Electron Density Clouds Research Articles

From quantum similarity measures to quantum analogy functors: tools for QShAR, quantitative shape-activity relations

An analogy can be regarded as a relation between two families of similarities, and the mathematical tool of functor has been proposed for certain chemical applications where not just one type of similarity, but entire families of similarities, hence, analogies, are playing important roles. Some of the relevant background important in molecular applications, especially, in studies of chemical and biochemical activity problems are discussed, where several factors of various levels of similarities are determining the overall chemical processes. Such analogies are highly relevant in the interpretation of complex biochemical actions, as well as in pharmaceutical drug design. The Quantum Similarity Measures and alternative measures based on quantum chemistry are combined into a Quantum Analogy Functor model, with special emphasis on the 3D molecular shapes represented by the electron density clouds, and the associated Quantitative Shape-Activity Relations, QShAR. Some aspects of the Quantum Analogy Functor approach, with focus on Molecular Shapes and QShAR are discussed in this contribution.

Zerovalent Selenium Adsorption Mechanisms on CaO Surface: DFT Calculation and Experimental Study.

Zerovalent Se (Se atom and small Se2 molecule) adsorption mechanisms on a CaO surface were studied by both density functional theory (DFT) calculations and adsorption experiments. Nonvalent Se adsorption on the CaO(001) surface was simulated using a slab model. The adsorption energy, adsorption structure, electron density clouds, and electron properties were calculated. Different Se surface coverages were investigated to elucidate the adsorption process. In the experiments, the Se adsorption products were prepared in a U-shaped quartz reactor at 300 °C. The properties were investigated by X-ray photoelectron spectroscopy (XPS), inductively coupled plasma atomic emission spectroscopy (ICP-AES), field emission scanning electron microscopy/energy dispersive X-ray spectroscopy (FE-SEM/EDS), and X-ray diffraction (XRD), respectively. The experimental results match up with the DFT results, which reveal fundamentalmonochemisorption mechanisms of zerovalent Se on the CaO surface.

Fuzzy electron density fragments in macromolecular quantum chemistry, combinatorial quantum chemistry, functional group analysis, and shape-activity relations.

Conspectus Just as complete molecules have no boundaries and have "fuzzy" electron density clouds approaching zero density exponentially at large distances from the nearest nucleus, a physically justified choice for electron density fragments exhibits similar behavior. Whereas fuzzy electron densities, just as any fuzzy object, such as a thicker cloud on a foggy day, do not lend themselves to easy visualization, one may partially overcome this by using isocontours. Whereas a faithful representation of the complete fuzzy density would need infinitely many such isocontours, nevertheless, by choosing a selected few, one can still obtain a limited pictorial representation. Clearly, such images are of limited value, and one better relies on more complete mathematical representations, using, for example, density matrices of fuzzy fragment densities. A fuzzy density fragmentation can be obtained in an exactly additive way, using the output from any of the common quantum chemical computational techniques, such as Hartree-Fock, MP2, and various density functional approaches. Such "fuzzy" electron density fragments properly represented have proven to be useful in a rather wide range of applications, for example, (a) using them as additive building blocks leading to efficient linear scaling macromolecular quantum chemistry computational techniques, (b) the study of quantum chemical functional groups, (c) using approximate fuzzy fragment information as allowed by the holographic electron density theorem, (d) the study of correlations between local shape and activity, including through-bond and through-space components of interactions between parts of molecules and relations between local molecular shape and substituent effects, (e) using them as tools of density matrix extrapolation in conformational changes, (f) physically valid averaging and statistical distribution of several local electron densities of common stoichiometry, useful in electron density databank mining, for example, in medicinal drug design, and (g) tools for combinatorial quantum chemistry approaches using fuzzy fragment databanks and rapid construction of a large number of approximate electron densities for large sets of related molecules, relevant in theoretical molecular and nanostructure design.

