A theoretical study on 1H-indole-2,3-dione complexes with lithium, sodium, and potassium cations.

CONTEXT: A comparative study of the change in different properties of electronic and structural of the free 1H-indole-2,3-dione molecule and its complexes has been obtained. HOMA analysis was performed to investigate the effects of lithium sodium and potassium cations on the aromaticity of lithium sodium and potassium complexes of 1H-indole-2,3-dione. METHODS: Several 1H-indole-2,3-dione complexes with lithium, sodium, and potassium cations were optimized at the B3LYP/6-311G(d,p) level. The cation and π interaction has been investigated from different aspects, including interaction energy calculations, charge transfer values, and changes in the aromaticity of the ring upon complexation. The charge transfer and natural population analysis for the complexes were performed with the natural bond orbital (NBO) analysis. The properties of bond critical points in complexes were studied by applying the quantum theory of atoms in molecules (QTAIM). Finally, the aromaticity change of phenyl induced upon complex formation was evaluated by applying the harmonic oscillator model of aromaticity (HOMA). [Li-INa]+ and [[Li-INb]+ were optimized with the wB97XD function using a version of Grimme's D2 dispersion model, and the absorption energy was compared with the calculation made with the B3LYP functional.

Synthesis and characterization of new 1,3,4-thiadiazole derivatives: study of their antibacterial activity and CT-DNA binding.

1,3,4-Thiadiazole molecules (1-4) were synthesized by the reaction of phenylthiosemicarbazide and methoxy cinnamic acid molecules in the presence of phosphorus oxychloride, and characterized with UV, FT-IR, 13C-NMR, and 1H-NMR methods. DFT calculations (b3lyp/6-311++G(d,p)) were performed to investigate the structures' geometry and physiochemical properties. Their antibacterial activity was screened for various bacteria strains such as Enterobacter aerogenes, Escherichia coli ATCC 13048, Salmonella kentucky, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus and Gram positive such as Staphylococcus aureus ATCC 25923, Listeria monocytogenes ATCC 7644, Enterococcus faecium, Enterococcus durans, Staphylococcus aureus ATCC, Serratia marcescens, Staphylococcus hominis, Staphylococcus epidermidis, alfa Streptococcus haemolyticus, Enterococcus faecium and found to have an inhibitory effect on Klebsiella pneumoniae and Staphylococcus hominis, while molecules 1, 3 and 4 had an inhibitory effect on Staphylococcus epidermidis and alpha Streptococcus haemolyticus. The experimental results were supported by the docking study using the Kinase ThiM from Klebsiella pneumoniae. All the investigated compounds showed an inhibitory effect for the Staphylococcus epidermidis protein. In addition, the mechanism of the 1-4 molecule interaction with calf thymus-DNA (CT-DNA) was investigated by UV-vis spectroscopic methods.

Synthesis of Cyano-Benzylidene Xanthene Synthons Using a Diprotic Brønsted Acid Catalyst, and Their Application as Efficient Inhibitors of Aluminum Corrosion in Alkaline Solutions.

Novel cyano-benzylidene xanthene derivatives were synthesized using one-pot and condensation reactions. A diprotic Brønsted acid (i.e., oxalic acid) was used as an effective catalyst for the promotion of the synthesis process of the new starting xanthene-aldehyde compound. Different xanthene concentrations (ca. 0.1-2.0 mM) were applied as corrosion inhibitors to control the alkaline uniform corrosion of aluminum. Measurements were conducted in 1.0 M NaOH solution using Tafel extrapolation and linear polarization resistance (LPR) methods. The investigated xanthenes acted as mixed-type inhibitors that primarily affect the anodic process. Their inhibition efficiency values were enhanced with inhibitor concentration, and varied according to their chemical structures. At a concentration of 2.0 mM, the best-performing studied xanthene derivative recorded maximum inhibition efficiency values of 98.9% (calculated via the Tafel extrapolation method) and 98.4% (estimated via the LPR method). Scanning electron microscopy (SEM) was used to examine the morphology of the corroded and inhibited aluminum surfaces, revealing strong inhibitory action of each studied compound. High-resolution X-ray photoelectron spectroscopy (XPS) profiles validated the inhibitor compounds' adsorption on the Al surface. Density functional theory (DFT) and Monte Carlo simulations were applied to investigate the distinction of the anticorrosive behavior among the studied xanthenes toward the Al (111) surface. The non-planarity of xanthenes and the presence of the nitrile group were the key players in the adsorption process. A match between the experimental and theoretical findings was evidenced.

