Valence Molecular Connectivity Index Research Articles

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.

Definition and application of a novel valence molecular connectivity index

In this paper, we defined a novel delta value δ i in molecular connectivity, and then obtained a novel kind of valence molecular connectivity index. The potential usefulness of the novel kind of valence molecular connectivity index in QSAR/QSPR is evaluated by its correlation with a number of molecules and by a favorable comparison with models based on molecular connectivity index.

Comparative QSPR studies with molecular connectivity, molecular negentropy and TAU indices. Part I: molecular thermochemical properties of diverse functional acyclic compounds.

Molecular thermochemical properties (heats of formation and atomization) of diverse functional acyclic compounds have been correlated with TAU indices and the relations have been compared to those involving molecular negentropy and first order valence molecular connectivity indices to unravel the diagnostic feature of the TAU scheme and to explore the relative suitability of the scheme in describing physicochemical parameters. For both the properties it was found that TAU relations could satisfactorily explain the variances of the thermochemical parameters and the relations were comparable to those involving molecular negentropy and molecular connectivity. Moreover, specific contributions of functionality, branchedness, shape and size factors to the thermochemical properties could be found from the relations involving TAU parameters.

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.

A quantitative structure–activity relationship study on some matrix metalloproteinase and collagenase inhibitors

A quantitative structure–activity relationship (QSAR) study is made on some hydroxamic acid-based inhibitors of matrix metalloproteinases (MMPs) and a bacterial collagenase, namely Clostridium histolyticum collagenase (ChC), that also belongs to an MMP family, M-31, using Kier's valence molecular connectivity index 1χ v of the substituents and electrotopological state (E-state) indices of some atoms. The results indicate that out of the four MMPs (MMP-1, MMP-2, MMP-8, and MMP-9) studied, MMP-2 and MMP-9 can be structurally quite similar, but widely differing from MMP-1 and MMP-8 and ChC. For MMP-2 and MMP-9, the inhibition activity of compounds is shown to depend on both 1χ v and E-state indices, while for MMP-1 and MMP-8 it is shown to depend only on E-state indices and for ChC only on 1χ v. However, in all the cases, an aromatic group like C 6F 5 or 3-CF 3–C 6H 4 attached to SO 2 moiety in the compounds is indicated to be equally beneficial, due to probably the involvement of fluorine atom(s) in charge–charge interactions with the Zn 2+ ion of the enzymes or in the formation of the hydrogen bonds with some sites of the receptors.

Modeling blood-brain barrier partitioning using the electrotopological state.

The challenging problem of modeling blood-brain barrier partitioning is approached through topological representation of molecular structure. A QSAR model is developed for in vivo blood-brain partitioning data treated as the logarithm of the blood-brain concentration ratio. The model consists of three structure descriptors: the hydrogen E-State index for hydrogen bond donors, HS(T)(HBd); the hydrogen E-State index for aromatic CHs, HS(T)(arom); and the second order difference valence molecular connectivity index, d(2)chi(v) (q(2) = 0.62.) The model for the set of 106 compounds is validated through use of an external validation test set (20 compounds of the 106, MAE = 0.33, rms = 0.38), 5-fold cross-validation (MAE = 0.38, rms = 0.47), prediction of +/- values for an external test set (27/28 correct), and estimation of logBB values for a large data set of 20 039 drugs and drug-like compounds. Because no 3D structure information is used, computation of logBB by the model is very fast. The quality of the validation statistics supports the claim that the model may be used for estimation of logBB values for drug and drug-like molecules. Detailed structure interpretation is given for the structure indices in the model. The model indicates that molecules that penetrate the blood-brain barrier have large HS(T)(arom) values (presence of aromatic groups) but small values of HS(T)(HBd) (fewer or weaker H-Bond donors) and smaller d(2)chi(v) values (less branched molecules with fewer electronegative atoms). These three structure descriptors encode influence of molecular context of groups as well as counts of those groups.

A quantitative structure–activity relationship study on some HIV-1 protease inhibitors using molecular connectivity index

A quantitative structure–activity relationship (QSAR) study has been made on two different series of tetrahydropyrimidinones acting as HIV-1 protease inhibitors. A structural parameter, the first order valence molecular connectivity index (1χv), has been used to account for the variation in the activity. The protease inhibition activity as well as the antiviral potency of the compounds are found to be significantly correlated with 1χv of P2/P2′ substituents attached to the two nitrogens N1 and N3, suggesting that substituents containing less electronegative and more saturated atoms, meaning thereby the less polar or more hydrophobic substituents, will be more advantageous. Further, if P2 and P2′ are dissimilar, the former is found to be more effective than the latter. This difference is attributed to a conformational change in the enzyme that may be more favorable to P2 binding than to P2′ binding.

Carbon Fiber Adsorption Using Quantitative Structure-Activity Relationship

Adsorption capacities of adsorbents are necessary for selecting and designing adsorption systems for separation and removal processes, such as air quality control devices, because they are indicators of service life. This paper describes the use of the Dubinin-Radushkevich (DR) equation and the quantitative structure-activated relationship to predict the equilibrium adsorption of select organic vapor by activated carbon fiber (ACF) adsorbents. The DR isotherm parameter, k, depends on the adsorbate as well as the adsorbent, and the prediction for k can be obtained indirectly from the affinity coefficient. A correlation is developed to compute the affinity coefficient from the modified, first-order, valence molecular connectivity index. This method provides an improved way to predict equilibrium adsorption capacities for select volatile organic compound adsorbates and activated carbon fiber adsorbents.

