Visual exploration of structure–activity relationship using maximum common framework

To help tracking all molecules made in a typical medicinal chemistry project, we have developed an algorithm to generate a maximum common framework (MCF) hierarchy and an interactive tool for its visualization and analysis. By identifying all unique frameworks for a set of molecules and all molecules containing each framework, we were able to simplify the MCF hierarchy build up steps and, as a result, speed up the entire process significantly. By allowing compounds to be assigned to multiple MCFs, users can easily remove bad branching nodes and concentrate on interesting ones. MCF hierarchies provide an effective and intuitive visualization for tracking medicinal chemistry lead optimization projects. We will provide examples to illustrate its usefulness.     

PROLIX: rapid mining of protein-ligand interactions in large crystal structure databases

A central problem in structure-based drug design is understanding protein-ligand interactions quantitatively and qualitatively. Several recent studies have highlighted from a qualitative perspective the nature of these interactions and their utility in drug discovery. However, a common limitation is a lack of adequate tools to mine these interactions comprehensively, since exhaustive searches of the protein data bank are time-consuming and difficult to perform. Consequently, fundamental questions remain unanswered: How unique or how common are the protein-ligand interactions observed in a given drug design project when compared to all complexed structures in the protein data bank? Which interaction patterns might explain the affinity of a tool compound toward unwanted targets? To answer these questions and to enable the systematic and comprehensive study of protein-ligand interactions, we introduce PROLIX (Protein Ligand Interaction Explorer), a tool that uses sophisticated fingerprint representations of protein-ligand interaction patterns for rapid data mining in large crystal structure databases. Our implementation strategy pursues a branch-and-bound technique that enables mining against thousands of complexes within a few seconds. Key elements of PROLIX include (i) an intuitive interface that enables users to formulate complex queries easily, (ii) exceptional speed for results retrieval, and (iii) a sophisticated results summarization. Herein we describe the algorithms developed to enable complex queries and fast retrieval of search results, as well as the intuitive aspects of the user interface and summarization viewer.     

Controlling Through‐Space and Through‐Bond Exchange Pathways in Bis‐Cobaltocenes for Molecular Spintronics

Pinching molecules via chemical strain suggests intuitive consequences, such as compression at the pinched site and clothespin‐like opening of other parts of the structure. If this opening affects two spin centers, it should result in reduced communication between them. We show that for naphthalene‐bridged biscobaltocenes with competing through‐space and through‐bond pathways, the consequences of pinching are far less intuitive: despite the known dominance of through‐space interactions, the bridge plays a much larger role for exchange spin coupling than previously assumed. Based on a combination of chemical synthesis, structural, magnetic, and redox characterization, and a newly developed theoretical pathway analysis, we can suggest a comprehensive explanation for this non‐intuitive behavior. These results are of interest for molecular spintronics, as naphthalene‐linked cobaltocenes can form wires on surfaces for potential spin‐only information transfer.     

Pauli repulsion in the open shell species BeH and Co+

Using the natural bond orbital method, one may associate the valence bond configuration and Lewis structure concepts to wave functions consisting of molecular orbitals and thus gain intuitive insight into the molecular potential energy curves. Natural bond orbital analysis of the restricted open shell Hartree–Fock and unrestricted Hartree–Fock wave functions for the BeH ground state provides an intuitive model to help understand the nature of the bonding in this open shell species. The contrasting behavior of the bonding orbitals for different spins can be attributed to differences in the Pauli repulsive interactions with the lonepair orbitals. Such behavior occurs in BeH(²Σ) but does not in CO⁺(²Π) because the Pauli repulsion depends on the orbital overlap.     

Influence of the composition on the electronegativity and on the oxygen charge distribution in a binary hydrotalcite-like by modified Sanderson method

An intuitive and computationally non-intensive model for the classification of Hydrotalcite-like compounds (HTLCs) based simply on the chemical composition using the Sanderson Method led to good prediction of basicity and different basic sites (oxygen atoms with different charge). That model was evaluated at different M³⁺ /(M²⁺+M³⁺) ratio and with different divalent and trivalent metallic cations.AMS subject classification: 92E10     

探索人体健康与疾病现象的实体

通过对各种化学元素、化合物在人体中的作用与影响作出分析与总结,从现代科学的角度直观地解释了中医学中如阴虚、阳虚、正、邪、湿、热等的多个抽象概念和理论。为研究抽象而深奥难懂的中医学概念和理论提供了一个新的思路,使之转化为具体而直观的符合现代科学概念的理论。     

Pu(IV) polymer formation

Nearest-neighbor coagulation is proposed as a mechanism for Pu(IV) polymer formation. The distribution of colloids generated by this process is intuitive and easy to understand.     

