First-order Molecular Connectivity Research Articles

Prediction of enthalpies of sublimation of fullerenes from first-order molecular connectivity theory

The first-order molecular connectivity, 1χ v, is determined for each C 2 n (fullerene) and used to predict the enthalpy of sublimation, Δ H sub, of each C 2 n solid. The prediction is based upon a linear regression fit of the enthalpies of vaporization of polycyclic aromatic hydrocarbons as a function of 1χ v. For C 60 and C 70, the calculated (and experimental) values - in kcal/mol - are C 60: 40.8 (40.5) and C 70: 46.6 (45). The theory is also used to predict the van der Waals volume, V, of the fullerenes. It is evident that this simple approach works for Δ H sub for C 60 and C 70, but it needs to be checked with experimental data for the larger fullerenes.

Determinants of the short-term dynamics of PCB uptake by plankton

Many studies relate the ecological fate of a contaminant to its chemical structure, but few combine quantitative structure-activity relationships with environmental properties that may modulate those effects, so the modulating role of such properties remains unquantified. This study determines the effects of variations in suspended biomass, dissolved and colloidal organic carbon, and pH on the time course of 2, 2[prime], 4, 4[prime], 5, 5[prime]-hexachlorobiphenyl uptake by laboratory cultures of Selenastrum capricornutum Printz. Variations in pH had no effect, but uptake increased with biomass and decreased at higher levels of organic carbon, measured as absorbance at 440 nm (Abs, per meter). Coefficients for these effects combined with existing relations based on simple first-order molecular connectivity ([chi]) or capacity ratio (K[prime]) yielded semi-empirical equations to predict the instantaneous rate of uptake and bioconcentration factor (BCF) of organic contaminants: log rate = [minus]3.30 + 0.32[chi] + 1.1 log biomass [minus] 0.42 log Abs; log BCF = 4.11 + 0.86 log K[prime] [minus] 0.87 log biomass [minus] 0.22 log Abs. These equations, entirely based on pure laboratory cultures, were assessed by comparing predicted uptake with the time courses of polychlorinated biphenyl (PCB) uptake by plankton in water from 11 Quebec lakes and proved tomore » be more effective than predictions based on contaminant properties alone.« less

Synthesis and taste properties of sodium disubstituted phenylsulfamates. Structure-taste relationships for sweet and bitter/sweet sulfamates

Forty ring disubstituted phenylsulfamates have been synthesized as their sodium salts. These compounds display a variety of tastes including sweet, bitter and sour. Seven of them gave a predominantly sweet taste, twelve displayed a bitter taste followed by a sweet aftertaste, eleven showed predominant bitterness, five sourness and five gave an aniline- or hydrocarbon-like taste and were not assessed further by the panellists. A plot of z (width of molecule, measured using Corey-Pauling-Koltun (CPK) models) versus first-order molecular connectivity, 1 x v placed the seven predominantly sweet compounds on the line described by z = 2·27 1x v − 0·158 . Summation of Hammett sigma (σ) values for the X and Y substituents gives Σ σ, and with these the following structure-taste relationships were derived: Predominant sweetness: Σ σ ≥ 0·6, V CPK ≤ 300 A ̊ 3 and a meta-electron with drawing substituent, no para-substituent. Bitter/sweet aftertaste: Σ σ ≤ 0·22, V CPK ≤ 300 A ̊ 3 . Some of the starting disubstituted anilines have been reported to be sweet and sulfamation modifies or destroys this sweetness. This is also discussed.

Calculation of retention indices by molecular topology: III. Chlorinated dibenzodioxins

A model is developed, based entirely on chemical structure, for the accurate prediction of the retention of chlorinated dibenzodioxins (PCDDs) on a non-polar stationary phase (DB-5) and for reproducing their experimental elution sequence. The first-order molecular connectivity inex ( 1χ) and six other topological properties, the specific mono-, di- and trichloro substitution patterns, were used as structural descriptors. Thus, one can predict the retention index for any given PCDD having only a knowledge of its chlorine substitution pattern. The agreement between observed and calculated retention indices (the average residual of 1.8 units) indicates that this model works fairly well to describe the retention indices of all analysed PCDDs (37 tetra- to octachlorinated congeners). The developed model was successfully validated by extrapolation on a small set of retention indices determined for di- and trichlorinated PCDD congeners and by interpolation on a set of sixteen retention indices determined for tetra- to octachlorinated PCDDs on a low-polarity HP-5 capillary column. The regression analysis shows that the PCDD retention indices are primarily influenced by their bulk properties, i.e., the size of these molecules. This property, described best by the 1χ index, accounts for more than 97% of the variation in the retention index data. The other factors that control the magnitude of the retention indices are various chlorine substitution patterns, having either a positive or a negative effect on the magnitude of the retention indices. Finally, a mechanism for the interaction of PCDDs with the non-polar stationary phase is also discussed.

