Computational Chemistry Methods Research Articles

Theoretical insights into the transformation mechanism and eco-toxicity effects of 5-Fluorouracil by O3 and ·OH in waters

The existences of non-biodegradable 5-Fluorouracil (5-FU) in aquatic systems and its potential toxic effects on aquatic organisms have caused widespread concern. In this work, two typical oxidants (O3 and ·OH) were selected to investigate the mechanism, kinetics, and the potential eco-toxicology assessment of 5-FU using computational chemistry methods. Results show that 5-FU can be degraded rapidly by O3 and ·OH, which subsequently undergoes ring-opening, decomposition, defluorination, and hydroxylation steps. The rate constants of initiation reactions are suppressed as the temperature increases. The half-lives of 5-FU determined by O3 and ·OH are on the order of seconds in the advanced oxidation processes (AOPs) system. Fifteen structures of transformation products were identified by theoretical calculation, including five experimental products. The toxicity assessment results show that the acute and chronic toxicities of the degradation process to aquatic organisms gradually decreased, but the developmental toxicity and mutagenicity of several products on human still exist. In addition, the main products have been found to decompose into some small molecules (NO, Formic acid, Acetic acid, etc.). This result could help to reveal the transformation behaviors and risk assessment of 5-FU in aquatic environments, and further design the experimental and industrial infrastructure.

Boron‐Rich Boron Nitride Nanotubes as Highly Selective Adsorbents for Selected Diatomic Air Pollutants: A DFT Study

AbstractBoron‐rich boron nitride nanotubes (BN‐BNNTs), which have boron antisite defects (BN), adsorb gas molecules more favorably as compared to their pristine counterparts because of the localized states of antisites. Using computational chemistry methods, the structural, adsorptive, and electronic properties of selected diatomic air pollutants (CO, NO, and SO) on BN‐BNNT (8,0), with a particular focus on the antisites, are investigated. It is found that CO adsorbs on BN with 180° angle (∠BNCO) while NO and SO adsorb with 142° angle (∠BNNO) and 116° angle (∠BNSO), respectively. This difference is ascribed to the repulsive interaction originated from lone pair electrons on N and S. Adsorption energy of CO, NO, and SO molecules dominates over that of O2 and N2 and is independent of their radii of BN‐BNNTs. The practical capacity of these pollutant molecules is calculated to be ≈5 mmol g–1 (14 wt%) under ambient conditions. Therefore, our results show that BN‐BNNT can be used as a highly selective adsorbent for diatomic air pollutants. BN‐BNNT as sensing materials in terms of change in bandgap and work function through the adsorption is also discussed.

Geometric Analysis of Shapes in Ion Mobility-Mass Spectrometry.

Experimental ion mobility-mass spectrometry (IM-MS) results are often correlated to three-dimensional structures based on theoretical chemistry calculations. The bottleneck of this approach is the need for accurate values, both experimentally and theoretically predicted. Here, we continue the development of the trend-based analyses to extract structural information from experimental IM-MS data sets. The experimental collision cross-sections (CCSs) of synthetic systems such as homopolymers and small ionic clusters are investigated in terms of CCS trends as a function of the number of repetitive units (e.g., degree of polymerization (DP) for homopolymers) and for each detected charge state. Then, we computed the projected areas of expanding but perfectly defined geometric objects using an in-house software called MoShade. The shapes were modeled using computer-aided design software where we considered only geometric factors: no atoms, mass, chemical potentials, or interactions were taken into consideration to make the method orthogonal to classical methods for 3D shape assessments using time-consuming computational chemistry. Our modeled shape evolutions favorably compared to experimentally obtained CCS trends, meaning that the apparent volume or envelope of homogeneously distributed mass effectively modeled the ion-drift gas interactions as sampled by IM-MS. The CCSs of convex shapes could be directly related to their surface area. More importantly, this relationship seems to hold even for moderately concave shapes, such as those obtained by geometry-optimized structures of ions from conventional computational chemistry methods. Theoretical sets of expanding beads-on-a-string shapes allowed extracting accurate bead and string dimensions for two homopolymers, without modeling any chemical interactions.

