Bond critical points (BCPs) in the quantum theory of atoms in molecules (QTAIM) are shown to be a consequence of the molecular topology, symmetry, and the Poincaré-Hopf relationship, which defines the numbers of critical points of different types in a scalar field. BCPs can be induced by a polarizing field or by addition of a single non-bonded atom to a molecule. BCPs and their associated bond paths are therefore suggested not to be a suitable means of identifying chemical bonds, or even attractive intermolecular interactions.
Density functional theory (DFT) was utilized to elucidate the reaction mechanisms of and the key factors that influence the Ni(0)-catalyzed cross-dimerization and -trimerization of trimethylsilylacetylene (R1) and diphenylacetylene (R2). Calculated results revealed that the electron-donating ability of the ligand plays a crucial role in determining the regionselectivity of this tandem reaction. The use of strongly electron-donating ligands favors the formation of cross-dimer intermediates, whereas cross-trimer products can easily be synthesized using weakly electron-donating ligands. A simple method of estimating the electron-donating abilities of different ligands based on the Mulliken charge distribution of the ligand–ligand pair was employed. The present theoretical results allow us to elucidate the reaction mechanisms for and to identify the factors that exert the greatest influence on the ligand-controlled cross-dimerization and -trimerization of trimethylsilylacetylene and diphenylacetylene. Guidelines for the design of novel ligand systems with Ni(0) catalysts are also proposed.
There are four types of aromaticity criteria: energetic, electronic, magnetic and geometric. The delocalization, density and degeneracy-based index of aromaticity, D3BIA, is an electronic aromaticity index from QTAIM that is not reference dependent and can be used for aromatic, homoaromatic, sigma aromatic and other aromatic systems with varying ring size containing hetereoatoms or not. We used B3LYP, MP2 and MP3 methods to search for linear relations between well-known aromaticity indices and D3BIA for a series of acenes. We found that the D3BIA versus FLU correlation exceeded 91 % and reasonably good correlations exist between D3BIA and HOMA and between D3BIA and PDI. Previous works have shown that D3BIA can be used for homoaromatic systems and tetrahedrane derivatives (sigma aromaticity), but no previous work has validated D3BIA for benzenoid systems. This is the first time we have shown that D3BIA can be used successfully for benzenoid systems, for example, acenes. This work supports and validates the use of D3BIA in classical aromatic systems.
In this study, the doped defects in nitromethane crystals were investigated using first-principles calculations for the first time. We introduce dopant atoms in the interstitial sites of the nitromethane lattice, aiming to study the effects of element-doping on the structural properties, electronic properties, and sensitivity characteristics. The obtained results show that doped defects obviously affect the neighboring nitromethane molecules. The modification of electronic properties shows that the band gaps are significantly influenced by doped defects. Partial density of states and population analysis further reveal the mechanism for sensitivity control of nitromethane. It is shown that the new electronic states were introduced in the forbidden bands and the doped defects resulted in charge redistributions in the systems.
A post-calculation correction is established for PM7 band gaps of transition-metal oxides. The correction is based on the charge on the metal cation of interest, as obtained from MOPAC PM7 calculations. Application of the correction reduces the average error in the PM7 band gap from ~3 eV to ~1 eV. The residual error after correction is shown to be uncorrelated to the Hartree–Fock method upon which PM7 is based.
Graphical Abstract Comparison between calculated band gaps and experimental band gaps for binary oxides. The orange crosses are for corrected PM7 band gaps. Blue squares are uncorrected values. The orange crosses fall closer to the diagonal dashed line, showing an overall improvement of the accuracy of calculated values
A perfectly planar Al13+ cluster (CI) and a quasi-planar Al13+ cluster (CII) have been found for the first time. Both clusters have a triangular core surrounded by a set of ten Al atoms in the form of a ring. These cationic clusters have substantial aromatic character. The planar CI cluster has local antiaromatic patches within global aromatic sea. It is doubly aromatic having both σ and π aromatic character. The quasi-planar CII cluster is also aromatic but it has more σ-delocalization.
The conversion of 2-phenylbenzimidazole using o-phenylenediamine and benzaldehyde can be improved significantly under β-cyclodextrin (β-CD). The density functional theory (DFT) method was applied to study the whole process. According to energy parameters (binding energy, deformation energy) and structural deformation, entry models and the reaction process can be pinpointed, with o-phenylenediamine embedding β-CD from a wide rim, and then benzaldehyde passing into the inclusion from the narrow rim. Subsequently, natural bonding orbital (NBO), Mulliken charge, frontier orbital, FuKui function and nuclear magnetic resonance (NMR) methods were employed to reveal the mechanism of electron transfer. The results illustrate that β-CD plays a catalytic role in synthesis reaction mechanism on the secondary side, improving the reactivity and selectivity of the process.
