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In this work, an attempt is made to theoretically substantiate the experimentally known facts of the influence of halogen concentration on the catalytic properties of the neodymium-based Ziegler–Natta system. Based on the structural and thermochemical data obtained using modern methods of quantum chemistry, the process of the 1,3-butadiene cis-1,4-polymerization under the model active centers of the neodymium Ziegler–Natta catalysts with different contents of chloride ions was studied. Results are presented that explain the increase in the cis-stereospecificity and activity of the polymerization system with an increase in the content of the chloride ions in the neodymium catalytic system. Reasons were established for the decrease in the concentration of active centers relative to the introduced Nd(III) with an excess of chloride ions and the occurrence of the anti-syn isomerization as a source of the formation of the trans-1,4-structures in the cis-1,4-polybutadiene.

To understand the scavenging action of chlorophyll (Chla) found in most of the vegetables towards hydroxyl ( OH ∙ ) radicals, its reactions with OH ∙ radicals via RAF, HAT, and SET mechanisms have been investigated theoretically using two layer ONIOM [M06-2X/6-31G(d) (High):M06-2X/3-21G (Low)] method and M06-2X/6–311 + G(d,p) level of density functional theory. The molecular electrostatic potential (MEP), highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) plots, HOMO–LUMO energy gap, global hardness (η), global softness (S), electronegativity (χ), and electrophilicity index (ω) of Chla molecule were computed and analyzed to determine its stability and reactive sites. It is found that RAF and HAT reactions are exergonic in both gaseous and aqueous media whereas SET reactions are endergonic in both media. However, all the RAF, HAT and SET reactions studied here are found to be more favourable in aqueous media vs. gas phase. The rate constants of RAF reactions at different sites are found to be of the order of ~ 6.2 × 107–1.8 × 1010 s−1 indicating that RAF reactions would be appreciably fast. This study concludes that chlorophyll can efficiently scavenge OH ∙ radicals preferably via RAF and HAT mechanisms and intake of water with chlorophyll can enhance its scavenging actions. [ABSTRACT FROM AUTHOR]

In this work, an attempt is made to theoretically substantiate the experimentally known facts of the influence of halogen concentration on the catalytic properties of the neodymium-based Ziegler–Natta system. Based on the structural and thermochemical data obtained using modern methods of quantum chemistry, the process of the 1,3-butadiene cis-1,4-polymerization under the model active centers of the neodymium Ziegler–Natta catalysts with different contents of chloride ions was studied. Results are presented that explain the increase in the cis-stereospecificity and activity of the polymerization system with an increase in the content of the chloride ions in the neodymium catalytic system. Reasons were established for the decrease in the concentration of active centers relative to the introduced Nd(III) with an excess of chloride ions and the occurrence of the anti-syn isomerization as a source of the formation of the trans-1,4-structures in the cis-1,4-polybutadiene. [ABSTRACT FROM AUTHOR]

This paper proposes a novel approach to the extraction of cluster structures from a ZSM-5 zeolite lattice. The approach involves transforming the zeolite crystalline structure into a directed molecular graph followed by identifying cycles from which cluster structures are generated. One advantage of this approach is the complete similarity of the resultant cluster structures at equal input data, making the DBSCAN clustering method applicable to the identification of unique structures. Furthermore, this approach is effective in identifying the active and extended regions within a multilevel ONIOM model for subsequent quantum-chemical calculations. Finally, the proposed approach makes it possible to automate the extraction of cluster structures from ZSM-5 crystals and to select the most important structures for further analysis. To validate its efficiency, the novel approach was applied to identify the most probable location of Zn2+ cation-exchange sites in ZSM-5. [ABSTRACT FROM AUTHOR]

In present work, using the double layer ONIOM methodology, we simulated the stages of initiation and growth of the polymer chain during the polymerization of butadiene on a neodymium‐based Ziegler–Natta catalyst. The DFT methods B3LYP and PBE0 in combination with the Def2‐TZVP atomic basis set were used as high‐level methods in ONIOM. Grimme's semi‐empirical XTB1 method was used as a low‐level method. In our previous work, the mechanism of butadiene polymerization on a neodymium‐containing Ziegler–Natta catalyst was studied in detail. The polymerization activation energy of 61 kJ/mol was found to be slightly higher than the experimentally determined values of this parameter. In the present work, the influence of a high‐level method and a model of taking into account dispersion interactions on the quality of calculation of activation parameters of the polymerization reaction was studied. Experimental activation energy for the polymerization of dienes in the presence of Ziegler–Natta catalysts is in the range of 30–60 kJ/mol, but neodymium‐based catalysts have an activation energy somewhat closer to the lower limit of this range. For comparison, semi‐empirical Grimme models D3 and D4 were used. It has been established that the both models reveal within the B3LYP method the activation energy practically the same, while within the PBE0 method it decreases to 41 kJ/mol. Thus, using the PBE0 as a high‐level method within the ONIOM methodology and taking into account dispersion interactions within the D4 model leads to results in much better agreement with experimental data. [ABSTRACT FROM AUTHOR]

Accurate thermochemical data are of great importance in developing quantitatively predictive reaction mechanisms for transportation fuels, such as diesel and jet fuels, which are primarily composed of large hydrocarbon molecules, especially large straight-chain alkanes containing more than 10 carbon atoms. This paper presents an ONIOM[QCISD(T)/CBS:DFT]-based theoretical thermochemistry study on the hydrogen abstraction reactions of straight-chain alkanes, n-CnH2n+2, (n = 1–16) by hydrogen (H), hydroxyl (OH), and hydroperoxyl (HO2) radicals. These reactions, with n ≥ 10, pose significant computational challenges for prevalent high-level ab initio methods. However, they are effectively addressed using the ONIOM-based method. One notable aspect of this study is the consideration of the high symmetry of straight-chain alkanes. This symmetry allows us to study half of the reactions, employing a generalized approach. Therefore, a total of 216 reactions are systematically studied for the three reaction systems. Our results align very well with those from the widely accepted high-level QCISD(T)/CBS method, with discrepancies between the two generally less than 0.10 kcal/mol. Furthermore, we compared large straight-chain alkanes (n-C16H34 and n-C18H38) with large methyl ester molecules (C15H31COOCH3 and C17H33COOCH3) to elucidate the impact of functional groups (ester group and C=C double bond) on the reactivity of the long-chain structure. These findings underscore the accuracy and efficiency of the ONIOM-based method in computational thermochemistry, particularly for large straight-chain hydrocarbons in transportation fuels. [ABSTRACT FROM AUTHOR]

