First-order Molecular Connectivity Research Articles

Fluorescence Study of the Influence of the Structure and Hydrophobicity of Fluorescent Dyes and Cationic Surfactants on their Association in Aqueous Solutions

The statistical characteristics of the dependences of the fluorescence signal of analytical systems as a function of the integral parameters of the structure of fluorescent reagents and cationic surfactants on their association in aqueous solutions has been investigated. Molecular weight, surface area, and their first-order molecular connectivity index have been taken as parameters of the structure of the reagents and cationic surfactants. The influence of the hydrophobicity of the reagent and cationic surfactants, such as the octanol–water distribution constant and octanol–water partition coefficient, on the fluorescence signal of the reagent–cationic surfactant associates have also been investigated. It is shown that the associates of anionic reagents with cationic surfactant counter ions are characterised by high stability and a higher analytical signal compared with associates in which there is no electrostatic attraction between the reagent and the surfactant ion. The effect of hydrophobicity of the reagent and cationic surfactant in the absence of electrostatic attraction between the interacting particles is similar. The increase in the role of the influence of the structure of cationic reagents in their association with cationic surfactants, when the electrostatic attraction is absent and the stability of the associates is due mainly to hydrophobic interactions, is noticeable. The regularities of the influence of the colloid-chemical state on the analytical signal of associated cationic surfactants in solutions have been investigated. The study made it possible to formulate a rational basis for the search and design of analytical systems for the determination of large cations by the fluorescence method.

Novel Atom-Type-Based Topological Descriptors for Simultaneous Prediction of Gas Chromatographic Retention Indices of Saturated Alcohols on Different Stationary Phases

In this work, novel atom-type-based topological indices, named AT indices, were presented as descriptors to encode structural information of a molecule at the atomic level. The descriptors were successfully used for simultaneous quantitative structure-retention relationship (QSRR) modeling of saturated alcohols on different stationary phases (SE-30, OV-3, OV-7, OV-11, OV-17 and OV-25). At first, multiple linear regression models for Kovats retention index (RI) of alcohols on each stationary phase were separately developed using AT and Randic’s first-order molecular connectivity (1χ) indices. Adjusted correlation coefficient (R2adj) and standard error (SE) for the models were in the range of 0.994-0.999 and 4.40-8.90, respectively. Statistical validity of the models were verified by leave-one-out cross validation (R2cv > 0.99). In the next step, whole RI values on the stationary phases were combined to generate a new data set. Then, a unified model, added McReynolds polarity term as a descriptor, was developed for the new data set and the results were satisfactory (R2adj=0.995 and SE=8.55). External validation of the model resulted in the average values of 8.29 and 8.69 for standard errors of calibration and prediction, respectively. The topological indices well covered the molecular properties known to be relevant for retention indices of the model compounds.

Synthesis, antimicrobial activities and QSAR studies of heterocyclic Schiff base ligands with organosilicon(IV) halides

A series of heterocyclic Schiff base ligands 4-hydroxy-3-[1-{(2-hydroxy-aryl) imino}-ethyl]-6-methyl-pyran-2-one; aryl = phenyl, 4-methylphenyl, 4-chlorophenyl or 4-nitrophenyl (1–4) and their organosilicon(IV) complexes R2Si(L) (R = Et, Bu or Ph) (5–16) were synthesized and characterized. The elemental analyses, molar conductance and spectral (IR, 1H, 13C and 29Si NMR) data suggested pentacoordinated environment around the silicon atom, where tridentate ligands coordinate through the azomethine nitrogen and oxygen of hydroxyl groups. The ligands and their organosilicon complexes were tested in vitro against pathogenic bacteria and fungi to assess their antimicrobial properties. The activity of the ligands improved against most of the strains of the tested microorganisms on complexation to the organosilicon groups. The antimicrobial activities were correlated with QSAR studies using the linear free energy relationship model which indicate the importance of topological parameters, third-order and valence first-order molecular connectivity indices (3 χ v and 1 χ v ), to explain the antibacterial and antifungal activities of all synthesized compounds.

