Applying Density Functional Theory Calculations Research Articles

Biginelli dihydropyrimidines carrying azole rings: Synthesis, computational studies, and evaluation of alpha‐glucosidase inhibitory and antimicrobial activities

In the current study, we designed three novel compounds by merging two valuable nitrogen-containing pharmacophores, namely dihydropyrimidine (DHPM) and azole, within a single molecule. To obtain the target molecules, azole-linked benzaldehydes were initially synthesized via nucleophilic aromatic substitution reaction between 4-fluorobenzaldehyde and pyrazole, imidazole, or 1,2,4-triazole. Afterward, Biginelli reaction was applied to yield azole-carrying DHPMs. Following structural confirmation, the obtained compounds were tested for their alpha (α)-glucosidase inhibitory and antimicrobial activities. According to the biological data, DHPM-P and DHPM-T showed strong inhibition values whereas DHPM-I failed to effectively inhibit the α-glucosidase enzyme. This situation was explained by molecular docking studies of all compounds into the binding site of alpha-glucosidase. The title compounds also presented moderate antibacterial and antifungal activities. Computational methods based on density functional tight binding (DFTB) and density functional theory (DFT) calculations, along with molecular dynamics (MD) simulations were used to analyze the reactive properties of the compounds. A combination of DFTB and DFT calculations was applied to obtain the lowest energy conformations of the molecules. Further computational analysis included calculations of local reactivity descriptors, such as molecular electrostatic potential and average local ionization energy, by applying DFT calculations. DFT calculations were also used to study intramolecular non-covalent interactions. MD simulations were employed to understand how the title molecules behave in water and to obtain their solubility parameters.

(Invited) First Principles Examination of Multiple Criteria of Organic Solvent Oxidative Stability in Batteries

Oxidative instability of the liquid electrolyte at or near battery cathode oxide surfaces has significant detrimental effects on batteries. Organic solvent molecules are often the fuel and precurors of such degradation processes, releasing electrons and protons that react with cathode oxides and electrolyte anions. These reactions contribute to cathode electrolyte interphase (CEI) film formation, transition metal ion dissolution, and phase transformation of the surface regions of the cathode. Here we apply Density Functional Theory calculations to examine four criteria of oxidative stability (oxidation potential, hydrogen removal energies, and initial reactivity on two types of oxide facets) using four different solvent/additive molecules (ethylene carbonate, fluoroethylene carbonate, 1,3-dioxolane, and dimethyl ether). The ranking of molecular stability differs with each criterion. Surprisingly, the all-oxygen terminated basal planes of layered oxides exhibit lower reaction barriers than spinel surface facets with exposed transition metal cations, especially for ether solvents; the calculations also suggest basal planes contribute to the dissolution of transition metal ions. The structure-degradation relation complexity underscores the challenge of understanding the function of the CEI, but also offers a guide to future degradation-mitigation strategies including facet-engineering. Our predictions and models help establish a framework for future studies relevant to high voltage conditions.Sandia National Laboratories is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525. This paper describes objective technical results and analysis. Any subjective views or opinions that might be expressed in the document do not necessarily represent the views of the U.S. Department of Energy or the United States Government.

Comprehensive Scheme for Identifying Defects in Solid-State Quantum Systems.

A solid-state quantum emitter is a crucial component for optical quantum technologies, ideally with a compatible wavelength for efficient coupling to other components in a quantum network. It is essential to understand fluorescent defects that lead to specific emitters. In this Letter, we employ density functional theory (DFT) to demonstrate the calculations of the complete optical fingerprints of quantum emitters in hexagonal boron nitride. Our results suggest that instead of comparing a single optical property, like the zero-phonon line energy, multiple properties should be used when comparing simulations to the experiment. Moreover, we apply this approach to predict the suitability of using the emitters in specific quantum applications. We therefore apply DFT calculations to identify quantum emitters with a lower risk of misassignments and a way to design optical quantum systems. Hence, we provide a recipe for classification and generation of universal quantum emitters in future hybrid quantum networks.