On the base of structural and thermodynamic data using modern methods of quantum chemistry, a comparative theoretical study of the elementary acts of initiation and growth of a polymer chain during the polymerization of 1,3‐butadiene was carried out. Ziegler–Natta catalysts based on Nd(III) and Gd(III) were used as polymerization initiators. It was shown that the higher stereospecificity of the action of gadolinium catalytic complexes in comparison with neodymium complexes is due to the increased stability of the anti‐form of the π‐allylic terminal structure of the growing polymer chain, and the reduced activity is due to the higher activation energy of the processes of initiation and chain growth. [ABSTRACT FROM AUTHOR]

Fluorescent molecular sensors are widely used in biological research. They allow straightforward viscosity, temperature or polarity measurements at the microscopic level, including live cells. Maps of desired physical properties can be obtained by applying fluorescence lifetime imaging microscopy (FLIM) to cells. One of the most important properties of a cell is viscosity, as it affects other parameters, such as the rate of biochemical reactions and particle diffusion. Boron-dipyrromethene (BODIPY) compounds are widely used for viscosity measurements, but current variants have the undesirable sensitivity to polarity, and more suitable alternatives are being sought using theoretical computations. The polarizable continuum model (PCM) used in previous studies did not adequately take into account the influence of the polar environment when calculating the BODIPY activation energy associated with polarity sensitivity. After applying the multilayer ONIOM method in polar and non-polar environments, the calculated maximum wavelengths of the fluorescence spectra of the 8PhBODIPY compound were closer to the experimental results compared to PCM. The activation energy was also calculated, its value in polar and non-polar environments qualitatively corresponded to the experimental results, and the quantitative agreement was reached using the empirical correction. [ABSTRACT FROM AUTHOR]

Fragmentation‐based methods for nuclear magnetic resonance (NMR) chemical shift calculations have become more and more popular in first‐principles calculations of large molecules. However, there are many options for a fragmentation‐based method to select, such as theoretical methods, fragmentation schemes, the number of levels of theory, etc. It is important to study the optimal combination of the options to achieve a good balance between accuracy and efficiency. Here we investigate different combinations of options used by a fragmentation‐based method, the eXtended ONIOM (XO) method, for 13C chemical shift calculations on a set of organic and biological molecules. We found that: (1) introducing Hartree‐Fock exchange into density functional theory (DFT) could reduce the calculation error due to fragmentation in contrast to pure DFT functionals, while a hybrid functional, xOPBE, is generally recommended; (2) fragmentation schemes generated from the molecular tailoring approach (MTA) with small level parameter n, for example, n = 2 and the degree‐based fragmentation method (DBFM) with n = 1, are sufficient to achieve satisfactory accuracy; (3) the two‐level XO (XO2) NMR calculation is superior to the calculation with only one level of theory, as the second level (i.e., low level) of theory provides a way to well describe the long‐range effect. These findings are beneficial to practical applications of fragmentation‐based methods for NMR chemical shift calculations of large molecules. [ABSTRACT FROM AUTHOR]

Locked azobenzenes (LAB) derivatives are recognized as photoswitchable potassium ion channel blockers. Here we report the effect of tetraethyl ammonium ion (TEA) substituent and KcsA K+‐ion channel protein environment on the thermodynamic stability and vertical excitation energy of locked azobenzene. The complete active space self‐consistent field (CASSCF and state‐averaged CASSCF, SA2‐CAS) with complete active space perturbation theory (state‐averaged CASPT2, SA2‐CASPT2) and our own n‐layered integrated molecular orbital and molecular mechanics—mechanical embedding (ONIOM‐ME) followed by electronic embedding (ONIOM‐EE) methods were employed for the study. The Z‐isomer of LAB is thermodynamically more stable as compared to E‐isomer. The substitution of tetraethyl ammonium ion does not influence the thermodynamic stability. On the other hand, the thermodynamic stability is reversed in the protein environment. Furthermore, the vertical excitation energies (VEE) and geometrical parameters show that the photochemistry of LAB is unaffected by para‐substituted TEA. However, geometrical changes imposed by the protein on the confined LAB‐TEA decreases the VEE. [ABSTRACT FROM AUTHOR]

The present work reports the physicochemical interaction between DNA and 1,8-napthalimide drugs to enlighten the field of drug discovery. Molecular dynamic studies of 1,8-napthalimide interacted DNA revealed distortions and destabilisation of the DNA. Among the drugs (Amonafide Azonafide and NNM-25), NNM-25 is found to have a strong interaction with DNA in gas and water phases by using the ONIOM method by investigating deformation and interaction energies. The reason for the higher interaction energy is attributed to the higher deformation of DNA during the interaction with NNM-25. Furthermore, the complex is investigated by the quantum chemical method to find the detailed observation of the direct Interaction of the 1,8-napthalimides with the DNA base pairs. NBO analysis is done to understand the charge transfer mechanism of 1,8-napthalimides' interacted DNA and also it is observed that highly stabilised complexes are found to have the highest interaction energies. The density functional theory is used to calculate the chemical reactivity and site selectivity of the molecular system to explore the results that may call for further experimental studies. [ABSTRACT FROM AUTHOR]

