcholine (PC) liposomes are selected as biomembrane surrogates, and contaminant effects are explored by (i) fluorescence anisotropy and generalized polarization assays using membrane fluorescence probes (laurdan and prodan) and UV–Vis spectroscopy, (ii) 1H NMR measurements to ascertain supramolecular interactions with PC and (iii) molecular dynamics simulations. In particular, un-regulated model compounds with distinct physico-chemical properties that are representative of three different classes of emerging contaminants in environmental compartments are chosen for validation of the holistic approach: (i) diclofenac as a model of anti-inflammatory drug; (ii) triclosan as an anti-microbial agent; and (iii) bisphenol A as a plastic-borne compound, and compared with chlorpyrifos as a legacy insecticide. Laurdan anisotropic measurements are in good agreement with 1H NMR data and both approaches pinpoint that triclosan and chlorpyrifos are highly bioaccumulative in membranes. Molecular dynamic studies indicate that the lateral diffusion of the lipid bilayer is much lower with the incorporation of either triclosan or chlorpyrifos into the bilayer. The theoretical simulations also allowed estimating absolute bioavailability data under passive diffusion (<0.1%, 63%, 73% and 89% for diclofenac, bisphenol A, triclosan and chlorpyrifos, respectively) given as the percentage of time that a given species is located in the region of the fatty acyl chains. Our findings indicate that PC-based liposome assays serve as a fast and cost-effective in-vitro approach, notwithstanding its low resolution features, for environmental bioavailability studies of emerging contaminants for which insufficient or inconsistent ecotoxicological data are identified in the literature. Unlabelled Image • Liposomes as models for in-vitro investigation of contaminant biovailability • Multidisciplinary approach based on fluorescence and NMR data and molecular dynamics • Application to emerging organic pollutants with different physicochemical properties • Fluorescent probes for fast insight into contaminant permeation across lipid bilayers [ABSTRACT FROM AUTHOR]

• Synthesis of novel quinolin-4(3 H)-one based ligand and its Cd(II), Cu(II) and Zn(II) complexes. • X-ray crystal structure of ligand was determined. • Breast cancer cell line (MCF-7) was used to test the antitumor potential of the compounds. • DFT calculations are performed to know the chemical reactivity of the ligand and its complexes. This work reports the synthesis of a novel quinolin-4(3H)-one based Schiff base ligand 3-[(E)-(2,5-dimethoxyphenyl)methylidene]amino-2-methylquinazolin-4(3H)-one (DMPAQ) and its coordination complexes of the type [M(DMPAQ)(phen)]X (1a-1c) , where M = Cu(II), Zn(II) and Cd(II) ions, respectively, phen = 1,10-phenanthroline. All the synthesized compounds were characterized using UV–Visible, elemental analysis, FT-IR, 1H NMR, Mass spectroscopy and TGA techniques. The triclinic structure of the DMPAQ is determined by employing single crystal X-ray crystallographic analysis. The characterization results suggested that the ligand, DMPAQ is bidentate and coordinate to the metal center through the lactum oxygen and the azomethine nitrogen. The synthesized DMPAQ ligand and complexes (1a-1c) were screened for their in vitro anticancer activity against the human breast adenocarcinoma cell line, MCF-7. The complexes 1a and 1b displayed significant anticancer activity against MCF-7 cells even at lower GI50 value (GI 50 = 0.016 µM) than the standard drug doxorubicin (GI 50 = 0.018 µM). Further, we have performed computational DFT studies on the chemical reactivity of the ligand and the three complexes by means of Conceptual Density Functional Theory (CDFT) through the "Koopmans in DFT" (KID) approximation to support the experimentally obtained results. [ABSTRACT FROM AUTHOR]

The reaction of adenine with 2-chloropyrimidine yields as a major product the unexpected N7-(2-pyrimidyl)-adenine (1) and as a minor one N9-(2-pyrimidyl)-adenine (2). Both compounds have been characterized by X-ray diffraction analysis. Moreover, we report the formation of a 1:1 co-crystal (3) composed by compound (1) and adenine that was formed serendipitously during the synthesis of (1). Unexpectedly, the treatment of (1) with Brönsted acids like HCl or HNO 3 causes the opening of the imidazole ring of the N7-substituted adenine, yielding N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine (4 – 7) which we have X-ray characterized in its neutral, (4), monoprotonated [nitrate salt (6)] and diprotonated forms [hydrochloride salt (5) and, also, a tetrachlorozincate salt (7)]. Finally, we have used compound (5) as ligand to synthesize and X-ray characterize its complexes with Ir(III) and Ag(I) (compounds (8) and (9) , respectively), where the latter is a 2D coordination polymer and the former is a discrete mononuclear complex. We have studied the supramolecular assemblies formed in the solid state by using density functional theory (DFT) calculations. Finally, DNA-docking studies of several compounds have been carried out in order to analyze their ability to interact with the DNA. Seven new adenine derivatives have been synthesized and X-ray characterized. In some compounds an opening of the imidazole ring of the adenine occurs, yielding N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine molecule that has been used as ligand to synthesize and X-ray characterize Ir(III) and Ag(I) complexes. DNA-docking studies of several compounds have been carried out in order to analyze their ability to interact with the DNA. Unlabelled Image • N7- and N9-(2-pyrimidyl)-adenine isomers are structurally characterized. • N7-(2-pyrimidyl)-adenine in acidic conditions yields N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine. • Ir(III) and Ag(I) complexes of N5-(pyrimidin-2-yl)pyrimidine-4,5,6-triamine have been characterized. • Supramolecular assemblies have been studied using theoretical calculations. • Molecular docking studies revel affinity of the ligands for the minor groove of ADN. [ABSTRACT FROM AUTHOR]

Muscovite (Ms) and phlogopite (Phl) belong to the 2:1 dioctahedral and trioctahedral layer silicates, respectively, and are the end members of Ms-Phl series minerals. This series was studied in the 2M1 polytype and modeled by the substitution of three Mg2+ cations in the Phl octahedral sites by two Al3+ and one vacancy, increasing the substitution up to reach the Ms. The series was computationally examined at DFT level as a function of pressure to 9 GPa. Cell parameters as a function of pressure and composition, and bulk moduli as a function of the composition agrees with the existing experimental results. The mixing Gibbs free energy was calculated as a function of composition. From these data, approximated solvi were calculated at increasing pressure. A gap of solubility is found, decreasing the gap of solubility at high pressure. [ABSTRACT FROM AUTHOR]