Studying the inhibition mechanism of human acetyl-CoA carboxylase by aromatic ligands in the treatment of fatty acid metabolic syndrome using computational chemistry methods

Background: Metabolic syndrome is a consequence of excess fatty acid accumulation in the human body, causing metabolic disorders related to the role of the two acetyl-CoA carboxylase (ACC) isoforms, ACC1 and ACC2. Inheriting the results from our previous research about "the effective model of human acetyl-CoA carboxylase inhibition by aromatic-structure inhibitors", this research explains the inhibition mechanism of the enzyme by studying the interaction direction, preferential binding sites of aromatic ligands on the isoforms and conformational changes of enzyme-ligand complexes in the body’s environmental conditions (temperature 37 degrees Celsius and water solvent). Methods: This research applies hard docking combined with molecular dynamics and virtual screening of 14 inhibitory ligand groups, which have 50% enzyme inhibitor (IC50) values determined by experiments, including bipiperidylcarboxamide derivatives, polyketides, aryloxyphenoxypropionate, cyclohexanedione, synthetic acyl-CoA fatty acid chains, acylsulfonamide derivatives, Taisho inhibitors, Sanofi-Aventis inhibitors, AstraZeneca inhibitors, Takeda inhibitors, Pfizer inhibitors, Nimbus inhibitors, Amgen inhibitors and Boehringer Ingel-heim inhibitors. The geometric structures of the ligands are modeled and optimized by quantum mechanical methods, including PM3 for ACC1 and DFT at the B3LYP/6-31G(d,p) level for ACC2 based on our previous research about the QSAR enzyme-inhibition models, using Gaussian 09 W software. Results: Binding energy values at the identified preferential binding sites of aromatic ligands are closely correlated with the experimental log(IC50), which has statistical significance (p < 0.05): R2ACC1 = 96.3% and R2ACC2 = 78.9%. Those sites reveal the five reaction niches on ACC1, involving the two preferential binding regions in the order of amino acids 152 to 643 and 1632 to 2100, and the four reaction niches on ACC2, involving the two preferential binding regions in the order of amino acids 270 to 704 and 1831 to 2299. The molecular dynamic simulation of enzyme-ligand complexes in the body’s environmental conditions confirms that if ligands have fewer stereogenic interactions and are ready to form four types of bonds, including hydrogen, pi-alkyl, pi-cation and alkyl-alkyl bonds, their inhibitory activity will be higher. Conclusion: The research clarifies the inhibition mechanism of the enzyme in which ligands prefer to interact with amino acids 152 to 643 and 270 to 704 on the biotin carboxylase domain of ACC and amino acids 1632 to 2100 and 1831 to 2299 on the carboxyl transferase domain of ACC. In addition, the fewer stereogenic interactions of ligands and the easier it is to form four types of bonds, including hydrogen, pi-alkyl, pi-cation and alkyl-alkyl bonds, the higher their inhibitory activity.

Behavior Estimation Focusing on the Existing Form of Hydrogen in Sodium in Sodium-Cooled Fast Reactors

In the cooling system of sodium-cooled fast reactors, it is required to identify and rapidly detect hydrogen explosively produced by the sodium-water reaction when a water leak occurs due to damage of a heat exchanger tube in a steam generator (SG), in contrast to low-concentration background hydrogen permeating through SG tubes during normal operation. In the present study, we focus on the difference between the background hydrogen and the hydrogen generated by the sodium-water reaction, and theoretically estimate the hydrogen behavior in liquid sodium by using computational chemistry methods. We find that dissolved H or NaH, rather than H2, is the predominant form of the background hydrogen in liquid sodium, and that hydrogen produced in large amounts by the sodium-water reaction can exist stably as fine bubbles with a NaH layer on their surface.

