Use Of Computational Chemistry Research Articles

Repurposing Drugs: An Empowering Approach to Drug Discovery and Development.

Drug discovery and development is a time-consuming and costly procedure that necessitates a substantial effort. Drug repurposing has been suggested as a method for developing medicines that takes less time than developing brand new medications and will be less expensive. Also known as drug repositioning or re-profiling, this strategy has been in use from the time of serendipitous drug discoveries to the modern computer aided drug designing and use of computational chemistry. In the light of the COVID-19 pandemic too, drug repurposing emerged as a ray of hope in the dearth of available medicines. Data availability by electronic recording, libraries, and improvements in computational techniques offer a vital substrate for systemic evaluation of repurposing candidates. In the not-too-distant future, it could be possible to create a global research archive for us to access, thus accelerating the process of drug development and repurposing. This review aims to present the evolution, benefits and drawbacks including current approaches, key players and the legal and regulatory hurdles in the field of drug repurposing. The vast quantities of available data secured in multiple drug databases, assisting in drug repurposing is also discussed.

Molecular Simulation Techniques as Applied to Silica and Carbon-Based Adsorbents for Carbon Capture

There has been ongoing interest in research to mitigate climate change through carbon capture (CC) by adsorption. This guideline is meant to introduce computational chemistry techniques in CC by applying them to mesoporous structures and disordered morphologies. The molecular simulation techniques presented here use examples of literature studies on silica and carbon-based adsorbents. An initial summary of molecular simulation techniques and concepts is first presented. This is followed by a section on molecular simulation applications in mesoporous amorphous silica, both functionalized and not. Novel strategies to validate and output useful results are discussed, specifically when modelling chemisorption. The use of computational chemistry to build upon experimental results is reviewed, and a similar summation is presented for carbon-based adsorbents. The final section provides a short review of computational chemistry methods in novel applications and highlights potential complications. Computational chemistry techniques provide a streamlined method of gathering data across a range of conditions. Alongside experimental studies, these techniques can provide valuable information on underlying molecular mechanisms. This paper aims to be a starting point for navigating these numerical methods by providing an initial understanding of how these techniques can be applied to carbon capture while clarifying the current and inherent limitations present.

Dual Emission, Aggregation, and Redox Properties of Boron Difluoride Hydrazones Functionalized with Triphenylamines

Abstractπ‐Conjugated molecular materials often exhibit interesting photoluminescence, redox, and optoelectronic properties that grant them utility as light‐harvesting materials in solar cells, as the emissive component of organic light‐emitting diodes, and as fluorescence sensors. Preparing dye conjugates by appending multiple dyes together to generate π‐conjugated molecules is a common strategy to enhance the properties of these materials as it often imparts traits that cannot be achieved by the building blocks independently. Herein, we report molecular materials that incorporate boron difluoride hydrazone (BODIHY) and triphenylamine (TPA) units that exhibit charge‐transfer character, dual‐emission, and aggregation‐induced emission. The title compounds have low‐energy absorption bands (λabs=455–493 nm) that are red‐shifted relative to BODIHYs with smaller π‐systems and exhibit dual‐emission in the solution, solid, and aggregate states. TPA–BODIHY (donor‐acceptor) conjugates show multiple reversible redox events and, in combination, the data presented herein indicate that there is electronic communication throughout the donor‐acceptor and acceptor‐donor‐acceptor π‐systems. These results are rationalized with the use of computational chemistry and solid‐state structural analysis. This study provides new opportunities for the design of molecular materials that are comprised of redox‐active photoluminescent dyes, including BODIHY, and their potential applications.

Theoretical Insights into Volcano Correlations of the Oxygen Reduction Reaction with MN4 Catalysts

