Manuela Weber

Experimental electron density of sumanene, a bowl-shaped fullerene fragment; comparison with the related corannulene hydrocarbon

The experimental electron density of sumanene, C(21)H(12), was extracted from a high resolution X-ray data set measured at 100 K and topologically analyzed. In addition to bond topological and atomic properties, information about the density distribution between adjacent molecules, which show close C···C approaches of ~3.4 Å within the columnar π-stacks in the crystal lattice, are discussed. A comparison is made with the electron density of the related corannulene molecule based also on the analysis of Electron Localizability Indicator (ELI-D) calculations.

How to easily replace the independent atom model – the example of bergenin, a potential anti-HIV agent of traditional Asian medicine

Bergenin, which has been isolated from a variety of tropical plants, has several pharmacological applications in traditional Asian medicine. Its electron-density distribution was obtained from a room-temperature low-resolution X-ray data set measured with point detection making use of multipole populations from the invariom library. Two refinement models were considered. In a first step, positional parameters and ADPs were refined with fixed library multipoles (model E1). This model was suitable to be input into a second refinement of multipoles (model E2), which converged smoothly although based on Cu Kalpha room-temperature data. Quantitative results of a topological analysis of the electron density from both models were compared with Hartree-Fock and density-functional calculations. With respect to the independent atom model (IAM) more information can be extracted from invariom modelling, including the electrostatic potential and hydrogen-bond energies, which are highly useful, especially for biologically active compounds. The reliability of the applied invariom formalism was assessed by a comparison of bond-topological properties of sucrose, for which high-resolution multipole and invariom densities were available. Since a conventional X-ray diffraction experiment using basic equipment was combined with the easy-to-use invariom formalism, the procedure described here for bergenin illustrates how it can be routinely applied in pharmacological research.

Structure of the tannin geraniin based on conventional X-ray data at 295 K and on synchrotron data at 293 and 120 K

Geraniin, C41H28O27.7H2O, is the main tannin from Geranium thunbergii Sieb. et Zucc., which is one of the most popular folk medicines and also an official antidiarrheic drug in Japan. Conventional X-ray diffractometer data at 295 K and synchrotron data at 293 and 120 K (at EMBL/DESY Hamburg with a MARRESEARCH imaging plate) were measured. The structure could not be determined with any of the currently distributed direct-methods programs, but was easily solved with DIRDIF using several conformers of the hexahydroxydiphenoyl group as input fragments into a vector-search procedure. A molecular structure was established where a cyclohexenetrione moiety attached to O4 of a central glucose unit was in a hydrated six-membered hemiacetal ring structure, as expected from the NMR study of crystalline geraniin. Owing to the high oligocyclic substitution the glucopyranosyl ring is in the unusual 1C4 conformation. Refinement of the low-temperature synchrotron data allowed identification of almost all the H atoms, even within the seven water molecules, so that a rather complex system of approximately 30 different hydrogen bonds can be studied in some detail.

Transferability and reproducibility in electron-density studies--bond-topological and atomic properties of tripeptides of the type L-alanyl-X-L-alanine.

In the last decade three different data bank approaches have been developed that are intended to make electron-density examinations of large biologically important molecules possible. They rely on Baders concept of transferability of submolecular fragments with retention of their electronic properties. Therefore, elaborate studies on the quantification of transferability in experiment and theory are still very important. Tripeptides of the type L-alanyl-X-L-alanine (X being any of the 20 naturally encoded amino acids) serve as a model case between amino acids and proteins. The two experimental electron-density determinations (L-alanyl-L-histidinyl-L-alanine and L-alanyl-L-phenylalanyl-L-alanine, highly resolved synchrotron X-ray diffraction data sets) performed in this study and theoretical calculations on all 20 different L-alanyl-X-L-alanine molecules contribute to a better estimation of transferability in the peptide case. As a measure of reproducibility and transferability, standard deviations from averaging over bond-topological and atomic properties of atoms or bonds that are considered equal in their chemical environments were calculated. This way, transferability and reproducibility indices were introduced. It can be shown that experimental transferability indices generally slightly exceed experimental reproducibility indices and that these larger deviations can be attributed to chemical effects such as changes in the geometry (bond lengths and angles), the polarization pattern and the neighboring sphere due to crystal packing. These effects can partly be separated from each other and quantified with the help of gas-phase calculations at optimized and experimental geometries. Thus, the degree of transferability can be quantified in very narrow limits taking into account experimental errors and chemical effects.

Pyridyl-Functionalised 3H-1,2,3,4-Triazaphospholes: Synthesis, Coordination Chemistry and Photophysical Properties of Low-Coordinate Phosphorus Compounds