Molecular topology/fragment contribution method for predicting soil sorption coefficients

The first-order molecular connectivity index ( 1 χ) has been successfully used to predict soil sorption coefficients (K oc ) for nonpolar organics, but extension of the model to polar compounds has been problematic. To address this, we developed a new estimation method based on 1 χ and a series of statistically derived fragment contribution factors for polar compounds. After developing an extensive database of measured K oc values, we divided the dataset into a training set of 189 chemicals and an independent validation set of 205 chemical.

Relationship between gas chromatographic retention indices and molecular connectivity indices of chlorinated pesticides and structurally related compounds

The ability of the molecular connectivity model to predict retention indices using both statistical correlation coefficients and correctly predicted elution sequences as criteria of fitness was tested. The tests were performed with chlorinated pesticides and some structurally related compounds. The effect on the retention index of increasing replacement by chlorine of hydrogen atoms bonded to one carbon of the aliphatic part of the molecule was excellently correlated by 1χ v, the first-order valence molecular connectivity index, using a quadratic polynomial equation. This equation also fits 1χ v with the retention indices of halobenzenes and halobiphenyl compounds. On the other hand, 1χ v was the most significant connectivity index, using a single linear regression equation to correlate the retention indices of all the compounds. However, 1χ v alone was not sufficient to distinguish significantly some isomers and the correct elution sequence giving a relatively low correlation coefficient. Therefore, other connectivity indices and the consequently use of multiple linear regression equations were necessary in order to represent more completely the molecules and to obtain more accurate results.

Retention of hydrophobic solutes on reversed-phase liquid chromatography supports: Correlation with solute topology and hydrophobicity indices

Retention of several nonpolar solutes on two reversed-phase liquid chromatography (RPLC) supports was examined during isocratic, isothermal elution with binary mixtures of methanol/water and acetonitrile/water. Changes in chromatographic retention factors (k) were correlated with the following indices of solute hydrophobicity and molecular topology: octanol-water partition coefficient (K ow), hydrophobic surface area (HSA), and first-order molecular connectivity ( 1 χ). For each sorbent-solvent combination, one regression equation was required to describe the data for polycyclic aromatic hydrocarbons and halobenzenes, and another for the alkylbenzenes. This distinctive behavior was attributed to the differences in the nature of the interaction of these two groups of solutes with the bonded, n-alkyl chains. Solute molecular size, shape, and conformation as well as hydrophobicity appear to be the dominant factors controlling solute retention by RPLC supports.

Chromatographic study of methylcyclopentadiene dimers and iso-dimers and determination of their boiling points

The Kováts retention indices ( I R) of a family of mono- and polycycloolefins with one or more endo- or exocyclic double bonds on stationary phases of different polarity are related to their boiling points, molar volume, molar refractivity and first-order molecular connectivity. The boiling points of methylcyclopentadiene dimers and their iso-dimers containing an exocyclic double bond were estimated from the relationships between I R (on squalane at 100°C), boiling point and molecular connectivity obtained from a group of cycloolefins selected at random.

Quantitative modeling of soil sorption for xenobiotic chemicals.

Experimentally determining soil sorption behavior of xenobiotic chemicals during the last 10 years has been costly, time-consuming, and very tedious. Since an estimated 100,000 chemicals are currently in common use and new chemicals are registered at a rate of 1000 per year, it is obvious that our human and material resources are insufficient to experimentally obtain their soil sorption data. Much work is being done to find alternative methods that will enable us to accurately and rapidly estimate the soil sorption coefficients of pesticides and other classes of organic pollutants. Empirical models, based on water solubility and n-octanol/water partition coefficients, have been proposed as alternative, accurate methods to estimate soil sorption coefficients. An analysis of the models has shown (a) low precision of water solubility and n-octanol/water partition data, (b) varieties of quantitative models describing the relationship between the soil sorption and above-mentioned properties, and (c) violations of some basic statistical laws when these quantitative models were developed. During the last 5 years considerable efforts were made to develop nonempirical models that are free of errors imminent to all models based on empirical variables. Thus far molecular topology has been shown to be the most successful structural property for describing and predicting soil sorption coefficients. The first-order molecular connectivity index was demonstrated to correlate extremely well with the soil sorption coefficients of polycyclic aromatic hydrocarbons (PAHs), alkylbenzenes, chlorobenzenes, chlorinated alkanes and alkenes, heterocyclic and heterosubstituted PAHs, and halogenated phenols. The average difference between predicted and observed soil sorption coefficients is only 0.2 on the logarithmic scale (corresponding to a factor of 1.5). A comparison of the molecular connectivity model with the empirical models described earlier shows that the former is superior in accuracy, performance, and range of applicability. It is possible to extend this model, with the addition of a single, semiempirical variable, to take care of polar and ionic compounds and to accurately predict the soil sorption coefficients for almost 95% of all organic chemicals whose coefficients have been reported. No empirical or nonempirical models have ever predicted the soil sorption coefficients to such a high degree of accuracy on such a broad selection of structurally diverse compounds. An additional advantage of the molecular connectivity model is that it is sufficient to know the structural formulas to make predictions about soil sorption coefficients.(ABSTRACT TRUNCATED AT 400 WORDS)