Carbazochrome carbon nanotube as drug delivery nanocarrier for anti-bleeding drug: quantum chemical study.

The interaction between drugs and single-walled carbon nanotubes is proving to be of fundamental interest for drug system of delivery and nano-bio-sensing. In this study, the interaction of pristine CNT with carbazochrome, an anti-hemorrhagic or hemostatic agent, was investigated with M06-2X functional and 6-31G* basis set. All probable positions of related adsorption for these kind drugs were thought-out to find out which one is energetically suitable. Based on the achieved data, the stronger interactions appeared the oxygen atom of C = O group and nitrogen atom of imine groups. The topology analysis of QTAIM (quantum theory of atoms in a molecule) method was accomplished to understand the properties of interactions between the CNT and carbazochrome. Frontier molecular orbital energies of all systems, global index including stiffness, softness, chemical Gibbs energies, and electrophilicity parameters, as well as some other important physical data such as dipole moment, polarizability, anisotropy polarisibility, and hyperpolaribility were calculated, evaluated, and then compared together. The essence of the formed bonding model progress along the reaction roots was further validated using electron localization function (ELF) calculations. The highest values of adsorption energies were determined in the range of 18.24 up to 22.12 kcal mol-1 for these kind systems. The acceptable recovery time of 849 s was obtained for the desorption of carbazochrome from the CNT surface under UV-light. The final results exhibit that carbazochrome can serve as a promising carrier and also as sensitive sensors in any kind of practical application.

Theoretical B3LYP Study on Electronic Structure of Contrast Agent Iopamidol.

Nonionic low-osmolar contrast agents are thought about safe for intravenous or intra-arterial administration. Iopamidol is one of the contrast agents used for diagnostic clinical computed tomography (CT) protocols last four decades years.The molecular structure of Iopamidol was calculated by the B3LYP density functional model with the LANL2DZ basis set by the Gaussian program. The natural bond orbital analysis in terms of the hybridization of atoms and the electronic structure of the title molecule have been analyzed by using the data obtained from the quantum chemical results. First-order hyperpolarizability (ßtot), the dipole moment (µ) and polarizability (α) and anisotropic polarizability (∆α) of the molecule have been reported. HOMO and LUMO energies and parameters related to energies, and dipole moment, polarizability and hyperpolarizability show minor dependences on the solvent polarity. The hardness of Iopamidol decreases with increasing solvent polarity. The stability of the Iopamidol contrast agent with the hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital analysis. In addition, thermodynamic properties were obtained in the range of 200-1000 K.

Adsorption behavior and corrosion inhibitive characteristics of newly synthesized cyano-benzylidene xanthenes on copper/sodium hydroxide interface: Electrochemical, X-ray photoelectron spectroscopy and theoretical studies.

