Presence Of Electronegative Atoms Research Articles

Chemometric modeling of pharmaceuticals for partitioning between sludge and aqueous phase during the wastewater treatment process.

Computational techniques, such as quantitative structure-property relationships (QSPRs), can play a significant role in exploring the important chemical features essential for the degree of sorption or sludge/water partition coefficient (Kd) towards sewage sludge of wastewater treatment process to evaluate the environmental consequence and risk of pharmaceuticals. The current research work aims to construct a predictive QSPR model for the sorption of 148 diverse active pharmaceutical ingredients (APIs) in sewage sludge during wastewater treatment. For the development of the model, we employed easily computable 2D descriptors as independent variables. The model has been developed following the Organization for Economic Cooperation and Development's (OECD) guidelines. It has undergone internal and external validation using a variety of methodologies, as well as been tested for its applicability domain. A measure of hydrophobicity, i.e., MLOGP2, showed the most promising contribution in modeling the sorption coefficient of APIs. Among other parameters, the number of tertiary aromatic amines, the presence of electronegative atoms like N, O, and Cl, the size of a molecule, the number of aromatic hydroxyl groups, the presence of substituted aromatic nitrogen atoms and alkyl-substituted tertiary carbon atoms were also found to be influential for the regulation of solid water partition coefficient of APIs during the wastewater treatment process. The statistical validity tests performed on the developed partial least squares (PLS) model showed that it is statistically evident, robust, and predictive (R2Train = 0.750, Q2LOO = 0.683, Q2F1 = 0.655, Q2F2 (or R2Test) = 0.651). In addition, the predictivity of the constructed model was further inspected by using the "prediction reliability indicator" tool for 14 external APIs.

Unraveling structural requirements of amino-pyrimidine T790M/L858R double mutant EGFR inhibitors: 2D and 3D QSAR study

EGFR is an important drug target in cancer. However, the ineffectiveness of first generation inhibitors due to the occurrence of a secondary mutation (T790M) results in the relapse of the disease. Identification of reversible inhibitors against T790M/L858R double mutants (TMLR) thus is a foremost requirement. In this study, various 2 D and 3 D Quantitative Structure–Activity Relationship models were built for amino-pyrimidine compounds with their known biological activity against TMLR mutants. The model developed using multiple linear regression statistical method via stepwise forward-backward variable selection technique showed the best results in terms of internal and external predictivity. The 2D-QSAR model indicated that the presence of electronegative atom, H-bond donors, moderate slogp, count of number of N atoms separated from O (T_N_O_4), 4pathClusterCount and number of S atom connected with two single bonds (SssSE-index), is required for increasing the inhibitory potential of compounds. Also, the 3D-QSAR model suggested that electronegative group at certain positions along with the presence of bulky groups is beneficial for good inhibition activity of the compounds. Thus, the QSAR models developed in the present work can be used for predicting the TMLR bioactivity of a new series of amino-pyrimidine derivatives. To the best of the author’s knowledge, this is the first study which deals with the development of 2 D and 3D-QSAR models for double mutant TMLR inhibitors.

Oxidative N-Dealkylation of Tertiary Amines with Tetraethylammonium Periodate Catalyzed by Metal Complexes

The oxidative N-dealkylation of tertiary amines, N,N-dimethylaniline and N,N-diethylaniline, catalyzed by some sterically hindered FeIII complexes and tetraethylammonium periodate as oxidant gave the corresponding N-dealkylated and mono-oxygenated products in good yields. The presence of electronegative atoms on the catalyst complexes influenced the product yield. The presence of H-atom abstractor 2,6-di-tert-butyl-4-methylphenol did not influence product formation, thereby suggesting that the reaction proceeded predominantly via a one-electron transfer mechanism rather than via hydrogen abstraction. Tetraethylammonium periodate favoured oxygen transfer to the substrate.

Conformational analysis investigation into the influence of nano-porosity of ultra-permeable ultra-selective polyimides on its diffusivity as potential membranes for use in the "green" separation of natural gases

Nano-porous polymers of intrinsic microporosity, PIM, have exhibited excellent permeability and selectivity characteristics that could be utilized in an environmentally friendly gas separation process. A full understanding of the mechanism through which these membranes effectively and selectively allow for the permeation of specific gases will lead to further development of these membranes. Three factors obviously influenced the conformational behavior of these polymers, which are the presence of electronegative atoms, the presence of non-linearity in the polymeric backbones (backbone kinks) and the presence of bulky side groups on the polymeric chains. The dipole moment increased sharply with the presence of backbone kinks more than any other factor. Replacing the fluorine atoms with bulky alkyl groups didn't influence the dipole moment greatly indicating that the size of the side chains had much less dramatic influence on the dipole moment than having a bent backbone. Similarly, the presence of the backbone kinks in the polymeric chains influenced the polymeric chains to assume less extended configuration causing the torsional angles around the interconnecting bonds unable to cross the high potential energy barriers. The presence of the bulky side groups also caused the energy barriers of the cis-configurations to increase dramatically, which prevented the polymeric segments from experiencing full rotation about the connecting bonds. For these polymers, it was clear that the fully extended configurations are the preferred configurations in the absence of strong electronegative atoms, backbones kinks or bulky side groups. The addition of any of these factors to the polymeric structures resulted in the polymeric chains being forced to assume less extended configurations. Rather interestingly, the length or bulkiness of the side groups didn't affect the end-to-end distance distribution to a great deal since the presence of quite large bulky side chain such as the pentyl group has caused the polymeric chains to revert back to the fully extended configurations possibly due to the quite high potential energy barriers that the chains have to cross to reach the less extended configurational states.

