Biomedical subjects

W A Seitz

Publications and source records attributed to W A Seitz.

9 recordsLinked to original sources

PubMed2001

Directed self-avoiding walks in random media.

Two types of directed self-avoiding walks (SAW's), namely, three-choice directed SAW and outwardly directed SAW, have been studied on infinite percolation clusters on the square lattice in two dimensions. The walks on the percolation clusters are generated via a Monte Carlo technique. The longitudinal extension R(N) and the transverse fluctuation W(N) have been measured as a function of the number of steps N. Slight swelling is observed in the longitudinal direction on the random lattices. A crossover from shrinking to swelling of the transverse fluctuations is found at a certain length N(c) of the walks. The exponents related to the transverse fluctuations are seen to be unchanged in the random media even as the percolation threshold is reached. The scaling function form of the extensions are verified.

Journal Article↗

PubMed2001

Quantitative structure-retention relationships for gas chromatographic retention indices of alkylbenzenes with molecular graph descriptors.

Quantitative structure-retention relationships (QSRR) represent statistical models that quantify the connection between the molecular structure and the chromatographic retention indices of organic compounds, allowing the prediction of retention indices of novel, not yet synthesized compounds, solely from their structural descriptors. Using multiple linear regression, QSRR models for the gas chromatographic Kováts retention indices of 129 alkylbenzenes are generated using molecular graph descriptors. The correlational ability of structural descriptors computed from 10 molecular matrices is investigated, showing that the novel reciprocal matrices give numerical indices with improved correlational ability. A QSRR equation with 5 graph descriptors gives the best calibration and prediction results, demonstrating the usefulness of the molecular graph descriptors in modeling chromatographic retention parameters. The sequential orthogonalization of descriptors suggests simpler QSRR models by eliminating redundant structural information.

Alkylation↗

PubMed1994

Modeling the anticarcinogenic action of retinoids by making use of the OASIS method. 3. Inhibition of the induction of ornithine decarboxylase by arotinoids.

A series of 15 congeneric aromatic retinoids (arotinoids) was subjected to a study of the conformational dependence of basic molecular descriptors, and the anticarcinogenic potency of the compounds was modeled by the sophisticated OASIS (optimized approach based on structural indices set) method. A high correlation was obtained for both two-variable models and three-variable models. The best models of these two kinds had correlation coefficients of 0.956 vs 0.988 and standard deviations s2 = 0.14 vs 0.04, respectively. The most significant variables were several interatomic and topological distances, which specify the optimum geometric drug-receptor fit. The group of significant electronic descriptors included characteristic pi-bond orders, the electronic charge at one atomic position in the tetrahydronaphthalene ring, the total electronic energy, and two electronic-topological indices. An electrostatic drug-receptor interaction was conjectured on this basis. A contribution of the through-cell membrane transport was inferred from the importance of molecular refraction in the best three-variable model. The models derived were validated by the leave-one-out procedure and by reproducing the activities of five arotinoids not included in the correlation sample.

Anticarcinogenic Agents↗

PubMed1994

The conformational flexibility of aromatic retinoids.

AM1 and PM3 complete geometry optimizations were performed on 19 arotinoids congeneric with (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)-1-propenyl] benzoic acid (TTNPB), a very potent agent in carcinoprevention and carcinotherapy. Sixteen TTNPB conformations with close energy were obtained and characterized; four representative conformations were then studied for 14 derivative compounds, for which we found a substantial non-planarity of the two aromatic moieties. Large rotational flexibility of the arotinoid ring fragments was predicted by both methods. Very low barriers (0.4-3.9 kcal/mol) were found for the tetralenyl ring rotation. The two methods also agreed in predicting benzoic acid moiety rotation in a wide range of torsion angle values except those close to 0 or 180 degrees for which the PM3 rotational barriers were found to be considerably lower than the AM1 ones. This high conformational flexibility of arotinoid molecules may facilitate their favorable orientation in the process of fitting to the receptor sites.

Benzoates↗

PubMed1993

Modeling the anticancer action of some retinoid compounds by making use of the OASIS method.