Adsorption and Movement of Carbofuran in Four Different Soils Varying in Physical and Chemical Properties

Laboratory studies were conducted to determine the adsorption and movement of carbofuran on four divergent textured Indian soils at a fixed volume fraction (fs = 0.1) of methanol/water mixtures using batch equilibrium and soil thin layer chromatography (soil TLC) techniques. The measured equilibrium adsorption isotherms for silt loam (FSL and ASL) and loam (KL) soils were L-shaped and for sandy loam (BSL) soil S-shaped, all being well fitted by the Freundlich isotherm. A higher adsorption of carbofuran was observed on FSL followed by ASL, KL and BSL soils as anticipated by the values obtained for the Freundlich constant, KF and partition coefficient, KD. The Frontal Retardation factor (FRf) values obtained from soil TLC studies were inversely proportional to the KF and KD values. The affinity of carbofuran towards organic carbon, organic matter and clay content of the soils was evaluated by calculating the KOC, KOM and KC values. The negative magnitude of the Gibbs'free energy (ΔG0) indicated the spontaneity of the adsorption of carbofuran onto the soils studied. The leaching index (LI) of carbofuran calculated for the soils studied indicated its high potential to leach into shallow aquifers and ground water. Pearson's correlations calculated for KF and KD against the soil properties showed a highly significant correlation with the clay + silt content of the soils. Multiple regression of KF and KD against the soil properties indicated that the mineral content of the soils (clay and clay + silt) is the best predictor of carbofuran adsorption, followed by soil pH. Predicted log KOM values were also evaluated by using the aqueous solubility, the 1-octanol/ water partition coefficient (KOW), the adsorbability index (AI) and the first-order molecular connectivity index (1χ) of carbofuran. Use of the aqueous solubility, and the 1-octanol/water partition coefficient (KOW) to predict the extent of adsorption gave values which displayed a considerable error in comparison to those measured experimentally, whereas the use of the adsorbability index (AI) and the first-order molecular connectivity index (1χ) of carbofuran improved the predictions considerably.

A Quantitative Structure-Activity Relationship Study on a Novel Series of Hydroxamic Acid Analogs Acting as Matrix Metalloproteinase Inhibitors

A Quantitative structure-activity relationship study (QSAR) has been made on a novel series of hydroxamic acid-based matrix metalloproteinase (MMP) inhibitors. The inhibition potencies of the compounds against two MMPs, MMP-2 and MMP-3, are found to be significantly correlated with Kiers first-order valence molecular connectivity index (1xv) and Hammetts electronic constant of the substituents. It is thus found that in addition to zinc-binding group of inhibitors interacting with the zinc ion present in the MMPs, some other groups also in the molecules may have some sorts of physicochemical interactions with the sub-sites of MMPs Keywords: Quantitative structure-activity relationship, Matrix metalloproteinase inhibitors, Hydroxamic acids

A Quantitative Structure-Activity Relationship Study on Some Na+ and K+ Channel Blockers: Role of Molecular Connectivity Index

A quantitative structure-activity relationship (QSAR) study is made on a series of Na+ channel blockers (diphenylacetamide derivatives) and on a series of K+ channel blockers (blockers of cardiac delayed rectifier potassium current IKs) (benzodiazepine derivatives). In both the cases, the blocking activity is found to be significantly correlated with Kiers first-order valence molecular connectivity index.

Polyparameter Linear Free Energy Relationships for Estimating the Equilibrium Partition of Organic Compounds between Water and the Natural Organic Matter in Soils and Sediments

Values of the organic-carbon-based partition coefficient (Koc) have often been estimated using one-parameter linear free energy relationships (op-LFERs), which include both correlations between log Koc and log Kow, where Kow is the octanol-water partition coefficient, and op-LFERs that are based on first-order molecular connectivity indices. For chemicals with tendencies toward strong hydrogen-bonding or other specific interactions with the organic phase, however,these methods are notsufficientlyaccurate. Polyparameter LFERs (pp-LFERs) address these shortcomings by explicitly considering contributions toward free energy change from multiple kinds of molecular interactions with both water and bulk organic phases. This paper reviews pp-LFER theory and presents the development of a new pp-LFER for organic chemical partitioning with soil/sediment organic matter (SOM) using a data set of 356 carefully selected experimental values of log Koc for 75 chemicals, including apolar, monopolar, and bipolar compounds. The paradigm of representing SOM by a single pp-LFER is qualitatively supported by our results, and the set of coefficients for the regression log Koc= (1.10+/-0.10)E - (0.72+/-0.14)S + (0.15+/-0.15)A - (1.98+/-0.14)B + (2.28+/-0.14)V + (0.14+/-0.10) represents a proposed set of water-SOM-specific properties for estimating log Koc. The developed correlation outperformed other currently recommended approaches with the given Koc data set and also compared favorably against the use of new multiple class-specific op-LFER regressions. Overall, the pp-LFER approach is recommended over other current methods for the purpose of Koc estimation and especially for polar chemicals.