2D-QSAR study of 1,4-benzodiazepine-2-ones as potent anti-trypanosomal agents

2D-QSAR is one of the oldest methods of structure activity relationship analysis which provide many breakthroughs in the medicinal field. This method can provide a direct correlation between various physicochemical properties of a molecule with its structural characteristics. The correlations established by this method are based on the relative contribution of various descriptors. In the present study, this technique is utilized to develop a correlation equation between the anti-human African trypanosomiasis activity and the physicochemical parameters depicted by various descriptors utilized within the study. This series consists of 67 compounds with widespread range of activity between 0.78 and 3.13 μM. In addition, an effective correlation was obtained between SaasCE-index, Slogp, NitrogensCount, 0PathCount, Chi4pathCluster, CarbonsCount, and the biologic activity. These contributed descriptors illustrate that various physicochemical properties of the molecules responsible for the activities. The model suggests that the hydrophobicity has positive impact on the activity, while the presence of electronegative atom especially nitrogen and flexibility of the molecules also provide favorable effect on the activity.

Structural analysis of α-glucosidase inhibitors by validated QSAR models using topological and hydrophobicity based descriptors

In the present investigation, QSAR analysis was performed on a data set consist of structurally diverse compounds in order to investigate the role of its structural features on their α-glucosidase inhibitory activity. The computational and statistical analyses were performed with V-life MDS and Statistica software. The models derived from multiple linear regression analysis were validated by LOO, LMO, Y-randomization and external test validation methods to investigate its reliability and robustness. The MLR models for the complete data set were also developed with the same descriptors to examine the reliability of the contributed descriptors (in the training set models) for the activity prediction. The validated QSAR models show that the molecular connectivity descriptors (ChiV3cluster and ChiV4), electrotopological descriptors (SdOE-Index and SaasCE-Index) and the hydrophobicity descriptor are contributed significantly for the stability of the models. The molecular connectivity descriptors reveal that the molecules with less number of branches on carbon or hetero atoms along with the presence of electronegative atoms are important for the inhibitory activity. The hydrophobicity descriptor, XKMosthydrophilichydrophobic distance (XKMHD) (calculated by Kellog method using XlogP) demonstrates that the XlogP values between the hydrophobic and hydrophilic distance should be low for favorable activity. The electrotopological descriptors such as the number of oxygen atoms connected with one double bond (SdOE-Index) and the number of carbon atom connected with one single bond along with two aromatic bonds (SaasCE-Index) are favorable for the activity. This study concluded that the presence of balanced hydrophobic and hydrophilic (polar and/or electron negative) properties on the vdW surface area is responsible for hydrogen bonding and other electrostatic interaction (aromatic) of inhibitors with the enzyme for favorable α-glucosidase inhibitory activity.

QSTR with extended topochemical atom (ETA) indices. 14. QSAR modeling of toxicity of aromatic aldehydes to Tetrahymena pyriformis

Aldehydes are a toxic class of chemicals causing severe health hazards. In this background, quantitative structure–toxicity relationship (QSTR) models have been developed in the present study using Extended Topochemical Atom (ETA) indices for a large group of 77 aromatic aldehydes for their acute toxicity against the protozoan ciliate Tetrahymena pyriformis. The ETA models have been compared with those developed using various non-ETA topological indices. Attempt was also made to include the n-octanol/water partition coefficient (log K o/w) as an additional descriptor considering the importance of hydrophobicity in toxicity prediction. Thirty different models were developed using different chemometric tools. All the models have been validated using internal validation and external validation techniques. The statistical quality of the ETA models was found to be comparable to that of the non-ETA models. The ETA models have shown the important effects of steric bulk, lipophilicity, presence of electronegative atom containing substituents and functionality of the aldehydic oxygen to the toxicity of the aldehydes. The best ETA model (without using log K o/w) shows encouraging statistical quality ( Q int 2 = 0.709 , Q ext 2 = 0.744 ). It is interesting to note that some of the topological models reported here are better in statistical quality than previously reported models using quantum chemical descriptors.

