Computational Chemistry Techniques Research Articles

Mechanistic study of polyaspartic acid (PASP) as eco-friendly corrosion inhibitor on mild steel in 3% NaCl aerated solution

Corrosion inhibition mechanism of Polyaspartic acid (PASP) as eco-friendly polymer on mild steel in aerated 3% NaCl solution was investigated utilizing electrochemical, thermodynamic, microscopic and computational chemistry techniques. Electrochemical results confirm moderate inhibition efficiency of PASP reaching 61% at 2.0g/L by forming an adsorption layer on metal surface. Zinc ion addition enhanced the efficiency to 97% at 0.5g/L of PASP through a synergistic effect mechanism. Scanning electronic microscopy (SEM) and Atomic force microscopy (AFM) micrographs revealed the morphology of adsorption layer indicates anodic inhibition mechanism of PASP. Quantum calculation and Monte Carlo simulation provided molecular level insights into the adsorption mechanism of PASP on steel surface which were consistent to the experimental findings.

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S.12.04 - A novel approach to map induced activation of neuronal networks using chemogenetics and functional neuroimaging

The effects of four pyridazine derivatives namely, 2-(6-chloropyridazin-3-yl)-2-phenylacetonitrile (P1), 3-(6-chloro-3-pyridazinyl)-1H-indole (P2), 4-(6-chloropyridazin-3-yl)benzoic acid (P3) and 3-(6-chloropyridazin-3-yl)benzoic acid (P4) on electrochemical dissolution of mild steel in 1 M HCl were studied using electrochemical, spectroscopic, and theoretical computational chemistry techniques. The inhibition efficiency increases with increasing concentration of the inhibitors and the shift in corrosion potentials obtained revealed that the compounds are mixed-type inhibitors and steel dissolution was found to be a charge transfer process with the steel/electrolyte interface showed pseudo-capacitive behaviour. P1 and P2 showed the best protection performances for mild steel in the studied medium, attributable to the presence of more nitrogen atoms and unsaturated groups in their molecules compared to P3 and P4. The experimental adsorption data obeyed the Langmuir and Temkin isotherm models and was found to involve both physisorption and chemisorption. Spectroscopic studies revealed that the inhibitor molecules interact chemically with mild steel and the pyridazine ring is actively involved in these interactions. Quantum chemical calculations also showed that pyridazine ring has the tendency of interacting with metallic atoms via both forward and backward donations. Molecular dynamic simulation revealed that the molecules can adsorb strongly onto the surface of iron in a near flat orientation.

Surface astrochemistry: a computational chemistry perspective

AbstractMolecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. Especially, saturated, hydrogen-rich molecules are formed through surface chemistry. Astrochemical models have developed over the decades to understand the molecular processes in the interstellar medium, taking into account grain surface chemistry. However, essential input information for gas-grain models, such as binding energies of molecules to the surface, have been derived experimentally only for a handful of species, leaving hundreds of species with highly uncertain estimates. Moreover, some fundamental processes are not well enough constrained to implement these into the models.The proceedings gives three examples how computational chemistry techniques can help answer fundamental questions regarding grain surface chemistry.

Experimental and theoretical investigation of the inhibitory effect of new pyridazine derivatives for the corrosion of mild steel in 1 M HCl

The effects of four pyridazine derivatives namely, 2-(6-chloropyridazin-3-yl)-2-phenylacetonitrile (P1), 3-(6-chloro-3-pyridazinyl)-1H-indole (P2), 4-(6-chloropyridazin-3-yl)benzoic acid (P3) and 3-(6-chloropyridazin-3-yl)benzoic acid (P4) on electrochemical dissolution of mild steel in 1 M HCl were studied using electrochemical, spectroscopic, and theoretical computational chemistry techniques. The inhibition efficiency increases with increasing concentration of the inhibitors and the shift in corrosion potentials obtained revealed that the compounds are mixed-type inhibitors and steel dissolution was found to be a charge transfer process with the steel/electrolyte interface showed pseudo-capacitive behaviour. P1 and P2 showed the best protection performances for mild steel in the studied medium, attributable to the presence of more nitrogen atoms and unsaturated groups in their molecules compared to P3 and P4. The experimental adsorption data obeyed the Langmuir and Temkin isotherm models and was found to involve both physisorption and chemisorption. Spectroscopic studies revealed that the inhibitor molecules interact chemically with mild steel and the pyridazine ring is actively involved in these interactions. Quantum chemical calculations also showed that pyridazine ring has the tendency of interacting with metallic atoms via both forward and backward donations. Molecular dynamic simulation revealed that the molecules can adsorb strongly onto the surface of iron in a near flat orientation.