The design of metal complex catalysts for the oxygen reduction reaction (ORR) [1] can be assisted with the use of computational chemistry and Quantum Mechanics (QM) methods. In this work, we have implemented theoretical models and have used the computational chemistry for the rational design of MN4 catalysts with optimal catalytic efficiency for ORR. The application of ab initio and DFT-based methodologies were employed to assess binding energies on the interaction of O2 and the metal center of MN4 systems. [2] The energetic assessment on reactive paths has proved to be affected, in organic systems, by dynamical effects and strongly influenced by the electronic structure of substituents [3,4]. Hence, the electrocatalytic performance of porphyrins and phthalocyanines were assessed by the analysis of volcano correlations against computed binding energies. In these plots, substitution patterns on the catalysts include both in-plane and axial ligands. Besides the binding energies, other descriptors were assessed as well (e.g., the DFT-based hardness). The systematic study of volcano plots provided a deeply understanding on the the pivotal role of the ligands and the nature of electronic effects underlying the Sabatier principle for the electrocatalysis of the ORR by MN4 molecular systems. Acknowledgements The authors want to acknowledge the funding of Anillo Project ACT 192175 References [1] A. Kulkarni, S. Siahrostami, A. Patel, J. K. Nørskov, Chem. Rev. 2018, 118, 2302.[2] J.H. Zagal, M.T.M. Koper, Angew. Chem. Int. Ed. 201 6, 5 5, 14510.[3] R.A. Matute and K.N. Houk, Angew. Chem. Int. Ed., 2012, 51, 13097.[4] D.E. Ortega, R.A. Matute, J. Phys. Chem. A 2020, 124, 3573.

Computational approach for predicting the adsorption properties and inhibition of some antiretroviral drugs on copper corrosion in HNO3

The use of computational chemistry as an effective means of designing eco-friendly organic corrosion inhibitors has been greatly enhanced by the development of Density Functional Theory (DFT). In this study, the inhibitory activity of four antiretroviral drugs, namely, lamivudine, emtricitabine, didanosine and stavudine, was analyzed by this theory. The quantum chemical parameters/descriptors calculated using DFT at B3LYP/6-31G(d) level were used to explain the mechanism of electron transfer between the inhibitors and the copper surface. The results showed that these compounds adsorb on copper surface. It is important to consider the effect of films formed by the adsorption products. In addition, the Fukui functions and the dual descriptor were used as indicators to locate the electrophilic and nucleophilic attack sites within each compound. Finally, the DFT has enabled to accurately predict the adsorption properties and the good inhibition performance of the molecules in the solution studied.

Thermochemical Properties: Enthalpy, Entropy, and Heat Capacity of C2-C3 Fluorinated Aldehydes. Radicals and Fluorocarbon Group Additivity.

Thermochemical properties of fluorinated aldehydes are important for understanding their stability and reactions in the environment and in thermal processes. Structures and thermochemical properties of C1 to C3 fluorinated aldehydes are determined by use of computational chemistry. Standard enthalpies of formation for 30 C2- and C3-fluorinated aldehydes and 31 radicals were calculated with 11 different ab initio and density functional theory methods: CBS-APNO, CBS-4M, CBS-QB3, M06-2X, ωB97X, B3LYP, G-2, G-3, G-4, and W1U via several series of isodesmic reactions. Entropy, S°298, and heat capacities, C p( T)'s (300 ≤ T/K ≤ 1500) from vibration, translation, and external rotation contributions are calculated on the basis of the vibration frequencies and structures obtained from the B3LYP/6-31++G(d,p) density functional method. Potential barriers for the internal rotations are also from this method and used to calculate hindered rotor contributions to S°298 and Cp(T)'s using direct integration over energy levels of the internal rotational potential curves. Literature data on standard enthalpies of formation of fluorinated aldehydes are compared. Thermochemical properties for the fluorinated carbon groups CO/C/F, C/CO/F3, C/CO/F/H2, C/C/CO/F/H, C/C/CO/F2, and C/C/CO/F/H are developed. Non-next nearest neighbor terms for the strong interactions resulting from fluorine atoms on adjacent and on second nearest carbon atoms are unfortunately, needed. The required non-next-neighbor interactions significantly reduce the practical application of group additivity for thermochemical properties of highly fluorinated halocarbons.

A Critical Overview on the Effect of Microwave Irradiation in Organic Synthesis.

Despite the great success of Microwave Assisted Organic Synthesis (MAOS) there is still a lack of knowledge about the interaction of the electromagnetic radiation with matter. In consequence, it has been very difficult to rationalize the effect of microwave irradiation in chemistry, to determine the existence of microwave effects (thermal and non-thermal) and to develop predictive models on the characteristics required for a reaction to be improved under microwaves. This has been a handicap to develop new chemistry under microwave irradiation and the origin of many controversies. This personal account collects some new findings in this field and our work on the use of computational chemistry to develop predictive models and to determine parameters related to thermal and non-thermal effects, with clear advantages over experimental methods where separation of these effect is almost impossible.

