Semiempirical Quantum Calculations Research Articles

Detection of H. pylori outer membrane protein (HopQ) biomarker using electrochemical impedimetric immunosensor with polypyrrole nanotubes and carbon nanotubes nanocomposite on screen-printed carbon electrode

Helicobacter pylori (H. pylori) is classified as a class I carcinogen that colonizes the human gastrointestinal (GI) tract. The detection at low concentrations is crucial in combatting H. pylori. HopQ protein is located on H. pylori's outer membrane and is expressed at an early stage of contamination, which signifies it as an ideal biomarker. In this study, we presented the development of an electrochemical impedimetric immunosensor for the ultra-sensitive detection of HopQ at low concentrations. The sensor employed polypyrrole nanotubes (PPy-NTs) and carboxylated multi-walled carbon nanotubes (MWCNT-COOH) nanocomposite. PPy-NTs were chosen for their excellent conductivity, biocompatibility, and redox capabilities, simplifying sample preparation by eliminating the need to add redox probes upon measurement. MWCNT-COOH provided covalent binding sites for HopQ antibodies (HopQ-Ab) on the biosensor surface. Characterization of the biosensor was performed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), contact angle measurements, and electrochemical impedance spectroscopy (EIS), complemented by numerical semiempirical quantum calculations. The results demonstrated a dynamic linear range of 5 pg/mL to 1.063 ng/mL and an excellent selectivity, with the possibility of excluding interference using EIS data, specifically charge transfer resistance and double-layer capacitance as multivariants for the calibration curve. Using two EIS components, the limit of detection is calculated to be 2.06 pg/mL. The biosensor was tested with a spiked drinking water sample and showed a signal recovery of 105.5% when detecting 300 pg/mL of HopQ. This novel H. pylori biosensor offers reliable, simple, portable, and rapid screening of the bacteria.

Calculation of stability constants of new metal-thiosemicarbazone complexes based on the QSPR modeling using MLR and ANN methods

In this study, the stability constants (logβ11) of twenty-eight new complexes between several ion metals and thiosemicarbazone ligands were predicted on the basis of the quantitative structure property relationship (QSPR) modeling. The stability constants were calculated from the results of the QSPR models. The QSPR models were built by using the multivariate least regression (QSPRMLR) and artificial neural network (QSPRANN). The molecular descriptors, physicochemical and quantum descriptors of complexes were generated from molecular geometric structure and semi-empirical quantum calculation PM7 and PM7/sparkle. The best linear model QSPRMLR involves five descriptors, namely Total energy, xch6, xp10, SdsN, and Maxneg. The quality of the QSPRMLR model was validated by the statistical values that were R2train = 0.860, Q2LOO = 0.799, SE = 1.242, Fstat = 54.14 and PRESS = 97.46. The neural network model QSPRANN with architecture I(5)-HL(9)-O(1) was presented with the statistical values: R2train = 0.8322, Q2CV = 0.9935 and Q2test = 0.9105. Also, the QSPR models were evaluated externally and achieved good performance results with those from the experimental literature. In addition, the results from the QSPR models could be used to predict the stability constants of other new metal-thiosemicarbazones.

QSPR MODELLING OF STABILITY CONSTANTS OF METAL-THIOSEMICARBAZONE COMPLEXES USING MULTIVARIATE REGRESSION METHODS AND ARTIFICIAL NEURAL NETWORK

In this study, the stability constants of metal-thiosemicarbazone complexes, logb11 were determined by using the quantitative structure property relationship (QSPR) models. The molecular descriptors, physicochemical and quantum descriptors of complexes were generated from molecular geometric structure and semi-empirical quantum calculation PM7 and PM7/sparkle. The QSPR models were built by using the ordinary least square regression (QSPROLS), partial least square regression (QSPRPLS), primary component regression (QSPRPCR) and artificial neural network (QSPRANN). The best linear model QSPROLS (with k of 9) involves descriptors C5, xp9, electric energy, cosmo volume, N4, SsssN, cosmo area, xp10 and core-core repulsion. The QSPRPLS, QSPR PCR and QSPRANN models were developed basing on 9 varibles of the QSPROLS model. The quality of the QSPR models were validated by the statistical values; The QSPROLS: R2train = 0.944, Q2LOO = 0.903 and MSE = 1.035; The QSPRPLS: R2train = 0.929, R2CV = 0.938 and MSE = 1.115; The QSPRPCR: R2train = 0.934, R2CV = 0.9485 and MSE = 1.147. The neural network model QSPRANN with architecture I(9)-HL(12)-O(1) was presented also with the statistical values: R2train = 0.9723, and R2CV = 0.9731. The QSPR models also were evaluated externally and got good performance results with those from the experimental literature.