2-(2- İyodofenil)isoindolin-1,3-dion) Molekülünün Hesaplamalı Kimya Yöntemiyle Yapısal Analizi

The aim of this study includes the re-examination of the molecule of 2-(2-iodophenyl)isoindolin-1,3-dione, C14H8INO2 [1], whose structure solution was carried out by x-ray diffraction, by computational chemistry method. Theoretical calculations of the molecule were made using Density Functional Theory (DFT) and Lee-Yang-Par, the B3LYP method, which is a 3-parameter Becke mixed model with correlation energy, and the 6-311++G(d,p) fundamental basis set. The boundary orbitals of the molecule and their derived parameters, Mulliken and Natural Charge Analysis (NPA), Molecular Electrostatic Potential (MEP) maps were determined. In addition, the electrophilic and nucleophilic regions of the molecule were determined by performing Hirsfeld Surface analysis of the molecule.

QSAR Analysis of the Effect of Metal Ions on the Peptidase Bacillus thuringiensis var. israelensis IMV B-7465 Activity

Background. The catalytic activity of enzymes, which is their most important characteristic, can change significantly under the influence of effectors, for example, metal ions, and is the subject of special studies that are important for biochemistry, biotechnology, medicine, and other branches of science. Usually, the activity of enzymes in the presence of metals is assessed by the change in the rate of the enzymatic reaction. However, conducting such experimental studies, especially for new enzymes, as in the case of peptidase Bacillus thuringiensis var. israelensis IMV B-7465, requires significant resources and extensive kinetic studies. Therefore, it is advisable to use the methods of computational chemistry, the basic task of which is to search for the structure–property relationship, to build a model that can assess the effect of metal ions on peptidase activity with a high degree of probability. Objective. We are aimed to develop QSAR models for analysis and prediction of the effect of metal ions on the activity of peptidase Bacillus thuringiensis var. israelensis IMV B-7465. Methods. The effect of metal ions was studied by determining the proteolytic activity of peptidase after co-incubation for 30 min in 0.0167 M Tris-HCl buffer solution (pH 7.5, 37 °C). The final concentration of metal chlorides Li+; Na+; K+; Cs+; Cu2+; Be2+; Mg2+; Ca2+; Sr2+; Ba2+; Zn2+; Cd2+; Hg2+; Cr3+; Mn2+; Co2+; Ni2+ in the buffer solution was 4 mmol/dm3. To search for the quantitative structure–property relationship, we used the reference data on the properties of metal ions, as well as trend vector and random forest methods. Results. A study of the effect of metal ions on the proteolytic activity of peptidase Bacillus thuringiensis var. israelensis IMV B-7465 showed that some metal ions (Li+, Mn2+ и Co2+) activated peptidase, while others (Cu2+, Be2+, Cd2+, Hg2+, Cr3) inhibited the enzyme activity. Adequate statistical models without classification errors and activity class prediction errors for the test set were constructed by nonlinear trend vector and random forest methods. Both models show that the most important characteristics of metal ions affecting enzyme activity are electronegativity (ENPol), the first ionization potential (IP1), the entropy of ions in aqueous solution (S), and the electron affinity energy (Eae). Conclusions. QSAR analysis methods in combination with nonlinear trend vector and random forest methods allow adequately describing the effect of metal ions on the peptidase Bacillus thuringiensis var. israelensis IMV B-7465 activity due to descriptors reflecting a certain balance of their electron-donating and electron-accepting properties (electronegativity, the first ionization potential, the electron affinity energy) and thermodynamic properties in aqueous solution (entropy of solvation). Both statistical methods give similar values of the importance of descriptors, but only the trend vector method allows us to analyze the direction of influence of specific characteristics of ions.

Hapten Synthesis and Monoclonal Antibody Preparation for Simultaneous Detection of Albendazole and Its Metabolites in Animal-Origin Food.