In Silico Study and Bioprospection of the Antibacterial and Antioxidant Effects of Flavone and Its Hydroxylated Derivatives.

Flavonoid compounds are widely used as natural protective species, which can act as anti-inflammatory, antioxidant, anticoagulant, antihypertensive and antitumor agents. This study set out to investigate the probable pharmacological activities, along with the antibacterial and antioxidant effects, of flavone and its hydroxy derivatives: 3-hydroxyflavone, 5-hydroxyflavone and 6-hydroxyflavone. To do so, we investigated their pharmacological characteristics, using in silico tests that indicate likelihood of activity or inactivity, with the PASS online software, and the antimicrobial potential against Gram positive and Gram negative bacteria was also analyzed, including bacteria of clinical importance. We also tested for oxidant and antioxidant potential in these molecules in the presence of reactive oxygen species (ROS) and phenylhydrazine (Ph). The results revealed the following characteristics: pharmacological activities for the flavonoids as agonists of cell membrane integrity and as permeability inhibitors, as antagonists of anaphylatoxin receptors, as inhibitors of both kinase and peroxidase, and as having both antimutagenic capacity and vaso-protective potential. All of the flavonoids exhibited moderate antibacterial activity against Gram positive and Gram negative strains, with the flavones being bactericidal at 200 μg/mL for the strains of P. aeruginosa ATCC 8027, S. aureus ATCC 25619 and E. coli 104; the other flavonoids revealed bacteriostatic action. The substances did not promote erythrocyte oxidation and behaved as sequestrators and antioxidants of hydrogen peroxide (H2O2) and phenylhydrazine (Ph). It was concluded that the analyzed compounds have various pharmacological activities in accordance with the predictions of PASS online, as their antibacterial and antioxidant activities were confirmed. The study also helps to consolidate the use of computational chemistry in silico tools to guide new drug search and discovery protocols.

Computational Drug Design and Molecular Dynamic Studies-A Review

Drug designing and molecular dynamic studies were an intense, lengthy and an inter-disciplinary venture. At present, a new approach towards the use of computational chemistry and molecular modeling for in-silico drug design. Computational in-silico drug design skills are used in bioinformatics, computational biology and molecular biology. Drug designing using in-silico methods is cost effective in research and development of drugs. Currently, a vast number of software’s used in drug design. In-silico drug designing and molecular dynamic studies can be performed by using different methods namely homology modeling, molecular dynamic studies, energy minimization, docking and QSAR etc. By using in-silico drug designing we can produce an active lead molecule from the preclinical discovery stage to late stage clinical development. The lead molecules which are developed will help us in selection of only potent leads to cure particular diseases. Therefore in-silico methods have been of great importance in target identification and in prediction of novel drugs.

ChemInform Abstract: The Rise of Organic Electrode Materials for Energy Storage

AbstractReview: 198 refs.

More rabbits from fewer hats

BASF used to be the company that—with a flourish—would announce record R&D spending every year. It is still the only chemical firm in the world to have an R&D bill of more than $2 billion, but BASF is now looking to squeeze more innovation out of the same amount of money—or even less. “The company needs to adapt its established approaches to changing conditions,” Martin Brudermüller, BASF’s board member responsible for technology, told journalists at a briefing in Ludwigshafen, Germany. “Our research commitment will not increase at the same rate as before, but our commitment to R&D will not go down.” One of the ways BASF intends to generate more without increasing spending is by conducting R&D faster. The firm plans to achieve this by, among other things, working more closely with academia and doing away with some lab experiments by first predicting outcomes with the use of computational chemistry.

Integration of Computational Chemistry into the Undergraduate Organic Chemistry Laboratory Curriculum

Advances in software and hardware have promoted the use of computational chemistry in all branches of chemical research to probe important chemical concepts and to support experimentation. Consequently, it has become imperative that students in the modern undergraduate curriculum become adept at performing simple calculations using computational software, interpreting computational data, and applying computational data to explain chemical phenomena. We utilize computational chemistry in a high-enrollment (>1200 students/year), undergraduate organic chemistry laboratory course in a manner similar to that of organic chemistry researchers. We have employed WebMO as a web-based, easy-to-use, and free front-end interface for Gaussian09 that allows our students to complete ab initio and density functional theory (DFT) calculations throughout the curriculum. Rather than an isolated exposure to computational chemistry, our students use computational chemistry to obtain a deeper understanding of their experimental...