Prediction of Soil Sorption Coefficients of Hydrophobic Organic Pollutants by Adsorbability Index

Abstract The adsorbability index proposed by Abe et al. to predict the activated carbon adsorption of organic compounds from aqueous solution was well correlated with the soil sorption coefficients of polycyclic aromatic hydrocarbons (PAHs), alkylbenzenes, chlorobenzenes, chlorinated alkanes and alkenes, heterocyclic and substituted PAHs, and halogenated phenols. The adsorbability index was also found to be well correlated with the first-order molecular connectivity index and the total molecular surface areas of these compounds.

A simulation model for the fate of pesticide residues in a field soil

The model employed for simulating the fate of pesticides in soil was based on the one dimensional convective-dispersive-reaction equation. The model assumed a constant pore-water velocity (v), linear equilibrium adsorption, and first-order degradation. The adsorption parameter (kd) was calculated from molecular structure with the help of a first-order molecular connectivity index. On the basis of the results of sensitivity analysis the model was made partially stochastic in order to account for horizontal heterogenity in a field soil. Concentration profiles were obtained by employing the mode, median and mean values of (v, D) while the values of kd and t1/2 were kept constants; where D and t1/2 were the apparent diffusion coefficient and the degradation half-life, respectively. The resulted extremes in concentration profiles were expected to be observed within a relatively small area of the heterogeneous filed soil. A random variable, namely the contaminated depth, ζ was defined so that the soil beneath it would be practically free of pesticide during its entire life-time. The values of (ξ1, ξ2, ξ3) under continuous leaching were (0.14, 0.56, 1.00 m), (0.29, 1.50, 2.62 m), and (0.65, 2.25, 4.00m) for DDT, toxaphene and lindane, respectively; where ξ1, ξ2 and ξ3 were values of ζ calculated by employing the mode, median, and mean values of (v, D), respectively. Within a relatively small area the first value would be frequently observed whereas the others would be less pronounced. The depth and shape of the resultant base of the contaminated zone were substantially more sensitive to changes in the surface rates of recharge than to changes in the values of the chemical parameters kd and t1/2. The implication of the results for the assesment of pesticide contamination of groundwaters were discussed.

Semi-quantitative and quantitative structure–taste relationships for carboand hetero-sulphamate (RNHSO3–) sweeteners

Seventeen carbosulphamates (eight synthesised in this study) and 23 heterosulphamates (seven synthesised here) have been examined with a view to extending previously developed1,2 structure–taste relationships for sulphamates (RNHSO3–). Measurements of defined parameters x, y, z, and V(V=xyz) for R using Corey–Pauling–Koltun space-filling models for the 17 carbosulphamates have shown that their taste can be predicted in most cases using the previously developed semi-QSAR established. Predictions made from a recent pattern-recognition method study of sulphamate taste are shown to be partially incorrect.The heterosulphamates were also examined using CPK models and first-order molecular connectivity (1xv) measurements. The use of linear discriminant analysis on seven subsets of the five variables measured i.e. x, y, z, V, and 1xv showed that the subset, x, z, 1xV misclassified only three of the 23 heterocompounds, i.e. the percentage misclassified was 13%.Mapping of the sulphamate receptor site on the basis of the measurements carried out suggests that the carbo- and hetero-sulphamates use different sites to bind. This present work brings the database of taste-assessed sulphamates reported to over 120 compounds.

Retention behaviour and molecular structure of diols in reversed-phase liquid chromatography

Correlations between the retention behaviour of diols in reversed-phase liquid chromatography and their molecular structures have been studied using hydrophobicity (log P) and topological indices (χ R, χ V R , W, W*, J, J*, C T). It has been shown that the retention behaviour of diols in an eluent of acetonitrile-water (50:50) is best described by a polynomial equation of second degree involving hydrophobicity. Topological indices fail to predict the elution sequence of diols but the use of a parameterization scheme for topological indices calculated from the distance matrix improves the results. The combination of log P with the Wiener index and the first-order valence molecular connectivity indices gives reliable predicted capacity factors.