QSTR with Extended Topochemical Atom Indices. 10. Modeling of Toxicity of Organic Chemicals to Humans Using Different Chemometric Tools

In this communication, we have developed quantitative predictive models using human lethal concentration values of 26 organic compounds including some pharmaceuticals with extended topochemical atom (ETA) indices applying different chemometric tools and compared the extended topochemical atom models with the models developed from non-extended topochemical atom ones. Extended topochemical atom descriptors were also tried in combination with non-extended topochemical atom descriptors to develop better predictive models. The use of extended topochemical atom descriptors along with non-extended topochemical atom ones improved equation statistics and cross-validation quality. The best model with sound statistical quality was developed from partial least squares regression using extended topochemical atom descriptors in combination non-extended topochemical atom ones. Finally, to check true predictability of the ETA parameters, the data set was divided into training (n = 19) and test (n = 7) sets. Partial least squares and genetic partial least squares models were developed from the training set using extended topochemical atom indices and the models were validated using the test set. The extended topochemical atom models developed from different statistical tools suggest that the toxicity increases with bulk, chloro functionality, presence of electronegative atoms within a chain or ring and unsaturation, and decreases with hydroxy functionality and branching. The results suggest that the extended topochemical atom descriptors are sufficiently rich in chemical information to encode the structural features for QSAR/QSPR/QSTR modeling.

Aromatic solvent induced shifts (ASIS) in 1H N.M.R. spectra; A graphical analysis

By plotting ASIS values determine in the conventional way against ASIS values for a polyprotic solute in C 6D 6 approximately straight lines are obtained the slopes of which represent ASIS effects for solvents in comparison with that of benzene. These values are independent of effects introduced by choice of reference solvent and standard, whether internal or external. Any modification of benzene that introduces an electronegative atom or group reduces the positive ASIS slope of benzene. The effect of several modifications is incremental and eventually produces a marked negative slope. By themselves, ASIS values are not a measure of ring current ir of aromaticity. It is only the presence of electronegative atoms or groups that affects ASIS slopes; orientation is immaterial showinf that dipoles in aromatic solvents are not concerned in the ASIS phenomenon. Mixtures (1:1) of benzene and hexafluorobenzene shield every proton in a solute; the resulting ASIS slopes are nearly zero as expected, but this is not a consequence of competition between the solvents but of a roughly additive property in shieldings. No evidence was obtained in support of the view that ASIS deshielding exists, or that there is any strong tendency of solvent molecules to cluster about a dipolar solute. The following solvents were studied: benzene, eleven fluorobenzenes, nitrobenzene, 1,2-fluoronitrobenzene, 1,2,4-fluorodinitrobenzene, pyridine, pyrimidine, pyridazine, 3-methylpyridine oxide, pyrrole, thiophene, furan, 3,5-dimethylisoxazole, 1,2-dimethylimidazole, methoxybenzene, 1,3-dimethoxybenzene, methylenedioxybenzene. The chief solute was ethyl 4-dimethylaminobenzoate.

Modification of chemisorption properties by electronegative adatoms: H 2 and CO on chlorided, sulfided, and phosphided Ni(100)

The effect of preadsorbed electronegative atoms Cl, S and P on the adsorption-desorption behavior of CO and H 2 on Ni(100) has been studied using thermal desorption, LEED and AES. It is found that the presence of the electronegative atoms causes a reduction of the adsorption rate, the adsorption bond strength and the capacity of the Ni(100) surface for CO and H 2 adsorption. The poisoning effect becomes stronger with increasing electronegativity of the preadsorbed atoms. In the case of CO adsorption the most tightly bound β 2 -state is suppressed most significantly. The variation of the initial sticking coefficient of CO as a function of the adlayer precoverage shows that at low Cl and S coverages the effective number of the influenced Ni surface atoms is more than four. The observed reduction of CO and H 2 adsorption and the difference in the poisoning effect of Cl, S and P is generally interpreted in terms of the changes in the surface electron density in the presence of electronegative atoms.

Modification of chemisorption properties by electronegative adatoms: H 2 and CO on chlorided, sulfided, and phosphided Ni(100)

Abstract The effect of preadsorbed electronegative atoms Cl, S and P on the adsorption-desorption behavior of CO and H2 on Ni(100) has been studied using thermal desorption, LEED and AES. It is found that the presence of the electronegative atoms causes a reduction of the adsorption rate, the adsorption bond strength and the capacity of the Ni(100) surface for CO and H2 adsorption. The poisoning effect becomes stronger with increasing electronegativity of the preadsorbed atoms. In the case of CO adsorption the most tightly bound β2 -state is suppressed most significantly. The variation of the initial sticking coefficient of CO as a function of the adlayer precoverage shows that at low Cl and S coverages the effective number of the influenced Ni surface atoms is more than four. The observed reduction of CO and H2 adsorption and the difference in the poisoning effect of Cl, S and P is generally interpreted in terms of the changes in the surface electron density in the presence of electronegative atoms.