Use of distance-based topological indices for the estimation of 13C NMR shifts : A case of benzene derivatives

A pool of distance-based topological indices has been used for the estimation of 1 3 C NMR shifts in benzene derivatives. The regression analysis of the data has shown that Wiener (W)-. Szeged (Sz)-, PI (Padmakar-Ivan)- and first-order molecular connectivity ( 1 Χ)- indices gave more or less similar results, 1 Χ gave slightly better results. The use of other indices were less significant.

A quantitative structure–activity relationship study of hydroxamate matrix metalloproteinase inhibitors derived from funtionalized 4-aminoprolines

A quantitative structure–activity relationship (QSAR) study has been made on the inhibitions of some matrix metalloproteinases (MMPs) by functionalized 4-aminoproline based hydroxamates. Attempts have been made to correlate the inhibition potencies of these hydroxamates with Kier's first-order valence molecular connectivity index ( 1χ v) of substituents and electrotopological state (E-state) indices of some atoms. The correlations obtained for the inhibitions of all the enzymes studied, i.e. MMP-1, MMP-2, MMP-3, MMP-7, and MMP-13, were not so uniform, but suggested that in almost all the cases the substituents at the amide nitrogen may be conducive to the activity, though the whole amide group may be sterically unfavourable. Similarly, in most of the cases, the substituens at the phenyl moiety have been found to be beneficial to the inhibition potency and in many cases an electronic role of SO 2 group of the sulfonylphenyl moiety has been indicated.

A Comparative QSAR Study on Carbonic Anhydrase and Matrix Metalloproteinase Inhibition by Sulfonylated Amino Acid Hydroxamates

A quantitative structure-activity relationship (QSAR) study is made on the inhibition of a few isozymes of carbonic anhydrase (CA) and some matrix metalloproteinases (MMPs), both zinc containing families of enzymes, by sulfonylated amino acid hydroxamates. For both enzymes, the inhibition potency of the hydroxamates is found to be well correlated with Kier's first-order valence molecular connectivity index 1χv of the molecule and electrotopological state indices of some atoms. From the results, it is suggested that while hydroxamate-CA binding may involve mostly polar interactions, hydroxamate-MMP and hydroxamate-ChC (ChC: Clostridium histolyticum collagenase, another zinc enzyme related to MMPs) bindings may involve some hydrophobic interactions. Both MMPs and ChC also possess some electronic sites of exactly opposite nature to the corresponding sites in CAs. A group such as C 6 F 5 present in the sulfonyl moiety is shown to be advantageous in both CA and MMP (also ChC) inhibitions, which is supposed to be due to the interaction of this group with Zn 2+ ion present in the catalytic site of both families of enzymes.

QSAR Study on Binding Affinity of PATs (Rodenticides) to the [3H]-Mepyramine-Labelled H1 Receptor In Rat and Guinea Pig Brain

The binding of a series of PAT analogues (rodenticides) to the [3H]-mepyramine-labelled H1 receptor in rat and guinea pig brain was investigated topologically using negentropy (N), molecular redundancy (MRI), first-order molecular connectivity (1X v ), Wiener (W), and Szeged (Sz) indices. Multiple regression analyses showed that MRI provided excellent results upon introduction of indicator parameters. Predictive ability of the proposed models was discussed using cross-validation parameters.

A nonlinear group contribution method for predicting the free energies of inclusion complexation of organic molecules with alpha- and beta-cyclodextrins.

A group-contribution method was developed for calculating the binding constants or the free energies of complexation between native alpha- or beta-cyclodextrin (CD) and organic guest molecules. The nonlinear models for binary (1:1 stoichiometry) complexes of alpha- and beta-CDs were derived with squared correlation coefficients (r(2)) of 0.868 and 0.917 based on a database consisting of 102 and 218 diverse guest molecules, respectively. The parameters used in the models are first-order molecular connectivity index as a measure of molecular bulk and atom/group counts in the guest molecules. The models allow accurate estimations for the wide range of guests containing C, H, N, O, S, and/or all halogens by summing the contribution values of each defined group present in the chemical structure of the guest along with guest's molecular size factors (linear and square terms) and then the summation to a constant coefficient value. The predictive performance of the models was tested by extra set of 27 compounds which were not included in the original data set. The predicted values by the models are in good agreement with the experimentally determined data.

