A structural systematic study of four isomers of difluoro-N-(3-pyridyl)benzamide

The four isomers 2,4-, (I), 2,5-, (II), 3,4-, (III), and 3,5-difluoro-N-(3-pyridyl)benzamide, (IV), all with formula C12H8F2N2O, display molecular similarity, with interplanar angles between the C6/C5N rings ranging from 2.94 (11)° in (IV) to 4.48 (18)° in (I), although the amide group is twisted from either plane by 18.0 (2)-27.3 (3)°. Compounds (I) and (II) are isostructural but are not isomorphous. Intermolecular N-H...O=C interactions form one-dimensional C(4) chains along [010]. The only other significant interaction is C-H...F. The pyridyl (py) N atom does not participate in hydrogen bonding; the closest H...Npy contact is 2.71 Å in (I) and 2.69 Å in (II). Packing of pairs of one-dimensional chains in a herring-bone fashion occurs via [pi]-stacking interactions. Compounds (III) and (IV) are essentially isomorphous (their a and b unit-cell lengths differ by 9%, due mainly to 3,4-F2 and 3,5-F2 substitution patterns in the arene ring) and are quasi-isostructural. In (III), benzene rotational disorder is present, with the meta F atom occupying both 3- and 5-F positions with site occupancies of 0.809 (4) and 0.191 (4), respectively. The N-H...Npy intermolecular interactions dominate as C(5) chains in tandem with C-H...Npy interactions. C-H...O=C interactions form R22(8) rings about inversion centres, and there are [pi]-[pi] stacks about inversion centres, all combining to form a three-dimensional network. By contrast, (IV) has no strong hydrogen bonds; the N-H...Npy interaction is 0.3 Å longer than in (III). The carbonyl O atom participates only in weak interactions and is surrounded in a square-pyramidal contact geometry with two intramolecular and three intermolecular C-H...O=C interactions. Compounds (III) and (IV) are interesting examples of two isomers with similar unit-cell parameters and gross packing but which display quite different intermolecular interactions at the primary level due to subtle packing differences at the atom/group/ring level arising from differences in the peripheral ring-substitution patterns

Structure of Equilenin at 100 K: an estrone-related steroid

The structure of the estrone-related steroid, Equilenin, C18H18O2 (systematic name 3-hy-droxy-13-methyl-11,12,13,14,15,16-hexa-hydro-cyclo-penta-[a]phen-anthren-17-one), has been determined at 100 K. The crystals are ortho-rhom-bic, P212121, and the absolute structure of the mol-ecule in the crystal has been determined by resonant scattering [Flack parameter = -0.05 (4)]. The C atoms of the A and B rings are almost coplanar, with an r.m.s. deviation from planarity of 0.0104 Å. The C ring has a sofa conformation, while the D ring has an envelope conformation with the methine C atom as the flap. The keto O atom and the methyl group are translated 0.78 and 0.79 Å, respectively, from the equivalent positions on 17β-estrone. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming chains parallel to the c-axis direction

Stereochemistry of Polypeptide Conformation in Coarse Grained Analysis

The conformations available to polypeptides are determined by the interatomic forces acting on the peptide units, whereby backbone torsion angles are restricted as described by the Ramachandran plot. Although typical proteins are composed predominantly from {\alpha}-helices and {\beta}-sheets, they nevertheless adopt diverse tertiary structure, each folded as dictated by its unique amino-acid sequence. Despite such uniqueness, however, the functioning of many proteins involves changes between quite different conformations. The study of large-scale conformational changes, particularly in large systems, is facilitated by a coarse-grained representation such as provided by virtually bonded C{\alpha} atoms. We have developed a virtual atom molecular mechanics (VAMM) force field to describe conformational dynamics in proteins and a VAMM-based algorithm for computing conformational transition pathways. Here we describe the stereochemical analysis of proteins in this coarse-grained representation, comparing the relevant plots in coarse-grained conformational space to the corresponding Ramachandran plots, having contoured each at levels determined statistically from residues in a large database. The distributions shown for an all-{\alpha} protein, two all-{\beta} proteins and one {\alpha}+{\beta} protein serve to relate the coarse-grained distributions to the familiar Ramachandran plot.Comment: 12 pages, 3 figures, Postprint of book chapter submitted to the Biomolecular Forms and Functions, M. Bansal and N. Srinivasan, Eds. copyright (2013) [copyright World Scientific Publishing Company

