Semiempirical PM3 Method Research Articles

Interaction of Dyes with Cationic Surfactants in Solutions: Determination of Critical Micelle Concentration

Interactions of sulforhodamine B or ethyl eosin (as the anionic dye) with cetylpyridinium bromide (as a cationic surfactant) have been investigated by visible spectroscopy in aqueous solution. The object of research is the association between an anion of dye and of cationic surfactant in aqueous solutions and its features. Computer simulation of these interactions was carried out with the use of AM1 and PM3 semi-empirical methods. A new spectrophotometric method was developed for determination of critical micelle concentration of cationic surfactants.

Temperature effects on anharmonic infrared spectra of large compact polycyclic aromatic hydrocarbons

Aims. Large compact polycyclic aromatic hydrocarbon molecules (PAHs) present special interest in the astrochemical community. A key issue in analyses of large PAHs is understanding the effect that temperature and anharmonicity have on different vibrational bands, and thus interpreting the infrared (IR) spectra for molecules under various conditions. Methods. Because of the huge amount of interactions/resonances in large PAHs, no anharmonic IR spectrum can be produced with static/time-independent ab initio method, especially for the molecules with D6h symmetry, e.g., coronene and circumcoronene. In this work, we performed molecular dynamics simulations to generate anharmonic IR spectra of coronene and circumcoronene. Results. The method is validated for small PAHs, i.e., naphthalene and pyrene. We find that the semiempirical method PM3 produces accurate band positions with an error <5 cm−1. Furthermore, we calculate the spectra at multiple temperatures and find a clear trend toward band shifting and broadening.

Berberine as Source of Antiproliferative Hybrid Compounds: In Vitro Antiproliferative Activity and Quantitative Structure-activity Relationship.

Despite advances for cancer treatment, it still remains a major worldwide public health problem. Compounds derived from natural sources are important alternatives to combat this mortal disease. Berberine is an isoquinoline alkaloid with a wide variety of pharmacological properties, including antiproliferative activity. Previously, we have found that fatty acids also show antiproliferative activity against cancer cell lines.. To combine berberine and fatty acids, or carboxylic acids, in order to improve their antiproliferative properties. We synthetized six new hybrid derivatives through a simple methylenedioxy group-cleavage method followed by the reaction with fatty acids, or carboxylic acids. The structure of the compounds was elucidated by IR, NMR and HRMS. The in vitro antiproliferative activity against four human cancer cell lines (HeLa, A-549, PC-3 and LS-180) and one normal cell line (ARPE-19), was evaluated by the MTT method. Chemical structures were drawn using SPARTAN '08 software and the conformational analysis was carried out with a molecular mechanic level of theory and the SYBIL force field. All molecular structures were subjected to geometrical optimization at the semi-empirical method PM3. Molecular descriptors were calculated using DRAGON 5.4 and SPARTAN ´08 programs. The geranic acid and berberine hybrid compound (6) improved the antiproliferative activity shown by natural berberine, even more than the 16- to 18-carbon atoms fatty acids. Compound 6 showed IC50 values of 2.40 ± 0.60, 1.5 ± 0.24, 5.85 ± 1.07 and 5.44 ± 0.24 μM, against HeLa, A-549, PC-3 and LS-180 human cancer cell lines, respectively. Using this information, we performed a quantitative structure-activity relationship (QSAR) of the hybrid molecules and found that the molecular descriptors associated with the antiproliferative activity are: hydrophobic constant associated with substituents (π(A) = 6.5), molecular volume descriptor (CPKvolume≈ 700 Å3), EHOMO, number of rotatable bonds (RBN) and number of 6-membered rings (nR06). The methylendioxy and methoxyl groups in berberine are important for the antiproliferative activity shown by its derivatives. Better results in antiproliferative activity were obtained in compound 6 with the prenyl moiety. The QSAR indicates that the molecular descriptors which associated positively with the antiproliferative activity are: hydrophobic constant associated with substituents (π(A) = 6.5), molecular volume descriptor (CPKvolume≈ 700 Å3) and EHOMO. This research gave the basis for the design and preparation of new, easily afforded molecules derived from berberine and carboxylic acids, with improved antiproliferative activity.