Psychoactive natural products are potent serotonergic agonists capable of modulating brain functions such as memory and cognition. These substances have shown therapeutic potential for treating various mental disorders. The fact that N , N -dimethyltryptamine (DMT) is produced endogenously in several plants and animals, including humans, makes it particularly attractive. As an amino acid-derived alkaloid, the DMT biosynthetic pathway is part of the L-tryptophan biochemical cascade and can be divided into the decarboxylation by an aromatic L-amino acid decarboxylase (AADC) for tryptamine formation and the subsequent double-methylation by the indolethylamine- N -methyltransferase (INMT) through the cofactor S -adenosyl-L-methionine (SAM), a methyl donor. Unlike the decarboxylation mechanism of L-tryptophan, the molecular details of the double methylation of tryptamine have not been elucidated. Therefore, we propose an in silico model using molecular dynamics (MD), non-covalent interaction index (NCI) and density functional theory (DFT) calculations with the ONIOM QM:MM B3LYP/6-31+G(d,p):MM/UFF level of theory. Based on the obtained energetic data, the potential energy surface (PES) indicates an S N 2 mechanism profile, with the second methylation energy barrier being the rate-limiting step with δ G ‡ = 60 k J ∙ m o l − 1 larger than the previous methylation, following the NCI analysis showing more repulsive interactions for the second transition state. In addition, the hybridization information of each reaction step provides geometric details about the double-methylation. [Display omitted] • Human N , N -dimethyltryptamine double-methylation mechanism is not fully elucidated. • Enzymatic reaction of tryptamine with S -adenosyl-L-methionine was explored. • ONIOM method calculations studies the potential energy surface of the methylations. • N , N -dimethyltryptamine second energy barrier is more considerable than the first. • Second energy barrier double-methylation S N 2 mechanism is the rate-limiting step. [ABSTRACT FROM AUTHOR]

The adsorption analysis of some organic inhibitors consisting of benzotriazole, 8-hydroxyquinoline, 2-mercaptobenzothiazole onto aluminum alloy surface based on optimized coordination of binding on the Al–X (Mg, Ga, Si) surface has been accomplished. In this work, the ONIOM approach has been performed with a three-layered level of high level of DFT method using EPR-III, 6-31+G(d,p) and LANL2DZ basis sets by the physico-chemical software of Gaussian 16 revision C.01 program, a medium semi-active part that includes important electronic contributions, and a low level part that has been handled using MM2 force field approaches. The physico-chemical properties of adsorption -surface complexes are one of the principal parameters for determining and choosing the Langmuir adsorption through IR, NMR, UV–Vis, HOMO/LUMO and charge distribution results. Comparing to amounts approved a good agreement among computed results, as well as the correctness of the selected isotherm for the adsorption process of benzotriazole → Al–Mg, benzotriazole → Al–Ga, benzotriazole → Al–Si, 8-hydroxyquinoline → Al–Mg, 8-hydroxyquinoline → Al–Ga, 8-hydroxyquinoline → Al–Si, 2-mercaptobenzothiazole, 2-mercaptobenzothiazole → Al–Mg, 2-mercaptobenzothiazole → Al–Ga, and 2-mercaptobenzothiazole → Al–Si. Nuclear magnetic resonance has certainly has focused on the aluminum shielding in the intra-atomic interaction with magnesium, gallium and silicon and simultaneously interatomic interaction with other atoms in organic inhibitors through variety of high, medium and low layers of ONIOM method. Al–Si with highest fluctuation in the shielding tensors of NMR spectrum generated by intra-atomic interaction leads us to the most influence in the neighbor atoms generated by interatomic reaction. Moreover, based on the computed amounts of UV–Vis spectra for benzotriazole, 8-hydroxyquinoline and 2-mercaptobenzothiazole adsorb on the Al(111)-alloy surface, there are maximum adsorption bands between 200–280 nm for benzotriazole, 225–350 nm for 8-hydroxyquinoline and 210–280 nm for 2-mercaptobenzothiazole, respectively; and maximum adsorption bands for benzotriazole, 8-hydroxyquinoline, and 2-mercaptobenzothiazole has observed around 230, 300, and 240 nm, respectively. [ABSTRACT FROM AUTHOR]

In this study, we investigated the abilities of nitrogen and sulfur heterocyclic carbenes of benzotriazole, 2-mercaptobenzothiazole, 8-hydroxyquinoline, and 3-amino-1,2,4-triazole-5-thiol regarding adsorption on an Al-Mg-Si alloy toward corrosion inhibition of the surface. Al-Si(14), Al-Si(19), and Al-Si(21) in the Al-Mg-Si alloy surface with the highest fluctuation in the shielding tensors of the "NMR" spectrum generated by intra-atomic interaction directed us to the most influence in the neighbor atoms generated by interatomic reactions of N → Al, O → Al, and S → Al through the coating and adsorbing process of Langmuir adsorption. The values of various thermodynamic properties and dipole moments of benzotriazole, 2-mercaptobenzothiazole, 8-hydroxyquinoline, and 3-amino-1,2,4-triazole-5-thiol adsorbed on the Al-Mg-Si increased by enhancing the molecular weight of these compounds as well as the charge distribution between organic compounds (electron donor) and the alloy surface (electron acceptor). Finally, this research can build up our knowledge of the electronic structure, relative stability, and surface bonding of various metal alloy surfaces, metal-doped alloy nanosheets, and other dependent mechanisms such as heterogeneous catalysis, friction lubrication, and biological systems. [ABSTRACT FROM AUTHOR]

Proton exchange membrane fuel cells (PEMFCs) are promising candidates for clean and efficient power sources. Zeolite nanoparticle membranes have been introduced as potential new membrane materials to improve the performance of PEMFCs. Understanding the proton transport mechanism on zeolite nanoparticle membranes at the atomic level is crucial in developing more efficient PEMFCs. We investigated the influence of aluminium to initiate proton transfer within zeolite fragments by performing geometry conformation of hydrated propylsulfonic acid‐functionalized zeolite ZSM‐5 clusters from one to six water molecules using four different ONIOM schemes; ONIOM(B3LYP:HF) and ONIOM(B3LYP:PM3) in gas phase and within polarizable continuum model (PCM) of water system. Results show that four water molecules are required for second proton dissociation to occur in Al systems, whereas at least five water molecules are needed in their counterpart systems. Analysis of the results suggests that the presence of Al atom in the zeolite backbone increases the electronegativity of the oxygen atom of the sulfonic acid. The oxygen provides an active site for the acidic proton to participate and increased the ability of hydrogen to dissociate itself and form hydronium cations. Our ONIOM calculation proves that ONIOM(B3LYP:PM3) method of calculation provides a reliable result with minimal computational cost. [ABSTRACT FROM AUTHOR]