Graphical Abstract Density functional theory study of the effects of β-cyclodextrin in synthesis of 2-phenylbenzimidazole via benzaldehyde and o-phenylenediamine
The solubility advantage (SA) of meloxicam cocrystalized with mono- and dicarboxylic acids was expressed in terms of equilibrium constants involving active pharmaceutical ingredient and coformer in aqueous solutions. It is argued that SA can be quantified by concentration of pairs formed in water. The pH and concentration of dissolved components is included explicitly in the model. The alternative behavior of mono- and dicarboxylic acids was emphasized and addressed to different structural motifs. The structural and energetic properties of meloxicam and its complexes with carboxylic acids were characterized, including tautmerism and dissociation in aqueous media. In particular, performed in silico modeling confirmed experimental observation that meloxicam dissolved in water or modest acidic solutions is expected to be a mixture of anionic form in equilibrium with at least five neutral isomers. Tautomer-related diversity of pairs formation and the possibility of salt formation is also discussed.
In this article, we explore the capacity of formed Schiff base complexes to trap metal atoms or ions, using their aromatic ends. The intrinsic geometry of each complex defines the process of substitution. Two cases were studied; one involving a trans Schiff base complex and the other considering how a salen ligand, with nickel systems traps chromium. We also assessed the nature of the new bonds and the frontier molecular orbitals.
In this work, through a docking analysis of compounds from the ZINC chemical library on human β-tubulin using high performance computer cluster, we report new polycyclic aromatic compounds that bind with high energy on the colchicine binding site of β-tubulin, suggesting three new key amino acids. However, molecular dynamic analysis showed low stability in the interaction between ligand and receptor. Results were confirmed experimentally in in vitro and in vivo models that suggest that molecular dynamics simulation is the best option to find new potential β-tubulin inhibitors.
DSS1 is a small acidic intrinsically disordered protein (IDP) that can fold upon binding with PCID2 TREX-2. The resulting complex plays a key role in mRNA export. However, the binding mechanism between DSS1 and PCID2 is unsolved. Here, three independent 500-ns molecular dynamics (MD) simulations were performed to study the DSS1–PCID2 binding mechanism by comparing apo-PCID2 and bound PCID2. The results show that the conformational variation of bound PCID2 is smaller than that of apo-PCID2, especially in the binding domain of two helices (helix IV and VIII). The probability of coil formation between helix III and helix IV of bound PCID2 increases, and a short anti-parallel β-sheet forms upon DSS1 binding. The decomposition of binding free energy into protein and residue pairs suggests that electrostatic and hydrophobic interactions play key roles in the recognition between DSS1 and PCID2. There is a hydrophobic core of seven residues in DSS1 favorable to the binding of PCID2. These analytical methods can be used to reveal the recognition mechanisms of other IDPs and their partners.
Mechanisms for the activation of water, ammonia, and other small molecules by the PCcarbeneP nickel pincer complex were studied computationally with the aid of density functional theory. The calculation results indicate that the strongly donating, nucleophilic carbene center can engage in a variety of heterolytic splitting of E?H (E=H, C, N, O) bonds, some of which are reversible. The cleavage of E?H bonds across the Ni=C bond represents a new mode of bond activation by ligand cooperativity in nickel pincer complex. On the basis of the calculations, we also demonstrate that reversible H2 activation across the Ir=C bond via the PCcarbeneP iridium pincer complex was observed in the experiments, while other E?H (E=C, N, O) bonds were not activated. Our calculations are in good agreement with experimental observations and could provide new insights into ligand cooperativity in nickel pincer complexes.
Ionic liquids (ILs) constitute a fast growing class of compounds finding multiple applications in science and technology. Morpholinium-based ILs (MBILs) and their mixtures with polar molecular co-solvents are interesting as sustainable electrolyte systems for electrochemistry. We investigate local structures of protic and apropic morpholinium cations in acetonitrile (ACN) using semi-empirical molecular dynamics (MD) simulations. An impact of an anion (acetate) on the cation solvation regularities is discussed. Unlike oxygen, nitrogen of the morpholine ring is a strong electrophilic binding center. This site is responsible for the interactions of the cation with the solvent and with the anion. In protic MBILs, the role of nitrogen is delegated to the proton, which is linked to nitrogen. The acetate anion weakens solvation of the cation due to occupation of space near nitrogen or proton. The analysis reveals a favorable solvation of MBILs in ACN, which is a prerequisite for a new high-performance electrolyte system. The reported structural data were validated through point-to-point comparison with the MP2 post-Hartree-Fock theory and density functional theory.