Studies of the Association of Dyes with Surfactants in Aqueous Solutions: Spectrophotometry and Computer Simulation

The association of cationic dye (pinacyanol, PC) with anionic dyes (ethyleosin, EE, or rhodamine 200 C, R200C), and also the interaction “dye+surfactant” has been investigated in aqueous solutions by visible spectroscopy and computer simulation. Cetylpyridinium bromide (CPB), sodium dodecylsulfate (SDS) and triton X-100 (TX) were used as cationic, anionic and non-ionic surfactants respectively. The formation of “dye+surfactant” associates takes place at low dye concentrations (≥10‑6 M) and concentrations of surfactant, which are much smaller than the critical micelle concentrations (CMC). In contrast, similar concentrations (10‑6 – 10‑4 M) of small cations of tetramethylammonium or tetraethylammonium have no noticeable effect on the absorption spectra of the dye in the “dye+tetraalkylammonium salt” systems; it indicates the absence of formation of new compound between the dye and salt. The standard enthalpy of formation of “dye+dye” or “dye+surfactant” associates has been determined by AM1 and PM3 semiempirical methods. The computer simulation confirms that the formation of these associates is energetically beneficial.

Моделирование электронной структуры композитного материала графен-поливинилиденфторид

AbstractTheoretical models of shockproof composite materials based on two-layer graphenes and multilayer polyvinylidene fluoride C_124H_40 + n (H–(C_2H_2F_2)_5–H) ( n = $$\overline {1,\;8} $$ ) are constructed. The electronic structure is studied using the semiempirical PM3 method that is one of version of the molecular orbital method. The orbital energies, ionization potentials, total electron energies, strength, and other properties of the considered material are calculated based on the theoretical models. The outlooks for application of these materials in the military field for manufacturing superstrong and lightweight flak jackets are considered.

Simulation of the Electronic Structure of Graphene–Polyvinylidene Fluoride Composite Material

Theoretical models of shockproof composite materials based on two-layer graphenes and multilayer polyvinylidene fluoride C124H40 + n(H–(C2H2F2)5–H) (n = $$\overline {1,\;8} $$ ) are constructed. The electronic structure is studied using the semiempirical PM3 method that is one of version of the molecular orbital method. The orbital energies, ionization potentials, total electron energies, strength, and other properties of the considered material are calculated based on the theoretical models. The outlooks for application of these materials in the military field for manufacturing superstrong and lightweight flak jackets are considered.

Theoretical Description of Mixed Film Formation at the Air/Water Interface: Carboxylic Acids-Alcohols.

The thermodynamic parameters of formation and clusterization of aliphatic alcohols CnH2n+1OH and carboxylic acids CnH2n+1COOH (n = 6–16) are calculated using the quantum-chemical semiempirical PM3 method. Four types of dimers are constructed in two directions of the spread monolayer comprising the most energetically advantageous monomer structures. The hydrophobic chains of alcohol and carboxylic acid molecules in the regarded dimers are found to be tilted within 12° to the normal of the spread monolayer. The structures of the mixed and pure surfactant dimers are the basis for the mixed alcohol–carboxylic acid monolayers of the following types: two dimensional (2D) film 1 with single distribution of the individual component in the other one, when the molecules of the first component do not interact with each other but are completely surrounded by the molecules of the second component; 2D film 2 with domain structure, when the film consists of “islands” of the individual components. The dependences of the clusterization Gibbs’ energy per one monolayer molecule on the molar fraction of the components for the mixed 2D films 1 formed by surfactants with equal alkyl chain length are found to be limited from top to bottom by the corresponding dependences for pure components. This indicates the absence of synergetic interaction between the hydrophilic head groups of carboxylic acids and alcohols and conforms to the available experimental data. The formation of the described types of mixed films is competitive. The preferential formation of 2D films 1 with single distribution of the first component among the molecules of the second one is possible when the length of the carboxylic acid hydrocarbon chain is longer by Δn = 1–2 methylene units than that of the corresponding alcohol alkyl chain. According to the fractionally linear law, the highest possible content of the carboxylic acids in such 2D films 1 depends on the Δn value and does not exceed 33.3%.