Elegant process for synthesis of 3-(7H-dibenzo[c,h]xanthen-7-yl)benzaldehyde (3), as new starting material to create a set of novel xanthene analogues, 2-(3-(7H-dibenzo[c,h]xanthen-7-yl)benzylidene)malononitrile (4), 3-(3-(7H-dibenzo[c,h]xanthen-7-yl)phenyl)-2-cyanoacrylic acid (5), and Ethyl-3-(3-(7H-dibenzo[c,h]xanthen-7-yl)phenyl)-2-cyanoacrylate (6), was achieved starting with available materials under mild conditions. Various concentrations (ca. 0.1-1.0 mM) of the synthesized cyano-benzylidene xanthene derivatives, namely compounds 3-6, were tested as inhibitors to control copper corrosion in alkaline solutions employing polarization and electrochemical impedance spectroscopy (EIS) measurements. Results revealed that the four studied xanthenes derivatives served as efficient (mixed-type) inhibitors. The inhibition efficiency increased with increase in inhibitor concentration.The inhibition performance of studied compounds varied according to their chemical structures. The best inhibitor, compound (5), achieved a maximum inhibition efficiency of 98.7% (calculated from corrosion current densities) and ~ 95% (estimated from charge-transfer resistance values) at a concentration of 1.0 mM. The morphology of the corroded and inhibited copper surfaces was studied by scanning electron microscopy (SEM). The adsorption of the inhibitor molecules was confirmed by high-resolution X-ray photoelectron spectroscopy (XPS) profiles. XPS data were used to compare the inhibition efficiencies exhibited by studied compounds. The oxidation rate of the Cu surface was found to be frivolous, referring to high inhibition efficiency, only in the presence of inhibitor (5), and Cu0 share is 87% of all copper components. The shares of Cu0 were significantly reduced to 43%, 26% and 20% for inhibitors (3), (4) and (6), respectively. These findings go parallel with the results obtained from electrochemical measurements. The quantum-chemical calculations of the investigated molecules were performed to support electrochemical findings, and their correlations with the inhibition efficiency of the synthesized compounds were discussed.

Analysis of DNA protection, interaction and antimicrobial activity of isatin derivatives.

Isatin, thiosemicarbazone and their derivatives have been widely used in biological applications such as antimicrobial, antiviral and anticancer therapies. Herein, eight isatin and thiosemicarbazone derivative compounds were re-synthesized and evaluated for DNA binding analysis including DNA protection studies using plasmid DNA (pUC19) and DNA interaction experiments using calf thymus DNA (CT-DNA). All compounds were also utilized in vitro assay to assess the antimicrobial activity of compounds against different pathogenic bacterial strains. All isatin and thiosemicarbazone derivative compounds exhibited DNA protection activity which ranged from 23.5 to 59.5%. Among them, I3-(N-2-MP)-TSC had the greatest DNA protective activity. For DNA binding analysis, all compounds had the same constant concentration (40 µM), which interacts with CT-DNA. It was also observed that DNA interactions gave a high intrinsic binding constant (Kb = 1.72 × 104 M-1-9.73 × 105 M-1). Besides, several derivatives of isatin thiosemicarbazone exhibited significant and selective antibacterial activity with low concentration. These compounds primarily affected Gram-positive bacteria, but were not effective against P. vulgaris and E. coli. The Gram-positive methicillin-resistant S. aureus ATCC 43300 (MRSA) was the most influenced strain by these compounds. It was found that methyphenyl group at isatin was essential for its antibacterial activity for MRSA.

Synthesis and characterization of poly(3-hexylthiophene): improvement of regioregularity and energy band gap.

The organic solar cell (OSC) is a current hot topic in the context of energy related issues in order to capture energy in an economic and environmentally friendly manner from the most abundant natural source, the sun. However, the efficiency of OSCs achieved so far is not up to the mark. Major components of OSCs are the electron acceptor material, such as fullerene, and the electron donor material, such as poly(3-hexylthiophene), P3HT. Fullerene is an ideal acceptor material but molecular level engineering of P3HT is required to enhance the efficiency of OSCs. Optoelectronic properties of P3HT can be improved by controlling the regioregularity, energy band gap, and molar mass of the polymer. Additionally, p-doping of the semiconducting polymer can also help in broadening the optical spectrum of P3HT. In this study, we propose methods for the improvement of the above-mentioned properties during the synthesis of P3HT. The main focus was the improvement of the regioregularity of the synthesized P3HT, which was achieved by polymerization of 3-hexylthiophene under an electric field for the first time. The effect of molar mass and p-doping on the band gap is evaluated systematically and theoretical predictions are confirmed by experimental results.

The Quantum Chemical and QSAR Studies on Acinetobacter Baumannii Oxphos Inhibitors.

