AM1 Method Research Articles

Testing and Optimizing the Drude Polarizable Force Field for Blocked Amino Acids Based on High-Level Quantum-Mechanical Energy Surfaces

The correct reproduction of conformational substates of amino acids was tested for the CHARMM Drude polarizable force field. This was achieved by evaluating the reorganization energies for all low lying energy minima occurring in all 15 neutral blocked amino acids on a quantum-mechanical (QM) energy surface at the MP2/cc-pVDZ level. The results indicate that the bonded parameters of the N-acetyl (ACE) and N-Methylamide (CT3) blocking groups lead to significant discrepancies. A reparametrization of five bond angles significantly improved the agreement with the QM energy surface. The corrected Drude force field exhibits almost the same average reorganization energies relative to the MP2 energy surface as the AM1 and PM3 semi-empirical methods.

Comparative study of DFT, AM1, and PM3 optimization methods modeling new psychotropic amphetamines

In order to improve the determination of physico-chemical descriptors of organic substances, it is necessary to optimize the computational representations of their molecular structures. The computerized estimation of these descriptors is especially useful in the case of drugs of abuse, as clinical studies are not recommended for new compounds belonging to classes known to have a high toxicity. The optimization of molecular structures allows the improvement of the accuracy in determining the physico-chemical descriptors and consequently of the associated quantitative structure - property or structure - activity relationships (QSAR). We are presenting a comparative study regarding the effect of the AM1, PM3, and DFT optimization methods, which were applied in the case of a series of new psychotropic amphetamines for their physico-chemical characterization based on molecular descriptors.

Study of Stability and Reactivity of Cyclopolic Acid Compounds and Their Derivatives Using Semi-empirical Methods AM1 and PM3

The semi-empirical method is a method can be selected in computational chemistry. This method can be used to study the stability and reactivity of cyclopolic acid compounds and their derivatives. This method is simple method in optimizing a compound in calculating the parameters possessed by the atom. Cyclopolic acid is an organic compound that can be found in corn and beans. Analysis using two methods on HyperChem Professional application are AM1 and PM3. Analysis Result has shown the that total energy and gradient of each compound do not have significant differences in calculations. As in the structure of 2-formyl-3-(hydroxymethyl)-6-methoxy-5-methylterephthalic acid has a total energy of -80608.1868567 (kcal/mol) and a gradient of 0.0898817 (kcal/mol/Ang) with the AM1 method and total energy of -74935.9180118 (kcal/mol) and a gradient of 0.0874369 (kcal/mol/Ang) with the PM3 method. The stable structure is in the structure of the 2-formyl-3-(hydroxymethyl)-6-methoxy-5-methylterephthalic acid based on the calculation of the total energy and gradient. Meanwhile, according to the calculation of the difference between LUMO-HOMO, it has different results. Where according to the calculation of the energy difference between LUMO-HOMO, the most stable compound structure is the structure of 2-formyl-3-(hydroxymethyl)-4-isocyano-6-metoxy-5-methylbenzoic acid but is not reactive. Likewise, the 2-formyl-4-hidroxy-3-(hydroxymethyl)-6-methoxy-5-methylbenzoic acid, 2-formyl-3-(hydroxymethyl)-6-methoxy-5-methyl-4-(oxo-λ6-methyl)benzoic acid and 2-formyl-3-(hydroxymethyl)-6-methoxy-5-methylterephthalic acid are reactive but unstable compound structure.

Spectroscopic Determination of Dissociation Constants of Some 4- nitrobenzaldehyde-4-substituted phenyl-1-carbonylhydrazones in Sodium Hydroxide Media

Purpose: Hydrazones are a class of azomethines with a wide spectrum of pharmacological properties which are influenced by pH of the media. The purpose of this study was investigation of acid-base properties of five 4-nitrobenzaldehyde-4-substitutedphenyl1-carbonylhydrazones in sodium hydroxide media (14>pH>7). Method: The dissociation process was followed by UV-Vis spectroscopy, in the ethanol-water (V/V, 1:1) solutions, at room temperature. Semiempirical methods AM1 and PM3 were applied for determination of the deprotonation enthalpies. Results: The changes in the UV-Vis spectra, as well as the deprotonation enthalpies, suggested that the dissociation process for four investigated hydrazones with an amide group took place in one step. The exception with two dissociation steps was hydrazone with amide and hydroxyl group. The pH region of dissociation was from pH 10.8 to pH 11.6 for the first step and between pH 11.7 and pH 12.1 for the second step of dissociation. The influence of the ethanol on the UV-Vis spectra was eliminated by the method of Characteristic Vector Analyses (CVA). The stoichiometric dissociation constants were determined numerically (pKHA = n·pH + logI) and graphically (intercept of the dependence of logI on pH) from the absorbance data using experimental and reconstructed UV-Vis spectra, at three different ionic strengths. Thermodynamic dissociation constants were estimated graphically as an intercept of dependence of dissociation constant on the square root of the ionic strength. Conclusion: The obtained results demonstrated that the influence of the substituents on pKHA values was not significant, except for hydrazone with amide and hydroxyl group. Namely, the dissociation of the amide group of this hydrazone was retarded due to the influence of the phenolic group.