Novel conjugated, pyridyl-functionalised triazaphospholes with either tBu or SiMe3 substituents at the 5-position of the N3 PC heterocycle have been prepared by a [3+2] cycloaddition reaction and compared with structurally related, triazole-based systems. Photoexcitation of the 2-pyridyl-substituted triazaphosphole gives rise to a significant fluorescence emission with a quantum yield of up to 12 %. In contrast, the all-nitrogen triazole analogue shows no emission at all. DFT calculations indicate that the 2-pyridyl substituted systems have a more rigid and planar structure than their 3- and 4-pyridyl isomers. Time-dependent (TD) DFT calculations show that only the 2-pyridyl-substituted triazaphosphole exhibits similar planar geometry, with matching conformational arrangements in the lowest energy excited state and the ground state; this helps to explain the enhanced emission intensity. The chelating P,N-hybrid ligand forms a Re(I) complex of the type [(N^N)Re(CO)3 Br] through the coordination of nitrogen atom N(2) to the metal centre rather than through the phosphorus donor. Both structural and spectroscopic data indicate substantial π-accepting character of the triazaphosphole, which is again in contrast to that of the all-nitrogen-containing triazoles. The synthesis and photophysical properties of a new class of phosphorus-containing extended π systems are described.

dl-Cysteine at 298K

In the room-temperature structure of DL-cysteine, C 3 H 7 NO 2 S, the L-enantiomer has the -gauche conformation [χ 1 = -62.3 (2)°], and this is the third conformation to be found in the cysteine molecule. In addition to three N-H...O hydrogen bonds, an intermolecular S-H...S contact exists with S...S = 3.854 (2) A. Two hydrogen-bond cycles were identified, each consisting of two DL-pairs.

Synthesis of indolylquinolines under Friedel-Crafts reaction conditions

Abstract A one-pot synthesis of some novel indolylquinoline analogues of biological interest using indole or its 5-subtituted derivatives as substrates under Friedel-Crafts acylation conditions is reported. The synthesis of the compounds was accomplished by the employment of excess amounts of the substrates and higher temperature. The complete structure of the derivative obtained by using indole as substrate and dichloroacetyl chloride as acylating agent was unequivocally established as 2-(2″-dichloroacetamidobenzyl)-3-(3′-indolyl)-quinoline 2a by single crystal X-ray analysis. The structures of other similar indolylquinolines 2b-2e and 3 were defined by spectroscopic analysis. The mechanism of formation of the analogues has also been rationalised

Reactivity Differences between α,β-Unsaturated Carbonyls and Hydrazones Investigated by Experimental and Theoretical Electron Density and Electron Localizability Analyses

It is still a challenge to predict a compounds reactivity from its ground-state electronic nature although Bader-type topological analyses of the electron density (ED) and electron localizability indicator (ELI) give detailed and useful information on electron concentration and electron-pair localization, respectively. Both ED and ELI can be obtained from theoretical calculations as well as high-resolution X-ray diffraction experiments. Besides ED and ELI descriptors, the delocalization index is used here; it is likewise derived from theoretical calculations as well as from experimental X-ray results, but in the latter case, demonstrated here for the first time. We investigate α,β-unsaturated carbonyl and hydrazone compounds because resonance exhibited by these compounds in the electronic ground-state determines their reactive behavior. The degree of resonance as well as the reactivity contrast are quantified with the electronic descriptors. Moreover, competitive mesomeric substituent effects are studied using the two biologically important compounds acrolein and acrylamide. The reactivity differences predicted from the analyses are in line with the known reactivity of these compounds in organic synthesis. Hence, the capability of the ED and ELI for rationalizing and predicting different and competing substituent effects with respect to reactivity is demonstrated.

Electron density of two bioactive oligocyclic indole and oxindole derivatives obtained from low-order X-ray data and invariom application

For two indole and oxindole bioactive molecules, low-order room-temperature X-ray data were used to generate aspherical electron density (ED) distributions by application of the invariom formalism. An analysis of the ED using the quantum theory of atoms in molecules (QTAIM) was carried out, which allowed for quantitatively examining bond orders and charge separations in various parts of the molecules. The inspection of electrostatic potentials (ESPs) and Hirshfeld surfaces provided additional information on the intermolecular interactions. Thus, reactive regions of the molecules could be identified, covalent and electrostatic contributions to interactions could be visualized, and the forces causing the crystal packing scheme could be rationalized. As the used invariom formalism needs no extra experimental effort compared to routine X-ray analysis, its wide application is recommended because it delivers information far beyond the normally obtained steric properties. In this way, complementary contributions to drug design can be given as is demonstrated for indoles in this study, which are involved in the metabolism of plants and animals as well as in cancer therapy.

Electron Density of Corannulene from Synchrotron Data at 12 K, Comparison with Fullerenes

The electron density of corannulene, C20H10, was derived from a high-resolution synchrotron data set (sinθ /λ = 1.11 Å−1) measured at 12 K and from an ab-initio geometry optimization on the B3LYP/6-31G* level. A full topological analysis yielded atomic and bond-topological properties which were compared between experimental and theoretical findings and, as far as steric congruences exist, with corresponding fragments of the fullerene C70. For the four different types of C-C bonds in corannulene, a rather close bond-order range between 1.3 and 1.8 was found indicating a considerable delocalization in this molecule. As was already found earlier in fullerene cages, the deformation density on the C-C bonds is not arranged symmetrically. There is more density located outside than inside the corannulene bowl so that in total, charge accumulation is shifted to the outer surface of the molecule. The electrostatic potential suggests an H...π stacking in the crystal which directs the relative orientation of the two crystallographically independent corannulene molecules. The positively charged rim region of one molecule is oriented almost perpendicular to the negative potential region at the bottom of a second molecule. Graphical Abstract Electron Density of Corannulene from Synchrotron Data at 12 K, Comparison with Fullerenes