Computer-aided drug discovery research at a global contract research organization

Computer-aided drug discovery started at Albany Molecular Research, Inc in 1997. Over nearly 20years the role of cheminformatics and computational chemistry has grown throughout the pharmaceutical industry and at AMRI. This paper will describe the infrastructure and roles of CADD throughout drug discovery and some of the lessons learned regarding the success of several methods. Various contributions provided by computational chemistry and cheminformatics in chemical library design, hit triage, hit-to-lead and lead optimization are discussed. Some frequently used computational chemistry techniques are described. The ways in which they may contribute to discovery projects are presented based on a few examples from recent publications.

Structural effects of chirally mutated Enkephalin neurotransmitters: An argument for biological homochirality

In living organisms all peptides and proteins used endogenously are homochiral. However, heterochiral peptides, formed by post-translational modifications in some species, are used exclusively exogenously. These puzzling facts, accomplished at significant metabolic cost, are investigated here. A systematic study of the effect of chiral substitutions on structure and non-covalent interactions afforded by Ala(2)-Leu-Enkephalins by a combination of mass spectrometry/ion mobility spectrometry and techniques of computational chemistry is reported. The data show that chiral substitutions of amino acid residues have drastic consequences for peptide structure and their interactions as gauged by self- and cross assembly. Our data suggest that an organism based on homochiral polymers has a much higher evolvability than an organism based on heterochiral polymers.

Theoretical infrared spectra of MAON molecules

Techniques of computational quantum chemistry (CQC) are used to explore the vibrational modes of complex organic molecules with mixed aromatic and aliphatic structures.

Estimation of Radiative Efficiency of Chemicals with Potentially Significant Global Warming Potential.

Halogenated chemical substances are used in a broad array of applications, and new chemical substances are continually being developed and introduced into commerce. While recent research has considerably increased our understanding of the global warming potentials (GWPs) of multiple individual chemical substances, this research inevitably lags behind the development of new chemical substances. There are currently over 200 substances known to have high GWP. Evaluation of schemes to estimate radiative efficiency (RE) based on computational chemistry are useful where no measured IR spectrum is available. This study assesses the reliability of values of RE calculated using computational chemistry techniques for 235 chemical substances against the best available values. Computed vibrational frequency data is used to estimate RE values using several Pinnock-type models, and reasonable agreement with reported values is found. Significant improvement is obtained through scaling of both vibrational frequencies and intensities. The effect of varying the computational method and basis set used to calculate the frequency data is discussed. It is found that the vibrational intensities have a strong dependence on basis set and are largely responsible for differences in computed RE values.

CADRE-SS, an in Silico Tool for Predicting Skin Sensitization Potential Based on Modeling of Molecular Interactions.

Using computer models to accurately predict toxicity outcomes is considered to be a major challenge. However, state-of-the-art computational chemistry techniques can now be incorporated in predictive models, supported by advances in mechanistic toxicology and the exponential growth of computing resources witnessed over the past decade. The CADRE (Computer-Aided Discovery and REdesign) platform relies on quantum-mechanical modeling of molecular interactions that represent key biochemical triggers in toxicity pathways. Here, we present an external validation exercise for CADRE-SS, a variant developed to predict the skin sensitization potential of commercial chemicals. CADRE-SS is a hybrid model that evaluates skin permeability using Monte Carlo simulations, assigns reactive centers in a molecule and possible biotransformations via expert rules, and determines reactivity with skin proteins via quantum-mechanical modeling. The results were promising with an overall very good concordance of 93% between experimental and predicted values. Comparison to performance metrics yielded by other tools available for this endpoint suggests that CADRE-SS offers distinct advantages for first-round screenings of chemicals and could be used as an in silico alternative to animal tests where permissible by legislative programs.

Antiviral Drugs Targeting Influenza Virus Surface Proteins: A Computational Structural Biology Approach

For the prevention and control of infectious viral diseases, vaccines and antiviral drugs targeting viral proteins are of great importance. Amino acid substitutions in viral proteins occasionally cause the emergence of antibody-escape and drug-resistant mutants. With regard to this, we have studied the proteins of several viruses, especially the influenza A virus, by using techniques of computational chemistry and biology such as molecular modeling, molecular docking, and molecular dynamics simulations. Influenza A virus is a zoonotic pathogen that is transmitted from animals to humans. This virus has two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The HA of influenza viruses plays a key role in the initiation of viral infection. And HA is also the major target of antibodies that neutralize viral infectivity. Some amino acid substitutions in the antigenic epitope on HA could decrease the interaction between HA and antibodies, leading to the generation of antigenic variants with novel antigenic structures of HA. In addition, HA protein seems to be a favorable target for anti-influenza drugs, but effective HA inhibitors have not been developed due to the emergence of drug-resistant viruses with amino acid substitutions on the HA. To understand how amino acid substitutions affect changes in drug susceptibility, we have been computationally analyzing the three-dimensional structures of influenza virus proteins. In this paper, we review the results obtained through our current analysis.

