The Nowotny chimney ladder phases: following the c(pseudo) clue toward an explanation of the 14 electron rule

We account for two empirical rules of the Nowotny chimney ladder phases (NCLs, intermetallic compounds of the form T(t)E(m); T, groups 4-9; E, groups 13-15). The first rule is that for late transition metal NCLs the total number of valence electrons per T atom is 14. The second is the appearance of a pseudoperiodicity with a spacing, c(pseudo), which is directly related to the stoichiometry, T(t)E(m), by (2t - m) c(pseudo)= c. Both rules are accounted for by viewing the NCLs as twinned structures constructed from blocks of the parent compound, RuGa(2) of thickness c(pseudo)/2, with the successive layers rotated relative to each other by 90 degrees. Sterically encumbered E atoms are then deleted at the interfaces between layers, followed by relaxation.     

The Limited Predictive Power of the Pauling Rules

The Pauling rules have been used for decades to rationalise the crystal structures of ionic compounds. Despite their importance, there has been no statistical assessment of the performances of these five empirical rules so far. Here, we rigorously and automatically test all five Pauling rules for a large data set of around 5000 known oxides. We discuss each Pauling rule separately, stressing their limits and range of application in terms of chemistries and structures. We conclude that only 13 % of the oxides simultaneously satisfy the last four rules, indicating a much lower predictive power than expected.     

The Limited Predictive Power of the Pauling Rules

The Pauling rules have been used for decades to rationalise the crystal structures of ionic compounds. Despite their importance, there has been no statistical assessment of the performances of these five empirical rules so far. Here, we rigorously and automatically test all five Pauling rules for a large data set of around 5000 known oxides. We discuss each Pauling rule separately, stressing their limits and range of application in terms of chemistries and structures. We conclude that only 13 % of the oxides simultaneously satisfy the last four rules, indicating a much lower predictive power than expected.     

On the Additivity of Molecular Fragment Dipole Moments of 5‐Substituted Indole Derivatives

The estimate of the magnitude and the orientation of molecular electric dipole moments from the vector sum of bond or fragment dipole moments is a widely used approach in chemistry. However, the limitations of this intuitive model have rarely been tested experimentally, particularly for electronically excited states. Herein, we find rules for a number of indole derivatives by using rotationally resolved electronic Stark spectroscopy and ab initio calculations. Based on a natural‐bond‐orbital analysis, we discuss whether the vector additivity rule can be applied in a given electronic state. From a comparison of the experimental data with ab initio calculations, we deduced that the additivity model does not apply when the flow of electron density from the substituent is opposed to that inside the chromophore.     

Three characteristic reactions of organocobalt compounds in organic synthesis

Organocobalt compounds in organic synthesis have three characteristic reactions. The first occurs because cobalt has a high affinity to carbon–carbon π‐bonds or carbon–nitrogen π‐bonds. The second occurs because cobalt has a high affinity to carbonyl groups. The third is due to cobalt easily tending to form square‐planar bipyramidal six‐coordination structures with four nitrogen atoms or two nitrogen atoms and two oxygen atoms at the square‐planar position, and to bond with one or two carbon atoms at the axial position. The first characteristic reactions are the representative reactions of organocobalt compounds with a mutually bridged bond between the two π‐bonds of acetylene and the cobalt–cobalt bond of hexacarbonyldicobalt. These are reactions with a Co₂(CO)₆ protecting group to reactive acetylene bond, the Nicholas reactions, the Pauson–Khand reactions ([2 + 2 + 1] cyclizations), [2 + 2 + 2] cyclizations, etc. These reactions are applied for the syntheses of many kinds of pharmaceutically useful compounds. The second reactions are carbonylations that have been used or developed as industrial processes such as hydroformylation for the manufacture of isononylaldehyde, and carbonylation for the production of phenylacetic acid from benzyl chloride. The third reactions are those reactions with the B₁₂‐type catalysts, and they have recently been used in organic syntheses and are utilized as catalysts for stereoselective syntheses. These reactions have been used as new applications for organic syntheses. Copyright © 2007 John Wiley & Sons, Ltd.     

