Semiempirical AM1 Method Research Articles

Theoretical investigations on electronic structure and optoelectronic properties of vinyl fused monomeric and oligomeric benzimidazole derivatives using DFT and TDDFT techniques.

The present work encompasses the theoretical investigation of 14 benzimidazole-based (seven vinyl fused monomeric benzimidazole (VFMBI) and seven vinyl fused oligomeric benzimidazole (VFOBI)) derivatives using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) techniques. The effects of electron donor and acceptor groups on the electronic structure such as HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energies, HOMO-LUMO energy gap, ionization potentials (IPs), electron affinities (EAs), internal reorganization energies of holes and electrons (λh/e), and excited state properties have been explored in the present work. In addition, natural bond orbital (NBO) analysis of these compounds has been investigated to reveal the typical stabilization interactions in these molecules. Hence, the aim of the present work is to explore the electronic structures and optoelectronic properties of the title molecules on the basis of the DFT quantum chemical calculations and to make an idea on the parameters influencing the optoelectronic efficiency toward a better understanding of the structure-property relationships. Moreover, the calculated results reveal the suitable optoelectronic properties of benzimidazole oligomer derivatives using theoretical techniques. Of the investigated molecules, 4_MABIMCY and 4_MABIOCY show potential optoelectronic properties and can be used as a potential charge transport material due to their narrow band gap, high hyperpolarizability, low ionization potential, and high electron affinity. The larger λab and λem values favor the system to be used as a potential optoelectronic material with better optical properties. All quantum chemical calculations were carried out using Gaussian09 theoretical chemistry code. Ground state calculations were made using the B3LYP/6-31+G(d,p) method. All excited state calculations had been computed using TDB3P86/6-311++(d,p). The initial structure for excited state calculations was optimized using the AM1 semi-empirical method.

Transferable Machine Learning Interatomic Potential for Bond Dissociation Energy Prediction of Drug-like Molecules.

We present a transferable MACE interatomic potential that is applicable to open- and closed-shell drug-like molecules containing hydrogen, carbon, and oxygen atoms. Including an accurate description of radical species extends the scope of possible applications to bond dissociation energy (BDE) prediction, for example, in the context of cytochrome P450 (CYP) metabolism. The transferability of the MACE potential was validated on the COMP6 data set, containing only closed-shell molecules, where it reaches better accuracy than the readily available general ANI-2x potential. MACE achieves similar accuracy on two CYP metabolism-specific data sets, which include open- and closed-shell structures. This model enables us to calculate the aliphatic C-H BDE, which allows us to compare reaction energies of hydrogen abstraction, which is the rate-limiting step of the aliphatic hydroxylation reaction catalyzed by CYPs. On the "CYP 3A4" data set, MACE achieves a BDE RMSE of 1.37 kcal/mol and better prediction of BDE ranks than alternatives: the semiempirical AM1 and GFN2-xTB methods and the ALFABET model that directly predicts bond dissociation enthalpies. Finally, we highlight the smoothness of the MACE potential over paths of sp3C-H bond elongation and show that a minimal extension is enough for the MACE model to start finding reasonable minimum energy paths of methoxy radical-mediated hydrogen abstraction. Altogether, this work lays the ground for further extensions of scope in terms of chemical elements, (CYP-mediated) reaction classes and modeling the full reaction paths, not only BDEs.

QSAR ANALYSIS USING SEMI-EMPIRICAL AM1 METHOD, MOLECULAR DOCKING, AND ADMET STUDIES OF CHALCONE DERIVATIVES AS ANTIMALARIAL COMPOUNDS