Albendazole (ABZ) is one of the benzimidazole anthelmintics, and the overuse of ABZ in breeding industry can lead to drug resistance and a variety of toxic effects in humans. Since the residue markers of ABZ are the sum of ABZ and three metabolites (collectively referred to as ABZs), albendazole-sulfone (ABZSO2), albendazole-sulfoxide (ABZSO), and albendazole-2-amino-sulfone (ABZNH2SO2), an antibody able to simultaneously recognize ABZs with high affinity is in urgent need to develop immunoassay for screening purpose. In this work, an unreported hapten, 5-(propylthio)-1H-benzo[d]imidazol-2-amine, was designed and synthesized, which maximally exposed the characteristic sulfanyl group of ABZ to the animal immune system to induce expected antibody. One monoclonal antibody (Mab) that can simultaneously detect ABZs was obtained with IC50 values of 0.20, 0.26, 0.77, and 10.5 μg/L for ABZ, ABZSO2, ABZSO, and ABZNH2SO2 in ic-ELISA under optimized conditions respectively, which has been never achieved in previous reports. For insight into the recognition profiles of the Mab, we used computational chemistry method to parameterize cross-reactive molecules in aspects of conformation, electrostatic fields, and hydrophobicity, revealing that the hydrophobicity and conformation of characteristic group of molecules might be the key factors that together influence antibody recognition with analytes. Furthermore, the practicability of the developed ic-ELISA was verified by detecting ABZs in spiked milk, beef, and liver samples with recoveries of 60% to 108.8% and coefficient of variation (CV) of 1.0% to 15.9%.

Thermodynamics of the Isomerization of Monoterpene Epoxides.

In this contribution, the thermodynamic analysis of α- and β-pinene epoxide isomerization over Fe and Cu supported on MCM-41 is presented using computational chemistry and group contribution methods (GCMs). Some physical–chemical data (Tc, Pc, vc, Zc, ω, Tb, Tfus) and thermodynamic (S°298.15, Cp,298.15°, Cv,298.15°, ΔHf,298.15°, ΔGf,298.15°, ΔHvb°, ΔHfus, CpL) properties obtained by different GCMs are reported for several monoterpenes and monoterpenoids, which significantly contribute to the knowledge of the properties of these compounds. Density functional theory (DFT), PBE-D3/6-311G(d,p), was employed for determining the Gibbs free energy and the heat of reaction associated with the transformation of monoterpene epoxides into aldehydes, ketones, and related oxygenated compounds in the presence of different solvents and at several temperatures. The calculations were compared with available data reported and the experimental results of the catalytic reactions. The transformation of α- and β-pinene epoxides into aldehydes appears to be more spontaneous and favorable than their transformations into alcohols in a wide range of temperatures. These results are in agreement with the experiments over Fe/MCM-41 and Cu/MCM-41, where α-pinene epoxide isomerization yields campholenic aldehyde (50–80% selectivity) as the main product. The 1.7Fe/MCM-41 material was more active in all solvents than 1.3Cu/MCM-41 for both α- and β-pinene epoxide isomerization. However, perillyl alcohol (20–70% selectivity) was the most favored for the isomerization reaction, except when ethyl acetate was the solvent. Enthalpy and Gibbs free energy of the studied reactions estimated by both GCMs and DFT calculations did not show large differences for most of the reactions at evaluated temperatures.

BSE49, a diverse, high-quality benchmark dataset of separation energies of chemical bonds

We present an extensive and diverse dataset of bond separation energies associated with the homolytic cleavage of covalently bonded molecules (A-B) into their corresponding radical fragments (A. and B.). Our dataset contains two different classifications of model structures referred to as “Existing” (molecules with associated experimental data) and “Hypothetical” (molecules with no associated experimental data). In total, the dataset consists of 4502 datapoints (1969 datapoints from the Existing and 2533 datapoints from the Hypothetical classes). The dataset covers 49 unique X-Y type single bonds (except H-H, H-F, and H-Cl), where X and Y are H, B, C, N, O, F, Si, P, S, and Cl atoms. All the reference data was calculated at the (RO)CBS-QB3 level of theory. The reference bond separation energies are non-relativistic ground-state energy differences and contain no zero-point energy corrections. This new dataset of bond separation energies (BSE49) is presented as a high-quality reference dataset for assessing and developing computational chemistry methods.