"Amide resonance" correlates with a breadth of C-N rotation barriers

Complete basis set calculations (CBS-QB3) were used to compute the CN rotation barriers for acetamide and eight related compounds, including acetamide enolate and O-protonated acetamide. Natural resonance theory analysis was employed to quantify the "amide resonance" contribution to ground-state electronic structures. A range of rotation barriers, spanning nearly 50 kcal/mol, correlates well to the ground-state resonance weights without the need to account for transition-state effects. Use of appropriate model compounds is crucial to gain an understanding of the structural and electronic changes taking place during rotation of the CN bond in acetamide. The disparate changes in bond length (DeltarCO < DeltarCN) are found to be consonant with the resonance model. Similarly, charge differences are consistent with donation from the nitrogen lone pair electrons into the carbonyl pi* orbital. Despite recent attacks on the resonance model, these findings demonstrate it to be a sophisticated and highly predictive tool in the chemist's arsenal.     

Electronic structure of persistent radicals: nitroxides

The molecular and electronic structures of 10 free nitroxide radicals have been investigated by HeI/HeII photoelectron spectroscopy (UPS), DFT calculations, and comparison with the spectra of related compounds. We observe that the electronic structure of the nitroxide group is unaffected by substitution except in a carbonyl derivative where nitroxide group orbitals are noticeably stabilized. Also, we have detected small variations in the photoionization cross-sections for singlet and triplet states of cation, the states belonging to the same electron configuration. The relationship between electronic structure and radical reactivity is discussed, and an experimentally based estimate of delocalization energy of the unpaired electron is given. Some conflicting kinetic data on radical reactivity have been analyzed in view of the UPS results.     

Computational modeling of the optical rotation of amino acids: a new look at an old rule for pH dependence of optical rotation

The molar rotation of a solution of a natural alpha amino acid is changed in the positive direction by addition of a strong acid. Three decades ago, an attempt to rationalize this old rule, named for Clough, Lutz, and Jirgensons (CLJ), was made by assigning circular dichroism octants for overlapping carbonyl n to pi* transitions. Modern quantum chemical methods allow us to take a new look at this phenomenon. Time-dependent density functional theory was used to model the electronic structure and transitions responsible for CLJ. We show that sector rules originally developed for circular dichroism (CD) can be applied to the optical rotation in this case, but with some restrictions, and with great caution, due to the change of the overall charge of the acids upon protonation and the distortion of the COO- chromophore in the zwitterions. We have prepared sector maps based on first-principles computations to study the correspondence between CD and optical rotation for zwitterionic and protonated l-amino acid chromophores. The CLJ effect is correctly obtained from the computations for all 12 amino acids studied in this work.     

Chemoselective Synthesis of Substituted Imines,Secondary Amines,and β‐Amino Carbonyl Compounds from Nitroaromatics through Cascade Reactions on Gold Catalysts

Substituted imines, α,β‐unsaturated imines, substituted secondary amines, and β‐amino carbonyl compounds have been synthesized by means of new cascade reactions with mono‐ or bifunctional gold‐based solid catalysts under mild reaction conditions. The related synthetic route involves the hydrogenation of a nitroaromatic compound in the presence of a second reactant such as an aldehyde, α,β‐unsaturated carbonyl compound, or alkyne, which circumvents an ex situ reduction process for producing the aromatic amine. The process is shown to be highly selective towards other competing groups, such as double bonds, carbonyls, halogens, nitriles, or cinnamates, and thereby allows the synthesis of different substituted nitrogenated compounds. For the preparation of imines, substituted anilines are formed and condensed in situ with aldehydes to provide the final product through two tandem reactions. High chemoselectivity is observed, for instance, when double bonds or halides are present within the reactants. In addition, we show that the Au/TiO₂ system is also able to catalyze the chemoselective hydrogenation of imines, so that secondary amines can be prepared directly through a three‐step cascade reaction by starting from nitroaromatic compounds and aldehydes. On the other hand, Au/TiO₂ can also be used as a bifunctional catalyst to obtain substituted β‐amino carbonyl compounds from nitroaromatics and α,β‐unsaturated carbonyl compounds. Whereas gold sites promote the in situ formation of anilines, the intrinsic acidity of Ti species on the support surface accelerates the subsequent Michael addition. Finally, two gold‐catalyzed reactions, that is, the hydrogenation of nitro groups and a hydroamination, have been coupled to synthesize additional substituted imines from nitroaromatic compounds and alkynes.     