First-Principles Examination of Multiple Criteria of Organic Solvent Oxidative Stability in Batteries

Oxidative instability of the liquid electrolyte at or near battery cathode oxide surfaces has significant detrimental effects on batteries. Organic solvent molecules are often the fuel and precursors of such degradation processes, releasing electrons and protons that react with cathode oxides and electrolyte anions. These reactions contribute to cathode–electrolyte interphase (CEI) film formation, transition-metal ion dissolution, and phase transformation of the surface regions of the cathode. Here we apply density functional theory calculations to examine four criteria of oxidative stability (oxidation potential, hydrogen removal energies, and initial reactivity on two types of oxide facets) using four different solvent/additive molecules (ethylene carbonate, fluoroethylene carbonate, 1,3-dioxolane, and dimethyl ether). The ranking of molecular stability differs with each criterion. Surprisingly, the all-oxygen-terminated basal planes of layered oxides exhibit lower reaction barriers than spinel surface facets with exposed transition-metal cations, especially for ether solvents; the calculations also suggest basal planes contribute to the dissolution of transition-metal ions. The structure–degradation relation complexity underscores the challenge of understanding the function of the CEI but also offers a guide to future degradation-mitigation strategies including facet engineering. Our predictions and models help establish a framework for future studies relevant to high-voltage conditions.

Discovery and Computational Studies of Potent Covalent Kinase Inhibitors with α-Substituent Electrophiles Targeting Cysteine.

Both reversible noncovalent inhibitors and irreversible covalent inhibitors targeting tyrosine kinases have their disadvantages. The reversible covalent inhibitors with electrophilic group cyanoacrylamide as warheads reacting with cysteine residues could solve the dilemmas. However, there are still several unresolved issues regarding the electrophilic groups. In this manuscript, a series of EGFR inhibitors with double electron-withdrawing substituents introduced into the Cα position on the olefin bond were designed and synthesized. The binding structures and characteristics of inhibitors with the kinase in both the first noncovalent binding phase and the second covalent binding step were explored and combined with molecular docking and molecular dynamics simulations. Then, the reverse β-elimination reactions of the thiol-Michael adducts were investigated by applying density functional theory calculations. In addition, the effects of different electrophilic substituents of Cα on the binding between the inhibitors and kinase were elucidated. The results suggested that the electrophilicity and size of the electron-withdrawing groups play an important role in the specific interactions during the reaction. The compounds with the electron-withdrawing groups that had medium electrostatic and steric complementarity to the kinase active site could cooperatively stabilize the complexes and showed relatively good potent activities in the kinase assay experiment. The mechanical and structural information in this study could enhance our understanding of the functioning of the electron-withdrawing groups in the covalent inhibitors. The results might help to design efficient cysteine targeting inhibitors in the future.

Research on carbon-based and metal-based negative electrode materials via DFT calculation for high potassium storage performance: a review

The key R&D concern in the domain of new energy in recent years has been the large-scale development of electrochemical energy storage. However, the steep increase in pricing has constrained the further expansion of lithium-ion batteries, primarily due to the ongoing depletion of their scarce lithium supplies. A potential candidate material at the moment is the potassium-ion battery (KIB), which has an anode made of carbon and/or an alloy and rich reserves, offering an excellent theoretical capacity and ideal working voltage. More significant advancements are still required to achieve long life and high energy density, despite the fact that some significant breakthroughs have been reported. The most recent findings from research on carbon-based [graphite, hard carbon (HC), and nanoporous carbon] and alloy-based (mainly including Sb, Sn, P, and its compounds) anodes for KIBs are compiled in this document. Numerous simulations at the atomic level based on particular chemical interactions, phase transitions, ion/electron transport dynamics, and conduction band spin utilizing density functional theory (DFT) calculations have been conducted to thoroughly investigate the storage mechanism of K+ on various electrode materials. Moreover, this paper examined contemporary structural modification techniques used in carbon- and alloy-based anode electrode materials and applied DFT calculations to confirm the advancement of its thorough tests. To promote the manufacturing of rechargeable KIBs, the challenges and potential of KIBs were also explored in future research.

