Quantitative molecular similarity analysis (QMSA) methods for property estimation: A comparison of property-based,arbitrary, and tailored similarity spaces

Three classes of arbitrary quantitative molecular similarity analysis (QMSA) methods have been computed using atom pairs, topological indices, and physicochemical properties. Tailored QMSA models have been developed using a selected number of TIs chosen by ridge regression. The methods have been applied to the K -nearest neighbor based estimation of log P of two sets of chemicals. Results show that the property-based and tailored QMSA methods are superior to the arbitrary similarity methods in estimating log P of both sets of chemicals     

Quantitative molecular similarity analysis (QMSA) methods for property estimation: a comparison of property-based,arbitrary, and tailored similarity spaces

Three classes of arbitrary quantitative molecular similarity analysis (QMSA) methods have been computed using atom pairs, topological indices, and physicochemical properties. Tailored QMSA models have been developed using a selected number of TIs chosen by ridge regression. The methods have been applied to the K-nearest neighbor based estimation of log P of two sets of chemicals. Results show that the property-based and tailored QMSA methods are superior to the arbitrary similarity methods in estimating log P of both sets of chemicals     

VANADYL(IV) COMPLEXES OF SULFUR-CONTAINING LIGANDS WITH BIOLOGICAL AND PHARMACOLOGICAL RELEVANCE

Abstract

The behavior of thiosalicylic acid (H₂TSA) and 6-mercaptopurine (MP) with vanadyl(IV) cation has been studied in solution at different ligand-to-metal ratios and pH values. The preparation and characterization of VO/TSA(I) and VO/MP(II) complexes in the solid state is reported. The chemical environment of V in (I) is consistent with S and O atoms of TSA and two hydroxy bridges between two metal centers. The nearest neighbor atoms to V in (II) are S and N provided by the ligand and O atoms from hydroxyl groups. These results have been supported by physicochemical studies.     

Changes of Refractive Indices for the Ternary Mixture Acetone + Methanol + N-Hexane at 288.15 and 298.15 K

Abstract

The refractive indices of the ternary mixture acetone + methanol + n-hexane have been measured at 288.15 and 298.15 K and atmosphere in the whole composition diagram. Parameters of polynomial equations which represent the composition dependence of physical and derived property are gathered. the use of a multicomponent extension of Heller equation in order to predict excess molar volumes from refractive indices on mixing are tested against literature data, a comparative accuracy with currently available models being obtained.     

the statistical mechanical local composition theory II. Effects of molecular size and energy differences in Lennard-Jones and Kihara mixtures

Integral equation theory is used to determine the variations of the local mole fractions in binary mixtures of molecules differing considerably in size and energy of interaction. We model two types of mixtures, i.e., molecules interacting with the Lennard—Jones potential and molecules with the Kihara potential. The size ratio ranges from σ_BB/σ_AA = 1.0 to 1.75 and energy ratio for ϵ_BB/ϵ_AA = 1.21 to 9.14. Results are compared with simulation data of Hoheisel and Kohler and Nakanishi et al. Findings indicate that the coordination numbers and nearest neighbor numbers are strong functions of size ratio, but depend only weakly on energy disparity. In a mixture, large differences in size promote ‘mixing’ while large differences in energy induce ‘demixing’ of the components. It is found that the packing of nearest neighbors depends, to a large extent, on available ‘local surfaces’. the Seaton—Glandt ‘solid angle’ fractions turn out to be good correlators in nearest neighbor statistics. All local quantities are variable with changes in temperature, density and composition. The assumption of constant Wilson parameters is not valid for the systems studied.     

Aun (n＝2～20)团簇的遗传算法和密度泛函方法研究

在遗传算法和Gupta多体势系统地搜索金属团簇初始结构基础上, 应用密度泛函理论和基于局域密度近似 (LDA)或广义梯度近似(GGA)的超软赝势和投影扩充波(PAW)方法分别系统地研究了金属团簇Au_n (n≤20)的最稳定构型和电子性质. 发现LDA或GGA近似下, 最稳定构型存在一定的差异: LDA方法中, Au团簇最稳定构型从Au₇ 处就发生了从二维结构向三维结构的转化, 而GGA近似下Au₁₃的最稳定异构体仍然保持平面构型. 计算结果表明, 平均最近邻距、平均配位数和结合能随着尺寸的增大呈递增趋势, 而二阶差分能、费米能级、HOMO-LUMO能隙、垂直电离势和电子亲和势出现了明显的奇偶交替现象. 其结果丰富了目前对金团簇的理论和实验的研究.     