Enhanced molecular first hyperpolarizability in s-triazine derivatives: Combined experimental and computational studies

Molecular first hyperpolarizabilities (nonlinear optical responses) of selected s-triazine based heteroaromatic molecules are determined using experimental methods. A large enhancement in nonlinear optical response, in spite of a relatively weak donor–acceptor system, is observed. We have carried out a detailed analysis using computational chemistry techniques to account for this behavior.

Theoretical Screening of Novel Host Oxide Materials Suitable for Eu2+ Doped Yellow and Red Luminescence Phosphor

Theoretical screening of host materials suitable for Eu2+ doped phosphor applicable to light emitting diodes was carried by using computational chemistry techniques and crystal structure database. It is well known that an energy level of Eu 4f and 5d orbitals are shifted by the interaction with host crystals that causes a significant spread of Eu 5d orbital. Hence, a control of emission properties of phosphors would be possible by selecting a suitable host material. In this study, emission wavelength and efficiency for more than 8000 oxide structures, almost which are not well investigated as a host structure for Eu2+, were screened by our original prediction method. We reported that there is the relationship between crystal structure and emission colors of Eu2+ doped phosphors, and a quantitative structure-property relationship (QSPR) was applied to reveal it. Developed QSPR model is confirmed to predict the emission wavelength of phosphors we investigated. Our suggested method for the estimation of emission efficiency of Eu2+-doped phosphors is based on the structural information. We defined an alkaline-earth network (ANet) to represent the magnitude of the interaction of alkaline earth atoms with Eu2+ atoms in the host crystal. ANet shows an inversely relationship to an internal quantum efficiency, which supports that ANet is a good index for searching a high efficient Eu2+-doped phosphors qualitatively. It is noted that they are estimated only from the structural information of host materials. In this paper, the prediction methods of emission properties were applied to explore novel host structures for Eu2+ doped phosphors applicable for LED. For more than 8000 oxide crystal candidates for host structure, are screening. Several oxide structure suitable for Eu2+ doped phosphor for LED are suggested.

Modeling SN2 and E2 Reaction Pathways and Other Computational Exercises in the Undergraduate Organic Chemistry Laboratory

Computational chemistry techniques have become increasingly important tools for chemists seeking to address scientific questions. As such, it is important that undergraduate chemistry students develop competence in this emerging field of chemistry. One strategy to gain proficiency involves exposing students to computational methods of increasing depth and complexity during each year of their laboratory curriculum, rather than solely at late stages of their education. The computational chemistry exercises described herein are designed to be completed in one introductory-level organic chemistry laboratory period, and they build upon concepts covered in traditional organic lecture and lab curricula. Students generate electrostatic potential maps for substituted acetic acids to analyze bond polarity and pKa, model acetate to explore resonance, and conduct conformation searches for monosubstituted cyclohexanes to examine the influence of sterics on conformational preference. They also generate reaction coordin...

Counterion-free molecular quantum-dot cellular automata using mixed valence zwitterions – A double-dot derivative of the [closo-1-CB9H10]− cluster

Molecular quantum-dot cellular automata (QCA) paradigm is a promising approach to molecular electronics. QCA cells can be implemented using mixed-valence compounds. However, the existence of counterions can perturb the local electric field and thus is detrimental to information encoding and processing. Here we examine the feasibility of using charge neutral, zwitterionic mixed-valence complex as QCA cells in which the positive and negative charges are found at different yet fixed locations within the molecule and therefore counterion effects are more predictable and controllable. A double-dot model molecule based on the derivative of the 1-carba-closo-decaborate monoanion [closo-1-CB9H10]− is investigated using computational chemistry techniques. The model molecule demonstrates bistability and switchability.

PH-Triggered Conformational Switching of the Diphtheria Toxin T-Domain: The Roles of N-Terminal Histidines

pH-induced conformational switching is essential for functioning of diphtheria toxin, which undergoes a membrane insertion/translocation transition triggered by endosomal acidification as a key step of cellular entry. In order to establish the sequence of molecular rearrangements and side-chain protonation accompanying the formation of the membrane-competent state of the toxin's translocation (T) domain, we have developed and applied an integrated approach that combines multiple techniques of computational chemistry [e.g., long-microsecond-range, all-atom molecular dynamics (MD) simulations; continuum electrostatics calculations; and thermodynamic integration (TI)] with several experimental techniques of fluorescence spectroscopy. TI calculations indicate that protonation of H257 causes the greatest destabilization of the native structure (6.9kcal/mol), which is consistent with our early mutagenesis results. Extensive equilibrium MD simulations with a combined length of over 8μs demonstrate that histidine protonation, while not accompanied by the loss of structural compactness of the T-domain, nevertheless results in substantial molecular rearrangements characterized by the partial loss of secondary structure due to unfolding of helices TH1 and TH2 and the loss of close contact between the C- and N-terminal segments. The structural changes accompanying the formation of the membrane-competent state ensure an easier exposure of the internal hydrophobic hairpin formed by helices TH8 and TH9, in preparation for its subsequent transmembrane insertion.