QSAR studies on estrogen receptor binding affinity of 2-phenylindoles using first-order valence molecular connectivity

The estrogen receptor binding affinity of 2-phenylindoles is found to be significantly correlated with Kier’s first-order valence molecular connectivity index. The correlation equations obtained provide a much simple rationale to design more potent compounds and help in predicting the potency of new compounds.

MOLECULAR CONNECTIVITY INDICES OF ORGANIC POLLUTANTS: CORRELATION WITH CESSATION OF BURROWING IN THE WHELKBULLIA DIGITALIS(DILLWYN)

SUMMARY Bullia digitalis is a sandy-beach whelk which displays a well-defined series of reactions to most pollutants. A marked sub-lethal response is cessation of burrowing, the animals either refusing to burrow or emerging from the sand if already buried. The concentrations of a series of organic substances eliciting the latter response are reported and a correlation is demonstrated between these concentrations and the first-order molecular valence connectivity indices of the substances concerned.

Effect of molecular size on the activity of adriamycin analogues: A quantitative structure-activity relationship study.

The in vitro anti-tumor activity (inhibition of human lymphoblastic leukemia cells) of some adriamycin analogues is found to be significantly correlated with the van Waals volume (VW) of the substituents. Activity is also found to be well correlated with first-order valence molecular connectivity index (1 chi V) but no correlation is found to exist between it and the hydrophobic parameter, log P (P: octanol-water partition coefficient). On the basis of these findings, it is suggested that the activity would be affected by the steric influence and to some extent by the electronic character of the substituents. From the correlating equations, it is observed that the size of C-7 glycoside ring and that of NHR2 group at its third position would greatly affect the activity. The size of C-14-R1 however, is not found to have much effect on the activity.

Calculation of retention indices by molecular topology: chlorinated alkanes

This study was undertaken to test the ability of the molecular connectivity model to predict retention indices using both statistical correlation coefficients and correctly predicted elution sequences as criteria of fit. The test was performe don three groups of chloroalkanes. Regression analyses show that the molecular connectivity model successfully predicts the retention indices of chlorinated alkanes on polar and non-polar stationary phases. However, first-order molecular connectivity indices alone are not sufficientk, higher order indices are demonstrared to be necessary. The results also indicate that different structural features determine the retention index values of mono- and dichlorides. For monochlorides the major factor is the size of the alkly chain, while for dichlorides the major factor is the toplogical relation between the two chlorine atoms. The comaparison of the results obtained with the molecular connectivity model and the empirical additive scheme reveals several important advantages of the molecular connectivity approach.

Quantitation of Solvent Polarity Based on Molecular Structure

A numerical index is proposed that ranks solvents according to their polarity. It is based entirely on structure, encoding the relative content of exterjacent electrons in the molecule. The index is the first-order valence molecular connectivity index, 1Xv The index is modified for the number of isolated functional groups in the molecule. A comparison with solvent polarity indexes based on several experimental methods reveals a good relationship. The polarity index proposed can be quickly calculated, it does not depend on the availability of the actual molecule, and it permits prediction of solvent polarity or the polarity of mixtures.

Gas chromatographic—mass spectrometric identification of geochemically significant isoalkane hydrocarbons

Computerized gas chromatography—mass spectrometry has been used for fingerprinting C 15C 40 methyl- and polymethylalkanes in geological extracts. With proper selection of the key ions, three different series of isoprenoid hyrocarbons, exhibiting iso- and anteiso- head-to-tail and tail-to-tail structures can be observed. The regularities displayed by these series in the fragmentograms have been rationalized on the basis of the chromatographic behaviour of their components. In this respect the possibility of predicting retention indices either by retention increments or by empirical relationships is discussed. The elution order of the isoalkanes identified is correctly established by the first-order molecular connectivity (χ), and a retention relationship giving mean absolute errors of 1.1 and 2.7 index units for Apiezon L and Dexsil, respectively, has been obtained for the C 15C 40 regular isoprenoid series.

Pattern Recognition of Steroids Using Fragment Molecular Connectivity

The use of pattern recognition methods to classify a set of steroids into five therapeutic categories was investigated. First-order fragment molecular connectivity values were determined for 10 positions on each molecule using a template-based method of position assignment. Learning set and test set classifications were performed. Although the numbers of compounds misclassified were comparable for all of the methods, the identities of the misclassified compounds varied depending on whether the classification method assumed a local or a global view of the data. The best classification results were comparable to those obtained by linear and quadratic discriminant analyses. For this set of compounds, it was concluded that pattern recognition methods offer no advantages over traditional discriminant analysis methods if classification alone is considered, especially since most discriminant analysis procedures utilize stepwise variable selection, which is not as common in pattern recognition analyses.