MOLECULAR DOCKING STUDIES OF SOME N-AMIDOALKYLATED DERIVATIVES OF 2-AMINO-1,3,4-OXADIAZOLE AS POTENTIAL INHIBITORS OF GLYCOGEN SYNTHASE KINASE-3β

Alzheimer's disease is a neurodegenerative disease characterized by pathological features of neurofibrillary tangles and β-amyloid plaques in the cerebral cortex. In Alzheimer's disease, tau protein undergoes excess phosphorylation, due to which its threads begin to merge and form neurofibrillary tangles within nerve cells. It has been shown that glycogen synthase kinase-3β is a key factor in the phosphorylation of tau protein, its increased activity leading to pathologies of neurofibrillary tangles and, consequently, to neurodegenerative changes in the brain. In this connection, the search for effective inhibitors of GSK-3β is a very important and urgent task, for their further use in the treatment of Alzheimer's disease. Aim of research.The aim of this study is to search new inhibitors of GSK-3β among N-amidoalkylated derivatives of 2-amino-1,3,4-oxadiazole by molecular docking methods. Materials and methods. We have carried out geometry optimization of analyzed structures within PM3 semi-empirical method, and GSK-3β molecular docking using software ArgusLab 4.0.1. The three-dimensional crystal structure of co-crystallizer GSK-3β and inhibitor has been loaded from the data bank of protein molecules (PDB ID: 3F7Z). Results. In this study it has been shown that the structures being studied mainly form stronger complexes with the enzyme compared to the known inhibitor. Based on the results of molecular docking, the compounds leaders N-(((5-(2-bromophenyl)-1,3,4-oxadiazol-2-yl)amino)methyl)benzamide and 2,4-dichloro-N-(2,2,2-trichloro-1-((5-(p-tolyl)-1,3,4-oxadiazol-2-yl)amino)ethyl)benzamide have been chosen. The structures of the compounds leaders have been tested for compliance with Lipinski criteria. Conclusions. Proposed compounds leaders can be recommended for further studies in the treatment of Alzheimer's disease. Despite the good results obtained in silico analysis, it is mandatory to perform biological tests in vitro and in vivo.

Komputasional Derivat Penisilin yang Tahan Asam dan Tahan Enzim Beta Laktamase

Penisilin adalah antibiotika yang masih banyak digunakan untuk mengatasi infeksi. Beberapa derivat penisilin diketahui mempunyai sifat tahan asam seperti penisilin V, ampisilin, amoksisilin dan metisilin. Derivat penisilin yang lain mempunyai sifat tahan terhadap enzim beta laktamase seperti metisilin, nafsilin dan kloksasilin. Kimia komputasi dapat menjelaskan mengapa hal tersebut dapat terjadi.Gugus yang bertanggung jawab terhadap proses terjadinya hidrolisa oleh asam dan peruraian oleh enzim dapat dihitung kerapatan elektronnya, sehingga dapat difahami mengapa derivat yang satu tahan asam dan yang lain tahan terhadap enzim beta laktamase. Penelitian dilakukan dengan mengoptimasi masing masing molekul menggunakan metoda semi empiris PM3, dengan gradien 0,01 dan menghitung kerapatan elektron pada karbonilnya. Dari hasil penelitian dapat disimpulkan bahwa pada penisilin yang tahan asam, kerapatan elektron atom O karbonil amida sebesar -0,335 pada penisilin V, -0,333 pada metisilin, -0,316 pada ampisilin , -0,315 pada amoksisilin, keempatnya kurang nukleofil dibanding kerapatan elektron atom O amida pada benzyl penisilin yang tidak tahan asam sebesar -0,347. Untuk penisilin yang tahan enzim beta laktamase dapat disimpulkan bahwa kerapatan elektron atom C karbonil lactam pada nafsilin +0,272, kloksasilin +0,270, metisilin +0,269 kurang elektrofil dibanding penisilin yang tidak tahan enzim beta laktamase sebesar +0,280.