Quantitative structure—activity relationships for the toxicity of chlorophenols to mammalian submitochondrial particles

The toxicity of a series of chlorophenols, determined by a short-term in vitro assay utilizing mammalian submitochondrial particles, was related to the physicochemical and structural properties of these compounds. Quantitative Structure-Activity Relationships were defined by correlating EC50 values with six molecular descriptors, chosen to represent lipophilic, electronic and steric effects: the n-octanol/water partition coefficient (log K OW), the constant of Hammett (Σσ), the acid dissocidtion constant (pK a), the first order valence molecular connectivity index ( 1 ζ v ), the perimeter of the efficacious section (ΣD) and the melting point (m.p.). The results of regression analysis showed that log K ow is the most successful descriptor, indicating that the ability of chlorophenols to partition into the lipid bilayer of the mitochondrial membrane has an important role in determining their toxic effects. These results are consistent with a molecular mechanism of uncoupling action based on the chemiosmotic theory and on the protonophoric properties of chlorophenols. The quality of the QSAR models confirms the suitability of the SNIP assay as a short-term prediction tool for aquatic toxicity of environmental pollutants acting on respiratory functions.

Evaluation of Molecular Connectivity Indices as a Predictive Method of log Kow for Different Classes of Chemicals

Abstract Molecular connectivity indices (MCI), were used to predict log Kow of several classes of chemicals (mainly pesticides). The modeling capability was first evaluated for each class of compounds using simple and valence MCI up to the 7th order (nX and nXv). Moreover, different molecular descriptors, derived from MCI but accounting for non-dispersive intermolecular interactions (ΔX and ΔXv) were included in the regression models. A general equation of the type: proved effective in producing highly reliable log Kow values within homogeneous classes of chemicals. For heterogeneous groups, a similar equation proved useful at least for preliminary screening evaluations.

Structure-activity study on antiinflammatory pyrazole carboxylic acid hydrazide analogs using molecular connectivity indices.

The relationship between molecular connectivity indices and the antiinflammatory activity of a series of pyrazole carboxylic acid hydrazide analogs has been investigated. The values of molecular connectivity index, valence molecular connectivity index, and a modified index, termed as atomic molecular connectivity index for 76 compounds, were computed and active ranges were identified. Each compound was assigned an activity which was subsequently compared with the reported activity against lipoxygenase enzyme. Predictions with a degree of accuracy above 80% were observed using the valence molecular connectivity index.

Structure–basicity relationships for pyridine extractants

AbstractTopological indices are determined for models of prospective pyridine extractants and the relationships structure–topological index and topological index–pyridine nitrogen basicity are described. The second order valence molecular connectivity index, the Balaban index and the Wiener number are appropriate structural descriptors of pyridine derivatives and, in several cases, permit the pyridine nitrogen basicity to be predicted. The relationships between pKa values and the structural descriptors are given and described.

Structure-activity study on anticonvulsant (thio) hydantoins using molecular connectivity indices.

The relationship between molecular connectivity indices and anticonvulsant activity of a series of hydantoin/thiohydantoin analogs has been investigated. The values of molecular connectivity index and valence molecular connectivity index of 82 compounds were computed and active ranges were identified. The activity assigned to each analog using these topological descriptors was subsequently compared with the reported activity against maximal electroshock convulsions. Predictions with high degree of accuracy were observed using these indices.

Structure property relationships of amino acids and some dipeptides

A molecular connectivity model of the crystal densities and specific rotations of some natural amino acids and of the longitudinal relaxation rates of some natural amino acids and cyclic dipeptides is presented. While crystal densities and relaxation rates are better described by a set of three valence molecular connectivity indices {D (v),(0) X (v),(1) X (v)}, specific rotations are better described by a set of two simple molecular connectivity indices {(1) X,(0) X}. Relaxation rates are, also, well described by the simple molecular connectivity {D,(1) X} index set. Use of orthogonal indices, derived from the corresponding ordinary indices shows, in the case of specific rotations, the possibility to condense the information by the aid of a single high quality descriptor underlining, thus, the versatility of these indices and also their dependence on the orthogonalisation process.

Quantitative modeling of environmental fate and impact of commercial chemicals

AbstractPresent laws in many countries require that all commercial chemicals be assessed for their environmental behavior and hazards. Because there are a large number of chemicals currently in common use (approximately 100,000) and new chemicals are being registered at a very high rate (1,000 per year), it is obvious that our human and material resources are insufficient to obtain experimentally even basic information about environmental fate and effects for all these chemicals. Thus, it is necessary to develop quantitative models that will accurately and rapidly predict environmental behavior for large sets of chemicals. During the last decade, a considerable effort has been made to develop methods that use molecular characteristics to describe environmental behavior of organic pollutants. Thus far, molecular connectivity indexes have been shown to be the most successful structural property for describing and predicting soil sorption coefficients, association coefficients with dissolved humic substances, Henry's law constants, bioconcentration factors in aquatic organisms and vegetation, biodegradation rates, and fish acute toxicity. The general quantitative model, based on the first‐order molecular connectivity index (MCI), has been developed for the accurate estimation of soil sorption coefficients for predominantly hydrophobic chemicals: polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), halogenated hydrocarbons, and phenols. It is possible to extend this model for many classes of agricultural chemicals. A similar model, based on the second‐order valence MCI, has been developed for fish bioconcentration factors of PCBs, chlorinated diphenyl oxides, halogenated hydrocarbons, PAHs, and phenols, plus substituted benzenes. Furthermore, a prototype expert system has been developed for classifying untested chemicals as readily or not readily biodegradable, based on their chemical structures. Finally, using a standardized data base for fish acute toxicity, we have obtained a simple linear correlation between the valence zero‐order MCI and the 96‐h LC50 data for a large group of 150 structurally diverse commercial chemicals.

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 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.

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.