Enzymatic Synthesis of 3'-5', 3'-5' Cyclic Dinucleotides, Their Binding Properties to the Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations.

The 3'-5', 3'-5' cyclic dinucleotides (3'3'CDNs) are bacterial second messengers that can also bind to the stimulator of interferon genes (STING) adaptor protein in vertebrates and activate the host innate immunity. Here, we profiled the substrate specificity of four bacterial dinucleotide synthases from Vibrio cholerae (DncV), Bacillus thuringiensis (btDisA), Escherichia coli (dgcZ), and Thermotoga maritima (tDGC) using a library of 33 nucleoside-5'-triphosphate analogues and then employed these enzymes to synthesize 24 3'3'CDNs. The STING affinity of CDNs was evaluated in cell-based and biochemical assays, and their ability to induce cytokines was determined by employing human peripheral blood mononuclear cells. Interestingly, the prepared heterodimeric 3'3'CDNs bound to the STING much better than their homodimeric counterparts and showed similar or better potency than bacterial 3'3'CDNs. We also rationalized the experimental findings by in-depth STING-CDN structure-activity correlations by dissecting computed interaction free energies into a set of well-defined and intuitive terms. To this aim, we employed state-of-the-art methods of computational chemistry, such as quantum mechanics/molecular mechanics (QM/MM) calculations, and complemented the computed results with the {STING:3'3'c-di-ara-AMP} X-ray crystallographic structure. QM/MM identified three outliers (mostly homodimers) for which we have no clear explanation of their impaired binding with respect to their heterodimeric counterparts, whereas the R2 = 0.7 correlation between the computed ΔG'int_rel and experimental ΔTm's for the remaining ligands has been very encouraging.

Current frontiers in quantum chemical simulations of NIR spectra – Polymers, biomolecules, aqueous matrix and interpretation of instrumental difference of handheld spectrometers

Analytical near-infrared (NIR) spectroscopy has developed rapidly over the past few decades and is today of incredible value for academic, industrial and institutional laboratories. These developments are closely related to the development of instruments and miniaturization, as well as the methods of multivariate analysis. The strong stimulus for the development of NIR spectroscopy originating from the application field resulted in the advancement of this technique to suite unitarian goals. By contrast, less actively explored have been the foundations of NIR spectroscopy. Much of the information contained in the NIR spectrum is still not easily accessible for the purpose of basic research. In the past few years, a promising development has been made in application of the methods of computational chemistry to NIR spectroscopy. In this article, the current frontier of this advancement is summarized. The scope of the recent accomplishments shifts closer to the challenging real-life problems, such as interactions of the analysed molecules with the matrix, including the aqueous environment. Particular attention was given to the interpretation of the chemical factors underlying instrumental differences between miniaturized NIR spectrometers using different technology and optical solutions. The applicability of the methods of computational chemistry to unravel intricate NIR spectral features of complex molecules such as biomolecules and polymers should be highlighted as well.

Experimental diffusivity of energetic compounds determined by peak parking

Diffusivities of several explosive compounds, as well as other complex organic compounds were experimentally derived using a peak parking methodology. High performance liquid chromatography (HPLC) with stop flow ‘parking’ was used to experimentally determine diffusivity based on band broadening associated with chemical diffusion within the HPLC column. This research builds on prior methods by determining an obstruction factor through comparing benzene diffusion in methanol in a C18 column to the previously published capillary column. The method is useful for structures not easily described by computational chemistry methods or for solvents that do not have association coefficients in published diffusivity models. Using the peak parking method, diffusivities (cm2/s) ranged from 6.29 × 10-7 to 1.06 × 10-6 for hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 4.82 × 10-5 to 1.26 × 10-4 for 3-nitro-1,2,4-triazol-5-one (NTO), 1.63 × 10-5 to 7.20 × 10-6 for nitroguanidine (NQ), 7.07 × 10-6 to 2.09 × 10-5 for pyrimidine-2-carboxylic acid, and 1.02 × 10-6 to 2.27 × 10-6 for streptomycin. Compared to diffusivities estimated computationally, the empirical diffusivities reported herein estimated by two different methods have percent differences averaging 142%, 174%, 27%, 85%, and 33% for RDX, NTO, NQ, pyrimidine-2-carboxylic acid, and streptomycin, respectively. NTO had experimental diffusivities greater than the computational values, while RDX and streptomycin had experimental diffusivities lower than computational values.

