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Biomedical subjects

L H Hall

Publications and source records attributed to L H Hall.

At least 19 recordsLinked to original sources
PubMed2003

E-state modeling of fish toxicity independent of 3D structure information.

Topological structure methods are used to model fish toxicity against three classes of organic chemicals. The models were obtained independent of 3D structure information. Further, no mechanism of partitioning was assumed, thus avoiding the problems associated with selection of partitioning system for computation of log P. QSAR models were developed for a set of 92 compounds, including phenols, anilines and substituted aromatic hydrocarbons, yielding excellent statistics: r2 = 0.87, s = 0.25 and q2 = 0.85 leave-one-out (LOO), that are better than those reported in the literature. The model is based on molecular connectivity valence chi-1 index [1chiv], the atom type E-State indices for chlorine [ST(-Cl)] and for ether oxygen [ST(-O-)], and the maximum hydrogen E-State atom value in a molecule [Hmax]. Each of the subgroups was also separately well modeled. The model for the full set is validated through use of external validation test sets and ten-fold cross-validation (repeated three times). The quality of the validation statistics supports the claim that the model may be used for estimation of pLC50 values for similar molecules. Detailed structure interpretation is given for the descriptors in the model. These four structure descriptors encode influence of molecular context of groups as well as counts of those groups, in addition to molecular skeletal structure.

Aniline Compounds↗
PubMed2001

Issues in representation of molecular structure the development of molecular connectivity.

Significant issues in the representation of molecular structure and the development of the molecular connectivity paradigm are presented. In the molecular connectivity paradigm, molecular structure is represented directly. Kier and Hall developed the method by creating ways to encode electronic information based on the paradigm developed from the Randić branching index. The simple and valence delta values were created to encode atomic and valence-state electronic information through counts of sigma, pi, and lone pair electrons. A family of indices was created to provide a wide range of structure information. The key aspects of the development are presented and discussed in such a way as to reveal, at least in part, the imaginative thinking involved in the process. Possible future roles for molecular connectivity chi indices are discussed.

Algorithms↗
PubMed2001

Molecular connectivity: intermolecular accessibility and encounter simulation.

The simple molecular connectivity indices are interpreted as summations of bond accessibilities to bimolecular encounters with another, identical molecule. To transcend this model, a molecule is treated as disjecta membra with each bond modeled as a discrete cell in a dynamic simulation of many molecules. Each bond accessibility is transformed into a cellular automata rule. The dynamics are run for each of 38 alkanes, recording the average number of cell encounters, beta. The beta values show a high correlation with the boiling points. The significance of the bond accessibilities and the concept of intermolecular encounters explaining the molecular connectivity indices is supported by these findings.

Alkanes↗
PubMed2001

Database organization and searching with E-State indices.

The electrotopological state (E-State) and its extension, the atom-type E-State, is presented as a representation of atom and molecular fragment structure useful for chemical database organization and management. An approach to database organization, using substituted esters and benzene derivatives as examples, reveals the descriptive power of the E-State paradigm. With a database, organized on the basis of structural relationships as described here, it is possible to search for similar molecular structures with potential for comparable activity. The searches using the atom-type E-State indices are demonstrated with several examples.

Benzene↗
PubMed1998

QSAR modeling with the electrotopological state indices: corticosteroids.

A structure-activity analysis of a series of steroids binding to corticosteroid-binding globulin was made using the electrotopological state index for each atom in the molecule. Two indices were found to correlate well with the binding affinity. The indices encode structural characteristics in the A and the D rings of the steroids in the study. One of the indices was formulated as the difference between two indices in the A ring. The two were not intercorrelated, suggesting that the composite index signals the influence of structure changes in or near the A ring that can be monitored by the composite index. This is a new observation using this structure-activity method. It is suggested that this model makes some contributions towards detection of the pharmacophore.

Adrenal Cortex Hormones↗
PubMed1996

E-state fields: applications to 3D QSAR.

The derivation of a new 3D QSAR field based on the electrotopological state (E-state) formalism is described. A complementary index and its associated field, the HE-state, describing the polarity of hydrogens is also defined. These new fields are constructed from a nonempirical index that incorporates electronegativity, the inductive influence of neighboring atoms, and the topological state into a single atomistic descriptor. The classic CoMFA steroid test data set was examined with models incorporating the E-state and HE-state fields alone and in combination with steric, electrostatic and hydropathic fields. The single best model was the E-state/HE-state combination with q2 = 0.803 (three components) and r2 = 0.979. Using the E-state and/or HE-state fields with other fields consistently produced models with improved statistics, where the E-state fields provided a significant, if not dominant, contribution.

Binding Sites↗
PubMed1994

Response surface analysis of bioconcentration by chlorinated organics using molecular connectivity.