Compartment-less Biofuel Cell: Fabricated with Pressed Graphite Pellets Incorporated Biocatalysts and Mediators as Bio-electrodes

More recently,there has been an upsurge in research on enzymatic BFCs,due to their most intuitive application in the implantable power sources for mierobioeleetronics such as cardiac pacemaker~([1,2]).     

Controlling Through-Space and Through-Bond Exchange Pathways in Bis-Cobaltocenes for Molecular Spintronics

Pinching molecules via chemical strain suggests intuitive consequences, such as compression at the pinched site and clothespin-like opening of other parts of the structure. If this opening affects two spin centers, it should result in reduced communication between them. We show that for naphthalene-bridged biscobaltocenes with competing through-space and through-bond pathways, the consequences of pinching are far less intuitive: despite the known dominance of through-space interactions, the bridge plays a much larger role for exchange spin coupling than previously assumed. Based on a combination of chemical synthesis, structural, magnetic, and redox characterization, and a newly developed theoretical pathway analysis, we can suggest a comprehensive explanation for this non-intuitive behavior. These results are of interest for molecular spintronics, as naphthalene-linked cobaltocenes can form wires on surfaces for potential spin-only information transfer.     

Electron group functions for the analysis of the electronic structures of molecules

The electronic structure of a vast majority of molecular systems can be understood in terms of electron groups and their wave functions. They serve as a natural basis for bringing intuitive chemical and physical concepts into quantum chemical calculations. This article considers the general electron group functions formalism as well as its simple geminal version. We try to characterize the wave function with the group structure and its capabilities in actual calculations. For this purpose we implement a variational method based on the wave function in the form of an antisymmetrized product of strongly orthogonal group functions and perform a series of electronic structure calculations for small molecules and model systems. The most important point studied is the relation between the choice of electron groups and the results obtained. We consider energetic characteristics as well as optimal geometry parameters. In view of practical importance, the structure of variationally optimized local one-electron states is considered in detail as well as intuitive characteristics of chemical bonds.     

Study on Electrochemical Fingerprints and Identification of Different Varieties of Rice and Mouldy Rice by B‐Z Oscillation Reaction System

The electrochemical fingerprints of different varieties of rice and mouldy rice were studied by Belousov‐Zhabotinskii (B‐Z) oscillation reaction system with malonic acid as dissipative material under the condition of constant temperature. The results indicated that the chemical composition of rice may influence the kinetic parameters of the B‐Z oscillation reaction, which lead to the electrochemical fingerprint characteristic parameters and the intuitive information changes obviously. The varieties of rice and mouldy rice can be identified and evaluated by the difference of the electrochemical characteristic information.     

Binding: A unifying notion or a pseudoconcept?

Communication between chemists and physicists working in different domains of physical chemistry may sound like a dream, but actually it must be established in order that the whole field may develop in a more efficient way. Binding is a unifying concept whose discussion may make it possible for specialists of different extractions to profit from each other's work. When different specialists speak of binding, they have some intuitive picture in mind. Does it correspond to a unique well-defined concept, or is it just a cover for ignorance? A tentative definition is proposed as a starting point for discussion, but it is also emphasized that only from an open-minded and thorough analysis of the various interpretations it should be possible to make real progress. An example showing very clearly the relationship between the various topics is that of biopolymers, whose understanding depends on the specification of the role of a variety of binding effects, from chemisorption to charge transfer to (one-dimensional) metallic binding.     

Nonbonded interactions in membrane active cyclic biopolymers. II. Ion binding by valinomycin

A possible mode for the capture of a cation by the carrier molecule valinomycin has been simulated. The intramolecular nonbonded energy and the binding energy for a centrally located potassium ion at different stages in the capture process have been evaluated using a method proposed earlier. Contrary to intuitive expectations the open conformation of valinomycin is also found to have a strong affinity for K⁺. There appears to be a rather high potential barrier between the open and closed symmetric conformations.     

Metric and multidimensional scaling: efficient tools for clustering molecular conformations

The application of metric and multidimensional scaling to conformer ensembles was demonstrated in this work. An automated process was devised to cluster and assign group memberships and cluster representatives. The method allows rapid clustering, leading to intuitive results that can be visually inspected. Multidimensional scaling was found to be superior to metric scaling for clustering conformers. The performance of different hierarchical clustering algorithms was compared using multidimensional plots, and the group average method was found to perform best.     

Water wettability of close-packed metal surfaces

We propose a new microscopic criterion to determine surface wetting: water wets the surface whenever its overlayer has a larger adsorption energy than three-dimensional clusters on the bare or water-covered substrate. This conceptually intuitive criterion is validated by detailed first-principles calculations of the energetics of layers and clusters of water on different metal surfaces. This criterion resolves naturally the current discrepancy between theory and experiment on the wetting behavior of undissociated water on Ru(0001), as well as the hydrophobic nature of the Au(111) surface. It also explains the Stranski-Krastanov ice growth on Pt(111) observed experimentally.