Isolation,Structural Characterization,and Validation of a New Compound Present in Non‐Carbonyl Curcuma longa (NCCL): A Potential Lead for Stroke

The hexane soluble extract of Curcuma longa (Turmeric) [herbal medicament (HM)] developed by Central Drug Research Institute, India, as a new antistroke agent. It contains carbonyl as well as non‐carbonyl compounds. To see the activity of non‐carbonyl compounds, HM was reacted with semicarbazide hydrochloride to remove the carbonyl compounds. This chemically modified fraction [non‐carbonyl Curcuma longa (NCCL)] of HM was found to be active at lower dose than HM against endothelial mediated inflammation in myocardial ischemia/reperfusion induced rats. It reduced significantly the serum CK‐MB levels, inflammatory cytokine mediators (TNF‐α, IL‐6, IFN‐γ), plasma endothelial microparticle level and also found useful in improving the endothelial functionality. It was also found active in anti‐inflammatory and cytotoxic activity for sepsis and leukemia. To find out the compounds that are responsible for its enhanced activity in comparison of HM, we have isolated two major peaks present in the high‐performance liquid chromatography (HPLC) fingerprint of NCCL and their structures were characterized. Based on the characterization, we found that these compounds are not the non‐carbonyl compounds present in HM but the new cyclic structures formed by the reaction of ar‐turmerone, α‐turmerone, and β‐turmerone with semicarbazide hydrochloride used in the reaction. This hypothesis was validated by isolation of ar‐turmerone, α‐turmerone, and β‐turmerone from HM and reacting them with semicarbazide hydrochloride using the same reaction conditions of NCCL formation. The same mass spectral data and same retention time (RT) value in high‐performance liquid chromatography analysis further confirms our hypothesis.     

Energy isosbestic points in third-row transition metal alloys

The total electronic energies of the six electrons per atom (e per atom) alloys W, TaRe, HfOs, and YIr and the seven electrons per atom alloys Re, WOs, TaIr, HfPt, and YAu have been calculated in the local density approximation of density functional theory. When one considers common alloy structures such as atomically ordered variants of the body-centered cubic, face-centered cubic, or hexagonally closest packed structures and plots the total electronic energy as a function of the unit cell parameter, one finds for both the six and seven electrons per atom series energetic isosbestic points. An energetic isosbestic point corresponds to a critical value of the size parameter for which all members of the 6 or 7 e per atom series of compounds have nearly identical total electronic energy. Just as in spectroscopy, where the existence of such isosbestic points is the hallmark of two compounds present in the mixture, an energy isosbestic point implies there are just two separate energy curves. For both series it is found that the total electronic energy can be viewed as the weighted sum of a purely covalent term and a purely ionic term. Two semi-quantitative models are proposed to account for these two separate energies. In the first model the total energy is viewed as the sum of the elemental structural energy plus an ionic energy based on the Born-Mayer ionic model. In the second model one considers within the confines of mu2-Hückel theory the evolution of the total electronic energy as the Coulombic Hii integrals change in value.     