Cluster analysis: significance,empty space,clustering tendency,non-uniformity. I--Statistical tests on the significance of clusters

The agglomerative clustering methods and the tests usually applied to evaluate the significance of clusters are critically evaluated. Many clustering techniques can provide erroneous information about the existence of clusters. The single linkage technique is suggested to identify natural, well separated, clusters. The existing statistical tests on the significance of clusters are not satisfactory. A new statistical test, based on the distribution of the distances between the objects and their first nearest neighbor, is presented. The performances of the test are compared with those of the Sneath test and of the variance-ratio test on some artificial and real data sets.     

Localized impurity states in the Hartree-Fock,LCAO approximation II. The F Center in KCI

We apply the techniques of a previous paper (I) to the F center in KCl. Our purpose is to place the application of Hartree-Fock methods to the F center on a firm theoretical basis by calculating in a consistent manner the magnitude and effect of approximations commonly made in less complete treatments. It is shown that the familiar point-ion approximations and crystal-field approximations with partial consideration of exchange effects are special cases of our results. We compute wave functions and energies step by step for each of the various levels of approximation possible with our model. It is found that the functions resulting from the point-ion model are not good approximations to the final wave functions. Our results show that exchange effects with at least the first two shells of nearest neighbors should be considered since they are of the same order of magnitude as terms in the point-ion model. Overlaps of the F-center function with ion functions out to sixth neighbors are considered. The absorption energy for the F center is calculated to be 0.1619 Ry as compared with the experimentally observed energy of 0.170 Ry. The magnetic hyperfine structure contact terms are calculated for the first two shells of nearest neighbor ions, using approximate orthogonalized functions, and found to be 29.7 Mc/h for the nearest neighbor K⁺ ions and 10.9 Mc/h for the next nearest neighbor Cl^? ions. The experimentally observed values are 21.6 and 7.0, respectively. Given these differences and the excessively low values of the one-electron energies, it is concluded that electronic and ionic polarization effects in the ionized crystal states must be considered to calculate accurate F-center wave functions and absolute energy levels.     

Magnetic susceptibilities of UO2ThO2 solid solutions

The magnetic susceptibility of UO₂ThO₂ solid solutions has been measured from room temperature to 2.0 K. The magnetic moment and the Weiss constant have been determined in the temperature range in which the Curie-Weiss law holds. For the solid solutions showing antiferromagnetic transition, the Néel temperature has been also determined. These values decrease monotonically with increasing ThO₂ concentration. The results were analyzed using the molecular field theory which includes the interaction between next-nearest neighbor spins. The interactions between nearest neighbor spins, J₁, and those between next-nearest neighbor spins, J₂, both decrease with increasing ThO₂ concentration. The change of J₁ with composition is larger than that of J₂. The effect of magnetic dilution with ThO₂ is considered to be stronger on the interaction between nearest neighbor uranium ions.     

Optimal neighbor selection in molecular similarity: comparison of arbitrary versus tailored prediction spaces

Three classes of arbitrary quantitative molecular similarity analysis (QMSA) methods have been computed using atom pairs (APs), topological indices (TIs), and principal components (PCs) derived from topological indices. Tailored QMSA models have been developed from TIs selected through ridge regression. K-nearest neighbor (kNN) based estimation has been applied to all of the methods to estimate normal vapor pressure (p(vap)) and water solubility (sol) for a set of 194 chemicals. Results show that the tailored QMSA methods are superior to arbitrary similarity methods in estimating both of these properties for the given set of chemicals.     

Large-scale similarity search profiling of ChEMBL compound data sets

A large-scale similarity search investigation has been carried out on 266 well-defined compound activity classes extracted from the ChEMBL database. The analysis was performed using two widely applied two-dimensional (2D) fingerprints that mark opposite ends of the current performance spectrum of these types of fingerprints, i.e., MACCS structural keys and the extended connectivity fingerprint with bond diameter four (ECFP4). For each fingerprint, three nearest neighbor search strategies were applied. On the basis of these search calculations, a similarity search profile of the ChEMBL database was generated. Overall, the fingerprint search campaign was surprisingly successful. In 203 of 266 test cases (～76%), a compound recovery rate of at least 50% was observed with at least the better performing fingerprint and one search strategy. The similarity search profile also revealed several general trends. For example, fingerprint searching was often characterized by an early enrichment of active compounds in database selection sets. In addition, compound activity classes have been categorized according to different similarity search performance levels, which helps to put the results of benchmark calculations into perspective. Therefore, a compendium of activity classes falling into different search performance categories is provided. On the basis of our large-scale investigation, the performance range of state-of-the-art 2D fingerprinting has been delineated for compound data sets directed against a wide spectrum of pharmaceutical targets.