Biological activity, molecular docking, and ADME predictions of amphibine analogues of Ziziphus spina-christi towards SARS-CoV-2 Mpro

The main protease of the SARS-CoV-2 virus, SARS-CoV-2 Mpro, can be discovered as a promising target to treat the COVID-19 pandemic. The peptide-based inhibitors may present better options than small molecules for inhibits SARS-CoV-2 Mpro. Ziziphus spina-christi species reported have a peptide-based of alkaloids group, i.e. Amphibine that the analogues can be identified the potential as an inhibitor of SARS-CoV-2 Mpro. The compound structure was drawn and optimized using semi-empirical AM-1 method using Quantum ESPRESSO v.6.6, then the biological activity using PASS Prediction server and molecular docking simulation using MGLTools 1.5.6 with AutoDock 4.2 were performed. Afterward, the ADME profiles were predicted using the SWISS-ADME server. PASS server was predicting Amphibine B-F and H showed potency both as antiviral and as a protease inhibitor. The molecular docking simulation of Amphibine analogues showed lower binding energy than the native ligand. The binding energy of the native ligand was −7.69 Kcal/mol compared to the lowest binding energy of Amphibine analogues was −10.10 Kcal/mol (Amphibine-F). The ADME prediction showed, as an oral drug Amphibine-F has the best bioavailability, Amphibine-B, C, and D have good bioavailability, and Amphibine-E and H have poor bioavailability. Concluded, Amphibine B-F and H of Amphibine analogues showed potency as COVID-19 treatment targeting SARS-CoV-2 Mpro.

Alkane/Water Partition Coefficient Calculation Based on the Modified AM1 Method and Internal Hydrogen Bonding Sampling Using COSMO-RS.

We introduce a physics-based model for calculating partition coefficients of solutes between water and alkanes, using a combination of a semi-empirical method for COSMO charge density calculation and statistical sampling of internal hydrogen bonds (IHBs). We validate the model on the experimental partition data (∼3500 molecules) of small organics, drug-like molecules, and statistical assessment of modeling of proteins and ligand drugs. The model combines two novel algorithms: a bond-correction method for improving the calculation of COSMO charge density from AM1 calculations and a sampling method to deal with IHBs. From a comparison of simulated and experimental partition coefficients, we find a root-mean-square deviation of roughly one log 10 unit. From IHB analysis, we know that IHBs can be present in two states: open (in water) and closed (in apolar solvent). The difference can lead to a shift of as much as two log 10 units per IHB; not taking this effect into account can lead to substantial errors. The method takes a few minutes of calculation time on a single core, per molecule. Although this is still much slower than quantitative structure–activity relationship, it is much faster than molecular simulations and can be readily incorporated into any screening method.

Influence of Complexation of Thiosemicarbazone Derivatives with Cu (II) Ions on Their Antitumor Activity against Melanoma Cells.

A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method. Selected compounds were converted into complexes of Cu (II) ions. The effect of complexing on anti-tumor activity has been investigated. The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method. Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere. G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection. Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated. The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells. The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.

A Computational Comparative Study for the Spectroscopic Evaluation of Triazine Derivative Dyes in Implicit Solvation Model Systems Using Semi-Empirical and Time-Dependent Density Functional Theory Approaches

The spectroscopic data for a range of cyclopenta-[d][1,2,3]-triazine derivative dyes have been evaluated using various standard computational approaches. Absorption data of these dyes were obtained using the ZINDO/S semi-empirical model for vertical excitation energies of structures optimised with the AM1, PM3, and PM6 methods. These studies were conducted under vacuum and solution states using the polarisation continuum model (PCM) for implicit solvation in the linear response model. The accuracy, along with the modest computational costs of using the ZINDO/S prediction, combined with the PM3 optimisation method for absorption data was reliable. While a higher computational cost is required for the time-dependent density functional theory (TDDFT), this method offers a reliable method for calculating both the absorption and emission data for the dyes studied (using vertical and adiabatic excitation energies, respectively) via state-specific solvation. This research demonstrates the potential of computational approaches utilising solvation in evaluating the spectroscopic properties of dyes in the rational design of fluorescent probes.