Evaluation of Computational Chemistry Methods for Predicting Redox Potentials of Quinone-Based Cathodes for Li-Ion Batteries

High-throughput computational screening (HTCS) is an effective tool to accelerate the discovery of active materials for Li-ion batteries. For the evaluation of organic cathode materials, the effectiveness of HTCS depends on the accuracy of the employed chemical descriptors and their computing cost. This work was focused on evaluating the performance of computational chemistry methods, including semi-empirical quantum mechanics (SEQM), density-functional tight-binding (DFTB), and density functional theory (DFT), for the prediction of the redox potentials of quinone-based cathode materials for Li-ion batteries. In addition, we evaluated the accuracy of three energy-related descriptors: (1) the redox reaction energy, (2) the lowest unoccupied molecular orbital (LUMO) energy of reactant molecules, and (3) the highest occupied molecular orbital (HOMO) energy of lithiated product molecules. Among them, the LUMO energy of the reactant compounds, regardless of the level of theory used for its calculation, showed the best performance as a descriptor for the prediction of experimental redox potentials. This finding contrasts with our earlier results on the calculation of quinone redox potentials in aqueous media for redox flow batteries, for which the redox reaction energy was the best descriptor. Furthermore, the combination of geometry optimization using low-level methods (e.g., SEQM or DFTB) followed by energy calculation with DFT yielded accuracy as good as the full optimization of geometry using the DFT calculations. Thus, the proposed calculation scheme is useful for both the optimum use of computational resources and the systematic generation of robust calculation data on quinone-based cathode compounds for the training of data-driven material discovery models.

Insights into Weak and Covalent Interactions, Reactivity sites and Pharmacokinetic Studies of 4-Dimethylaminopyridinium Salicylate Monohydrate using Quantum Chemical Computation method

The quantum chemical computation technique was utilised in this study to scrutinise the reactivity sites, weak interactions, and pharmacokinetic aspects of 4-Dimethylaminopyridinium Salicylate Monohydrate. Molecular Electrostatic Potential and Fukui function descriptors were used to examine the reactive sites and electron distribution. The chemical implication of the molecule was explained using Electron Localization function and localized orbital locator. Reduced Density gradient analysis and density Overlap Region Indicator analysis gives information about covalent and Non Covalent interactions. Electrostatic potential map and Fukui functions validate that electronegative oxygen and electropositive hydrogen atoms are sites for electrophilic and nucleophilic attack. The drug likeness criteria were computed in order to grasp the biological properties of the title molecule. Absorption, Distribution, Metabolism, Excretion and Toxicity properties analysis gives an idea about pharmacokinetic properties of titled molecule.

Design of Materials for Energy Storage and Conversion in High Temperature Environment