Scaffold hopping in drug discovery using inductive logic programming

In chemoinformatics, searching for compounds which are structurally diverse and share a biological activity is called scaffold hopping. Scaffold hopping is important since it can be used to obtain alternative structures when the compound under development has unexpected side-effects. Pharmaceutical companies use scaffold hopping when they wish to circumvent prior patents for targets of interest. We propose a new method for scaffold hopping using inductive logic programming (ILP). ILP uses the observed spatial relationships between pharmacophore types in pretested active and inactive compounds and learns human-readable rules describing the diverse structures of active compounds. The ILP-based scaffold hopping method is compared to two previous algorithms (chemically advanced template search, CATS, and CATS3D) on 10 data sets with diverse scaffolds. The comparison shows that the ILP-based method is significantly better than random selection while the other two algorithms are not. In addition, the ILP-based method retrieves new active scaffolds which were not found by CATS and CATS3D. The results show that the ILP-based method is at least as good as the other methods in this study. ILP produces human-readable rules, which makes it possible to identify the three-dimensional features that lead to scaffold hopping. A minor variant of a rule learnt by ILP for scaffold hopping was subsequently found to cover an inhibitor identified by an independent study. This provides a successful result in a blind trial of the effectiveness of ILP to generate rules for scaffold hopping. We conclude that ILP provides a valuable new approach for scaffold hopping.     

原子簇局部非定域分子轨道模型及其应用──（Ⅱ）CLD原子簇结构规则

在原子簇局部非定域分子轨道模型的基础上，导出一个既能包容以往许多结构规则，又能适用于各类高氧化态金属原子簇的结构新规则，并应用于簇合物结构和催化机理分析。     

Molecular-orbital realizations of the bent-bond model: Spiranic derivatives of cyclobutanone

In the frame of our studies on small-ring compounds, we deal here with structures in which a three-membered ring and a carbonylated four-membered ring are fixed in close proximity. The theoretical approach is through an allvalence electron semiempirical method. The experimental background, based on results of other workers, comprises mainly UV and IR spectral data. The main topics to be discussed are: charge-donation and charge-transfer from the 3-ring, hypsochromic and bathochromic shifts of electronic transitions related to the carbonyl, direct substituent effects on the carbonyl stretching frequency, and the across-ring interaction in cyclobutanone.Part XII in series. For previous papers, see Refs. [1, 2].     

N-(2-溴乙基)咔唑与N-乙烯基咔唑的气相HeI紫外光电子 能谱与电子结构研究

首次报道了N-(2-溴乙基)咔唑和N-乙烯基咔唑的气相HeI紫外光电子能谱(UPS),借助于Gaussian94采用RHF/6-31G基组优化几何构型,并用RHF/6-31G^*基组计算分子轨道及能级.在对咔唑和N-烷基咔唑系列分子UPS电离能变化规律研究的基础上,对这2个分子的UPS谱带给予指认,并讨论其电子结构.结果表明N-(2-溴乙基)咔唑的UPS谱与N-烷基咔唑的不同之处是在10.295,10.540eV处出现2个Br原子的孤对轨道;N-乙烯基咔唑的UPS谱带与咔唑的相比,电离能变化的特殊性说明乙烯基与咔唑环共平面。     

Ultrafast electron diffraction: excited state structures and chemistries of aromatic carbonyls

The photophysics and photochemistry of molecules with complex electronic structures, such as aromatic carbonyls, involve dark structures of radiationless processes. With ultrafast electron diffraction (UED) of isolated molecular beams it is possible to determine these transient structures, and in this contribution we examine the nature of structural dynamics in two systems, benzaldehyde and acetophenone. Both molecules are seen to undergo a bifurcation upon excitation (S(2)). Following femtosecond conversion to S(1), the bifurcation leads to the formation of molecular dissociation products, benzene and carbon monoxide for benzaldehyde, and benzoyl and methyl radicals for acetophenone, as well as intersystem crossing to the triplet state in both cases. The structure of the triplet state was determined to be "quinoidlike" of pipi(*) character with the excitation being localized in the phenyl ring. For the chemical channels, the product structures were also determined. The difference in photochemistry between the two species is discussed with respect to the change in large amplitude motion caused by the added methyl group in acetophenone. This discussion is also expanded to compare these results with the prototypical aliphatic carbonyl compounds, acetaldehyde and acetone. From these studies of structural dynamics, experimental and theoretical, we provide a landscape picture for, and the structures involved in, the radiationless pathways which determine the fate of molecules following excitation. For completeness, the UED methodology and the theoretical framework for structure determination are described in this full account of an earlier communication [J. S. Feenstra et al., J. Chem. Phys. 123, 221104 (2005)].     