The encapsulation of atomically-thin MgB2-based superconductors in two-dimensional material bilayers

Two-dimensional (2D) superconductors are a class of materials with unique properties that can potentially exhibit novel superconductivity at a reduced dimensionality, as well as pave the way for miniaturizing superconducting devices at the atomic limit. However, such materials are highly sensitive to interaction with their substrates and the environment, and therefore it is necessary to find potential methods for chemically isolating them. We address this problem by examining the possibility of isolating the medium-temperature 2D MgB2-based superconductors. We examine two possible structures: the monolayer stoichiometric MgB2 and the B-caged Mg3B8 structure. By solving the anisotropic Eliashberg equations, we predict that the latter possesses K upon application of a small lateral (3% tensile) strain, with an electron–phonon coupling of 0.88. To investigate protecting the superconductivity of these two layers, we apply density functional theory calculations to examine their encapsulation in a graphene bilayer or a hexagonal boron nitride bilayer. We find that both have high potential as encapsulation systems to protect the superconductivity of the 2D MgB2-based superconductors, in particular B-caged (B–Mg) n systems.

Phosphinophosphoranes: Mixed-Valent Phosphorus Compounds with Ambiphilic Properties.

Herein, we present a simple synthesis of mixed-valent phosphinophosphoranes bearing three- and five-coordinate phosphorus centers. Compounds with phosphorus-phosphorus bonds were synthesized via a reaction of lithium phosphides RR'PLi with cat2PCl (cat = catecholate), whereas derivatives with methylene-linked phosphorus centers were obtained via a reaction of phosphanylmethanides RR'CH2Li with cat2PCl. The presence of accessible lone-pair electrons on the P-phosphanyl atom of phosphinophosphoranes during the reaction of the title compounds with H3B·SMe2, where phosphinophosphorane-borane adducts were formed quantitatively, was confirmed. Furthermore, the Lewis basic and Lewis acidic properties of the phosphinophosphoranes in reactions with phenyl isothiocyanate were tested. Depending on the structure of the starting phosphinophosphorane, phosphinophosphorylation of PhNCS or formation of a five-membered zwitterionic adduct was observed. The structures of the isolated compounds were unambiguously determined by heteronuclear nuclear magnetic resonance spectroscopy and single-crystal X-ray diffraction. Moreover, by applying density functional theory calculations, we compared the Lewis basicity and nucleophilicity of diversified trivalent P-centers.

Density functional theory study on Ti/h-BN interface in resistance random access memory device

By applying density functional theory calculations, we analyzed the intrinsic propensity of the Ti/h-BN interface in a resistive random access memory (RRAM) device upon the existence of a Stone–Wales (SW) defect and boron vacancy (VB). Following the construction of the Ti(001) surface and h-BN(SW) stack, Ti/h-BN interface models with different configurations and terminated sites were proposed, among which h-BN(SW)I/Ti(001)_TN was identified as the most stable interface system according to the binding energy. The charge transfer from Ti(001) toward the h-BN layers, resulting in heavy doping, formed an Ohmic contact in the interface. Moreover, through analysis of structure optimization, an intrinsic tendency of Ti ion migration to pass through the interface was revealed in the presence of SW defects and VB in the h-BN interface layer. The result of the migration barrier suggested that SW defects, especially B–B bond heptagons, provide preferential pathways for the vertical penetration of Ti ions through the interface, whereas VB in defects contribute most to the facilitation of Ti ion migration. Finally, I–V curves of RRAM device models with different interface configurations showed that SW defects and VB in the interface are critical to resistive switching behavior and can improve performance parameters, such as set voltage and current on/off ratios.

α-Helix in Cystathionine β-Synthase Enzyme Acts as an Electron Reservoir.