Acute toxicity of substituted phenols to Rana japonica tadpoles and mechanism-based quantitative structure–activity relationship (QSAR) study

Acute 12 h and 24 h lethal toxicity (12 h-LC 50 and 24 h-LC 50) of 31 substituted phenols to Rana japonica tadpoles was determined. Results indicate that toxicity of phenols to tadpoles varied only slightly with length of exposure and the 12-h test could serve as surrogate of the 24-h test. A mechanism-based quantitative structure–activity relationship (QSAR) method was employed and 1-octanol/water partition coefficient (log K ow)-dependent models were developed to study different modes of toxic action. Most phenols elicited their response via a polar narcotic mechanism and an excellent log K ow-dependent model was obtained. Soft electrophilicity and pro-electrophilicity were observed for some phenols and a good log K ow-dependent model was also achieved. Additionally, the significant dissociation of carboxyl on benzoic acid derivatives sharply reduced their toxicity. A statistically robust QSAR model was developed for all studied compounds with the combined application of log K ow, energy of lowest unoccupied orbital ( E lumo), heat of formation (HOF) and the first-order path molecular connectivity dices ( 1χ p ) .

Effect of Cationic, Non-Ionic and Anionic Surfactants on the Adsorption of Carbofuran on Three Different Types of Indian Soil

The adsorption of carbofuran in aqueous surfactant-free and surfactant (cationic, non-ionic and anionic) solutions of different micellar concentration (½ × CMC, CMC and 2 × CMC) on three different types of Indian soil has been studied using the batch shaking technique. The measured equilibrium adsorption isotherms for the surfactant-free and surfactant/soil/water systems at different critical micellar concentrations were S-shaped and in close agreement to the Freundlich isotherms. Higher adsorption of carbofuran in both systems was observed on silt loam soil followed by loam and sandy soils, and was anticipated by the values obtained for the Freundlich constant, KF, and the partition coefficient, KD. The values of KF and KD obtained also confirmed that the adsorption of carbofuran in aqueous surfactant solutions followed the order cationic > nonionic > anionic at all the CMC values studied. The affinity of carbofuran towards organic matter and the clay content of the soils was evaluated by calculating the Kom and Kc values, when it was found that carbofuran adsorption was better correlated with the clay content than with the organic matter content. The predicted log Kom values were also obtained from the aqueous solubility, 1-octanol/water partition coefficient (Kow), adsorbability index (Al) and first-order molecular connectivity index (1χ) of carbofuran. Use of the aqueous solubility and the 1-octanol/water partition coefficient of carbofuran to predict the adsorption gave values with a considerable error in comparison with those measured experimentally, whereas the use of the absorbability index and first-order molecular connectivity index for carbofuran improved the predictions considerably. The results obtained are interesting in that they afford basic data relating to the possible use of surfactants for solving problems of soil contamination by carbofuran.

Studies on some 3(2H)-pyridazinone derivatives with antinociceptive activity.

Nineteen new [6-(4-methoxyphenyl)-3(2H)-pyridazinone-2-yl]-acetamide (1-10) and 3-[6-(4-methoxyphenyl)-3(2H)-pyridazin-one-2-yl]propanamide (11-19) derivatives have been synthesized in this study. The structures of the compounds have been elucidated by their IR and NMR spectral data and elemental analysis. Antinociceptive activity of the compounds has been investigated by modified Koster's Test in mice, using aspirin as a reference. All the compounds (at 100 mg/kg dose) except 1 and 9 have been found more potent than aspirin. Compound 6 in the group of acetamide derivatives and compound 15 in the group of propanamides exhibited the highest antinociceptive activity. In addition, the propanamides have generally been found more potent than acetamides. In addition to these studies, the quantitative relationships between some structural parameters (such as log P, parachor, molar refractivity, and molecular connectivity indices) and antinociceptive activity of the compounds have been investigated. Statistical regression analysis has shown a close relationship to exist between the first-order molecular connectivity index (1 chi) and the antinociceptive activity.

Quantitative Structure−Property Relationships for the Estimation of Boiling Point and Flash Point Using a Radial Basis Function Neural Network

Radial basis function (RBF) neural network models for the simultaneous estimation of flash point (Tf) and boiling point (Tb) based on 25 molecular functional groups and their first-order molecular connectivity index (1χ) have been developed. The success of the whole modeling process depended on a network optimization strategy based on biharmonic spline interpolation for the selection of an optimum number of RBF neurons (n) in the hidden layer and their associated spread parameter (σ). The RBF networks were trained by the Orthogonal Least Squares (OLS) learning algorithm. After dividing the total database of 400 compounds into training (134), validation (133), and testing (133), the average absolute errors obtained for the validation and testing sets ranges from 10 °C to 12 °C and 11 °C to14 °C for Tf and Tb, respectively, and are in agreement with the experimental value of about 10 °C. Results of a standard Partial Least Square (PLS) regression model for single output predictions range from 23 °C to 24 °C...

