Peter L. Warburton

A High-Resolution Shape-Fragment MEDLA Database for Toxicological Shape Analysis of PAHs

A new, high-resolution shape-fragment database has been developed for computing ab initio quality molecular electron densities for polyaromatic hydrocarbons (PAHs) which play a significant role as toxicants in the environment. Using the new PAH electron density fragment database and the Molecular Electron Density Lego Assembler (MEDLA) method, one can generate detailed and reliable electron densities for virtually any of the PAH molecules. Accurate electron density shape representations for these molecules is essential in the study of detailed shape-toxicity correlations. One of our goals is to investigate the potential of detailed molecular shape analysis as a predictive tool in toxicological risk assessment. In this study we report the results of the first phase of the study:  the construction and testing of a high quality shape-fragment database for PAHs.

Comparisons of Computational and Experimental Thermochemical Properties of α-Amino Acids

This study provides comprehensive benchmark calculations for the thermochemical properties of the common α-amino acids. Calculated properties include the proton affinity, gas-phase basicity, protonation entropy, ΔH°(acid), ΔG°(acid), and enthalpies of formation for the protonated and deprotonated α-amino acids. In order to determine the performance at various levels of theory, including density functional methods and composite methods, the calculated thermochemical properties are compared to experimental results. For all the common α-amino acids investigated, the thermochemical properties computed with the Gaussian-n theories were found to be quite consistent with each other in terms of mean absolute deviation from experiment. While all Gaussian-n theory values can serve as benchmarks, we focus on the G3MP2 values as it is the least resource-intensive of the Gaussian-n theories considered.

Capillary electrophoretic separation of anticoagulant rodenticides in aqueous electrolytes modified with organic solvents

Abstract The capillary electrophoretic separation of the anticoagulant rodenticides warfarin, chlorophacinone, diphacinone, bromadiolone, dicoumarol and coumatetralyl is described. Simple electrolytes, such as phosphate and borate, as well as phosphate modified with methanol (20-30%, v/v) or acetonitrile (5-30%, v/v) were used in an effort to optimize total analysis time and resolution. Micellar systems in phosphate electrolytes were also studied but with limited success. With the addition of methanol and acetonitrile modifiers it was possible to manipulate electroosmotic mobility, analyte electrophoretic mobility, and separation resolution and efficiency. Optimum resolution and analysis time (6 min) for all rodenticides was achieved in 0.015 mol/l phosphate (pH 7) modified with 22% (v/v) methanol. Separation efficiencies ranged between 459 200-548 800 theoretical plates, analyte migration reproducibility was between 0.1-0.6% R.S.D., and peak area reproducibility was in the range 1.9–9.8% R.S.D.

Stability and properties of polyhelicenes and annelated fused-ring carbon helices: Models toward helical graphites

The geometrical structures and properties of conjugated polyhelicenes and annelated fused-ring carbon helices with analogous frameworks were theoretically studied at the HF/6-31G and B3LYP/6-31G levels. These studies focused on the stability of the fused-ring structures with special emphasis on the helical geometrical arrangements. To elucidate bonding patterns, the orbitals, electron density contours, and the electrostatic potential of these helical compounds were analyzed. The structure of fused polynaphthalenes arranged in a helical spiral can be regarded as part of a locally helical graphite lattice that is expected to give rise to special electronic properties along the helically layered conjugated single sheet that can be regarded as a single extended pi system but also involving local layer-to-layer pi-pi interactions that are typical in ordinary graphite. This dual feature might lead to novel materials.

On the Balance of Simplification and Reality in Molecular Modeling of the Electron Density.

Fused-sphere (van der Waals) surfaces and their variants such as solvent accessible surfaces and molecular surfaces are simple molecular models that are commonly used for many diverse purposes across a broad range of scientific disciplines due to their low computational resource demands. Fused-sphere models require atomic radii to be defined. Many different atomic radii have been proposed, with each set of radii being applicable to a relatively limited scope of molecular types or situations. The large number of differing radii sets actually serves to emphasize the simplicity of the model and its inability to accurately represent the reality of the molecule: its electron density. By measuring the similarity of fused-sphere, fuzzy fused-sphere, and calculated electron density representations of a set of small molecules via symmetric volume differences and the shape group method, it can be seen that fused-sphere models are very poor at representing the real electronic charge distribution of small molecules, especially where π bond systems, lone pair electrons, and aromatic rings are involved. Larger molecules, conceivably, will be even more poorly represented. With advances in computational power and modeling techniques to arrive at high-quality calculated electron density representations for large molecules already in existence, abandoning the use of fused-sphere models should be considered for many applications.

Dimension Concepts and Reduced Dimensions in Toxicological QShAR Databases as Tools for Data Quality Assessment

The dimensions of databases can be defined based on a variety of concepts, ranging from the standard tools of principal component analysis to context-biased approaches. The effective dimensions of databases, in particular the effective dimensions involving continua such as electron density data, provide a set of important tools for database comparisons and for the evaluation of some aspects of database quality. The problems associated with database comparisons and database mergers, such as those occurring in the process of database unification in the actual merger of two pharmaceutical companies, provide challenging tasks and opportunities for data science. Some of the tools for effective dimension reduction and dimension expansion are reviewed in the context of database quality control and conditions for database compatibility are presented. A common misconception affecting data sampling techniques for data quality evaluation is discussed and methods for circumventing the associated sampling errors are described.

Atoms and bonds in molecules from radial densities.

Radial densities are explored as an alternative method for partitioning the molecular density into atomic regions and bonding regions. The radial densities for atoms in molecules are similar to those of an isolated atom. The method may also provide an alternative to Bragg-Slater radii.

Atoms and bonds in molecules: topology and properties

The atoms and bonds in molecules (ABIM) theory Warburton et al. (J Phys Chem A 115:852, 2011) partitions the molecular electron density into atomic and bonding regions using radial density. The concept is motivated by the radial distribution function of atoms which exhibit shell structure, where each shell contains a realistic number of electrons. In this paper, we define molecular radial density and investigate its topology in 2D planes of halogens, diatomics, and hydrides. The terminology employed to classify the radial density topology of atoms and molecules is then presented. The ABIM model quantifies both the molecular atom and bond. Here, we describe and calculate properties of ABIM and discuss how these properties correlate with expected trends. ABIM makes it possible to calculate the properties of atoms and bonds in molecules including number of electrons, shape, volume, dipole, and expectation values. The radial density model provides an intuitive description of ABIM.