BACKGROUND: Acinetobacter is a Gram-negative, catalase-positive, oxidase-negative, non-motile, and no fermenting bacteria. OBJECTIVE: In this study, some of the electronic and molecular properties, such as the highest occupied molecular orbital energy (EHOMO), lowest unoccupied molecular orbital energy (ELUMO), the energy gap between EHOMO and ELUMO, Mulliken atomic charges, bond lengths, of molecules having impact on antibacterial activity against A. baumannii were studied. In addition, calculations of some QSAR descriptors such as global hardness, softness, electronegativity, chemical potential, global electrophilicity, nucleofugality, electrofugality were performed. METHOD: The descriptors having impact on antibacterial activity against A. baumannii have been investigated based on the usage of 29 compounds employing two statistical methods called Linear Regression and Artificial Neural Networks. RESULTS: Artificial Neural Networks obtained accuracies in the range of 83-100% (for active/inactive classifications) and q2=0.63 for regression. CONCLUSION: Three ANN models were built using various types of descriptors with publicly available structurally diverse data set. QSAR methodologies used Artificial Neural Networks. The predictive ability of the models was tested with cross-validation procedure, giving a q2=0.62 for regression model and overall accuracy 70-95 % for classification models.

Electronic-topological and neural network approaches to the structure- antimycobacterial activity relationships study on hydrazones derivatives.

That the implementation of Electronic-Topological Method and a variant of Feed Forward Neural Network (FFNN) called as the Associative Neural Network are applied to the compounds of Hydrazones derivatives have been employed in order to construct model which can be used in the prediction of antituberculosis activity. The supervised learning has been performed using (ASNN) and categorized correctly 84.4% of them, namely, 38 out of 45. Ph1 pharmacophore and Ph2 pharmacophore consisting of 6 and 7 atoms, respectively were found. Anti-pharmacophore features socalled "break of activity" have also been revealed, which means that APh1 is found in 22 inactive molecules. Statistical analyses have been carried out by using the descriptors, such as EHOMO, ELUMO, ΔE, hardness, softness, chemical potential, electrophilicity index, exact polarizibility, total of electronic and zero point energies, dipole moment as independent variables in order to account for the dependent variable called inhibition efficiency. Observing several complexities, namely, linearity, nonlinearity and multi-co linearity at the same time leads data to be modeled using two different techniques called multiple regression and Artificial Neural Networks (ANNs) after computing correlations among descriptors in order to compute QSAR. Computations resulting in determining some compounds with relatively high values of inhibition are presented.

ETM and ANN study for polysubstituted 2H-pyran-2-ones.

The structure glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), acid phosphatase (ACP), alkaline phosphatase (ALP) and glutamate dehydrogenase (GlDH) activity relationships of 2H-pyran-2- ones polysubstitutes being a new class of hepatoprotective agents have been investigated by means of the Electronic- Topological Method (ETM) and two Statistical Analysis. Molecular fragments specific for active compounds were calculated for 2H-pyran-2-ones polysubstitutes by applying the ETM. QSAR descriptors such as molecular weight, EHOMO, ELUMO, ΔE, chemical potential, softness, electrophilicity index, dipole moment, etc were calculated. In order to examine the relationship between independent and dependent variables, both Partial Least Squares Regression and ANNs are employed to determine the relationship since the data set consists of highly nonlinearity and multicolinearity. It is observed that ANN has surpassed both PLS2 and PLS1 in terms of better modeling and validation.

Investigation of structure-activity relationship between chemical structure and CCR5 anti HIV-1 activity in a class of 1-[N-(Methyl)-N- (phenylsulfonyl)amino]-2-(phenyl)-4-[4-(substituted)piperidin-1-yl]butane derivatives: the electronic-topological approach.

The relationship between chemical structure and CCR5 anti HIV-1 activity was investigated in the series of 1-[N-(Methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-[4-(substituted) piperidin-1-yl]butanes derivatives including 114 molecules by using the Electron-Topological Method (ETM). In the frameworks of this approach, its input data were taken as the results of conformational and quantum-mechanical calculations. Conformational analysis and quantum-chemical calculations were carried out for each molecule. Then molecular fragments being specific for active molecules and non-active molecules were revealed by using ETM. The result of testing showed the high ability of ETM in predicting the activity and inactivity investigated series. In order to classify and to develop a model for those molecules, cluster and discriminant analyses are conducted. First, cluster analysis is implemented in order to classify similar molecules into the groups. Then, discriminant analysis is used to construct models including descriptors. By doing so, two obtained discriminant functions segregate those molecules into three different groups by using the descriptors called EHOMO, Dipole Moment and SEZPE.