The modulation of electron density at the Pyridoxal 5'-phosphate (PLP) catalytic center, because of charge transfer across the α-helix/PLP interface, is the determining factor for the enzymatic activities in the human Cystathionine β-Synthase (hCBS) enzyme. Applying density functional theory calculations, in conjunction with the real space density analysis, we investigated the charge density delocalization across the entire heme-α-helix-PLP electron communication channels. The electron delocalization due to hydrogen bonds at the heme/α-helix and α-helix/PLP interfaces are found to be extended over a very long range, as a result of redistribution of electron densities of the cofactors. Moreover, the internal hydrogen bonds of α-helix that are crucial for its secondary structure also participate in the electron redistribution through the structured hydrogen-bond network. α-Helix is found to accumulate the electron density at the ground state from both of the cofactors and behaves as an electron reservoir for catalytic reaction at the electrophilic center of PLP.

A First-Principles Study of CO2 Hydrogenation on a Niobium-Terminated NbC (111) Surface.

As promising materials for the reduction of greenhouse gases, transition-metal carbides, which are highly active in the hydrogenation of CO2 , are mainly considered. In this regard, the reaction mechanism of CO2 hydrogenation to useful products on the Nb-terminated NbC (111) surface is investigated by applying density functional theory calculations. The computational results display that the formation of CH4 , CH3 OH, and CO are more favored than other compounds, where CH4 is the dominant product. In addition, the findings from reaction energies reveal that the preferred mechanism for CO2 hydrogenation is thorough HCOOH* , where the largest exothermic reaction energy releases during the HCOOH* dissociation reaction (2.004 eV). The preferred mechanism of CO2 hydrogenation towards CH4 production is CO2 * →t,c-COOH* →HCOOH* →HCO* →CH2 O* →CH2 OH* →CH2 * →CH3 * →CH4 * , where CO2 * →t,c-COOH* →HCOOH* →HCO* →CH2 O* →CH2 OH* →CH3 OH* and CO2 * →t,c-COOH* →CO* are also found as the favored mechanisms for CH3 OH and CO productions thermodynamically, respectively. During the mentioned mechanisms, the hydrogenation of CH2 O* to CH2 OH* has the largest endothermic reaction energy of 1.344 eV.

Nitrogen diffusion in zinc oxide

Nitrogen migration in ZnO was investigated by nitrogen isotope diffusion. The samples were deposited using plasma-assisted pulsed laser deposition. Nitrogen concentration depth profiles were obtained from secondary-ion-mass spectrometry measurements, and in gas effusion measurements, the molecular nitrogen flux was measured as a function of the heating rate. Measurements performed on sample stacks that were doped with isotopically enriched 15N and 14N in the top and bottom half of the samples, respectively, clearly demonstrate that nitrogen diffusion is governed by atomic diffusion and molecules are formed primarily at the sample surface. At high nitrogen concentrations, the diffusion coefficient, D, is thermally activated, while for low concentration diffusion, D is independent of temperature. The data can be described by a model, where N diffusion occurs between minimum energy positions by surmounting the barrier between sites at a saddle point. Separated in energy from the transport sites are deep levels with a concentration of ≈1018 cm−3. For high-concentration diffusion, the N chemical potential, μN, resides at ≈1.36 eV below the migration saddle point. For low concentration diffusion, μN shifts deeper in energy with a rate of ≈2.8 meV/K as the temperature increases. From N effusion data, the nitrogen density-of-states is derived. For high N concentration diffusion, two peaks are observed at ES–μN = −0.93 and −1.26 eV, while for low N concentration diffusion, a prominent peak at ES–μN = −1.63 eV occurs. Applying density functional theory calculations, different microscopic diffusion mechanisms are evaluated, and the corresponding transition states are derived.

Breakdown of Hund's rule for CuFeAs

The ground-state properties of CuFeAs were investigated by applying density functional theory calculations within generalized gradient approximation (GGA) and GGA+U. We find that the bicollinear antiferromagnetic state with antiparallel orbital magnetic moments on each iron which violates the Hund's rule is favored by the on-site Coulomb interaction, which is further stabilized by Cu vacancy. The magnetic ground state can be used to understand weak antiferromagnetism in CuFeAs observed experimentally. We argue that breakdown of the Hund's rule may be the possible origin for reduced magnetism in iron pnictides, rather than magnetic fluctuations induced by electronic correlations.