Malaria is a serious caused by protozoan parasites such as Plasmodium groups and has fatal consequences for human health. The increase in the resistance of the Plasmodium parasites toward existing antimalarial drugs prompts the exploration of novel compounds. In this study, quantitative structure-activity relationship (QSAR) analysis using the semi-empirical AM1 method was conducted to identify the optimal model that relates physicochemical properties and biological activity of chalcone derivatives. In addition, ADMET prediction and molecular docking were also carried out. Multilinear regression calculations for statistical parameters of QSAR models revealed that Model 4, with 11 independent variables, provided the best predictions and exhibited a robust correlation with antimalarial activity represented by inhibitory concentration (IC50). ADMET predictions indicated favorable absorption, distribution, metabolism, excretion, and toxicity properties, particularly for B2D, showing promising antimalarial attributes. Molecular docking studies targeting 5 mutated PfDHODH proteins revealed B2D’s potential to reach therapeutic targets efficiently. It has low docking scores for mutations I (-10.5 kcal/mol), II (-8.6 kcal/mol), and V (-10.5 kcal/mol) with RMSD < 2Å, in carrying out its role for antimalarial activity. This research successfully identifies B2D as an efficient inhibitor of PfDHODH receptors. Thus, it is a highly promising novel antimalarial drug.

Shedding light into the biological activity of aminopterin, via molecular structural, docking, and molecular dynamics analyses

In this study, the structural and anticancer properties of aminopterin, as well as its antiviral characteristics, were elucidated. The preferred conformations of the title molecule were investigated with semiempirical AM1 method, and the obtained the lowest energy conformer was then optimized by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies of the optimized structure were calculated by the same level of theory and were compared with the experimental values. The vibrational assignments were performed based on the computed potential energy distribution (PED) of the vibrational modes. The molecular electrostatic potential (MEP) and frontier molecular orbitals (HOMO, LUMO) analyses were carried out for the optimized structure and the chemical reactivity has been scrutinized. To enlighten the biological activity of aminopterin as anticancer and anti-COVID-19 agents, aminopterin was docked into DNA, αIIBβ3 and α5β1integrins, human dihydrofolate reductase, main protease (Mpro) of SARS-CoV-2 and SARS-CoV-2/ACE2 complex receptor. The binding mechanisms of aminopterin with the receptors were clarified. The molecular docking results revealed the strong interaction of the aminopterin with DNA (−8.2 kcal/mol), αIIBβ3 and α5β1 integrins (−9.0 and −10.8 kcal/mol, respectively), human dihydrofolate reductase (−9.7 kcal/mol), Mpro of SARS-CoV-2 (−6.7 kcal/mol), and SARS-CoV-2/ACE2 complex receptor (−8.1 kcal/mol). Moreover, after molecular docking calculations, top-scoring ligand-receptor complexes of the aminopterin with SARS-CoV-2 enzymes (6M03 and 6M0J) were subjected to 50 ns all-atom MD simulations to investigate the ligand-receptor interactions in more detail, and to determine the binding free energies accurately. The predicted results indicate that the aminopterin may significantly inhibit SARS-CoV-2 infection. Thus, in this study, as both anticancer and anti-COVID-19 agents, the versatility of the biological activity of aminopterin was shown. Communicated by Ramaswamy H. Sarma

Computational Chemistry: QSAR of Dental Disease Causing Streptococcus mutans Using Eugenol Derivative Compounds from Clove Essential Oil

Research on the activity of eugenol derived compounds as antimicrobials using the qualitative structure-activity relationship (QSAR) model has been conducted. Molecular structure modeling was executed computationally using the ChemDraw Ultra 12.0 program package. Geometry optimization was performed using AM1 semi-empirical method to stabilize structure with the least energy level. Calculations of hydrophobic, electronic, and steric descriptors were done using Gaussian-09 and Marvin Sketch 64 softwares. Statistical calculations was conducted through multiple linear regression method using the IBM SPSS 25 program. Statistical analysis was carried out based on the statistical requirements of several equation models so that the best equation model was obtained. The analysis with the QSAR equation model obtained that the model 1 equation presented the best results.

Theoretical investigation of the performance of benzimidazole derivatives as mild steel organic corrosion inhibitors in acidic environments.