Cyclopentadienone Oxidation Reaction Kinetics and Thermochemistry for the Alcohols, Hydroperoxides, and Vinylic, Alkoxy, and Alkylperoxy Radicals.

Cyclopentadienone has one carbonyl and two olefin groups resulting in 4n + 2 π-electrons in a cyclic five-membered ring structure. Thermochemical and kinetic parameters for the initial reactions of cyclopentadienone radicals with O2 and the thermochemical properties for cyclopentadienone-hydroperoxides, alcohols, and alkenyl, alkoxy, and peroxy radicals were determined by use of computational chemistry. The CBS-QB3 composite and B3LYP density functional theory methods were used to determine the enthalpies of formation (ΔfH°298) using the isodesmic reaction schemes with several work reactions for each species. Entropy and heat capacity, S°(T) and Cp°(T) (50 K ≤ T ≤ 5000 K) are determined using geometric parameters, internal rotor potentials, and frequencies from B3LYP/6-31G(d,p) calculations. Standard enthalpies of formation are reported for parent molecules as cyclopentadienone, cyclopentadienone with alcohol, hydroperoxide substituents, and the cyclopentadienone-yl vinylic, alkoxy, and peroxy radicals corresponding to loss of a hydrogen atom from the carbon and oxygen sites. Entropy and heat capacity vs temperature also are reported for the parent molecules and for radicals. The thermochemical analysis shows The R(•) + O2 well depths are deep, on the order of 50 kcal mol(-1), and the R(•) + O2 reactions to RO + O (chain branching products) for cyclopentadienone-2-yl and cyclopentadienone-3-yl have unusually low reaction (ΔHrxn) enthalpies, some 20 or so kcal/mol below the entrance channels. Chemical activation kinetics using quantum RRK analysis for k(E) and master equation for falloff are used to show that significant chain branching as a function of temperature and pressure can occur when these vinylic radicals are formed.

Emerging carbon-based nanosensor devices: structures, functions and applications

Bionanosensors and nanosensors have been devised in recent years with the use of various materials including carbon-based nanomaterials, for applications in diagnostics, environmental science and microelectronics. Carbon-based materials are critical for sensing applications, as they have physical and electronic properties which facilitate the detection of substances in solutions, gaseous compounds and pollutants through their conductive properties and resonance-frequency transmission capacities. In this review, a series of recent studies of carbon nanotubes (CNTs) based nanosensors and optical systems are reported, with emphasis on biochemical, chemical and environmental detection. This study also encompasses a background and description of the various properties of the nanomaterials, and the operation mechanism of the manufactured nanosensors. The use of computational chemistry is applied in describing the electronic properties and molecular events of the included nanomaterials during operation. This review shows that resonance-based sensing technologies reach detection limits for gases, such as ammonia down to 10−24 level. The study also shows that the properties of the carbon nanomaterials give them unique features that are critical for designing new sensors based on electrocatalysis and other reactive detection mechanisms. Several research fields can benefit from the described emerging technologies, such as areas of research in environmental monitoring, rapid-on site diagnostics, in situ analyses, and blood and urine sampling in medical and sport industry. Carbon nanomaterials are critical for the operational sensitivity of nanosensors. Considering the low cost of fabrication, carbon nanomaterials can represent an essential step in the manufacturing of tomorrow’s commercial sensors.

Molecule VI: Sulfonimide or Sulfonamide?

The tautomerism of molecule VI, a benchmark system for crystal structure predictions, has been investigated by the use of computational chemistry. Ab initio and density functional calculations including dispersion corrections show that monomers of molecule VI strongly (11 kcal mol–1) prefer to exist as sulfonamide tautomer, while remarkably the equilibrium is shifted toward sulfonimide tautomers in larger aggregates due to formation of stronger hydrogen bonds for the imide tautomer.

A concise review of computational studies of the carbon dioxide–epoxide copolymerization reactions

The production of polycarbonates from carbon dioxide and epoxides is an important route by which waste CO2 is converted into useful products. This review surveys the use of computational chemistry toward understanding this reaction.