Mixed ab initio and semiempirical study of hydrogen-terminated finite germanium nanowires

We present a mixed ab initio and semiempirical method for the cohesive energy and electronic gap calculations of hydrogen passivated tetrahedral and clathrate germanium nanowires (∼ 1850 atoms) with acceptable accuracy, comparable to density functional theory results, and with a significantly lower computational cost. First, we find that the PM6 semiempirical method produce the most accurate geometries when compared with the DFT results; whereas other semiempirical methods such as AM1, PM3 and PM7 clearly underestimate (or overestimate). Second, we implement the DFT@PM6 mixed scheme for cohesive/binding energy and electronic gap calculations which shows promising results compared with reference values of DFT. However, the bulk energy gap and binding energy values from the quantum confinement fitting procedure slightly underestimate the results which can be easily overcome using suitable functional and basis set/ECP. Also, a comparison with previous work clearly shows that the calculated electronic gap for bulk germanium is extremely sensitive to the choice of framework. Further development in this research work is progressing.

Theoretical investigation of the mechanism for the reductive dehalogenation of methyl halides mediated by the CoI-based compounds cobalamin and cobaloxime.

Theoretical calculations focusing on the cleavage of the C-X bond in methyl halides (CH3X; X = Cl, Br, I) as mediated by CoI-based systems have been carried out using the hybrid functional ωB97-XD together with the basis set 6-311++G(2d,2p). A total of seven CoI-based compounds were evaluated: cob[I]alamin (CoICbl) in its base-on form and cobaloxime (CoICbx) with either no ligand or different ligands (either pyridine (PYR), tributylphosphine (TBP), dimethyl sulfide (DMS), cyclohexylisocyanide (CI), or 5,6-dimethylbenzimidazole (DMB)) at the lower axial position. For the large CoICbl system, an ONIOM scheme was employed, where the high layer was described at the DFT level and the low layer was computed using the semi-empirical method PM6. A full DFT model was employed for the CoICbx cases. An SN2-like mechanism was evaluated in all cases. The intrinsic reaction coordinate profiles suggested early transition states with activation energies of ≈ 12kcal/mol, ≈ 10kcal/mol, and ≈ 5kcal/mol for C-Cl, C-Br, and C-I cleavage, respectively, which is consistent with the leaving group abilities of these halides. The evolutions of the atomic charges in and the bond orders of Co-C and C-X were computed, and the results confirmed the existence of early transition states (δBav≈ 40%), where the polarization Cδ+-Xδ- (%Ev ≈ 43%) is the determining factor in the reaction process. Finally, a comparison of all the determined parameters showed that the reaction in the DMB-CoICbx system resembles the process that occurs in the larger CoICbl, suggesting that the former system could be a reliable model for the study of reductive dehalogenation mediated by vitamin B12, which is key to the anaerobic microbiological treatment of halocarbon contaminants.

SEMI-empirical PM6 method applied in the analysis of thermodynamics properties and molecular orbitals at different temperatures of adsorption drugs on chitosan hydrogels for type 2 diabetes

In this work, the computation modeling was used by the semi-empirical PM6 method that allowed to analyze the effect of temperature (308.15, 310.15 and 313.15 K, respectively) on the adsorption of metformin, glibenclamide as well as the glibenclamide/metformin complex on chitosan hydrogels crosslinked with genipin in which it was appreciated that the Gibbs free energy remained thermodynamically stable at an average of 99.857–100.215%, the dipole moments indicated differences in electronegativities that were verified by the electrostatic potential maps (MESP) where the nucleophilic and electrophilic zones were appreciated at different temperatures in the CH, NH, CO and OH bonds, respectively. On the other hand, the negative partition coefficient indicated that the solubility of the complex on the hydrogel chains is carried out even with changes in temperature. Also, the presence of deprotonation generated an increase in hydrogel swelling. Finally, the difference between the highest occupied molecular orbital and the lowest unoccupied molecular orbital orbitals indicated the presence of a molecular flow in the valence and conduction bands during the adsorption of complex, then these results indicate that is possibly designing a drug delivery system.