The efficiency of various benzimidazole derivatives as mild steel corrosion inhibitors in HCl and H2SO4 medium was evaluated using quantum chemical methods. The AM1 semi-empirical method and Density Functional Theory (DFT) at the B3LYP/6-31G* level were used. The orbital energies (EHOMO and ELUMO), Separation Energy (ELUMO-EHOMO), Dipole moment (µ), Log P, Polarizability, molecular volume, molecular weight, Hardness (η) and Softness (S) are the computed quantum chemical characteristics linked to inhibitory efficiency. There was a strong link between quantum chemical parameters and experimental inhibition efficiency. The findings revealed that the Inhibition Efficiency was linked to a number of quantum chemical factors. The 2-mercaptobenzimidazole derivative had a higher Inhibition Efficiency (IE) than the other benzimidazole derivatives, according to the results.

Analysis of Quantitative Structure-Activity Relationship (QSAR) Of 1,8-Napthalymide-4-Aminoquinoline Derivatives as Antimalarial Compounds

QSAR analysis from derivative compounds of 1,8-naphthalimide-4-aminoquinoline has been carried out with the aim of knowing the quantitative relationship between structure and activity based on the log IC50 value. The modelling was made with two dimensions and geometric optimization is carried out. The AM1 semi-empirical method was used to optimize the geometry of the total energy of 25 compounds. The descriptors in the QSAR calculation were dipole moment, atomic net charge, ELUMO, EHOMO, SAG, SAA, hydration energy, polarizability, and log P. The descriptors were used to find quantitative equations of the relationship between the structure and antimalarial activity.

Quantitative Relationships Between Structure and Activity of Gamma-Carboline Derivative Compounds as Anti-Bovine Viral Diarrhea Virus (BVDV) Using Semi-Empirical AM1 Method

This research aims to study the quantitative structure and activity relationship (QSAR) of gamma-carboline derivative compounds as anti-BVDV agents to get an equation that can predict the value of the anti-BVDV activity of gamma-carboline derived compounds. The research material is experimental EC50 data that convert to anti-BVDB activity. 14 gamma-carboline derivative compounds are divided into 2 groups, namely, 11 fitting compounds and 3 test compounds. QSAR analysis is based on multilinear regression calculations of the fitting compound by plotting the EC50 log as the dependent variable and the descriptor as the independent variable. The used descriptors are atomic net charge (q) and dipole moment (µ), which are involved in calculations using the AM1 semiempirical quantum mechanics method. In addition, the partition coefficient of n-octanol/water (Log P), molecular polarizability (α), molecular weight (BM), Van Der Waals surface area (A vdw), Van Der Waals volume (V vdw), and index of refraction (RD) are obtained from QSAR properties. The resulting QSAR equation is: Log pEC50 = -48.670 – 124.801 (qC11) – 12.661 (α) – 0.918 (µ) – 0.876 (RD) – 0.999 (Log P) + 1.863 (BM) + 0.043 (V vdw) with n = 14; r = 0.937; r2 = 0.878; SD = 0.244; Fcount/Ftable = 1.466; PRESS = 0.749; Sig. = 0.02 This equation can be used as an initial guide for designing the structure of new compounds of the gamma-carboline class by considering some of the most influential descriptors. Consequentially, new compounds can be designed that have a smaller predicted EC50 value than the known compounds derived from gamma-carboline.

Thermodynamic Study on Ionization Constant (Ka) Values for Some Imines derived from p,o-Aminobenzaldehydes and Cinnaldehyde by Conductance Method supported by Theoretical Studies

The synthesis of three imines derivatives from various aliphatic and aromatic aldehydes was achieved by standard methods. The main objective of the study was the estimation of Ka values for these imines using conductivity method in a range (293-333) K and to deal with thermodynamic parameters namely ΔG, ΔH, ΔS. The values of ionization constant of these imines under study were calculated. Based on AM1 and PM3 semiempirical methods, εHOMO, εLUMO, band gap Eg, hardeness η, chemical potential μ, softness S, electronegativity χ, elechtrophilicity ω and amount of charge transfer ΔN in electron volt (ev) for three imines derivatives.