Bioconcentration data for chlorinated organic compounds is analyzed in a response surface technique using molecular connectivity indices to represent the molecular structure of the compounds. The response surface method is described and applied to this data set. The model uses the zero order chi indices, 0 chi and 0 chi v, as the variables in a general two-dimensional parabolic equation. The statistical results suggest a good model for estimation of BCF values: [Formula: see text] The data set is analyzed further in terms of the sigma and delta chi zero indices: sigma x 0 = 0 chi + 0 chi v and delta x 0 = 0 chi - 0 chi v. These transformed chi indices are orthogonal and represent structure information in a useful manner. The sigma x 0 index encodes molecular size and the delta x 0 index encodes electronic features related to pi and lone pair electrons. The structure information in the data set is analyzed in terms of these significant structure features. The data are presented in the form of a contour plot which facilitates analysis and indicates the maximum BCF for this data set.

Chlorophenols↗
PubMed1990

An electrotopological-state index for atoms in molecules.

A new method for molecular structure description is presented in which both electronic and topological characteristics are combined. The method makes use of the hydrogen-suppressed graph to represent the structure. The focus of the method is on the individual atoms and hydride groups of the molecular skeleton. An intrinsic atom value is assigned to each atom as I = (delta v + 1)/delta, in which delta v and delta are the counts of valence and sigma electrons of atoms associated with the molecular skeleton. The electrotopological-state value, Si, for skeletal atom i is defined as Si = Ii + delta Ii, for second row atoms, where the influence of atom j on atom i, delta Ii, is given as sigma(Ii-Ij)/rij2; rij is the graph separation between atom i and atom j, counted as the number of atoms. The characteristics of the electrotopological state values are indicated by examples of various types of organic structures, including chain lengthening, branching, heteroatoms, and unsaturation. The relation of the E-state value to NMR chemical shift is investigated for a series of alkyl ethers. The E-state oxygen value gives an excellent correlation with the 17O NMR: r = 0.993 for 10 ethers. A biological application of the E-state values in QSAR analysis is given for the binding of barbiturates to beta-cyclodextrin.

Barbiturates↗
PubMed1989

Differential molecular connectivity in data-base fragment searching.

A general scheme is described in which molecular fragments are coded from molecular connectivity values. Specifically a fragment is described by the difference between a simple connectivity index of a certain order and the valence connectivity index of the same order. This numerical value is then used to search for that particular fragment among stored fragment values associated with a molecular connectivity calculation. Examples illustrate the method.

Chemical Phenomena↗
PubMed1987

Further consideration of flavin coenzyme biochemistry afforded by geometry-optimized molecular orbital calculations.

Investigation of lumiflavin and several other isoalloxazine ring derivatives has been carried out by geometry-optimized molecular orbital calculations. The results have provided insight into the flexibility of the flavin cofactor in the reduced and oxidized states, the regions of the fused three-ring system that should play an important role in flavin electron transfers, and the structural and functional role of the xylene and heteroatomic portions of the flavin system. The significance of these results is reviewed in relation to the experimentally identified chemical and biochemical properties of the flavin nucleotide coenzymes.

Chemical Phenomena↗
PubMed1983

General definition of valence delta-values for molecular connectivity.

The molecular connectivity valence delta-values have been defined in terms of the count of nonhydrogen valence electrons on a valence-state atom as screened from the nucleus by the core electrons. The core is defined as the nonvalence electrons minus 1. This general definition expresses the valence delta-values for second and third quantum level atoms and halogens. Valence delta-values have been derived for higher oxidation states of sulfur and phosphorus. The internal consistency of these delta-values is tested by their ability to closely correlate molar refraction values with 1 chi v. It is found that a second variable, the count of the number of alpha hydrogen atoms, greatly increases the quality of the correlation. Some biological SAR applications reveal the general utility of these findings.

Chemical Phenomena↗
PubMed1981

Derivation and significance of valence molecular connectivity.

The physical basis for valence molecular connectivity was studied. The delta v and delta values are cardinal numbers describing the electronic structure of atoms in their valence states. The value delta v + delta describes the volume of a bonding atom while the value delta v - delta describes the electronegativity. By using the principle of electronegativity equalization, bond electronegativity is defined as (delta vi delta vj)-1/2, and the valence molecular connectivity index (l chi v) is derived as a sum of these bond descriptions. The valence chi index is interpreted in terms of the information encoded, describing both the volume and electronic characteristics of bonds in molecules. Examples of close relationships with molecular volume and electronic properties are shown. A new way of estimating valence state electronegativity is proposed from a count of exterjacent electrons divided by the quantum number squared for at least the first three quantum levels.

Amino Acids↗
PubMed1979

Molecular connectivity study of halocarbon anesthetics.

The structure--activity relationships of 45 halogenated hydrocarbons using molecular connectivity were studied. A very good correlation was obtained between the anesthetic activity and the molecular connectivity term o chi v in addition to the polar hydrogen factor, QH. The equation reported accounts for the quantifies the known structure--activity observations on general anesthetics. The results are discussed briefly with reference to the mechanisms of action of general anesthetics.

Anesthetics↗