Edge-Propagation Discharge Mechanism in CFx Batteries—A First-Principles and Experimental Study

Graphite fluoride (CFx) cathodes coupled with lithium anodes yield one of the highest theoretical energy densities (>860 Wh/g) among primary batteries. In practice, the observed discharge voltage (~2.5 V) is significantly lower than thermodynamic limits (>4.5 V), the discharge rate is low, and so far Li/CFx has only been used in primary batteries. Understanding the discharge mechanism at atomic length scales will improve practical CFx energy density, rate capability, and rechargeability. So far, purely experimental techniques have not identified the correct discharge mechanism or explained the discharge voltage. We apply Density Functional Theory calculations to demonstrate that a CFx-edge propagation discharge mechanism based on lithium insertion at the CF/C boundary in partially discharged CFx exhibits a voltage range of 2.5 to 2.9 V -- depending on whether solvent molecules are involved. The voltages and solvent dependence agrees with our discharge and galvanostatic intermittent titration technique measurements. The predicted discharge kinetics are consistent with CFx operations. Finally, we predict Li/CFx rechargeability under the application of high potentials, along a charging pathway different from that of discharge. Our work represents a general, quasi-kinetic framework to understand the discharge of conversion cathodes, circumventing the widely used phase diagram approach which most likely does not apply to Li/CFx because equilibrium conditions are not attained in this system.

New information of dopaminergic agents based on quantum chemistry calculations

Dopamine is an important neurotransmitter that plays a key role in a wide range of both locomotive and cognitive functions in humans. Disturbances on the dopaminergic system cause, among others, psychosis, Parkinson’s disease and Huntington’s disease. Antipsychotics are drugs that interact primarily with the dopamine receptors and are thus important for the control of psychosis and related disorders. These drugs function as agonists or antagonists and are classified as such in the literature. However, there is still much to learn about the underlying mechanism of action of these drugs. The goal of this investigation is to analyze the intrinsic chemical reactivity, more specifically, the electron donor–acceptor capacity of 217 molecules used as dopaminergic substances, particularly focusing on drugs used to treat psychosis. We analyzed 86 molecules categorized as agonists and 131 molecules classified as antagonists, applying Density Functional Theory calculations. Results show that most of the agonists are electron donors, as is dopamine, whereas most of the antagonists are electron acceptors. Therefore, a new characterization based on the electron transfer capacity is proposed in this study. This new classification can guide the clinical decision-making process based on the physiopathological knowledge of the dopaminergic diseases.

Structural Optimization of Metal Oxyhalide for CO2 Reduction with High Selectivity and Current Density

Summary of main observation and conclusionElectrochemical CO2 reduction into value‐added liquid fuels using CO2 neutral renewable energy sources is very promising to solve climatic issues. In order to realize their practical applications, highly active and inexpensive electrocatalysts are urgently required. In this study, we have experimentally achieved high electrocatalytic activity towards CO2 reduction for the synthesis of formate with an enhanced current density of 15.1 mA·cm–2 and significantly improved Faradaic efficiency of 98.4% upon electrochemical reduced ultrathin bismuth oxybromide nanosheets. Moreover, the stable performance during 24 h of operation is also obtained. Furthermore, by detecting the exposed crystal plane after surface reorganization and applying density functional theory calculations, the possible reaction pathways and catalytic active plane of the derived bismuth catalyst are put forward, which would offer basic and design principles to directly develop the optimized metal Bi catalysts for enhanced electrocatalytic CO2 conversion to formate.

Computational study of a B36 borophene as an electronic sensor for the anti-cancer drug cisplatinum

The sensitivity and reactivity of a B36 borophene were inspected with regard to the drub cisplatinum, in the gas phase and in aqueous solution, applying density functional theory calculations. In the gas phase, the adsorption energy (Ead) was predicted to be −19.6 kcal/mol, and the drug adsorbed via its Cl and H atoms on the edge of the B36 borophene. We found that the B36 electronic properties are meaningfully sensitive to the cisplatinum drug, and so may be a potential sensor for cisplatinum detection. Because of a large HOMO destabilization upon the drug adsorption, the HOMO–LUMO gap (Eg) of the B36 borophene significantly decreased from 1.11 to 0.62 eV, increasing its electrical conductance. A short recovery time of 0.023 s was predicted for desorption of the cisplatinum drug from the B36 borophene surface at room temperature. Unlike the Eg, the Fermi level and work function of the B36 borophene were not changed detectibly by the process of drug adsorption. The adsorption of cisplatinum on the B36 sheet weakens in aqueous solution, and the Ead is −12.3 kcal/mol.