Reaction mechanism of the farnesyl pyrophosphate C-methyltransferase towards the biosynthesis of pre-sodorifen pyrophosphate by\xa0Serratia plymuthica\xa04Rx13

Classical terpenoid biosynthesis involves the cyclization of the linear prenyl pyrophosphate precursors geranyl-, farnesyl-, or geranylgeranyl pyrophosphate (GPP, FPP, GGPP) and their isomers, to produce a huge number of natural compounds. Recently, it was shown for the first time that the biosynthesis of the unique homo-sesquiterpene sodorifen by Serratia plymuthica 4Rx13 involves a methylated and cyclized intermediate as the substrate of the sodorifen synthase. To further support the proposed biosynthetic pathway, we now identified the cyclic prenyl pyrophosphate intermediate pre-sodorifen pyrophosphate (PSPP). Its absolute configuration (6R,7S,9S) was determined by comparison of calculated and experimental CD-spectra of its hydrolysis product and matches with those predicted by semi-empirical quantum calculations of the reaction mechanism. In silico modeling of the reaction mechanism of the FPP C-methyltransferase (FPPMT) revealed a SN2 mechanism for the methyl transfer followed by a cyclization cascade. The cyclization of FPP to PSPP is guided by a catalytic dyad of H191 and Y39 and involves an unprecedented cyclopropyl intermediate. W46, W306, F56, and L239 form the hydrophobic binding pocket and E42 and H45 complex a magnesium cation that interacts with the diphosphate moiety of FPP. Six additional amino acids turned out to be essential for product formation and the importance of these amino acids was subsequently confirmed by site-directed mutagenesis. Our results reveal the reaction mechanism involved in methyltransferase-catalyzed cyclization and demonstrate that this coupling of C-methylation and cyclization of FPP by the FPPMT represents an alternative route of terpene biosynthesis that could increase the terpenoid diversity and structural space.

Supercritical CO2–subcritical H2O system: A green reactive separation medium for selective conversion of glucose to 5-hydroxymethylfurfural

The supercritical CO2 (scCO2)-subcritical H2O (subH2O) system offers a metal- and additive-free reaction solvent that can be used for organic synthesis. The enhanced formation of carbonic acid and ionization of water under elevated pressures and temperatures promote the production of hydronium and hydroxyl ions that can catalyze the conversion of a number of organic compounds. Furthermore, the biphasic nature of the system allows for the simultaneous extraction of less polar products from the aqueous solution by a flowing scCO2 stream. In this study, we investigated the use of scCO2-subH2O as a reactive separation medium for the conversion of glucose to 5-hydroxymethylfurfural (HMF). The highest HMF yield achieved was 32.6 % with a selectivity of 52.7 %. These values corresponded to a 20.25 % and 41.9 % increase in the yield and selectivity that were achieved in the experiments performed under batch operations. The improvement was primarily attributed to the extraction of some of the HMF from the solution. The highest separation efficiency so far was 12.7 %. We also performed semi-empirical quantum calculations to determine a possible mechanism of the production of HMF from glucose. The two-step process, which involved the isomerization of glucose to fructose and the dehydration of fructose to HMF, was shown to proceed with only the OH– and H3O+ that are inherent in the solvent system as catalysts. Insights from both kinetic data and quantum calculations revealed that the reaction is highly favored in the acidic environment of the scCO2-subH2O system.