We use the TDDFT/PBE0/6-31+G* method to determine the electronic absorption and emission energies, in different media, of the four forms of tocopherol, which differ by the number and the position of methyl groups on the chromanol. Geometries of the ground state S0 and the first singlet excited state S1 were optimized in the gas phase, and various solvents. The solvent effect is evaluated using an implicit solvation model (IEF-PCM). Our results are compared to the experimental ones obtained for the vitamin E content in several vegetable oils. For all forms of tocopherols, the HOMO–LUMO first vertical excitation is a π–π* transition. Gas phase and non-polar solvents (benzene and toluene) give higher absorption wavelengths than polar solvents (acetone, ethanol, methanol, DMSO, and water); this can be interpreted by a coplanarity between the O-H group and the chroman, allowing a better electronic resonance of the oxygen lone pairs and the aromatic ring, and therefore giving an important absorption wavelength, whereas the polar solvents give high emission wavelengths comparatively to gas phase and non-polar solvents. Fluorescence spectra permit the determination, the separation, and the identification of the four forms of tocopherols by a large difference in emission wavelength values.
The interactions of the drugs amlodipine and paroxetine, which are prescribed respectively for treatment of hypertension and depression, with the metabolizing enzyme cytochrome CYP2B4 as the drug target, have been studied by molecular dynamics (MD) simulation. Poly ethylene glycol was used to control the drugs’ interactions with each other and with the target CYP2B4. Thirteen simulation systems were carefully designed, and the results obtained from MD simulations indicated that amlodipine in the PEGylated form prescribed with paroxetine in the nonPEGylated form promotes higher cytochrome stability and causes fewer fluctuations as the drugs approach the target CYP2B4 and interact with it. The simulation results led us to hypothesize that the combination of the drugs with a specific drug ratio, as proposed in this work, manifests more effective diffusivity and less instability while metabolizing with enzyme CYP2B4. Also, the active residues in the CYP2B4 enzyme that interact with the drugs were determined by MD simulation, which were consistent with the reported experimental results.
The structure of a hairpin loop—in particular its large accessible surface area and its exposed hydrogen-bonding edges—facilitate an inherent possibility for interactions. Just like higher-order RNA macromolecules, pre-microRNAs possess a hairpin loop, and it plays a crucial role in miRNA biogenesis. Upon inspecting the crystal structures of RNAs with various functions, we noticed that, along with a fairly long double helix, the RNAs contained sequentially different hairpin loops comprising four residues. We therefore applied molecular dynamics simulation to analyze six of these previously unexplored tetraloops, along with GNRA (where N is any nucleotide and R is a purine nucleotide) tetraloops, to understand their structural and functional characteristics. A number of analyses quantifying loop stability by examining base–base stacking, base–sugar and base–phosphate hydrogen bonding, and backbone variability were performed. Importantly, we determined the different interbase stacking preferences of the single-stranded unpaired bases of the hairpin loops, which had not previously been quantified in any form. Furthermore, our study indicates that canonical GNRA structural properties are exhibited by some structures containing non-GNRA loop sequences.
It is known that inhibiting α-amylase, an important enzyme in digestion of starch and glycogen, is a useful strategy for treating disorders in carbohydrate uptake. Two natural components distributed in many fruits and plants, oleanolic acid and ursolic acid, are endowed with important pharmacological activities and wide therapeutic possibilities. Until now, only a tiny fraction of their applications have been identified and exploited. Our in vitro inhibition studies demonstrated that oleanolic acid and ursolic acid non-competitively inhibit the activity and function of human salivary α-amylase. The molecular simulations revealed that oleanolic acid and ursolic acid interact with amino acid residues within the binding pocket of human salivary α-amylase, among which the side chain of Arg195 and Asp 197 was supposed to be important in imparting the inhibitory activity of triterpenoids. The present work will provide meaningful information for future development of functional drugs for the treatment of disorders in carbohydrate metabolism.
Graphical abstract This work is valuable for providing a deeper insight into the interaction mechanism of oleanolic acid and ursolic acid with α-amylase
