Molecular connectivity method

In the molecular connectivity method, numerical indexes are developed to represent and characterize molecular structure. The indexes are suitable for use in structure-property relationships that may be developed by standard regression methods, producing equations for estimation of property values. The indexes are also used as a basis for pattern recognition and discriminant analysis. ... 

The objective of the molecular connectivity method is the quantitation of molecular structure based on the topological and electronic character of the atoms in the molecule. The pursuit of this objective leads to topological indexes derived from graph theoretic concepts, definitions, and procedures. We need to have methods for broad application in structure-property models, especially QSAR models. From these methods, we seek a basis for better understanding of the relation between structure and properties. 

With these considerations as a general background, let us summarize our approach. In the molecular connectivity approach, the molecule is represented by the hydrogen-suppressed graph. The key feature in the quantitation of the graph is the characterization of the atom in the molecular skeleton. The molecular connectivity method explicitly introduces the electronic character of atoms into the graphic representation of molecules. Atom identity is specified through the molecular connectivity delta values the simple delta, 6, and the valence delta,... 

In the molecular connectivity method a series of indexes is developed, expressing structure information at several levels. The molecular skeleton is conceived as consisting of fragments of different sizes and complexity. The molecular graph may be decomposed into fragments called subgraphs, such as a skeletal bond, a pair of adjacent bonds, a cluster of bonds to a central atom, etc. 

Based on the use of chemical graph theory as described above, various indexes of molecular structure have been developed. These indexes may all be termed topological indexes. In the molecular connectivity method, indexes have been developed to characterize various aspects of molecular structure. The kappa shape indexes were developed so that shape measures could be directly entered in QSAR analyses. Each of these indexes characterizes the whole molecule with respect to one or more aspects of structure. In chemistry it is also of interest to characterize the skeletal atoms. In this final section we review briefly an investigation of the skeletal atoms as vertexes in the molecular graph as a basis for an atom descriptor. 

Correlation methods discussed include basic mathematical and numerical techniques, and approaches based on reference substances, empirical equations, nomographs, group contributions, linear solvation energy relationships, molecular connectivity indexes, and graph theory. Chemical data correlation foundations in classical, molecular, and statistical thermodynamics are introduced. 

On the basis of data obtained the possibility of substrates distribution and their D-values prediction using the regressions which consider the hydrophobicity and stmcture of amines was investigated. The hydrophobicity of amines was estimated by the distribution coefficient value in the water-octanole system (Ig P). The molecular structure of aromatic amines was characterized by the first-order molecular connectivity indexes ( x)- H was shown the independent and cooperative influence of the Ig P and parameters of amines on their distribution. Evidently, this fact demonstrates the host-guest phenomenon which is inherent to the organized media. The obtained in the research data were used for optimization of the conditions of micellar-extraction preconcentrating of metal ions with amines into the NS-rich phase with the following determination by atomic-absorption method. 

For a molecule as simple as Fl2, it is hard to see much difference between the valence bond and molecular orbital methods. The most important differences appear- in molecules with more than two atoms. In those cases, the valence bond method continues to view a molecule as a collection of bonds between connected atoms. The molecular- orbital method, however, leads to a picture in which the sane electron can be associated with many, or even all, of the atoms in a molecule. We ll have more to say about the similarities and differences in valence bond and molecular- orbital theory as we continue to develop their principles, beginning with the simplest alkanes methane, ethane, and propane. 

Gerstl Z, Helling CS. 1987. Evaluation of molecular connectivity as a predictive method for the adsorption of pesticides by soils. J Environ Sci Health B22 55-69. 

G.E. Martin and A.S. Zektzer, Two-dimensional NMR Methods for Establishing Molecular Connectivity, VCH Publishers, New York, NY (1988). 

Estimation from molecular connectivity index/fragment contribution method (Meylan et al. 1992, Lohninger 1994) ... 

March, J. (1992). Advanced Organic Chemistry. Fourth Edn. John Wiley Sons New York, Chichester, Brisbane, Toronto and Singapore Martin, G. H. and Zektzer, A. S. (1988). Two-dimensional NMR Methods for Establishing Molecular Connectivity A Chemist s Guide to Experiment Selection, Performance, and Interpretation. VCH Publishers Inc. Deerfield Beach. 

Various methods by which the Kow of PAHs could be calculated are based on their molecular structures, i. e., a quantitative structure-property relationship (QSPR) approach [ 1,199,200]. One of the most famous techniques involves summation of hydrophobic fragmental constants (or f-values) for all groups in a molecule of a specific compound. On the other hand, Aboul-Kassim [1] and Aboul-Kassim et al. [202, 203] introduced a modeling technique based on the molecular connectivity indices of various PAHs, ranging from low- to high-molecular weight compounds. More details are given in Chap. 4 of this volume. 

The measurement of the solubility of drugs in polar and non-polar media is very important in the pharmaceutical field. One method proposed to describe this solubility is the partition coefficient between octanol and water. The mathematical calculation of an octanol-water partition coefficient from values for functional groups was first proposed by Hansch et al. as Hansch s n constants,1 and was later developed by Rekker as hydrophobic fragmental constants (logP).2 This method was further improved by the use of molecular connectivities.17 The prediction of logP values can be performed by either a computer program or by manual calculation. For example, approximate partition coefficients (log P) have been calculated by Rekker s method ... 

L. B. Kier and L. H. HaU, Molecular Connectivity in Chemistry and Drug Research, Academic Press, New York, 1976 R. E. Merrifield and H. E. Simmons, Topological Methods in Chemistry, Wiley-Interscience, New York, 1989 A. T. Balaban (Ed), From Chemical Topology to Three-Dimensional Geometry, Plenum Press, New York, 1997. 

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