IN SILICO STUDIES OF SOPHORAFLAVANONE G: QUANTUM CHARACTERIZATION AND ADMET

Currently, the search for new drugs with greater therapeutic potential and less side effects has been fostered by the advancement of the use of molecular modeling drugs, which in addition to supporting the full characterization of the molecule, allow simple algorithms to predict pharmacokinetic. In this context the present work aimed to perform the electronic / structural characterization, to evaluate the pharmacokinetic properties and to perform a virtual screening of the possible biological targets of Sophoraflavonone G, a promising flavonone, which presents several pharmacological properties. Sophoraflavanone G was geometrically optimized by semi-empirical quantum calculations, plot the MESP, identifying the nucleophilic sites. Using the boundary orbitals, it was possible to identify a greater tendency for electron donation in relation to Naringeni, with lower ionization potential, higher hardness and less softness. With respect to pharmacokinetics Sophoraflavonone G confirmed the safety of the compound for oral administration with good skin permeability, which allows applications in topical formulations. Presents indications for gastro intestinal absorption, as for possible interactions with biological targets, interaction with the estrogen receptor alpha, sodium / glucose co-transporter 2, beta-secretase 1, cyclooxygenase-1.The data obtained from an early stage for a comparative analysis between its analogues and fundamental for future studies of relationships between the three-dimensional structure of Sophoraflavanone G and its biological activities.

METHYLCYTISINE ALCALOID POTENTIALLY ACTIVE AGAINST DENGUE VIRUS: A MOLECULAR DOCKING STUDY AND ELECTRONIC STRUCTURAL CHARACTERIZATION

Dengue fever is a serious disease acquired from the Aedes aegypti mosquito present in tropical and subtropical regions, deeply impacting the population's quality of life. Its control requires combating the virus, and the use of substances that do not cause damage to the environment is of fundamental importance. The present work was carried out in silico to perform the structural-electronic characterization of the alkaloid Methylcytisine, a tricyclic quinolizidine alkaloid that has insecticidal activities, identifying the molecular boundary orbitals and descriptors of global chemical reactivity and assessing the inhibitory potential of methylcytisine on NS5 methyltransferase enzyme dengue virus, as well as identifying possible biological targets in humans. Methylcytisine was geometrically optimized through semi-empirical quantum calculations with thermodynamically more stable conformation, characterizing its structure (atoms, angles and bonds) and its reactivity descriptors. The analysis of the molecular docking simulations showed that methylcytisine is coupled in the same active site of the NS5 enzyme methyltransferase DENV, very similar to the complexed ligand S-adenosyl-L-homocysteine. The intermolecular interactions found for the complex formed and the distance values of the enzyme residues, indicate that methylcytisine has potential application as a new inhibitor of the dengue virus, however it has a high possibility of interaction with human neuronal acetylcholine receptors.

THEORETICAL STUDY OF THE POTENTIAL ANTI-CHAGASIC PHARMACOLOGICAL TOOL MACHILIN G: A STUDY OF MOLECULAR DOCKING

Chagas disease caused by Trypanosoma cruzi, which affects thousands of people around the world. In recent years, research aimed at the discovery of new drugs has started to seek specific macromolecular targets for the disease. In this context, enzymes are therapeutic targets of great interest, since they play a fundamental role in many diseases. In this context, the present work aimed to characterize the Machilin G molecule conformationally and evaluate its interactions in the main therapeutic targets involved in the replication of T. cruzi. To understand the inhibitory mechanism of Machilin G on the evolutionary forms of T. cruzi, the molecule it was conformationally characterized, until reaching thermodynamic stability, and then it was submitted to molecule docking routines, having as protein targets the Cruzain enzymes, Tripanothione reductase and glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH). Machilin G had its structure optimized using semi-empirical quantum calculations, through this technique it was possible to generate the thermodynamically more stable conformation. Through the method of analysis of the computer simulations of molecular anchoring, it was demonstrated that the ligand Machilin G was coupled to the active site of the enzyme TcGAPDH, at distances close to the chalepin. In relation to Cruzain, it is possible to highlight that the ligand Machilin G does not interact with the amino acids of the active site of the enzyme, being at a considerable distance in relation to the ligand KB2. Regarding the enzyme Trypanothione reductase, the ligand Machilin G had few interactions with the amino acids of the active site. The intermolecular interactions found for the complex formed and the values obtained at a distance from the enzyme residues indicate that Machilin G has potential application as a new inhibitor of the enzyme Trypanosoma cruzi TcGAPDH. The present work being a fundamental step for the understanding of Machilin G mechanism of action in view of the evolutionary forms of the t-cruzi parasite.