• An antitumor, lipophilic Pd(II) complex was made and thoroughly characterized. • Its interaction with DNA and albumin was studied by spectral and viscosity techniques. • Its interaction was assayed by docking, molecular dynamics and DFT approaches. This research deals with the synthesis and analysis of a novel Pd(II) compound, [Pd(dach)(SA)], featuring 1,2-diaminocyclohexane (dach) and salicylic acid (SA). The compound's structure was refined and its electronic properties including HOMO-LUMO energies, molecular electrostatic potential and natural bond analysis were calculated using B3LYP functional of DFT. Biologically, the compound demonstrated significant antitumor efficacy against the K562 leukemia cell line (IC 50 = 37 μM). In-silico methods predicted the favorable characteristics and low risks of new compound. Interactions with DNA and serum albumin were explored using both experimental and computational techniques, revealing that the compound binds through hydrogen bonds and van der Waals forces having K b , DNA = 1.7 × 105, ΔG° DNA = - 7.32 kcal/mol, K b , BSA = 1.25 × 106 and ΔG° BSA = - 8.36 kcal/mol, as indicated by fluorescence spectroscopy. UV–Vis spectroscopy showed a reduction in the absorption spectra of both DNA and BSA upon interaction. DNA binding affinity was confirmed via gel electrophoresis and viscosity measurements. Molecular docking suggested the groove binding with DNA, and site I of BSA, primarily through hydrogen binding. The stability and conformational changes of these interactions over the time were affirmed by molecular dynamics simulations and QM/MM calculations. These comprehensive studies underscore the potential of [Pd(dach)(SA)] complex as a candidate for cancer therapy, highlighting its strong binding interactions with crucial biomolecules. [Display omitted] [ABSTRACT FROM AUTHOR]

Using modern methods of quantum chemistry, a theoretical substantiation of the high cis-stereospecificity of 1,3-butadiene polymerization catalyzed by the neodymium-based Ziegler–Natta system was carried out. For DFT and ONIOM simulation, the most cis-stereospecific active site of the catalytic system was used. By analyzing the total energy, as well as the enthalpy and Gibbs free energy of the simulated catalytically active centers, it was found that the coordination of 1,3-butadiene in the trans-form was more favorable than in the cis-form by 11 kJ/mol. However, as a result of π-allylic insertion mechanism modeling, it was found that the activation energy of cis-1,3-butadiene insertion into the π-allylic neodymium–carbon bond of the terminal group on the reactive growing chain was 10–15 kJ/mol lower than the activation energy of trans-1,3-butadiene insertion. The activation energies did not change when both trans-1,4-butadiene and cis-1,4-butadiene were used for modeling. That is, 1,4-cis-regulation was due not to the primary coordination of 1,3-butadiene in its cis-configuration, but to its lower energy of attachment to the active site. The obtained results allowed us to clarify the mechanism of the high cis-stereospecificity of 1,3-butadiene polymerization by the neodymium-based Ziegler–Natta system. [ABSTRACT FROM AUTHOR]

Computational enzymology is a rapidly developing area that uniquely provides deep insight into the fundamental processes of biological catalysis at the atomic level. Such in‐depth insight can ultimately be employed in designing potential inhibitors against the targets of interest. Computational enzymology covers a wide range of in‐silico approaches for investigating the enzyme‐catalyzed reaction mechanisms, among which combined quantum mechanics (QM) /molecular mechanics (MM) approaches have gained a lot of attention nowadays. This advanced approach generally involves a QM method (i. e. a method that estimates the electronic structure of the active site) and a simpler MM method (a method that includes the enzyme environment) to understand the enzymatic reactions. The QM/MM method has been widely tested in understanding the molecular mechanisms both at the structural and energetic levels and observed to best correlate with experimental studies of the enzymatic mechanism. It proposes a new mechanism that ultimately opens a new route for designing new potent, efficacious enzyme inhibitors. This review mainly covers wide applications of the ONIOM (Our own N‐layer Integrated molecular Orbital Molecular mechanics) method for decoding the enzymatic catalysis mechanism or designing potential small molecule inhibitors as treatment therapeutics in terms of free energy profiles. Moreover, this article also highlights employing QM/MM method in comprehending the mechanisms for drug metabolism and resistance (owing to mutations). This write‐up may encourage medicinal chemists and molecular biologists to explore this approach to propose more promising therapeutics to improve the quality of treatment. [ABSTRACT FROM AUTHOR]

The Bioactive compounds have actions in the body that may escalate in good health. They are being used in the studies of prevention of heart disease, cancer and even more. Isoprene plays an important role in atmospheric chemistry; source is largely from woody plants. The molecular geometry shows larger bond length, this may be due to high nuclear charge attraction. The relationship between molecular geometry and potential energy visualizes by using potential energy surface. The scaled frequencies, Infrad, Raman with their vibrational assessment along with potential energy distribution are carried out. From the low energy to extrapolated energy, the geometry connectivity using B3LYP/6-31G (d, p): UFF was found to be higher than the B3LYP/cc-pvqz: HF/3-21G (ONIOM). The sites of electrophile and nucleophile sites, the tittle of compound was calculated at the B3LYP/6-31G (d, p) optimized geometry. FMO and NLO study shows the chemical activity. Docking studies explains how small molecules bind to a macromolecular target.