The kinetics and thermodynamics of electrochemical energy storage and conversion technologies such as fuel cells and electrolyzers often times benefit from high temperature operation. For example, the thermodynamic electrical energy requirements for water electrolysis decrease substantially from 1.23 to below 1 volt by increasing the process temperature from ambient conditions to 850 °C. Unfortunately, materials degradation via sintering, crystal structure disproportion to thermodynamically more stable phases, and interfacial reactions also increases exponentially with increasing temperature. Lifetime requirements for energy conversion technologies often times exceed 10 years of usage with no more than 20% degradation.[1] The requirement of high gas/electrode/solid electrolyte interfacial area for large areal current densities repeatedly necessitates the usage of nano to micro structured materials, further acerbating materials degradation. Oftentimes it is much easier to synthesize a promising new electrode or electrolyte material than it is to characterize the long-term stability of a material in the extremely reducing or oxidizing high temperature environments.[2] We have developed experimental methods in conjunction with thermochemical modeling to evaluate the stability of important classes of perovskite and fluorite oxide materials.[3] We have performed thermogravimetric, FT-IR and electrochemical linear sweep voltammetry methods to rapidly determine oxide materials stability under operationally relevant conditions and these results are compared to stability calculations. Generalizations can be made to predict expected materials redox stability based on relatively straightforward chemical bonding principles, known cation coordination environments and more sophisticated computational chemistry methods. Stability determinations of perovskite oxide electrocatalysts for electrochemical oxidative coupling of methane offer an excellent examples of our approach towards evaluation of materials durability under challenging temperature and reducing conditions.[1] A. Hauch, S. D. Ebbesen, S. H. Jensen, and M. Mogensen, “Highly efficient high temperature electrolysis,” J. Mater. Chem., vol. 18, no. 20, pp. 2331–2340, 2008, doi: 10.1039/B718822F.[2] C. Zhu, S. Hou, X. Hu, J. Lu, F. Chen, and K. Xie, “Electrochemical conversion of methane to ethylene in a solid oxide electrolyzer,” Nat. Commun., vol. 10, no. 1, p. 1173, 2019, doi: 10.1038/s41467-019-09083-3.[3] F. H. G. Kannan P. Ramaiyan, Luke H. Denoyer, Angelica Benavidez, “Electrochemical oxidative coupling of methane to produce higher hydrocarbons using Sr2Fe1.5Mo0.5O6-d electrocatalysts,” Submitt. Commun. Chem., 2021.

The Spicy Story of Cannabimimetic Indoles.

The Sterling Research Group identified pravadoline as an aminoalkylindole (AAI) non-steroidal anti-inflammatory pain reliever. As drug design progressed, the ability of AAI analogs to block prostaglandin synthesis diminished, and antinociceptive activity was found to result from action at the CB1 cannabinoid receptor, a G-protein-coupled receptor (GPCR) abundant in the brain. Several laboratories applied computational chemistry methods to ultimately conclude that AAI and cannabinoid ligands could overlap within a common binding pocket but that WIN55212-2 primarily utilized steric interactions via aromatic stacking, whereas cannabinoid ligands required some electrostatic interactions, particularly involving the CB1 helix-3 lysine. The Huffman laboratory identified strategies to establish CB2 receptor selectivity among cannabimimetic indoles to avoid their CB1-related adverse effects, thereby stimulating preclinical studies to explore their use as anti-hyperalgesic and anti-allodynic pharmacotherapies. Some AAI analogs activate novel GPCRs referred to as “Alkyl Indole” receptors, and some AAI analogs act at the colchicine-binding site on microtubules. The AAI compounds having the greatest potency to interact with the CB1 receptor have found their way into the market as “Spice” or “K2”. The sale of these alleged “herbal products” evades FDA consumer protections for proper labeling and safety as a medicine, as well as DEA scheduling as compounds having no currently accepted medical use and a high potential for abuse. The distribution to the public of potent alkyl indole synthetic cannabimimetic chemicals without regard for consumer safety contrasts with the adherence to regulatory requirements for demonstration of safety that are routinely observed by ethical pharmaceutical companies that market medicines.

Evaluation of the Method of Binding Tamoxifen to DNA Experimentally and Computationally