QSAR modelling of soil sorption. Improvements and systematics of log K OC vs. log K OW correlations

A systematic study was performed to evaluate the quality and reliability of the quantitative relationships between the soil sorption coefficients and the n-octanol/water partition coefficients (log K OC vs. log K OW). A system of QSAR models has been derived which is based on a reliable set of experimental log K OW data (LOGPSTAR data) or reliable estimates calculated with the latest version of the ClogP algorithm. Particular emphasis has been made to clearly define the boundaries for application of developed models as well as the quality of estimates. Thus, for each developed model the application domain is clearly defined through the chemical (structural) domain, substituents domain, and X-variable domain. Finally, the QSAR model with the first-order molecular connectivity indices has been incorporated in the derived system of QSAR models since the soil sorption estimates of the predominantly hydrophobic chemicals based on the log K OW data have large uncertainties, particularly in the log K OW data range from 4 to 7.5.

Quantitative structure‐activity relationships for evaluating the influence of sorbate structure on sorption of organic compounds by soil

AbstractThe purpose of this work was to investigate the effect of sorbate structure, by using the quantitative structure‐activity relationship (QSAR) approach, on sorption of organic compounds by two soils with different amounts of organic matter. Miscible displacement experiments were performed with several organic contaminants representing six classes of nonpolar, nonionizable organic chemicals, including chlorinated aliphatics, chlorobenzenes, polycyclic aromatic hydrocarbons (PAHs), n‐alkylbenzenes, methylated benzenes, and polychlorinated biphenyls (PCBs). The breakthrough curves were analyzed by using a bicontinuum model wherein sorption is assumed to be instantaneous for a fraction of the sorbent and rate limited for the remainder. The QSAR approach was used to investigate the dependency of both equilibrium and nonequilibrium sorption coefficients on topological descriptors representing structural properties of the solutes. For both equilibrium and nonequilibrium parameters, the first‐order valence molecular connectivity (1Xv) was found to be the best topological descriptor. Most of the rate‐limited sorption behavior could be explained by accounting for the size and structure of the solute molecule, as indicated by the good correlation between the rate coefficient and 1Xv. This supports the contention that rate‐limited sorption in these systems is controlled by a physical diffusion mechanism, consistent with the polymer diffusion model. Based on this model, the calculated diffusion‐length ratios for the Borden and Mt. Lemmon soils, which have a large difference in organic‐matter contents, compare favorably to the values determined from the measured rate data.

Aqueous Solubilities of Alkylphenols and Methoxyphenols at 25 .degree.C

The aqueous solubilities of 25 phenolic substances (2-methylphenol; 3-methylphenol; 4-methylphenol; 2,3-dimethylphenol; 2,4-dimethylphenol; 2,5-dimethylphenol; 2,6-dimethylphenol; 3,4-dimethylphenol; 3,5-dimethylphenol; 2-ethylphenol; 4-ethylphenol; 2,3,5-trimethylphenol; 2,4,6-trimethylphenol; 3,4,5-trimethylphenol; 4-propylphenol; 2-isopropylphenol; 4-isopropylphenol; 4-butylphenol; 3-tert-butylphenol; 4-tert-butylphenol; 4-hexylphenol; 3,5-di-tert-butylphenol; 4-octylphenol; 3-methoxyphenol; and 4-methoxyphenol) were determined at 25 °C, by a conventional shake-flask, batch contacting method with analysis by high-pressure liquid chromatography with UV detection. Satisfactory agreement was obtained between measured and previously reported solubilities for 10 of these substances. The liquid or supercooled liquid solubilities are satisfactorily correlated with the solute's LeBas molar volume and with first-order valence molecular connectivity, yielding structure-property relationships that may be useful for predictive purposes.

Prediction of Temperature-Programmed Retention Indexes for Polynuclear Aromatic Hydrocarbons in Gas Chromatography

The objective of this study was to relate temperatureprogrammed GC retention indexes of nonsubstituted PAHs with calculated molecular properties. Prediction of retention was made by use of a partial least squares regression equation using the descriptors, i.e., first-order valence molecular connectivity, ionization potential, length, height, and quadrupole moment. Retention index predictabitity was studied with respect to individual molecular weight ranges. Pericondensed PAHs were more accurately predicted (RMS=1.6 index units (iu) or coefficient of variation of 0.31%) than catacondensed PAHs (RMS=5.8 iu or coefficient of variation of 1.1%) with the descriptor set employed