The inclusion complex of acylsulfonamide (ASL) with β-cyclodextrin (β-CD) was explored experimentally and by molecular modeling studies. The stoichiometric ratio of the complex was found to be 1 : 1 and the stability constant was evaluated using the Benesi–Hildebrand equation. Estimation of the thermodynamic parameters of the inclusion complex in vacuum demonstrates that it is an enthalpy driven process phase and an enthalpy–entropy simultaneous process in aqueous solution, which is consistent with the experimental results. Semi-empirical calculations using PM6 and ONIOM2 methods, in vacuum and in water, were undertaken and done. The energetically more favorable structure obtained with the ONIOM2 method leads to the rise of intermolecular hydrogen bonds between acylsulfonamide and β-cyclodextrin. These interactions were probed using the natural bond orbital (NBO). [ABSTRACT FROM AUTHOR]

Epigenetics regulates gene expression through post-translational modification of protein complexes accompanying DNA. The most significant modification in histone protein is deacetylation, regulated by HDAC enzyme. This study focuses on the HDAC inhibitors' effect on the HDLP enzyme's stability. Ab initio quantum mechanics (QM), Quantum mechanics/molecular mechanics (QM/MM), and Molecular dynamics (MD) analyses were executed to investigate the changes that occur in the HDLP enzyme due to inhibitor binding. LBH589, PCI24781, PXD101, LAQ824, SB939, and RAS2410 were selected as inhibitors, and SAHA was used as a reference inhibitor. The crystal structure of the HDLP enzyme was obtained from the Protein Data Bank, and the inhibitor structures were optimized using G09W. AutoDock-Vina was used to perform docking, and the resultant complex was used to perform MD simulation. The QM/MM two-layer binding energy studies revealed that the stabilities of HDLP-LBH589 and HDLP-PCI24781 are higher than the other studied complexes. Also, it was found that the pKa values of the inhibitors are correlated with their binding energy. Further, the trajectory analysis results showed that the complexes of HDLP with LBH589, PCI24781, and SAHA are comparatively more stable. Therefore, it is concluded that LBH589 and PCI24781 are excellent candidates to be studied as HDLP inhibitors. [ABSTRACT FROM AUTHOR]

The hybrid ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) formalism is employed to investigate the Diels–Alder reaction of the buckminsterfullerene C60. Our computations suggest that the ONIOM2(M06-2X/6-31G(d): SVWN/STO-3G) model, enclosing both the diene and the pyracyclene fragment of C60 in the higher-layer, provides a reasonable trade-off between accuracy and computational cost as it comes to predicting reaction energetics. Moreover, the frontier molecular orbital (FMO) theory and activation strain model (ASM) are jointly relied on to rationalize the effect of –OH and –CN substituents on the activation barrier of this reaction. Finally, reaction paths are scrutinized to get insight into the various forces underpinning the process of cycloadduct formation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two extended clusters representing portions of Cu-ZSM-5 were optimized. • A two-step procedure was adopted for ONIOM geometry optimization. • Vibrational analysis produced a number of imaginary/anomalous frequencies. • Vibrational artefacts are due to the improper treatment of link H atoms. • The article shows how to avoid imaginary frequencies in ONIOM IR spectra. Two extended clusters representing different portions of Cu-ZSM-5 were treated within a two-layer ONIOM approximation, employing DFT calculations for both the real and the model system. Despite a two-step optimization procedure successfully employed in previous work, a consistent number of imaginary and anomalous frequencies appeared after the vibrational analysis. These artefacts depend both on the basis set assigned to link atoms and on an improper setting of the O–H distances, where H are the link atoms at the boundaries of the model system. The latter problem, revealed for the first time in the present study, originates from the default scale factor employed by the ONIOM routine within Gaussian-09. Once basis set and g scale factor are properly set, all imaginary and anomalous frequencies disappear. The present findings may represent an interesting and practical solution to an annoying computational problem, whenever it occurs in the framework of ONIOM calculations. [ABSTRACT FROM AUTHOR]

The binding free energy of hydrogen-bonded complexes is generally inversely proportional to the solvent dielectric constant. This occurs because the solvent-accessible surface area of the complex is always smaller than that of the individual subsystems, leading to a reduction in solvation energy. The present study explores the potential for stabilizing hydrogen-bonded complexes in a solvent with higher polarity. Contrary to the established understanding, we have demonstrated that the hydrogen-bonded complex (CH 3 CH 2 COOH⋅⋅⋅2,4,6-trimethylpyridine) can be better stabilized in a solvent with higher polarity. In this case, a significant charge transfer between the subsystems results in an increased dipole moment of the complex, leading to its stabilization in a more polar solvent. The expected inverse relationship between binding free energy and solvent dielectric constant is observed when the charge transfer between the subsystems is low. Thus, the magnitude of the charge transfer between subsystems is possibly the key factor in determining the stabilization or destabilization of H-bonded complexes in different solvents. Here, we present a comprehensive study that combines experimental and theoretical approaches, including nuclear magnetic resonance (NMR), infrared (IR) spectroscopies and quantum chemical calculations to validate the findings., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Glycoside hydrolases (GH) bind tightly to the sugar moiety at the glycosidic bond being hydrolyzed to stabilize its transition state conformation. We endeavored to assess the importance of glucose-binding residues in GH family 116 (GH116) β-glucosidases, which include human β-glucosylceramidase 2 (GBA2), by mutagenesis followed by kinetic characterization, X-ray crystallography, and ONIOM calculations on Thermoanaerobacterium xylanolyticum TxGH116, the structural model for GH116 enzymes. Mutations of residues that bind at the glucose C3OH and C4OH caused 27–196-fold increases in KM for p-nitrophenyl-β-D-glucoside, and significant decreases in the kcat, up to 5000-fold. At the C6OH binding residues, mutations of E777 decreased the kcat/KM by over 60,000-fold, while R786 mutants increased both the KM (40-fold) and kcat (2–4-fold). The crystal structures of R786A and R786K suggested a larger entrance to the active site could facilitate their faster rates. ONIOM binding energy calculations identified D452, H507, E777, and R786, along with the catalytic residues E441 and D593, as strong electrostatic contributors to glucose binding with predicted interaction energies > 15 kcal mol−1, consistent with the effects of the D452, H507, E777 and R786 mutations on enzyme kinetics. The relative importance of GH116 active site residues in substrate binding and catalysis identified in this work improves the prospects for the design of inhibitors for GBA2 and the engineering of GH116 enzymes for hydrolytic and synthetic applications. [ABSTRACT FROM AUTHOR]