The investigation of structure-activity relationships of tacrine analogues: electronic-topological method.

In this study we investigated the structure-activity relationships by using the Electron- Topological Method (ETM) for a class of AChE inhibitors related to tacrine (9-amino-1,2,3,4-tetrahydroacridine) and 11 H-Indeno-[1,2-b]-quinolin-10-ylamine that tetracyclic tacrine analogues, a drug currently in use for the treatment of the AD. Molecular fragments being specific for active and inactive compounds were revealed by using ETM. The result of testing showed the high ability of ETM in predicting the activity and inactivity in investigated series.

Electron-Topological Method of the non-nucleoside HIV-1 RT inhibitors study: structure-activity relationships.

Structure activity relationships for a series of TIBO (4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-j,k][1,4] benzodiazepin-2(1H)-one) derivatives, which significantly inhibit HIV-1 replication are analyzed by the Electron-Topological Method (ETM) and Artificial Neural Networks (ANNs). Activities of the TIBO series including 91 compounds are given as IC(50). Conformational analysis and quantum-chemical calculations are carried out for each TIBO derivatives, and then molecular fragments being specific for active compounds and non-active compounds are revealed by using ETM. In this study, we used optimized geometry data and electronic characteristics to form Electron-Topological Matrices of Contiguity (ETMCs) for all compounds in the series of TIBO derivatives. Effective charges on atoms are taken as diagonal elements, bond characteristics and optimized distances represent non-diagonal elements. To obtain the algorithmic base for the activity prediction, ANNs were used after the ETM (the so-called combined ETM-ANN method). As the result, 6 pharmacophores and anti-pharmacophores were chosen as the most important ones. The statistical coefficients calculated by the proposed algorithm were q(2)=0.82, for training set and q(2)= 0.72, for external test set respectively Thus, the found results showed that ETM-ANNs approach is a good convenient tool for QSAR studies.

Synthesis and structure-antituberculosis activity relationship of 1H-indole-2,3-dione derivatives.

New series of 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones 2a-k and 5-fluoro-1-morpholino/piperidinomethyl-1H-indole-2,3-dione-3-thiosemicarbazones 3a-r were synthesized. The structures of the synthesized compounds were confirmed by spectral data, elemental and single crystal X-ray diffraction analysis. The new 5-fluoro-1H-indole-2,3-dione derivatives, along with previously reported 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 2l-v, 1-morpholino/piperidinomethyl-5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 4a-l, and 5-nitro-1H-indole-2,3-dione-3-[(4-oxo-1,3-thiazolidin-2-ylidene)hydrazones] 5a-s, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. Among the tested compounds, 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (2p, 2r, and 2s) and its 1-morpholinomethyl derivatives (4a, 4e, 4g, and 4i) exhibited significant inhibitory activity in the primary screen. The antituberculosis activity of molecules with diverse skeletons was investigated by means of the Electronic-Topological Method (ETM). Ten pharmacophores and ten anti-pharmacophores that have been found by this form the basis of the system capable of predicting the structures of potentially active compounds. The forecasting ability of the system has been tested on structures that differ from those synthesized. The probability of correct identification for active compounds was found as equal to 93% in average. To obtain the algorithmic base for the activity prediction, Artificial Neural Networks were used after the ETM (the so-called combined ETM-ANN method). As the result, only 9 pharmacophores and anti-pharmacophores were chosen as the most important ones for the activity. By this, ANNs classified correctly 94.4%, or 67 compounds from 71.

Synthesis and structure-antibacterial activity relationship investigation of isomeric 2,3,5-substituted perhydropyrrolo[3,4-d]isoxazole-4,6-diones.