Dimerization of Chirally Mutated Enkephalin Neurotransmitters: Implications for Peptide and Protein Aggregation Mechanisms

We have probed the structures and aggregation propensities of chirally substituted [Ala(2)]-Leu-Enkephalin peptides (i.e., Leu-Enkephalin G2A) with a combination of ion-mobility spectrometry/mass spectrometry and techniques of computational chemistry. Our IMS/MS data reveal a strong correlation between the propensity to form peptide dimers and the subsequent aggregation propensity. This correlation indicates that the dimerization process is fundamental to the overall self-assembly process. Our computational data correlate a conformational conversion during the peptide association process with a reduced experimental dimer formation and subsequent aggregation propensity. Furthermore, our analysis indicates that monomer activation does not precede peptide association and thus suggests that the entire-refolding or gain-in-interaction models are more realistic accounts of the peptide self-assembly process than the monomer-conversion model. In sum, our results suggest that conformational transitions of early peptide oligomers represent bottlenecks of the peptide self-assembly process and thus highlight the importance of structurally characterizing this reaction during amyloid formation.

Simple Structure-Based Approach for Predicting the Activity of Inhibitors of Beta-Secretase (BACE1) Associated with Alzheimer’s Disease

Beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) is a target of interest for treating patients with Alzheimer's disease (AD). Inhibition of BACE1 may prevent amyloid-ß (Aß) plaque formation and the development or progression of Alzheimer's disease. Known BACE1 inhibitors were analyzed using computational chemistry and cheminformatics techniques to search for quantitative structure-activity relationships (QSAR). A remarkable relationship was found with only two simple descriptors. The square of the linear correlation coefficient r(2) is 0.75. The main descriptor is the number of hydrophobic contacts in the range 4-5 Å between the atoms of the ligand and active site. The other descriptor is the number of short (<2.8 Å) hydrogen bonds. Our approach uses readily available structural data on protein-inhibitor complexes in the Protein Data Bank (PDB) but would be equally applicable to proprietary structural biology data. The findings can aid structure-based design of improved BACE-1 inhibitors. If an inhibitor has less observed activity than predicted by our correlation, the compound should be retested because the first assay may have underestimated the compound's true activity.

Noble Gas Atoms as Electron Donors: Is the Stabilization of Strongly Electrophilic Borylnitrenes Feasible?

AbstractThe possible interaction between an electrophilic borylnitrene, CatBN (Cat = Catecholato), with the noble gas atoms Rg (Rg = Kr, Xe) is probed by computational chemistry techniques including hybrid density functional (B3LYP), second‐order Møller–Plesset perturbation (MP2), and coupled‐cluster theory with singles, doubles, and a perturbative estimate of triple excitations [CCSD(T)] in conjunction with aug‐cc‐pVDZ and cc‐pVTZ and the corresponding small‐core pseudopotential correlation consistent basis sets for krypton and xenon. In the triplet manifold the interaction between CatBN and Rg is of the van der Waals type with a small N–Rg bond dissociation energy. In contrast, the singlet CatBNRg(1A′) has a short N–Rg distance (Kr: 1.962 Å; Xe: 2.029 Å) in agreement with a single bond character. The N–Xe bond dissociation energy is 17 kcal·mol–1 at the highest level of theory, while the N–Kr bond is significantly weaker. Experiments in xenon or xenon doped argon matrices do not give any indication for the formation of the CatBNXe(1A′) compound in spite of the strong N–Xe interaction predicted by theory. The experimental observation is explained by the existence of a crossing of singlet and triplet potential energy surfaces. At the geometry of triplet CatBNRg (large N–Rg distance) the singlet state is higher in energy whereas at the geometry of singlet CatBNRg (short N–Rg distance) the triplet is higher. Fast intersystem crossing to the lower lying triplet surface in the presence of Xe is assumed to preclude the formation of CatBNXe(1A′).

Synthesis of 1-aryl-1-phenylpropenes using an alkylation-rearrangement-methylation-isomerization one-pot reaction sequence

Abstract (Z/E)-1-(2-Methoxyaryl)-1-phenylpropenes have been prepared in good yields by heating a mixture of a phenolic substrate, cinnamyl chloride, tetramethylammonium chloride and K2CO3 in polyethyleneglycol at 180°C. The one-pot synthesis proceeds through four discrete reaction steps: alkylation of the phenol with cinnamyl chloride, Claisen rearrangement, O-methylation and double-bond migration. The configuration of one crystalline product was determined using a single-crystal X-ray diffraction analysis. The thermodynamic and structural features of the products were evaluated using computational chemistry techniques.