Insights on the Pseudo-Enantiomeric Properties of Bifunctional Cinchona Alkaloid Squaramide-Derived Organocatalyst.

The use of pseudo enantiomers is a well-known method of achieving products of complementary stereochemistry. Only rarely can different enantiomers of a product be accessed without modulation of the catalyst. Recently, a system was reported wherein two different enantiomers of spirocycles were obtained by a cascade reaction of unsaturated pyrrolin-4-ones with mercaptoacetaldehyde catalyzed by a single optimized cinchona alkaloid squaramide-derived organocatalyst. It was originally proposed that the E/Z geometry of the unsaturated pyrrolin-4-one dictated the stereochemistry of the spirocycle product, but this was not investigated further. In the present work, we have investigated the nature of a pseudo-enantiomeric organocatalyst conformation applying density functional theory calculations for investigating the transition states for the reaction. Furthermore, the influence of the double-bond geometry of the pyrrolin-4-one has been studied beyond what is possible to test experimentally. The results provide a greater understanding for this class of reactions that may be applicable in future methodology development.

Study of the harmine in hydrophobic, hydrophilic solvents and micelles using emission spectroscopy at 77 K and DFT calculations

Neutral harmine dissolved in methylcyclohexane, ethanol and ethanol plus 1% of 3,3,3,1,1,1-hexafluoroisopropanol and monocation harmine dissolved in water were investigated by emission spectroscopy at 77 K and applying Density Functional Theory calculations. The following species were found: monomeric harmine, in methylcyclohexane, hydrogen-bonded complex, coexisting with the monomeric harmine in ethanol, strong hydrogen-bonded complex in ethanol plus 1% of 3,3,3,1,1,1-hexafluoroisopropanol and monocation in water and in buffer solution (pH=7, I = 0.1 M). Each one of the species presented distinct photophysical properties. These results were used to identify which species of harmine are solubilized in the interior of neutral, anionic and cationic micelles prepared under physiological conditions. Two species were found to coexist in the interior of the neutral micelles, the monomeric harmine, anchored in hydrophobic region, and the hydrogen-bonded complex, anchored in the aqueous region. In the anionic micelle, strong hydrogen-bonded complex was the active species, anchored in the aqueous region, and in the cationic micelle, the monocation did not penetrate into the micelles, but rather, stayed outside the micelle. Those results may shed light on the different behaviors of this molecule in biological systems and help understand the drug transport through the membrane.

Toward probing of the local electron-phonon interaction in small-molecule organic semiconductors with Raman spectroscopy.

Electron-phonon interaction strongly affects and often limits charge transport in organic semiconductors (OSs). However, approaches to its experimental probing are still in their infancy. In this study, we probe the local electron-phonon interaction (quantified by the charge-transfer reorganization energy) in small-molecule OSs by means of Raman spectroscopy. Applying density functional theory calculations to four series of oligomeric OSs-polyenes, oligofurans, oligoacenes, and heteroacenes-we extend the previous evidence that the intense Raman vibrational modes considerably contribute to the reorganization energy in several molecules and molecular charge-transfer complexes, to a broader scope of OSs. The correlation between the contribution of the vibrational mode to the reorganization energy and its Raman intensity is especially prominent for the resonance conditions. The experimental Raman spectra obtained with various excitation wavelengths are in good agreement with the theoretical ones, indicating the reliability of our calculations. We also establish for the first time relations between the spectrally integrated Raman intensity, the reorganization energy, and the molecular polarizability for the resonance and off-resonance conditions. The results obtained are expected to facilitate the experimental studies of the electron-phonon interaction in OSs for an improved understanding of charge transport in these materials.