The synthesis of 2,3,5-substituted perhydropyrrolo[3,4-d]isoxazole-4,6-diones (44 compounds) has been accomplished by the cycloaddition reaction of N-methyl-C-arylnitrones with N-substituted maleimides. The compounds were screened for their antibacterial activities and most of them exhibited activity against Enterococcus faecalis (ATCC 29212) and Staphylococcus aureus (ATCC 25923). cis-3a and cis-3d were found fairly effective against E. faecalis (ATCC 29212) and S. aureus (ATCC 25923) with MIC values of 25 and 50microg/ml. With the changes of cis isomers of the compounds to trans, their antibacterial activities also changed against the bacteria studied. First, pharmacophoric fragments had been calculated in accordance with the rules of the electronic-topological method (ETM). Next, both active compounds and pharmacophores had been projected to the nodes of Kohonen's self-organizing maps (SOM) to obtain the weights of pharmacophore fragments as numerical descriptors, that were used after this for the associative neural networks (ASNN) training. A model for the activity prediction was developed as the result of training the ASNNs.

Ab initio and density functional computations of the vibrational spectrum, molecular geometry and some molecular properties of the antidepressant drug sertraline (Zoloft) hydrochloride.

Sertraline hydrochloride is a highly potent and selective inhibitor of serotonin (5HT). It is a basic compound of pharmaceutical application for antidepressant treatment (brand name: Zoloft). Ab initio and density functional computations of the vibrational (IR) spectrum, the molecular geometry, the atomic charges and polarizabilities were carried out. The infrared spectrum of sertraline is recorded in the solid state. The observed IR wave numbers were analysed in light of the computed vibrational spectrum. On the basis of the comparison between calculated and experimental results and the comparison with related molecules, assignments of fundamental vibrational modes are examined. The X-ray geometry and experimental frequencies are compared with the results of our theoretical calculations.

The structure--antituberculosis activity relationships study in a series of 5-(4-aminophenyl)-4-substituted-2,4-dihydro-3h-1,2,4-triazole-3-thione derivatives. A combined electronic-topological and neural networks approach.

Antituberculosis activity of several 5-(4-aminophenyl)-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones (1-9) and their thiourea derivatives (10-31) were screened for their antimycobacterial activities against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Of the synthesized compounds, 10-12, 30 were the most active derivatives exhibiting more than 90 % inhibition of mycobacterial growth at 12.5 microg/mL. Structure-activity relationships study was performed for the given series by using the Electronic-Topological Method combined with Neural Networks (ETM-NN). A system of prognosis was developed as the result of training associative neural network (ASNN) using weights of pharmacophoric fragments as descriptors. Descriptors were calculated by the projection of ETM compound and pharmacophoric fragments on the elements of Kohonen's self-organizing maps (SOM). From the detailed analysis of all compounds under study, the necessary requirements for a compound to possess antituberculosis activity were formulated. The analysis have shown that any requirements violation for a molecule implies a considerable decrease or even complete loss of its activity.

Synthesis of novel 5-aryl-2-thio-1,3,4-oxadiazoles and the study of their structure-anti-mycobacterial activities.

The preparation of novel 5-aryl-2-thio-1,3,4-oxadiazoles 4a-41 and the computer-aided study of their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) are reported. The average accuracy of the electronic-topological method and neural network methods applied to the activity prediction in leave-one-out cross validation is 80%.

Experimental and theoretical studies on the functionalization reactions of 4-benzoyl-1,5-diphenyl-1H-pyrazole-3-carboxylic acid and acid chloride with 2,3-diaminopyridine.

The 1H-pyrazole-3-carboxylic acid 2 was converted in good yield (69%) into the corresponding 1H-pyrazole-3-carboxamide 5 via reaction of the acid chloride 3 with 2,3- diaminopyridine (4). A different product, the 3H-imidazo[4,5-b] pyridine derivative 6, was formed from the reaction of 3 with 4 and base in benzene for 5 hours. The structures of the synthesized compounds were determined spectroscopically. The mechanism of the reaction between 3 and 4 was examined theoretically.