Vibrational spectroscopic studies of 3-hydroxyphenylboronic acid: molecular structure

In this work, optimized molecular structure, vibrational frequencies and corresponding vibrational assignments, HOMO–LUMO energy values and electron density clouds of 3-hydroxyphenylboronic acid have been calculated by ab initio Hatree–Fock (HF) and density functional theory methods. The compound has eight conformers depending on the directions of hydrogen atoms bonded to oxygen. The computational results have diagnosed the most stable conformer of the compound as cis–trans (ctt) form. The calculated frequencies and optimized geometry parameters (bond lengths and bond angles) for the most stable conformer are in a good agreement with the corresponding experimental data.

QSAR and the ultimate molecular descriptor: the shape of electron density clouds

The advantages of electron density representations of molecules in QSAR studies and the related shape descriptors and shape similarity measures are discussed, with special emphasis on molecules involving pi-bonded systems and aromatic rings.

Computer Aided Drug Design: Some Fundamental Aspects

Understanding the molecular basis of drug action and exploring the chemical interactions involved in the complex processes of drug delivery are among the most important goals of contemporary drug design. The major recent advances in the detailed, mechanistic interpretation of molecular interactions, the global and local shape analysis of electron density clouds making up the actual fuzzy bodies of molecules, novel similarity and complementary measures, the detailed and accurate computational visualization techniques of molecular level "Computational Microscopy", the advances in computer modeling of conformational processes and chemical reactions of drug molecules, the computer aided design of molecular templates fitting various receptor sites are among the powerful tools of computer aided drug discovery. In this contribution some of the latest advances are reviewed.

Shape‐similarity relations based on topological resolution

Shape‐similarities of electron density clouds of molecules provide important clues concerning chemical and physical properties, including information about their reactivities in biochemical systems. The concept of topological resolution is used for quantifying molecular similarities: within a hierarchy of finer and cruder topologies, the crudest topology that already provides discrimination between two objects (such as two fuzzy electron density clouds) is used to define a measure of their similarities. The finer this topology, the more similar the two objects. This approach, the method of topological resolution‐based similarity measures (TRBSM), can be combined with a geometrically motivated resolution‐based similarity measure (RBSM) within a metric space. Some of the relations between these two approaches are discussed in this contribution, with special emphasis on applications to electron densities.

The proof of the metric properties of a fuzzy chirality measure of molecular electron density clouds

A chirality measure of fuzzy electron density clouds is described, based on a dissimilarity distance defined in terms of a fuzzy set variant of the Hausdorff distance. A proof is presented for the metric properties of this dissimilarity distance that justifies the use of these numerical measures in comparison with the formal degrees of chirality for “almost achiral” and “prominently chiral” electron density clouds.

Relative Local Convexity Approaches for Accessibility Studies of Molecular Regions

In modern chemistry, biochemistry, supramolecular chemistry, and molecular engineering the study of the mutual accessibility of interacting molecular regions plays a prominent role. In this study the approach of Iso-Depth Contour Map of Molecular Surface, proposed earlier, is adapted to a scaleable, curvature-based accessibility description of local molecular regions, such as the pocket regions of enzymes. The approach is formulated within the framework of generalized convexity, using the alpha-hull concept that is a generalization of the convex hull, and using a further generalization based on the T-hull concept. The alpha-hull of an object A is the intersection of all balls of radius 1/alpha which contain the object A, whereas the T-hull of an object A is the intersection of all translated and rotated versions of a reference object T that contain the object A. These and additional local relative convexity approaches provide mathematical and computational tools for both local and global shape analysis of the electron density clouds of molecules, including macromolecules, such as proteins. Such generalized convexity approaches are advantageous if the recognition of the variability of effective local curvatures is of importance, providing a geometric-topological criterion for biochemical interactions. The scaleable alpha-hull and the scaleable T-hull approaches involve one or several reference curvature parameters which can be used to fine-tune the detection of accessible regions by molecules of various shapes, and to provide discrimination based on local shape and cavity size. The example of the dipeptide ALA-ALA is used to illustrate the new concepts and methods.