Prediction of photofading of N‐β‐hydroxyethylamino‐o‐nitrophenyl derivatives: a theoretical study

AbstractUntil now, the lightfastness of hair dyes had not been investigated using all‐valence molecular orbital methods. The results of calculations are used to obtain the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) frontier electron density, which can reflect the propensity for electrophilic or nucleophilic attack at an atom in a molecule. Using semi‐empirical quantum chemical methods AM1 and PM3, we have calculated the reactivity rates , superdelocalisability and electron density distribution in the tested dyes. We have found that the photooxidation of hair dyes (photochemical decomposition of hair dyes) and derivatives of N‐β‐hydroxyethylamino‐o‐nitrobenzene occurs through the degradation of the N‐β‐hydroxyethylamine substituent and on C2 or C4 atom (C4–NO2) in the process of electrophilic reaction with singlet oxygen 1O2 or nucleophilic reaction on the C1 carbon atom of the aromatic ring, with the use of superoxide anion radical O2●. The structures of the dyes were optimised using MM+, DM and AM1 or PM3 until constant energy value was realised with a 0.01 kcal/mol convergence criterion.

IRMOF‐8: Theoretical evaluation of aluminum doping on hydrogen, methane, and hydrogen sulfide adsorption

AbstractThe use of porous materials, aimed at increasing gas storage capacity at lower pressures, exploits physical adsorption and is an emerging strategy that is being widely investigated. In this scope, porous materials such as metal organic frameworks (MOFs) are a viable alternative, where structural modifications can enhance the properties of these materials and improve the degree of adsorption for a given gas. In this work, we evaluated the adsorption of methane, hydrogen, and hydrogen sulfide gases on pure isoreticular MOF (IRMOF)‐8 and aluminum‐doped IRMOF‐8 using density functional theory Perdew‐Burke‐Ernzerhof/DZVP and semiempirical AM1, PM3, PM6, PM6‐DH+, PM6‐DH2, PM6‐D3, and PM7 methods. Adsorption isotherms were calculated by means of Grand Canonical Monte Carlo simulations. It was found that doping did not provide a significant increase in the amount of adsorbed methane and hydrogen gases. Conversely, doping led to a considerable increase for hydrogen sulfide capture.

A Cyclic Periodic Wave Function Approach for the Study of Infinitely Periodic Solid-State Systems. I. Application to the C-H···π(C≡C) Hydrogen Bonding Systems.

The cyclic periodic wave function (CPWF) approach is applied at the AM1 and PM3 semiempirical levels of approximation to infinitely periodic solid-state systems stabilized by weak CH–pi (C–H···π) interactions between repeat units. The reliability of the AM1 and PM3 methods for modeling C–H···π bonding is first demonstrated using two representative dimer systems: the T-shaped ethyne dimer and the T-shaped propyne dimer. The CPWF method is then applied to two different crystal systems that are stabilized by C–H···π interactions: (1) pent-4-ynoic acid solid and (2) a series of three infinite crystal systems—tetrakis(4-ethynylphenyl)methane solid, tetraethynylmethane solid, and tetrabutadiynylmethane solid. A comparison of our results with available data demonstrates that the use of the CPWF approach at the AM1 and PM3 levels of approximation provides a convenient and reliable method for the study of infinitely periodic systems containing very weak C–H···π bonding.

Isopentyltriphenylphosphonium bromideionic liquid as a newly effective corrosion inhibitor on metal-electrolyte interface in acidic medium: Experimental, surface morphological (SEM-EDX & AFM) and computational analysis

The behavior of mild steel (MS) corrosion in isopentyltriphenylphosphonium bromide (IPTPPB) as a green inhibitor into 0.5 M H2SO4 medium was examined by electrochemical techniques (galvanostatic (GP) and potentiostatic polarizations (PP), and electrochemical impedance spectroscopy (EIS)). Different concentrations of inhibitor were tried; maximum inhibition efficiency (99%) is obtained at 10−2 M IPTPPB in 0.5 M H2SO4. The temperature and adsorption effect was examined by the temperature kinetic study and simulation. The polarization technique explains the mixed type behavior of the inhibitor. The nature of inhibition of MS-IPTPPB was also studied by energy dispersive X-ray spectroscopic (EDXS) technique using surface analysis methods; scanning electron microscopy (SEM) and at atomic force microscopy (AFM). The formation of the monolayer by self-assembly of surfactant molecules at metal surfaces increases the corrosion inhibition ability. Experimental conclusions were found to be consistent with the semi-empirical AM1 method and molecular dynamics (MD) simulation theoretical calculations findings.