Finding Free-Energy Landmarks of Chemical Reactions.

We propose a novel approach to search for free-energy landmarks, i.e., minima and the saddle points, of chemical reactions in an automated manner using a combination of steepest descent and gentlest ascent methods. A numerical approach is suggested to improve the sampling efficiency of the second derivatives of the free-energy surface, which is required in the gentlest ascent method. This technique opens a way to identify free-energy landmarks of bond-breaking/creating processes in which the underlying potential energy surface is described using on-the-fly electronic structure calculations. As demonstrations of the approach, we present applications to the ring-opening of cis-1,2-dimethylbenzocyclobutene using the semiempirical PM7 method, focusing on the temperature dependence of the paths and barrier of the reaction, and we study an SN2 reaction in aqueous solution using a semiempirical QM/MM approach combining PM7 with the TIP3P water model.

Synthesis and Spectroscopic Determination of the Coordination Differences of Cadmium and Zinc Complexes of Dehydroacetic Acid with Pyridine and g-Picoline

Various complexes of DHA with transition-metal cations are known for their antifungal properties. Here, four novel Zn and Cd complexes were prepared via the substitution of water by pyridine andg-picoline using Zn(DHA)2(H2O)2 (2) and Cd(DHA)2(H2O)2 (3) as starting materials. The products were characterized by IR, UV, elemental analysis, TGA and NMR techniques, including correlation times and intermolecular distance measurements using the NULL pulse sequence. The experimental data were compared to the molecular modeling results using DFT and the semiempirical method PM3, confirming that the pentacoordinated Zn complexes have bipyramidal geometry while the Cd complexes have the expected octahedral geometry. These results show that substitution of Zn by Cd leads to an important modification of the coordination structure, especially when strong ligands are involved.

Quantum chemical investigation of new model bent-shaped bis-azomethines for nonlinear optics applications

Quantum-chemical calculations of the E,E-, E,Z- and Z,Z-isomers structure of model bis-azomethines by the semiempirical PM3 method and the time-dependent theory of the density functional (DFT) are performed. It is shown that a completely satisfactory agreement between the theory and experiment is achieved using the B3LYP/cc-pVDZ calculation level and the INDO/S method for calculating the absorption spectra of the new bis-azomethines. The values of polarizability, first and second hyperpolarizability of model compounds are calculated. The used approach allows to make the screening of the most promising bis-azomethines for nonlinear optics applications.

QSAR modeling of some anticonvulsant molecules as γ-aminobutyrate-aminotransferase inhibitors

Abstract Quantitative structure-activity relationship study was done on 62 compounds with anticonvulsant activity in maximal electroshock-induced seizures test. The molecular structure of the compounds was optimized with parametric semi-empirical PM3 method available in Spartan 14 software. Quantum mechanical descriptors were extracted from the property and output module of the software. Combination of activity based-clustering and genetic function algorithm chemo-metric techniques were used to map molecular descriptors to activity values. A well-validated and robust quantitative structure-activity model was obtained with R 2 = 0.947, Q 2 = 0.924, F = 91.42 and R 2 pred(test) = 0.881. The descriptor contained in the model suggested an increase in the number of O and N atoms in the molecule augments the activity of the studied compounds. Also, the introduction of electron donating substituents is beneficial to the activity of the studied compounds. Armed with these, information, new hypothetical1H-pyrazole-5-carboxylic acid derivatives were designed using template approach and screened in silico . Compounds with hypothetic anticonvulsant activity better than the template were docked with γ-aminobutyrate-aminotransferase and their binding affinity was found to be comparable and even superior to that of 4-aminohex-5-enoic acid (vigabatrin), a known inhibitor of γ-aminobutyrate-aminotransferase.