To protect their intracellular proteins, extremophile microorganisms synthesize molecules called compatible solutes. These molecules are the result of the attachment of a small negatively charged molecule to a sugar molecule. It has been found that these molecules, not only protect the microorganism against osmotic stress but also against other extreme conditions. They can also confer protection against extreme conditions to isolated enzymes from different organisms making them an exciting prospect for potential biotechnological applications. One of the most widespread compatible solute in hyperthermophile organisms is the molecule 2‐O‐α‐D‐mannosyl‐D‐glycerate (MG). In addition to confer protection to proteins against extreme conditions, MG was found to prevent Alzheimer's β‐amyloid aggregation and reduce α‐synuclein fibril formation in Parkinson's disease. In this work we studied, using computational methods, the catalytic mechanism of the synthesis of MG by the enzyme mannosylglycerate synthase (MGS) from the thermophilic bacteria Rhodothermus marinus. [ABSTRACT FROM AUTHOR]

The translational accuracy in protein synthesis is contributed to by several mechanisms in the ribosome, generally called kinetic proofreading. This process in the ribosome inhibits the non-cognate codon-anticodon interaction. However, it is not sufficient for fidelity of protein synthesis since a wrong amino acid can easily be added to the growing polypeptide chain if a tRNA while cognate to the mRNA, carries a non-cognate amino acid. Therefore, additional to the kinetic proofreading, there must be some hitherto unknown characteristic in misacylated-tRNAs to stop the process of protein synthesis if such misacylated-tRNA is accommodated in the ribosomal A-site. In order to understand this characteristic, we have performed computational quantum chemistry analysis on five different tRNA molecules, each one attached to five different amino acids with one being cognate to the tRNA and the other four non-cognate. This study shows the importance of aminoacyl-tRNA binding energy in ensuring fidelity of protein synthesis. [ABSTRACT FROM AUTHOR]

Multi-photon absorption properties, particularly two-photon absorption (2PA), of fluorescent proteins (FPs) have made them attractive tools in deep-tissue clinical imaging. Although the diversity of photophysical properties for FPs is wide, there are some caveats predominant among the existing FP variants that need to be overcome, such as low quantum yields and small 2PA cross-sections. From a computational perspective, Salem et al. (2016) suggested the inclusion of non-canonical amino acids in the chromophore of the red fluorescent protein DsRed, through the replacement of the tyrosine amino acid. The 2PA properties of these new non-canonical chromophores (nCCs) were determined in vacuum, i.e., without taking into account the protein environment. However, in the computation of response properties, such as 2PA cross-sections, the environment plays an important role. To account for environment and protein–chromophore coupling effects, quantum mechanical/molecular mechanical (QM/MM) schemes can be useful. In this work, the polarizable embedding (PE) model is employed along with time-dependent density functional theory to describe the 2PA properties of a selected set of chromophores made from non-canonical amino acids as they are embedded in the DsRed protein matrix. The objective is to provide insights to determine whether or not the nCCs could be developed and, thus, generate a new class of FPs. Results from this investigation show that within the DsRed environment, the nCC 2PA cross-sections are diminished relative to their values in vacuum. However, further studies toward understanding the 2PA limit of these nCCs using different protein environments are needed.

L-6-Hydroxynicotine oxidase (LHNO) is a member of monoamine oxidase (MAO) family and catalyzes conversion of (S)-6-hydroxynicotine to 6-hydroxypseudooxynicotine during bacterial degradation of nicotine. Recent studies indicated that the enzyme catalyzes oxidation of carbon-nitrogen bond instead of previously proposed carbon-carbon bond. Based on kinetics and mutagenesis studies, Asn166, Tyr311, and Lys287 as well as an active site water molecule have roles in the catalysis of the enzyme. A number of studies including experimental and computational methods support hydride transfer mechanism in MAO family as a common mechanism in which a hydride ion transfer from amine substrate to flavin cofactor is the rate-limiting step. In this study, we formulated computational models to study the hydride transfer mechanism using crystal structure of enzyme-substrate complex. The calculations involved ONIOM and DFT methods, and we evaluated the geometry and energetics of the hydride transfer process while probing the roles of active site residues. Based on the calculations involving hydride, radical, and polar mechanisms, it was concluded that hydride transfer mechanism is the only viable mechanism for LHNO. [ABSTRACT FROM AUTHOR]

The present work analyzes the electronic and molecular properties of the 819 ([Fe(II)4]Cℓ) and metal-free knot ligand complexes obtained from X-ray crystal structure of molecular 819 knot complex [Fe(II)4(PF6)7]Cℓ. The studies were theoretically investigated by means of DFT, TD-DFT, and ONIOM approaches. Basis sets functions from all-electron calculations for bromine, iodine, and iron atoms were adapted to be used along with relativistic effective core potential, while H, C, N, O, and Cℓ atoms were described by Pople basis sets. The diffusion effect of halogen into the 819 cavity, UV-Vis, and Electronic Circular Dichroism spectra were also analyzed. All calculations were performed using solvent effect through the SCRF/SMD model and dispersion effects by Grimme methodology. The value of mean separation distance between Cℓ and iron atom (7.218 Å) is in good agreement with X-ray experimental result (7.258 Å). Circular dichroism spectrum of metal-free 819 knot ligand was calculated and the maximum absorption in 262 nm, Δ𝜖 obtained was 67 L mol− 1 cm− 1. These results are qualitatively similar to those obtained experimentally, 295 nm and 80 L mol− 1 cm− 1, respectively. In this study, we report the electronic and molecular properties of the 819 ([Fe(II)4]Cl and metal-free knot ligand complexes and compare with the results obtained from X-ray crystallographic data of 819 knot complex [Fe(II)4(PF6)7]Cl. The 819 knot were investigated by means of DFT, TD-DFT, and ONIOM approaches. Basis sets functions from all-electron for Br, I, and Fe atoms were adapted to be used along with relativistic effective core potential, while H, C, N, O, and Cl atoms were described by Pople basis sets. The objective was to understand the stability of the 819 knot as a function of the substitution of the central halogen atom (Cl), and the signal in the circular dichroism spectra. From the equilibrium geometries, we have obtained good results for values of the bond distance, bond angle, and dihedral angle along the molecular structure when these variables are compared with the results obtained from X-ray data. The diffusion effect of halogen into the 819 cavity, UV-Vis, and Electronic Circular Dichroism spectra was also analyzed. Circular dichroism spectrum of metal-free 819 knot ligand was calculated, and the maximum absorption is in good agreement with the experimental value. The ONIOM methodology combined with the relativistic effective core potential and the atomic basis sets provide good results for systems with a complex topology, such as knots. [ABSTRACT FROM AUTHOR]

