Biomedical subjects

A J Holder

Publications and source records attributed to A J Holder.

4 recordsLinked to original sources

PubMed2001

Quantum mechanical quantitative structure activity relationships to avoid mutagenicity in dental monomers.

The objective of this study was to identify through quantum mechanical quantitative structure activity relationships (Q-QSARs) chemical structures in dental monomers that influence their mutagenicity. AMPAC, a semiempirical computer program that provides quantum mechanical information for chemical structures, was applied to three series of reference chemicals: a set of methacrylates, a set of aromatic and a set of aliphatic epoxy compounds. QSAR models were developed using this chemical information together with mutagenicity data (Salmonella TA 100, Ames Test). CODESSA, a QSAR program that calculates quantum chemical descriptors from information generated by AMPAC and statistically matches these descriptors with observed biological properties was used. QSARs were developed which had r2 values exceeding 0.90 for each study series. These QSARs were used to accurately predict the mutagenicity of BISGMA. a monomer commonly used in dentistry, and two epoxy monomers with developing use in dentistry, GY-281 and UVR-6105. The Q-QSAR quantum mechanical descriptors correctly predicted the level of mutagenicity for all three compounds. The descriptors in the correlation equation pointed to components of structure that may contribute to mutagenesis. The QSARs also provided 'dose windows' for testing mutagenicity, circumventing the need for extensive dose exploration in the laboratory. The Q-QSAR method promises an approach for biomaterials scientists to predict and avoid mutagenicity from the chemicals used in new biomaterial designs.

Dental Enamel↗

PubMed2000

Evaluation of quantitative structure property relationships necessary for enantioresolution with lambda- and sulfobutylether lambda-carrageenan in capillary electrophoresis.

Lambda-carrageenan, a linear, high molecular weight sulfated polysaccharide, was successfully employed in both its native and sulfobutyl derivatized form as a chiral selector in capillary electrophoresis for the separation of enantiomers of basic pharmaceutical compounds. In order to characterize the chiral selectivity properties of this chiral selector, various structurally related racemic compounds were analyzed for enantiomeric interactions using capillary electrophoresis. The results of these studies were then rationalized and analyzed utilizing a general quantitative structure-property relationship (QSPR) evaluation in order to predict critical analyte structural requirements for successful enantiomeric separation. Important structural components of the analytes were found to include the aromatic content, the type of substitution on the aromatic ring, presence of a primary or secondary protonated amine, and an overall positive charge to the molecule.

Adrenergic beta-Antagonists↗

PubMed2000

Semiempirical and ab initio conformational analysis of 2-methylene-8,8-dimethyl-1,4,6,10-tetraoxaspiro[4.5] decane with application of GIAO-SCF methods to NMR spectrum interpretation.

The GIAO-SCF method for calculating isotropic nuclear magnetic shielding values has been utilized to explain certain features in the 1H-NMR spectrum of 2-methylene-8,8-dimethyl-1,4,6,10-tetraoxaspiro[4.5] decane. Population distributions of the low-energy conformers based on their ab initio energies were used to produce weighting factors for the individual calculated shielding values to calculate the weighted average of the shielding values for a complete set of conformers. The differences in 1H chemical shifts between the hydrogens of the two methyl groups and between the axial and equatorial hydrogens in 2-methylene-8,8-dimethyl-1,4,6,10-tetraoxaspiro[4.5] decane were shown to be due to energy differences between the chair and boat orientations of the six-membered ring and contribution from a twist-boat conformation. Results suggest a hypothesis that intramolecular differences in chemical shift might be calculated to a greater degree of accuracy than chemical shifts calculated relative to a standard.

Magnetic Resonance Spectroscopy↗

PubMed1992

A semiempirical computational investigation of the antipsoriatic drug anthralin.

A series of computational studies was carried out, by using the highly successful Austin Model 1 (AM1) semiempirical method, to illuminate more completely the fundamental, molecular-level forces that affect the function and utility of the antipsoriatic drug anthralin. First, examination of the keto-enol tautomeric equilibrium by AM1 showed that the keto tautomer of the drug is 9.5 kcal/mol more stable than the enol form. Strong electrostatic forces involving the hydrogens on the hydroxy groups (a partial charge of +0.25 in both forms) and the keto oxygen (a partial charge of -0.40) apparently overcome the effects of the increased aromatic stabilization present in the enol form. Second, AM1 was applied to the degradation products of anthralin, 1,8-dihydroxy-9,10-anthraquinone, 1,8,1',8'-tetrahydroxy-10,10'-dianthrone, and a further oxidized form of the dimer. These molecules have been implicated in some of the unpleasant side effects of anthralin. Third, AM1 was used to predict the preferred site of ionization of anthralin.

Anthralin↗