The effect of stretching or buckling behavior on the charge distribution of C, Si, P and S single atom chains

We used the semi-empirical quantum calculations to simulate the structural evolution of the isolated one-dimensional linear atomic chains of C, Si, S and P in the process of stretching and compression. The effects of stretching or buckling behavior on the charge distribution of C, Si, P and S single atom chains were studied. Our results show that the C and Si atomic chains tend to form stable linear structures, in which the charges are odd-evenly oscillated. For the first time we theoretically predict that S and P atoms can form stable curved chain structures. At the beginning of the elastic compression range, the linear atom chains of C and Si have a metastable transition state, that is, there is a bending point at which the chain’s binding energy suddenly reduces a little then increases with further compression. The charges in the chains are locally uneven and symmetrically distributed, and the number of charges fluctuates in the chains. The charge gain or loss of each C or Si atom is stable during compression, while change slightly during stretching.

Combined powder X-ray diffraction data and quantum-chemical calculations in EXPO2014

This paper describes new features implemented in the EXPO2014 software and aimed at assisting crystallographers in the use of quantum-chemistry calculations in combination with experimental powder diffraction data. The implemented tools are useful in particular in two important steps of the process of crystal structure determination from powder diffraction data: (1) preparing accurate structural model suitable for crystal structure determination by real-space methods; (2) validating structure determination. The combination of experimental/quantum-chemical methods in EXPO2014 is now managed easily thanks to the following capabilities: (a) converting crystallographic data in input files and reading molecular geometry from output files of a wide variety of computational chemistry packages (GAMESS-US, NWChem, Gaussian, CRYSTAL, ABINIT, QUANTUM ESPRESSO); (b) optimizing the geometry of a molecule using Open Babel's force fields; (c) a graphical interface to run semi-empirical quantum calculation by MOPAC (Molecular Orbital PACkage); (d) producing input file for dispersion-corrected density functional theory.

Detection of aspartame via microsphere-patterned and molecularly imprinted polymer arrays

Abstract A colloidal sphere-patterned polyterthiophene thin film sensor with high binding affinity and selectivity toward aspartame was fabricated using a technique combining molecular imprinting and colloidal sphere lithography. The successful imprinting of aspartame into electropolymerized molecularly imprinted polymer generated artificial recognition sites capable of rebinding aspartame into the microporous film, which was sensitively detected using quartz crystal microbalance measurements. The resulting sensor exhibited a good linear response after exposure to aspartame concentrations ranging from 12.5 μM to 200 μM and a detection limit of ∼31 μM. It also demonstrated a high selectivity toward aspartame as compared to other peptide-based analogs including alanine–phenylalanine (Ala–Phe), alanine–glutamine (Ala–Gln), glycylglycine (Gly–Gly), and arginylglycylaspartic acid (RGD). The formation of the highly ordered and micropatterned surface was induced and monitored in situ by electrochemical quartz crystal microbalance and atomic force microscopy. Analyte imprinting and removal were characterized using X-ray photoelectron spectroscopy. Based on molecular modeling (semi-empirical AM1 quantum calculations), the formation of a stable pre-polymerization complex due to the strong hydrogen bonding interactions between the terthiophene monomer and aspartame played a key role in the effective aspartame imprinting and detection.

Synthesis of Thiophene Derivative and its Use as Zinc Metal Corrosion Inhibitor in Hydrochloric Acid Solution

N-[(3-Bromo-2-methylthiophen-5-yl)methylene]-4-methoxyaniline) (5) has been synthesized and used as corrosion inhibitor for zinc metal in 2 M HCl at room temperature by using weight loss measurements. The obtained results showed that (5) is a good inhibitor and its inhibition efficiency (IE %) increased with the increase of inhibitor concentration. The surface coverage was 1.55 at 500 ppm inhibitor concentration; hence the optimum concentration was 500 ppm. Theoretical calculations investigate by studying the relationship between molecular structure and inhibition efficiency using semi-empirical molecular quantum calculations within the PM3 method as implemented in HyperChem package.