QSAR STUDIES ON DERIVATIVES OF QUINAZOLINE-4(3H)-ONES WITH ANTICONVULSANT ACTIVITIES

Quantitative structure-activity relationship study was done on some quinazoline-4(3H)-ones derivatives with anticonvulsant activity against maximal electroshock-induced seizure. The quinazoline derivatives used as dataset and their anticonvulsant activity value were obtained from the literature. The molecular structure of the dataset compounds was generated with Spartan 14 software. This was optimized with PM3 semi-empirical quantum mechanical method available in the software. Molecular descriptors were obtained from the optimized structures using the PaDEL-Descriptor software. Activity values of the compounds and molecular descriptors obtained from the optimized structure made up the database for the study. The database was divided into training and test sets with Kennard Stone algorithm. Genetic function algorithm was used to develop quantitative structure-activity relationship models. The best model obtained was stable, robust and had good statistical parameters including determination coefficient R2 (0.899), adjusted determination coefficient R2adj (0.888), variance ratio F (82.03), leave one out cross-validated determination coefficient Q2 (0.866) and predicted determination coefficient for the test set R2pred (0.7406). The model indicated that the anticonvulsant activity of the studied compounds was dependent on Broto-Moreau autocorrelation-lag2/weighted by Vander Waals volume (ATS2v), average coefficient sum of the last eigenvector from Barysz matrix/weighted by Vander Waals volume (VE2_DZv), largest absolute eigenvalue of Burden matrix-6/weighted by relative atomic mass (SpMax6_Bhm), average valence path of order 6 and radial distribution function at 4.5 interatomic distance weighted by first ionization potential (RDF45i).

Ferroelectric PVDF films and graphene-based composites

Advantages in the studies of new composite nanomaterials based on polymer ferroelectrics and graphene are presented. We analyzed the main results of the computational molecular modeling of nanostructures and the pyroelectric properties of the composites from polyvinylidene fluoride (PVDF) films and graphene layers. The pyroelectric effect was modelled and pyroelectric coefficients were calculated for several models using molecular dynamics simulation with quantum-chemical semi-empirical PM3 method from HyperChem tool. The results obtained provide important insights into our understanding of the mechanisms of pyroelectricity in the new nanocomposites, give us new prospective for further studies of the ferroelectric polymer–graphene multifunctional nanomaterials.

Synthesis, spectroscopic, thermal, fluorescence properties and molecular modeling of novel Pt(II) complex with schiff base containing NS donor atoms

New transition metal complex of Pt(II) of the Schiff base ligand with (E)-2-((1-(thiophen-2-yl)ethylidene)amino)phenol HL have been synthesized using the ultrasonic irradiation and characterized by physicochemical and spectroscopic methods. The IR spectrum of Pt(II) complex showed that the coordination in metal ions via the imine N and S atoms. Magnetic and UV–Vis spectra showed that the geometrical structure of Pt(II) complex is square planar. The molar conductance data revealed that Pt(II) complex is non-electrolyte. The thermodynamic parameters for thermal decomposition of Pt(II) complex was calculated from analysis of the TG-DTG curves using Hörowitz–Metzger method. The fluorescence of the ligand HL and its Pt(II) complex in different solvents and pH conditions have also been studied in detail. The quenching of the fluorescence intensity of the ligand can be noted obviously, in the presence of Pt(II) ion. Geometry optimization of the compounds was calculated by semiempirical molecular orbital theory PM3 method using Hyperchem 7.52 program.

Spectroscopy, molecular modeling and anti-oxidant activity studies on novel conjugates containing indole and uracil moiety

Herein we describe our results on the synthesis and molecular modeling of new conjugates containing indole and uracil moiety. This group of compounds has been synthesized by the reaction of indole alkaloid - gramine with appropriate uracil (uracil, 2-thiouracil, 6-methyl-2-thiouracil, thymine, 6-methyluracil and barbituric acid) using DMF as solvent. The structures of all products were confirmed by spectroscopic (1H NMR, 13C NMR, and FT-IR) analysis, mass spectrometry (EI) and PM5 semiempirical methods. Moreover the protonation constants for investigated compounds were determined. The obtained conjugates were screened in vitro for antioxidant and haemolytic activities, as well as for the protective effects against 2,2′-azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative haemolysis of human erythrocytes.