Theoretical and experimental examinations to substantiate the structure of coal derived asphaltene by formation of complex with o-chloranil

The structure of coal derived asphaltene (CDA) proposed by Mullins et al has been corroborated through theoretical and experimental examination by the virtue of its electron donor property. Here, o-chloranil has been used as an electron acceptor. Investigation of o-chloranil/CDA complex in gas phase has been performed by density functional theory (DFT) methods. The Charge transfer (CT) transition energy of the complex in gas phase was calculated by the time-dependent density function theory (TD-DFT) using the ground state optimized geometry at the respective levels of theory. For this, the three semi empirical methods AM1, PM3 and PM3MM were computed under the MPW1PW91, B3PW91, PBE1PBE, BPV86 and RCIS formalism. It is found that the two formalisms MPW1PW91 and PBEPBE under PM3 and PM3MM reproduced values close to the experimental one. However, all of them provide lower charge transfer (CT) transition energy values than that has been experimentally determined. Experimentally, FTIR spectra of the donor, acceptor and the complex further supported the understanding of complex formation and demonstrated close similarity with the theoretically determined CDA frequencies. These findings support the validity of the CDA structure to an extent.

QSAR Modeling of Compounds Derived from 1,2,3-Triazolopiperidine as DPP-4 Enzyme Inhibitors Using Semiempirical AM1

<p>This study aims to model the derived compounds of 1,2,3-triazolopiperidine using sem­iempirical method AM1 and determine the further derivation with the better IC<sub>50</sub> values against DPP-4 enzyme theoretically. This research employed ChemDraw Pro 12 software for for 2D struc­tural drawing, Hyperchem 8.0 for 3D modelling, and MLR statistical analysis for modeling QSAR equations. The semiempirical method was likely to be the appropriate platform to apply because the correlation coefficient of H<sup>1 </sup>NMR chemical shift between theoretical and actual value is rela­tively close, 0.8891. The multilinear regression analysis produced 4 equation models where the best one is equation 4 as detailed below:” IC<sub>50</sub> = 875,5116 + (-7400,27*qH35) + (-0,00133* Eat.is) + (-3230,72* qN23) + (3,30277* µ)” n = 25; r<sup>2</sup> = 0,594; <em>Adjusted r<sup>2</sup></em>= 0,486; PRESS = 1,2× 10<sup>4</sup><sup>. </sup>Finally, the theoretically promising substituent was -CN possessing IC<sub>50</sub> value = 1.61 nM. </p>

Accurate prediction of enthalpy of formation combined with AM1 method and molecular descriptors

An error correction model is established by combining the experimental values and the calculated values obtained by the semi-empirical method AM1, and using the multiple stepwise regression (MSR) method on the training set to obtain five descriptors that have a large effect on the error term, and the linear equation of the correction model is derived. The test set is used to verify the reliability of the calibration model. In the training set, the new corrected regression model increased the square of the coefficient of determination (R2) from 0.688 to 0.966 and reduced the root mean square error (RMSE) from 98.563 to 27.249. In the test set, the R2 increased from 0.872 to 0.884, and the RMSE decreased from 43.337 to 37.736. It has good fitting ability and stability. According to the results of multiple stepwise regression, the main atomic structure that causes errors is 〉S==, which indicates that we should take the electrical environment of highly electronegative atoms into consideration, which can provide guidance for accurate calculation of thermodynamic properties.

The Problem of Dynamic Process Manifestation in Identification of Organic Compounds by NMR Spectroscopy

The number, shape and position of NMR spectral lines depend on dynamic processes, and this creates certain difficulties in identification of pharmaceutical substances by NMR spectroscopy. The aim of the paper was to study instances of manifestation of intramolecular dynamic processes that affect identification of organic compounds by NMR, and to illustrate the potential of the methods used for their reduction, as well as associated problems.Materials and methods: 1H and 13C spectra of the following pharmaceutical substances: «buserelin acetate», «valsartan», «goserelin acetate», «iopromide», «clopidogrel hydrogensulfate», «omeprazole», «proroxan», «risperidone», «triptorelin acetate», and «enalapril maleate» were used to demonstrate negative effects of dynamic processes. The spatial structures of conformers were established by 1H-1H ROESY experiments. The quantum-chemical calculation of geometric and thermodynamic characteristics of different conformers was carried out by the PM3 method, and electronic characteristics—by the AM1 method with the help of the HyperChem software.Results: the authors analysed intramolecular dynamic processes which are most commonly encountered in expert work: pyramidal inversion of nitrogen in a heterocyclic compound (risperidone, proroxan, clopidogrel), rotation of molecular fragments around the amide bond (valsartan, iopromide, enalapril), prototropic rearrangements (buserelin, goserelin, omeprazole, triptorelin). The change in exchange rates was explained from the perspective of the change in the system of intra- and intermolecular nonvalent interactions.Conclusions: the use of traditional methods for increasing the rate of dynamic processes (increasing the temperature and changing the solvent) does not always eliminate the negative effects of intramolecular transformations. Methods of smoothing the spectral manifestations of dynamic processes have limited application due to strong intramolecular nonvalent interactions which prevent the conversion of the dynamic process rate into fast exchange. Experts and manufacturers should take into account the manifestation of dynamic processes during identification of pharmaceutical substances by NMR spectroscopy.