Photochemical Steps in the Prebiotic Synthesis of Purine Precursors from HCN

cis-2,3-diaminomaleonitrile (cis-DAMN, 1), which may be converted photochemically into an imidazole intermediate (4amino-1H-imidazole-5-carbonitrile, AICN, 2). Although this reaction has been investigated in detail since its discovery by Ferris and Orgel in 1966, the mechanism of the photochemical steps remains unresolved. Herein, we address this issue from a theoretical perspective: by the use of computational chemistry and chemical kinetics we show that among a number of possibilities, including all those previously proposed, there is only one sequence of steps that is thermodynamically and kinetically compatible with the experimental conditions. One of the most appealing features of the DAMN! AICN reaction is its robustness. It was observed in a large variety of solvents (polar and nonpolar), with several enaminonitrile derivatives, and at diverse concentrations and temperatures. The imidazole derivative 2 is photostable (5% reduction in absorbance after irradiation at 254 nm for 3 h; see also Ref. [7] on imidazole photostability) and resistant to hydrolysis (lifetime: 2000 years at pH 8). These characteristics imply that different prebiotic environments, either terrestrial or extraterrestrial, could have been the source of AICN (2) in the prebiotic world. The accumulation of AICN, however, requires relatively large HCN concentrations (> 10 m). This requirement sets a first relevant environmental constraint: such high HCN concentrations are only possible in low-temperature environments, such as ice and eutectic water–HCN phases. Therefore, any realistic mechanism cannot count on high thermal energy in addition to the photon energy. The number of photons and intermediates involved in the photochemical steps is unknown (Scheme 2). The process

Thermochemical Properties for Isooctane and Carbon Radicals: Computational Study

Thermochemical properties for isooctane, its internal rotation conformers, and radicals with corresponding bond energies are determined by use of computational chemistry. Enthalpies of formation are determined using isodesmic reactions with B3LYP density function theory and composite CBS-QB3 methods. Application of group additivity with comparison to calculated values is illustrated. Entropy and heat capacities are determined using geometric parameters, internal rotor potentials, and frequencies from B3LYP/6-31G(d,p) calculations for the lowest energy conformer. Internal rotor potentials are determined for the isooctane parent and for the primary, secondary, and tertiary radicals in order to identify isomer energies. Intramolecular interactions are shown to have a significant effect on the enthalpy of formation of the isooctane parent and its radicals. The computed standard enthalpy of formation for the lowest energy conformers of isooctane from this study is -54.40 ± 1.60 kcal mol(-1), which is 0.8 kcal mol(-1) lower than the evaluated experimental value -53.54 ± 0.36 kcal mol(-1). The standard enthalpy of formation for the primary radical for a methyl on the quaternary carbon is -5.00 ± 1.69 kcal mol(-1), for the primary radical on the tertiary carbon is -5.18 ± 1.69 kcal mol(-1), for the secondary isooctane radical is -9.03 ± 1.84 kcal mol(-1), and for the tertiary isooctane radical is -12.30 ± 2.02 kcal mol(-1). Bond energy values for the isooctane radicals are 100.64 ± 1.73, 100.46 ± 1.73, 96.41 ± 1.88 and 93.14 ± 2.05 kcal mol(-1) for C3•CCCC2, C3CCCC2•, C3CC•CC2, and C3CCC•C2, respectively. Entropy and heat capacity values are reported for the lowest energy homologues.

Stability and bonding in the borane–H2complexes

AbstractThe ability of substituted boranes, XnBH3−n, to form stable complexes with the hydrogen molecule is analyzed by making use of computational chemistry and local reactivity parameters. In these complexes, the hydrogen molecule acts as a Lewis base while the borane moiety is the Lewis acid. Electronegative groups (X = CF3, F, OH) are selected to increase the acidity of the borane and it is found that the energetic stability of the complexes is only increased for the trifluoromethyl‐substituted Lewis acids, at the MP2/6‐311++g(3df, 3pd) level. It is also found that the BLYP density functional underestimates the adduct stability of these species. On the other hand, fluoroboranes and hydroxyboranes do not form donor–acceptor adducts with the hydrogen molecule; instead, we find weakly bounded van der Waals complexes. Additional features on the intrinsic reactivity of boranes are analyzed with the molecular electrostatic potential and the acceptor Fukui function. The nature of the interaction among the boranes and the hydrogen molecule is explored by using the topological analysis of the electron density through the Bader's Atoms‐in‐Molecules theory. © 2012 Wiley Periodicals, Inc.

ChemInform Abstract: Heterocyclization of Allenes Catalyzed by Late Transition Metals: Mechanisms and Regioselectivity

AbstractReview: 87 refs.