N-(2-溴乙基)咔唑与N-乙烯基咔唑的气相HeI紫外光电子能谱与电子结构研究

首次报道了N-(2-澳乙基)咔唑和N-乙烯基咏唑的气相Hel紫外光电子能谱(UPS),借助于Gaussian 94采用RHF/6-3lG基组优化几何构型,并用RHF/6-31G基组计算分子轨道及能级.在对咔唑和N-烷基咔唑系列分子UPS电离能变化规律研究的基础上,对这2个分子的UPS谱带给予指认,并讨论其电子结构.结果表明N-(2-溴乙基)咔唑的UPS谱与N-烷基咔唑的不同之处是在10.295,10.540Ve处出现2个Br原子的孤对轨道;N-乙烯基咔唑的UPS谱带与咔唑的相比,电离能变化的特殊性说明乙烯基与咔唑环共平面.     

Structures and fluxional behaviour of transition metal cluster carbonyls

Conclusion We have examined the structures of transition metal cluster carbonyls M_m(CO)n from the point of view of the geometrical arrangement of the carbonyl ligands, and, in particular, the polyhedra defined by their oxygen atoms. Provided that the metal atom cluster is reasonably spherical (which is presumed to be predetermined by electronic factors), these polyhedra correspond well to the ideal forms calculated by optimisation of mutual repulsions between points on a sphere. Thus the concepts of coordination polyhedra about single central atoms may be successfully applied to the coordination of carbonyl ligands about entire clusters of metal atoms. This is in contrast to the more usual emphasis on the environment of individual metal atoms in the cluster. In the fine balance of factors governing the structures of these molecules and anions, we believe that steric interaction between carbonyl groups is of greater importance than previously thought. The steric crowding of ligands around the central metal atom cluster has important implications for the reactivity and catalytic activity of cluster carbonyls. Additionally, a new approach to the fluxionality of these species, based on the idea that carbonyl mobility may occur by rearrangements of the entire ligand polyhedron, has led to new insights into the behaviour of a number of systems.     

Electronic properties and aromaticity of substituted diphenylfulvenes in the ground (S<Subscript>0</Subscript>) and excited (T<Subscript>1</Subscript>) states

In the present account, we investigate electronic properties of diphenylfulvene and its derivatives substituted in phenyl rings. The results were compared with the analogous properties of fulvene and its derivatives with the same substituents at the exocyclic carbon atom. All properties were evaluated and compared in the ground electronic S₀ state and in the first excited T₁ triplet state. These properties are dipole moments, charges, number of π electrons, and aromaticity of the fulvenic, five-membered ring in the two sets of compounds. The latter property was estimated by the harmonic oscillator model for aromaticity (HOMA) index and, for the fulvenes group, by the calculation of aromatic stabilization energy in both electronic states. It was also investigated whether Baird’s rule alone can account for the aromaticity differences in the two electronic states.     

Structural unit analysis identifies lead series and facilitates scaffold hopping in combinatorial chemistry

Combinatorial chemistry and high-throughput screening technologies produce huge amounts of data on a regular basis. Sieving through these libraries of compounds and their associated assay data to identify appropriate series for follow-up is a daunting task, which has created a need for computational techniques that can find coherent islands of structure-activity relationships in this sea. Structural unit analysis (SUA) examines an entire data set so as to identify the molecular substructures or fragments that distinguish compounds with high activity from those with average activity. The algorithm is iterative and follows set heuristics in order to generate the structural units. It produces graphs that represent a set of units, which become SUA rules. Finding all of the input structures that match these graphs generates clusters. The Apriori algorithm for association rule mining is adapted to explore all of the combinations of structural units that define useful series. User-defined constraints are applied toward series selection and the refinement of rules. The significance of a series is determined by applying statistical methods appropriate to each data set. Application to the NCI-H23 (DTP Human Tumor Cell Line Screen) database serves to illustrate the process by which structural series are identified. An application of the method to scaffold hopping is then discussed in connection with proprietary screening data from a lead optimization project directed toward the treatment of respiratory tract infections at Bayer Healthcare. SUA was able to successfully identify promising alternative core structures in addition to identifying compounds with above-average activity and selectivity.