Comparative Studies of Infrared Spectral Simulation of Some Benzoyl Derivatives of N-Heterocyclic Compounds Using Semi-Empirical Methods

Simulation studies based on ab initio, semi-empirical or density functional (DFT) calculations are now becoming common among the researchers who are pursuing their intereset in theoretical chemistry. These studies are based on quantum chemical softwares. These studies provide better insight for the structural and other parameters of the compounds. The present paper includes the studies on synthesis or procurement along with the simulated IR spectra of some benzoyl derivatives of N-heterocyclic compounds viz. 2-aminopyridine, 4-aminoantipyrine, 2-aminopyrimidine or 3-aminopyridine using four different AM1, PM3, MNDO and ZINDO1 semi-empirical methods. Among the methods used for the study, AM1 method is more reliable and more accurate so far as the prediction of spectral results is concerned.

Quantitative structure activity relationship (qsar) study and biological evaluation on mono-ketone analogs of curcumin as antioxidant

The objective of this study was to design new mono-ketone analogs of curcumin and determine its lipid peroxidation inhibition. Molecular modeling studies were carried out by using the semi-empirical quantum chemical algorithm AM-1 method in MOE 2018.01.01 software. Build QSAR was used to generate an equation model that will be used to design new mono-ketone analogs of curcumin. Synthesis of new compounds produced from an aldol condensation reaction. Thiobarbituric acid reactive substance (TBARS) method was used to determine antioxidant activity by measuring lipid peroxide concentration. Promising predictions values of lipid peroxidation the QSAR study obtained inhibitory activity. The in vitro lipid peroxidation inhibition of 2,6-bis-(3’-ethoxy, 4’-hydroxybenzylidene)-cyclohexanone; 2,6-bis-(3’-Bromo,4’-methoxybenzylidene)-cyclohexanone; and 2,6-bis-(3’,4’-dimethoxybenzylidene)-cyclohexanone indicates good inhibitory with IC50 values of 2.95; 0.95; and 2.45μM respectively. The new mono-ketone analogs of curcumin compound from the QSAR study has been shown to have antioxidant activity by inhibiting lipid peroxidation by scavenging free radicals.

UV Spectrophotometric Determination of Thermodynamic Dissociation Constants of Some Aromatic Hydrazones in Acid Media

The spectral behavior of some p-nitro-p-substituted benzoylhydrazones in the perchloric acid media was followed, applying the UV spectroscopy. The position of the absorption maximum in the spectra was defined in acidic media and the electronic transitions were discussed, as well (7<pH<1). The equilibrium between neutral and protonated form was investigated in the ethanol-water (V/V, 1:1) solutions. The observed changes in the UV spectra suggested that protonation process took place in one step. The pH region of protonation ranges between 1.4 and 2.9. Using the changes in the UV spectra which appear as a result of the protonation reaction the stoichiometric dissociation constants were determined numerically (pKBH+ = n·pH + logI) and graphically (intercept of the dependence of logI on pH). Thermodynamic dissociation constants were estimated as an intercept of dependence of pKBH+ on square root of the ionic strength. In order to achieve that, measurements were performed at different ionic strengths: 0.1, 0.25 and 0.5 mol/dm3, adjusted with sodium perchlorate. The obtained thermodynamic pKBH+ values ranged between 2.07 and 2.58. In order to predict proton transfer at a given pH, semiempirical methods AM1 and PM3 were applied. The influence of the substituents present in the p-position of the benzene ring on pKBH+ values of investigated hydrazones was discussed, too. Total energy, binding energy, enthalpy of formation, Gibbs energies of formation, atomic charge and proton affinity values were used to predict protonation site in hydrazone molecule. Furthermore, the stability and the proton affinity of the isomers (E and Z) in which hydrazones exist and their protonated forms were defined.

Quantum chemical calculation of some acetanilide molecules by the AM1 method

Quantum chemical calculation of some acetanilide molecules by the AM1 method