In this study, the interaction of seven potential inhibitors in complex with SARS-CoV-2's M protease (Mpro) is modelled and optimized using ONIOM (Own N-layered Integrated molecular Orbital and molecular Mechanics; QM/MM) approach. Density functional theory is used for the small system and Universal Force Field is used for the rest of the molecule with ONIOM (m062x/6-311++G (d,p):UFF) model chemistry. The seven inhibitors that are used in this study are N3, ebselen, disulfiram, tideglusib, carmofur, shikonin and PX-12. The calculated interaction energy between the inhibitor and Mpro shows a strong inhibition of Mpro activity with N3, ebselen as well as PX-12 inhibitors. The two former inhibitors are previously reported as strong inhibitors; however, the strong inhibition effect of PX-12 has not been previously reported. The results of this study can provide useful insight into designing an effective inhibitor drug for SARS-nCoV, suggesting a better inhibition from PX-12 than ebselen. [ABSTRACT FROM AUTHOR]

The elongation method with intermediate mechanical and electrostatic embedding (ELG‐IMEE) is proposed. The electrostatic embedding uses atomic charges generated by a charge sensitivity analysis (CSA) method and parameterized for three different population analyses, namely, the Merz–Singh–Kollman scheme, the charge model 5, and the atomic polar tensor. The obtained CSA models were tested on two model systems. Test calculations show that the electrostatic embedding provides several times of decrease in the difference of energies of testing and reference calculations in comparison with the conventional elongation approach (ELG). The mechanical embedding is implemented in a combination of the conventional elongation method and the ONIOM approach. Moreover, it was demonstrated that the geometry optimization with the ELG‐IMEE reduces the errors in the optimized structures by about one order in root‐mean‐square deviation, when compared to ELG. [ABSTRACT FROM AUTHOR]

The correct balance between attractive, repulsive and peptide hydrogen bonding interactions must be attained for proteins to fold correctly. To investigate these important contributors, we sought a comparison of the folding between two 25‐residues peptides, the influenza A M2 protein transmembrane domain (M2TM) and the 25‐Ala (Ala25). M2TM forms a stable α‐helix as is shown by circular dichroism (CD) experiments. Molecular dynamics (MD) simulations with adaptive tempering show that M2TM monomer is more dynamic in nature and quickly interconverts between an ensemble of various α‐helical structures, and less frequently turns and coils, compared to one α‐helix for Ala25. DFT calculations suggest that folding from the extended structure to the α‐helical structure is favored for M2TM compared with Ala25. This is due to CH⋯O attractive interactions which favor folding to the M2TM α‐helix, and cannot be described accurately with a force field. Using natural bond orbital (NBO) analysis and quantum theory atoms in molecules (QTAIM) calculations, 26 CH⋯O interactions and 22 NH⋯O hydrogen bonds are calculated for M2TM. The calculations show that CH⋯O hydrogen bonds, although individually weaker, have a cumulative effect that cannot be ignored and may contribute as much as half of the total hydrogen bonding energy, when compared to NH⋯O, to the stabilization of the α‐helix in M2TM. Further, a strengthening of NH⋯O hydrogen bonding interactions is calculated for M2TM compared to Ala25. Additionally, these weak CH⋯O interactions can dissociate and associate easily leading to the ensemble of folded structures for M2TM observed in folding MD simulations. [ABSTRACT FROM AUTHOR]

Quantum mechanics/molecular mechanics (QM/MM) methods are presently a well‐established alternative for the study of enzymatic reaction mechanisms. They enable the description of a small part of the enzyme, where reactions take place through QM, while the majority of the thousands of atoms that comprise these biomolecules are handled through MM. While different "flavors" and variations in the QM/MM field exist, this review will focus more on the application of the ONIOM methodology, presenting a fresh perspective on the application of this popular method in light of the growth in computational power and level of sophistication of the different methodologies that it can combine. In addition to a brief presentation of the basic principles behind these methods, this review will discuss different examples of applicability, common choices, practical considerations, and main problems involved, stemming from our experience in this field. Finally, a reflection on the future challenges for the next decade in the QM/MM modeling of enzymatic mechanisms is presented. [ABSTRACT FROM AUTHOR]

In this work, geometries, stabilities, and electronic properties of the carbon monoxide (CO) molecule as an adsorbent in a simple carbon nanotube (CNT) and nitrogen (N), boron (B), sulfur (S)‐doped CNTs (NCNT, BCNT, and SCNT) with parallel and perpendicular configurations are fully considered using ONIOM, natural bond orbital, and quantum theory of atom in molecule (QTAIM) calculations. The adsorption energies (Ead) demonstrate that a CO molecule could be adsorbed on the surface of the simple CNT with parallel configuration and N‐doped CNT with perpendicular configuration in an exothermic process. QTAIM calculations showed the close‐shell (noncovalent) interactions between the CO molecule and CNT or N, B, S‐doped CNTs. In addition, the energy gap (Eg) values between the highest occupied molecular orbital and the lowest unoccupied molecular orbital are calculated. In accordance with the results of energy gap, simple and N‐doped CNTs could be used as CO sensors. [ABSTRACT FROM AUTHOR]

