Stephan Raub

Tetrahedral Gold(I) Clusters with Carba‐closo‐dodecaboranylethynido Ligands: [{12‐(R3PAu)2CC‐closo‐1‐CB11H11}2]

The increasing interest in the supramolecular chemistry of gold(I) compounds is a result of the unusual, for example optical properties, of these substances that are a result of interand intramolecular aurophilic interactions. In turn, the self-assembly is often based on the intermolecular gold– gold interactions. 5] Salts of the tetranuclear bis(triphenylphosphane gold(I))halonium dications A that contain four gold atoms in a distorted tetrahedral arrangement with four relatively short intermolecular Au···Au distances and two longer intramolecular Au···Au distances are unusual compounds of this type, which are only stable in the solid state. The bis(trigoldoxonium) dication B and the bis(tetraauriomethane) complex C are the only other examples with a similar arrangement. Similar to A, complexes B and C were only observed in the solid state and they dissociate in solution because of electrostatic repulsion. A series of other tetranuclear gold(I) clusters that consist of two dinuclear gold(I) complexes in which the four gold atoms lie at the corners of a distorted square is known, for example {[(Ph3PAu)2SCH2Ph]2} 2+ (D). An important class of building blocks for supramolecular gold(I) compounds are Au alkynyl complexes. Coinage-metal clusters can be prepared through the p-coordination of the alkynes to coinage-metal ions in combination with metallophilic interactions. Only a limited number of such coinage-metal clusters that solely consist of gold(I) cations with ethynido/alkyne ligands have been described. Herein we report distorted tetrahedral Au4 clusters with carboranylethynido ligands. These clusters are formed by selfassembly of two dinuclear gold(I) complexes and they are present in the solid sate and for the first time in solution, as well. Cesium ethynylcarba-closo-dodecaborate reacts with [R3PAuCl] and potassium bis(trimethylsilyl)amide in THF to give the neutral dinuclear gold(I) complexes [12-(R3PAu)2C C-closo-1-CB11H11] (R = Me (1), Et (2), iPr (3), tBu (4)) in 63–95% yield and which are thermally stable up to 220 8C (1; Scheme 1).

Expanding the Chemistry of Cationic N-Heterocyclic Carbenes: Alternative Synthesis, Reactivity, and Coordination Chemistry

A new synthetic route to complexes of the cationic N-heterocyclic carbene ligand 2 has been developed by the attachment of a cationic pentamethylcyclopentadienylruthenium ([RuCp*](+)) fragment to a metal-coordinated benzimidazol-2-ylidene ligand. The coordination chemistry and the steric and electronic properties of the cationic carbene were investigated in detail by experimental and theoretical methods. X-ray structures of three carbene-metal complexes were determined. The cationic ligand 2 is a poorer overall electron donor relative to the related neutral carbene, which is evident from cyclic voltammetry (CV) and IR measurements.

Molecular design of two sterol 14α-demethylase homology models and their interactions with the azole antifungals ketoconazole and bifonazole

SummarySterol 14α-demethylase (CYP51) is one of the known major targets for azole antifungals. Therapeutic side effects of these antifungals are based on interactions of the azoles with the human analogue enzyme. This study describes for the first time a comparison of a human CYP51 (HU-CYP51) homology model with a homology model of the fungal CYP51 of Candida albicans (CA-CYP51). Both models are constructed by using the crystal structure of Mycobacterium tuberculosis MT-CYP51 (PDB code: 1EA1).The binding mode of the azole ketoconazole is investigated in molecular dynamics simulations with the GROMACS force field. The usage of special parameters for the iron azole complex binding is necessary to obtain the correct complex geometry in the active site of the enzyme models. Based on the dynamics simulations it is possible to explain the enantioselectivity of the human enzyme and also to predict the binding mode of the isomers of ketoconazole in the active site of the fungal model.

AIScore — Chemically Diverse Empirical Scoring Function Employing Quantum Chemical Binding Energies of Hydrogen-Bonded Complexes

In this work we report on a novel scoring function that is based on the LUDI model and focuses on the prediction of binding affinities. AIScore extends the original FlexX scoring function using a chemically diverse set of hydrogen-bonded interactions derived from extensive quantum chemical ab initio calculations. Furthermore, we introduce an algorithmic extension for the treatment of multifurcated hydrogen bonds (XFurcate). Charged and resonance-assisted hydrogen bond energies and hydrophobic interactions as well as a scaling factor for implicit solvation were fitted to experimental data. To this end, we assembled a set of 101 protein-ligand complexes with known experimental binding affinities. Tightly bound water molecules in the active site were considered to be an integral part of the binding pocket. Compared to the original FlexX scoring function, AIScore significantly improves the prediction of the binding free energies of the complexes in their native crystal structures. In combination with XFurcate, AIScore yields a Pearson correlation coefficient of R P = 0.87 on the training set. In a validation run on the PDBbind test set we achieved an R P value of 0.46 for 799 attractively scored complexes, compared to a value of R P = 0.17 and 739 bound complexes obtained with the FlexX original scoring function. The redocking capability of AIScore, on the other hand, does not fully reach the good performance of the original FlexX scoring function. This finding suggests that AIScore should rather be used for postscoring in combination with the standard FlexX incremental ligand construction scheme.

Quantum chemical investigation of hydrogen‐bond strengths and partition into donor and acceptor contributions

We present a simple increment model for use in the rapid scoring of hydrogen bond strengths employing 15 chemically diverse donor and 28 acceptor terms. The increments cover a large variety of hydrogen bond donor and acceptor groups and are more specific than SYBYL atom types. The increments have been fitted to quantum chemical ab initio interaction energies of 81 small hydrogen‐bonded complexes determined at the level of second‐order Møller‐Plesset perturbation theory (MP2). The complexes have been chosen such as to represent the most important types of donor‐acceptor pairs found in biological systems. Sulphur is found to be a strong hydrogen bond acceptor while its donor capacities are weak. By taking CH acidic H donors into account, a linear correlation between MP2 energies and the increment model with a coefficient of correlation of r2 = 0.994 has been accomplished. The transferability of the fitted parameters has been assessed on a second set of complexes including larger molecules of biological relevance. Very good agreement has been achieved for noncyclic hydrogen bonds. Cooperative effects are not accounted for by the current increment model. For this reason, binding energies of strong cyclic hydrogen bonds, as e.g. present in DNA base pairs, are underestimated by about 30–40%.

Linking Genes and Brain Development of Honeybee Workers: A Whole-Transcriptome Approach.

Honeybees live in complex societies whose capabilities far exceed those of the sum of their single members. This social synergism is achieved mainly by the worker bees, which form a female caste. The worker bees display diverse collaborative behaviors and engage in different behavioral tasks, which are controlled by the central nervous system (CNS). The development of the worker brain is determined by the female sex and the worker caste determination signal. Here, we report on genes that are controlled by sex or by caste during differentiation of the worker’s pupal brain. We sequenced and compared transcriptomes from the pupal brains of honeybee workers, queens and drones. We detected 333 genes that are differently expressed and 519 genes that are differentially spliced between the sexes, and 1760 genes that are differentially expressed and 692 genes that are differentially spliced between castes. We further found that 403 genes are differentially regulated by both the sex and caste signals, providing evidence of the integration of both signals through differential gene regulation. In this gene set, we found that the molecular processes of restructuring the cell shape and cell-to-cell signaling are overrepresented. Our approach identified candidate genes that may be involved in brain differentiation that ensures the various social worker behaviors.