The powerful OASIS (optimized approach based on structural indices set) approach is applied to the anticancer activity of a series of vitamin A analogs. The best three- and four-variable models obtained via the OASIS technique have correlation coefficients of 0.973 vs. 0.990 and standard deviations s2 = 0.11 and 0.05, respectively. The models incorporate the hydrophobicity factor log P, two geometric parameters (topological indices and/or 3-D steric ones), and the molecular dipole moment. For a set of 15 compounds studied here, the activity measured by ED50 was well correlated by models with approximately equal contribution of the through cell membrane transport and the geometric drug-receptor correspondence while weak nonspecific electronic interaction was also found to play some role. Comparison to previous treatments of this data is given and extension to larger sets is discussed.

Antineoplastic Agents↗

PubMed1983

Self-similar self-avoiding structures: Models for polymers.

The hierarchy of m,n-self-similar self-avoiding structures on a lattice is introduced as a model for linear and branched polymers. The self-similarity condition permits exact solutions that use a generating-function renormalization procedure with full accounting for volume exclusion. Illustrative results are given for the 1,2-linear-chain model and for the 1,2-branched-structure model on a honeycomb lattice. Exponents for the dependence of polymer size on monomer number are obtained for these models, with that for branched structures being independent of the (nonzero) fraction of branch points. Exponents also are found involving branching probability and branching activity; the fact that those quantities are found to be distinct even in the dilute branching limit is a manifestation of the long-range nature of the excluded volume interaction.

Journal Article↗

PubMed1979

Self-avoiding random walks at finite concentrations: The bulk phase limit.

In infinitely dilute solutions, macromolecules exhibit non-Gaussian distributions for their end-to-end separations. This occurs under such circumstances because intramolecular interactions are more important than intermolecular forces. On the other hand, when a macromolecular solution becomes so concentrated that it approaches its bulk phase, then the end-to-end length distribution becomes substantially Gaussian. A theoretical explanation for the observed behavior is obtained by taking cognizance of a balance between inter-and intramolecular forces acting on self-avoiding random chains. Such a balance causes the chains to behave very much like random walks of order 2-that is to say, walks for which the only restriction against double occupancy is that identified with immediate return steps. This is demonstrated by taking Monte Carlo data for chains of various concentrations and analyzing the distributions of a component of length by using expansions involving orthogonal vectors. Although Gaussian behavior is more or less achieved for bulk polymers, slight deviations from that behavior still persist at the origin.

Journal Article↗

PubMed1978

Statistics of self-avoiding walks confined to strips and capillaries.

A long self-avoiding chain confined to a narrow strip or thin tube tends to be elongated in the direction of the strip or tube. The mean end-to-end separation of a long chain so confined becomes asymptotically proportional to the number of links in the chain as the contour chain length becomes infinite. By use of scaling arguments, it is shown that the mean end-to-end separation also becomes proportional to D(-1/3) for chains confined to two-dimensional strips and proportional to D(-2/3) for three-dimensional capillaries, where D is the width or diameter of the strip or capillary. These predictions have been verified by Monte Carlo studies of self-avoiding walks. The agreement is excellent for two-dimensional systems, but less certain for those of three dimensions since less data are available for verification.

Journal Article↗

PubMedDate not supplied

Wiener index extension by counting even/odd graph distances.

Chemical structures of organic compounds are characterized numerically by a variety of structural descriptors, one of the earliest and most widely used being the Wiener index W, derived from the interatomic distances in a molecular graph. Extensive use of such structural descriptors or topological indices has been made in drug design, screening of chemical databases, and similarity and diversity assessment. A new set of topological indices is introduced representing a partitioning of the Wiener index based on counts of even and odd molecular graph distances. These new indices are further generalized by weighting exponents which can be optimized during the quantitative structure-activity/-property relationship (QSAR/QSPR) modeling process. These novel topological indices are tested in QSPR models for the boiling temperature, molar heat capacity, standard Gibbs energy of formation, vaporization enthalpy, refractive index, and density of alkanes. In many cases, the even/odd distance indices proposed here give notably improved correlations.

Journal Article↗