Cancer is a very complex disorder, and it is urgent to find new ways to treat it. This study aims to evaluate the inhibition mechanism of ALK-5 (target related to breast cancer) from an electronic point of view. Computational simulations (QM/MM, NBO, QTAIM) were performed, and the ONIOM method (B3LYP/cc-pVDZ:UFF) was used to obtain the optimized geometries of the studied systems. The NBO analyses indicated that the most important electron transfer occurs between LP N (inhibitor 1) and BD* O–H (Tyr249) orbitals (ΔE2 = 11.89 kcal/mol). The weakest interaction occurs between the LP N (inhibitor 4) and BD* N–H (His283) orbitals (ΔE2 = 0.81 kcal/mol). The QTAIM analyses suggested that the most active inhibitors perform a greater number of hydrogen bonds with the major residues. Therefore, quantum mechanics methods proved to be important to better understand the inhibition of ALK-5, as well as helping the design of new inhibitors. [ABSTRACT FROM AUTHOR]

The study of photoexcitations in molecular aggregates faces the twofold problem of the increased computational cost associated with excited states and the complexity of the interactions among the constituent monomers. A mechanistic investigation of these processes requires the analysis of the intermolecular interactions, the effect of the environment, and 3D arrangements or crystal packing on the excited states. A considerable number of techniques have been tailored to navigate these obstacles; however, they are usually restricted to in‐house codes and thus require a disproportionate effort to adopt by researchers approaching the field. Herein, we present the FRamewOrk for Molecular AGgregate Excitations (fromage), which implements a collection of such techniques in a Python library complemented with ready‐to‐use scripts. The program structure is presented and the principal features available to the user are described: geometrical analysis, exciton characterization, and a variety of ONIOM schemes. Each is illustrated by examples of diverse organic molecules in condensed phase settings. The program is available at https://github.com/Crespo-Otero-group/fromage. [ABSTRACT FROM AUTHOR]

In pursuit of new acetylcholinesterase (AChE) inhibitors for treating Alzheimer's disease (AD), a series of ten previously synthesized isoconessimine compounds (7a - 7j) was in silico investigated for their binding interactions with AChE and pharmacokinetics based on absorption, distribution, metabolism, and excretion (ADME) properties using molecular docking, ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) method and SwissADME tools. Docking experiments showed that all compounds bind within the active site gorge of AChE (PDB entry 1C2B), posing its aryloxy-substitutional ethyl group to catalytic site and conessine skeleton to peripheral anionic site. ONIOM interaction energy was used as an ONIOM score to improve docking score, and it ranked 7b as the most potent AChE inhibitor, in agreement with previous experiment. Residues, ASP74, TRP86, GLY122, GLU202, TRP286, GLU292, SER293, ILE294, TYR337, TYR341, and HIS447 were identified as important for the binding of the AChE-isoconessimine complex. The SwissADME investigation suggested that four compounds (7a , 7c , 7d and 7f) agree with the rules of drug-likeness. The steric and electronic effects on the aryloxy-substitutional ethyl group as important factors in the AChE inhibition were also discussed, which brings a better understanding of Alzheimer's disease drug development. [Display omitted] • Ten isoconessimine compounds (7a - 7j) were investigated for their binding interactions with AChE. • Binding energy values between compounds and AChE ranged from −14.6 to −16.8 (docking) and −72.3 to −96.0 kcal/mol (ONIOM). • Four compounds (7a , 7c , 7d , 7f) agreed with the rules of drug-likeness. • Residues important for inhibitor binding were identified. • Effects of electron-withdrawing and donating aryloxy-substituted groups on the AChE inhibition. [ABSTRACT FROM AUTHOR]

Oxidation is an important cause of fruit spoilage, and therefore improving the antioxidant capacity of fresh fruits is beneficial to their preservation. Herein, fresh-cut bananas were used as a type of fresh fruit and soaked in 75% hydroalcoholic gels containing salicylic acid (SA) or SA/β-CD inclusion complex (SA/β-CD). After treatment, they were placed in an atmosphere at 85% relative humidity at 20 °C for 12 days. A significant reduction in spoilage in bananas treated with the hydroalcoholic gels in the presence of SA/β-CD was observed, compared with those treated with gels in the presence or absence of SA. The free-radical-scavenging performances of SA and its complex were investigated using the DPPH (1,1-diphenyl-2-picryl-hydrazil) method. Based on the results, the significant increase in antioxidant activity was attributed to the fact that the inclusion complex could break the intramolecular hydrogen bonding of SA, thus efficiently eliminating ROS in the fruits. The formation of the inclusion complex was confirmed by experiments and theoretical calculations. Our findings indicate that treatment with SA/β-CD can provide an efficient method of maintaining postharvest quality and extending the shelf life of bananas.

Three implicit solvation models, the conductor‐like polarizable continuum model (C‐PCM), the conductor‐like screening model (COSMO), and universal implicit solvent model (SMD), combined with a hybrid two layer QM/QM approach (ONIOM), were utilized to calculate the pKa values, using a direct thermodynamic scheme, of a set of Group 10 transition metal (TM) hydrides in acetonitrile. To obtain the optimal combination of quantum methods for ONIOM calculations with implicit solvation models, the influence of factors, such as the choice of density functional and basis set, the atomic radii used to build a cavity in the solvent, and the size of the model system in an ONIOM scheme, was examined. Additionally, the impact of Grimme's empirical dispersion correction and exact exchange was also investigated. The results were calibrated by experimental data. This investigation provides insight about effective models for the prediction of thermodynamic properties of TM‐containing complexes with bulky ligands. © 2019 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In this work, we focus our attention on chemical reactions confined within carbon nanotubes. As a result of the confinement within carbon nanotubes, novel physical and chemical properties are found for the confined materials. We consider the feasibility of proton transfer inside carbon nanotubes. To do that, we have chosen formamide as the simplest real model for exhibiting the tautomerization in DNA. We have used the quantitative structure–property relationship method, based on geometry optimization and quantum chemical structural descriptors, to illustrate the potential of using the confined space inside carbon nanotubes, which will provide comprehensive information about carbon nanotubes. All calculations have been carried out using density functional theory quantum calculations with the B3LYP functional. The geometries optimized by the Gaussian program were transferred to the computer software DRAGON to calculate pertinent descriptors that could be used in the quantitative structure–property relationship model. [ABSTRACT FROM AUTHOR]