Background and Aim: Tamoxifen is a group of drugs of selective estrogen receptor modulators, and is one of the drugs effective in the prevention and treatment of some cancers (such as breast cancer). In this study, the interaction of tamoxifen with DNA is investigated experimentally. Also, the electronic structure (at atomic scale) of the molecular system of tamoxifen was theoretically investigated, using atom in molecule (AIM) theory. Methods & Materials: First, in the experimental section of this study, the interaction of Tamoxifen with DNA were investigated by UV-ViS technique and hydrodynamic method (Viscometry). In addition, the analysis of the experimental results shows the obvious effect of concentration on the mechanism of how the tamoxifen molecule binds to DNA. Then, in the theoretical part of this research, using computational biophysical chemistry methods, some properties of tamoxifen molecular system, such as electronic Density of States (DOS), boundary orbital’s energy (HOMO/LUMO), Electrostatic Potential Energy (EPS) and electronic contour maps of the electron density and its Laplacian, will be calculated. Ethical Considerations: This article is a meta-analysis with animal sample. Results: Result of the UV-ViS spectroscopy technique and viscometry indicated hyperchromism and hypochromism effect. In addition, the result were depend on the concentration of the drug and affected the kind of binding of Tamoxifen to DNA. the analysis of computational studies on the drug tamoxifen suggests that the mechanism of the local charge/energy distribution in the molecular system of tamoxifen plays an important role in how this drug binds to DNA. Conclusion: Based on the experimental results of UV-ViS technique and viscometry, as well as the electronic/vibrational properties of the tamoxifen molecular system, it was defined that the Tamoxifen interacts significantly with all the binding sites of DNA.

Sinunanolobatone A, an Anti-inflammatory Diterpenoid with Bicyclo[13.1.0]pentadecane Carbon Scaffold, and Related Casbanes from the Sanya Soft Coral Sinularia nanolobata.

A novel diterpenoid, sinunanolobatone A (1), featuring an unprecedented bicyclo[13.1.0]pentadecane carbon framework, along with two new casbane diterpenoids (2 and 3), and five known related ones (4-8) were isolated from the Sanya soft coral Sinularia nanolobata. The structures of the new compounds were established by detailed spectroscopic analysis, X-ray diffraction analysis, chemical reactions, or a quantum chemical computation method. A plausible biosynthetic pathway of 1 was proposed. In bioassay, the novel compound 1 showed significant inhibitory activity against lipopolysaccharide (LPS) induced inflammation in BV-2 microglial cells.

Study Of Energy And Structure On Intermolecular Interactions In Organic Solvents Using Computational Chemistry Method

This study aims to determine the amount of energy, the difference in energy, the relationship between the amount of energy and the distance between compounds, and the interactions that occur in organic solvent molecules using computational chemistry methods. In determining the amount of energy and interactions that occur, computational chemistry calculations are used using NWChem software version 6.6 with the DFT method with the B3LYP hybrid function/basis set 6-31G, the calculation results are visualized using Jmol software. The results of calculations with large computations of energy for benzene are -230.62447487 KJ/mol, ethanol -154.01322923 KJ/mol, methanol -114.98816558 KJ/mol, hexane are -235.27001385 KJ/mol. Mixture of benzene and ethanol in a ratio of 1 : 1 -384.63823964 KJ/mol, 1 : 2 538.66009762 KJ/mol , and 2 : 1 - 615.26607558 KJ/mol. A mixture of benzene and methanol in a ratio of 1 : 1 -345.61255299 KJ/mol, 1 : 2 - 460.60826254 KJ/mol, and 2 : 1 -576.24044425 KJ/mol, a mixture of hexane and ethanol in a ratio of 1 : 1 - 389.28477268 KJ/mol, 1 : 2 -543.29869234 KJ/mol and 2 : 1 -624.55723290 KJ/mol. A mixture of hexane and methanol at a ratio of 1 : 1 -350.25984691 KJ/mol, 1 : 2 -465.26041654 KJ/mol and 2 : 1 -585.53373886 KJ/mole. The difference in energy is the most in a mixture of benzene and ethanol in a ratio of 1 : 2 -0.00916429 K /mol, in a mixture of benzene and methanol in a ratio of 1 : 2 - 0.00745651 KJ/mol, a mixture of hexane and ethanol in a ratio of 2 : 1 -0.00397597 KJ/mol, and a mixture of hexane and methanol in a ratio of 1 : 2 - 0.01407153 KJ/mol. and there is no relationship between the magnitude of the interaction energy of the mixture with the distance between the molecules.