Reliable gas-phase tautomer equilibria of drug-like molecule scaffolds and the issue of continuum solvation.

Accurate calculation of relative tautomer energies in different environments is a prerequisite to many parameters of relevance in drug discovery. This work provides a thorough benchmark of the semiempirical methods AM1, PM3 and GFN2-xTB, the force-field OPLS4, Hartree-Fock and HF-3c, the density functionals PBEh-3c, B97-3c, r2SCAN-3c, PBE, PBE0, TPSS, r2SCAN, ω-B97X-V, M06-2X, B3LYP, B2PLYP, and second-order perturbation theory MP2 versus the gold-standard coupled-cluster DLPNO-CCSD(T) using the def2-QZVPP basis set. The outperforming method identified is M06-2X, whereas r2SCAN-3c is the best-perfoming one in the set of cost-optimized methods. Application of the two methods on a challenging subset from the SAMPL2 challenge provides evidence that deviations from experiment are caused by deficiencies of current continuum solvation methods.

Association of 5,5′-Dibromo-o-Cresolsulfonphthalein Anions with Dye Cations in Aqueous Solution

The formation of associates in aqueous solutions between single- or double-charged anions of 5,5′-dibromo-o-cresolsulfonphthaleine and single-charged cations of cyanine dyes (quinaldine blue, quinaldine red) has been considered. Based on the spectrophotometric data, the equilibrium constants of the association were analyzed. The energy of cation-anion interactions (standard enthalpy of formation of ions and associates) was determined by the semi-empirical AM1 method and probable structures of associates were set. The consistency between experimental spectrophotometric and calculated quantum chemical data is discussed.

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.

Physico-chemical analysis, systematic benchmarking, and toxicological aspects of the JWH aminoalkylindole class-derived synthetic JWH cannabinoids

We are presenting the results obtained by computing different toxicity indices for some of the newest JWH synthetic cannabinoids, by using (Q)SAR models, ADME(T) predictions, simulations of NMR spectral techniques and other different computational dedicated software packages and forensic analytical tools. We have examined the main physical and chemical properties and evaluated the behavioral neurotoxicity and pharmacokinetic profile of 16 aminoalkylindole class-derived synthetic cannabinoids JWH as compared to the Delta-9-tetrahydrocannabinol (Δ9-THC), which was chosen as a standard compound. For this purpose, the geometries of the molecules have been optimized by using the AM1 semi-empirical quantum method. The conclusions of a comparative analysis of the toxicities of synthetic and natural cannabinoids are presented.

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.

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.

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.

Design of New 2,4-Substituted Furo [3,2-B] Indole Derivatives as Anticancer Compounds Using Quantitative Structure-Activity Relationship (QSAR) and Molecular Docking

This study aimed to propose new indole derivatives as anticancer through Quantitative Structure-Activity Relationship (QSAR) and molecular docking method. The best predicted anticancer activity of indole derivatives was recommended based on the QSAR equation. A data set consist of 18 indole derivatives from literature with anticancer activity against the A498 cell line was used to generate a QSAR model equation. The data set was divided randomly into training (14) and test (4) set compounds. The structure of indole compound was optimized first using AM1 semi-empirical methods, and the descriptors involved were analyzed using Multiple Linear Regression (MLR). The best QSAR equation obtained was Log IC50 = 65.596 (qC2) + 366.764 (qC6) – 92.742 (qC11) + 503.297 (HOMO) – 492.550 (LUMO) – 76.966. Based on the QSAR model, varying electron-withdrawing groups in C2 and C6 atom, as well as adding electron-donating groups in C11 were proposed could increase the anticancer activity of the indole derivatives. The QSAR analysis showed that compound 15 has the best predicted anticancer activity, supported by molecular docking results that showed hydrogen bond interaction with essential amino acids to build anticancer activity such as MET769, THR830, and THR766 residues.