Corrosion Inhibition of Zinc Metal in 2M Hydrochloric Acid Solution by Using GuaifenesinDrug as an Inhibitor and Theoretical Calculations

The inhibition of the corrosion of Zinc in 2 M HCl by guaifenesin has been investigated at room temperature using weight loss measurements. Results obtained showed that guaifenesin is a good inhibitor and its inhibition efficiency (IE %) increased with the increase of inhibitor concentration since it was 81%. At 300 ppm. The surface coverage was 0.81 at 300 ppm inhibitor concentration; hence the optimum concentration was 300 ppm. Theoretical calculations investigate by studying the relationship between molecular structure and inhibition efficiency by using semi-empirical molecular quantum calculations within the PM3 method as implemented in HyperChem package.

Free Energies of Binding from Large-Scale First-Principles Quantum Mechanical Calculations: Application to Ligand Hydration Energies

Schemes of increasing sophistication for obtaining free energies of binding have been developed over the years, where configurational sampling is used to include the all-important entropic contributions to the free energies. However, the quality of the results will also depend on the accuracy with which the intermolecular interactions are computed at each molecular configuration. In this context, the energy change associated with the rearrangement of electrons (electronic polarization and charge transfer) upon binding is a very important effect. Classical molecular mechanics force fields do not take this effect into account explicitly, and polarizable force fields and semiempirical quantum or hybrid quantum-classical (QM/MM) calculations are increasingly employed (at higher computational cost) to compute intermolecular interactions in free-energy schemes. In this work, we investigate the use of large-scale quantum mechanical calculations from first-principles as a way of fully taking into account electronic effects in free-energy calculations. We employ a one-step free-energy perturbation (FEP) scheme from a molecular mechanical (MM) potential to a quantum mechanical (QM) potential as a correction to thermodynamic integration calculations within the MM potential. We use this approach to calculate relative free energies of hydration of small aromatic molecules. Our quantum calculations are performed on multiple configurations from classical molecular dynamics simulations. The quantum energy of each configuration is obtained from density functional theory calculations with a near-complete psinc basis set on over 600 atoms using the ONETEP program.

Assembly and organization of poly(3-hexylthiophene) brushes and their potential use as novel anode buffer layers for organic photovoltaics

Buffer layers that control electrochemical reactions and physical interactions at electrode/film interfaces are key components of an organic photovoltaic cell. Here the structure and properties of layers of semi-rigid poly(3-hexylthiophene) (P3HT) chains tethered at a surface are investigated, and these functional systems are applied in an organic photovoltaic device. Areal density of P3HT chains is readily tuned through the choice of polymer molecular weight and annealing conditions, and insights from optical absorption spectroscopy and semiempirical quantum calculation methods suggest that tethering causes intrachain defects that affect co-facial π-stacking of brush chains. Because of their ability to modify oxide surfaces, P3HT brushes are utilized as an anode buffer layer in a P3HT-PCBM (phenyl-C₆₁-butyric acid methyl ester) bulk heterojunction device. Current-voltage characterization shows a significant enhancement in short circuit current, suggesting the potential of these novel nanostructured buffer layers to replace the PEDOT:PSS buffer layer typically applied in traditional P3HT-PCBM solar cells.

Theoretical Approach to Study Assembly Nature of Molecular Modeling System of Carbon Nanotube and a Nematic Liquid Crystal

Theoretical study for stable geometries of a nematic liquid crystal (LC) molecule assembled on the carbon nanotubes (CNT) wall by using semi-empirical molecular quantum calculations within the PM3 method as implemented in Hyperchem package. The interaction influence of ,-stacking between N-4`-Methoxybenzylidine-4-n-butylaniline (MBBA) liquid crystal molecule on the CNT wall led to formation of the local short range orientation order by LC molecules on the surface of the CNT due to the LC-CNT binding energy (,-stacking). The binding energy of the LC molecule on the CNT wall was within the typical van der Waals interaction. This binding originated from the electrostatic energy by a significant amount of charge transfer from the LC molecule to the CNT.

Study of the Molecularly Imprinted Polymers for Selective Binding of the Mono-Substituted Sulfonylurea Herbicides

A new molecularly imprinted polymer (MIP) was synthesized for the selective extraction of mono-substituted sulfonylurea herbicides, with monosulfuron as the template and acrylamide as the functional monomer. The recognition property and affinity of the MIP for monosulfuron and its analog, monosulfuron-ester, were evaluated by equilibrium adsorption and a chromatographic study. Computer modeling, including simulated annealing and semi-empirical quantum calculation, was employed to study the recognition mechanism. The computer modeling demonstrated that monosulfuron can form multiple hydrogen bonds with methacrylic acid and acrylamide, whereas monosulfuron-ester cannot form a stable complex with these two functional monomers, which aligns with the results of the rebinding experiment. The selectivity study further demonstrated that binding sites in the MIP interact with the hydrogen in the acylamino group of mono-substituted sulfonylurea. A comparison experiment also showed that monosulfuron-imprinted MIP offers better selectivity for monosulfuron-ester than the commercial C18 high-performance liquid chromatography stationary phase material.

Experimental and theoretical studies of the thermal degradation of a phenolic dibenzodioxocin lignin model

A large part of biphenyl structures in lignin are etherified by α- and β-carbons of another phenylpropane unit to give an eight-member ring called dibenzodioxocin. The behavior of a phenolic dibenzodioxocin lignin model, 4-(4,9-dimethoxy-2,11-n-dipropyl-6,7-dihydro-5,8-dioxa-dibenzo[a,c]cycloocten-6-yl)-2-methoxyphenol (DBDOH, 1), was studied by different mass spectrometry and thermal methods, leading to the conclusion that dibenzodioxocins are thermally unstable products. Both semi-empirical and density functional theory quantum calculations show that both C–O bonds, which connect the biphenyl part of the dibenzodioxocin molecule to the phenolic group, can be broken under increasing temperature. However, they do not play the same role since their dissociation occurs through different barrier heights. The C–O bond directly connected to the phenolic group (α–O-4) will dissociate first since its barrier energy for scission is lower than the other one (β–O-4), by roughly 12 kcal mol–1 (≈50 kJ mol−1). This conclusion is likely applicable to thermal degradation of DBDO units in lignin polymer.

Is cocaine a social drug? Exploration of the stereo-structure of cocaine’s pharmacophore

Based on a line of evidence (logP, pKa, 1H-, and 13C-NMR, and molecular modeling studies), it appears that cocaine undergoes a hydrophobic collapse which may account for its unprecedented ADME properties, in particular, its exceptional capacity to cross biological membranes. Using molecular simulation techniques, the hypothesis of hydrophobic collapse undergone by the protonated form of cocaine was substantiated using semi-empirical quantum calculations (mainly AM1 and PM3) performed as well as ab initio quantum calculations (6–31 G**). A molecular electrostatic potential map of the internally hydrogen-bonded structure was acquired under AM1 and showed a continuum of high electron density in the central part of the molecule around the methyl ammonium and the two ester moieties. This picture is consistent with the picture of the ammonium being locked between the two C=O and forming a strong “canonical” primary H bond with the methyl ester and a weaker secondary H bond (“non-canonical”) with the benzoate ester. Cocaine represents the prototypical example of molecular concision because the pharmacophore and the vector are embedded in the same molecular scaffold.

QCM sensing of a chemical nerve agent analog via electropolymerized molecularly imprinted polythiophene films

AbstractThe highly selective and sensitive detection of a chemical nerve agent analog pinacolyl methylphosphonate (PMP) was demonstrated using an electrochemically molecularly imprinted polymer (MIP) polythiophene film onto a quartz crystal microbalance (QCM) transducer surface. The fabrication and optimization of the sensor film was monitored by in situ electrochemistry‐QCM (EC‐QCM) measurements, which determined the change in mass and simultaneous change in redox properties of the polymer film. The film deposition, template loading, and template removal were evidenced by a combination of surface characterization techniques such as the attenuated total reflection infrared spectroscopy and high‐resolution X‐ray photoelectron spectroscopy. The fabricated MIP film demonstrated a limit of detection and a limit of quantification of ∼60 and ∼197 μM, respectively. The linear sensing range is between 125 and 250 μM concentration of PMP. Finally, theoretical modeling (AM1 semiempirical quantum calculations) studies revealed that a stable prepolymerization complex is formed in solution with the existence of H‐bonding interactions using the 2:1 monomer‐to‐template ratio. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012