Weak intermolecular interactions in organic systems: a concerted study involving x-ray and neutron diffraction and database analysis

This thesis can be divided broadly into two halves. The first half (Chapters 3 - 5) deals with crystallographic studies of compounds which contain weak intermolecular interactions or networks of these interactions. Whilst the later part (Chapters 7 - 9) describes the results of database surveys of three novel weak intermolecular interactions. In Chapters 3 and 4 the neutron derived structures of 3,5-dinitrocinnamic acid, 2-ethynyladamantan-2-ol, 2- and 3-ammophenol are presented. All of the compounds contain complex networks of weak hydrogen bonds. The neuron diffraction data are used to determine accurate hydrogen atom poistions and thus characterise these hydrogen bonded networks. Some theoretical work is also described. In Chapter 5, X-ray diffraction studies of a series of iodobenzene derivatives are described. These compounds were synthesised in an attempt to engineer structures mediated by novel X...O(_2)N interactions. The structures of three iodo nitrobenzenes are presented wherein symmetrical bifurcated I...O(_2)N interactions mediate the primary ribbon motif. The structure of TCNQ derivative, in which I...N=C play a structure determining role, is also described. Chapters 7, 8 and 9 describe database smdies of X...O(_2)N, C(ring)-H...O/N and C-F...H interactions. The frequencies and geometries of the interactions were determined and analysed. The data for X...O(_2)N interactions were used in conjunction with sophisticated IMPT calculations to determine prefered interaction geometries and interaction energies. Similar theoretical techniques were used to analyse the C(ring)-H...O/N and C-F..H interactions described in Chapters 8 and 9.Background information and overviews of the general experimental procedures followed when performing the crystallographic and database studies are given in Chapters 2 and 6

Introduction to protein folding for physicists

The prediction of the three-dimensional native structure of proteins from the knowledge of their amino acid sequence, known as the protein folding problem, is one of the most important yet unsolved issues of modern science. Since the conformational behaviour of flexible molecules is nothing more than a complex physical problem, increasingly more physicists are moving into the study of protein systems, bringing with them powerful mathematical and computational tools, as well as the sharp intuition and deep images inherent to the physics discipline. This work attempts to facilitate the first steps of such a transition. In order to achieve this goal, we provide an exhaustive account of the reasons underlying the protein folding problem enormous relevance and summarize the present-day status of the methods aimed to solving it. We also provide an introduction to the particular structure of these biological heteropolymers, and we physically define the problem stating the assumptions behind this (commonly implicit) definition. Finally, we review the 'special flavor' of statistical mechanics that is typically used to study the astronomically large phase spaces of macromolecules. Throughout the whole work, much material that is found scattered in the literature has been put together here to improve comprehension and to serve as a handy reference.Comment: 53 pages, 18 figures, the figures are at a low resolution due to arXiv restrictions, for high-res figures, go to http://www.pabloechenique.co

Theory of Adsorption on Metal Substrates

Contents: 5.1 Introduction 5.2 Concepts and definitions 5.3 The tight-binding picture of bonding 5.4 Adsorption of isolated adatoms 5.5 Alkali-metal adsorption: the traditional picture of on-surface adsorption 5.6 Substitutional adsorption and formation of surface alloys 5.7 Adsorption of CO on transition-metal surfaces - a model system for a simple molecular adsorbate 5.8 Co-adsorption [the example CO plus O on Ru(0001)] 5.9 Chemical reactions at metal surfaces 5.10 The catalytic oxidation of CO 5.11 Summary outline of main pointsComment: 73 pages including 44 figures. A version with high-resolution figures and related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized

Understanding protein structure is of crucial importance in science, medicine and biotechnology. For about two decades, knowledge based potentials based on pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been center stage in the prediction and design of protein structure and the simulation of protein folding. However, the validity, scope and limitations of these potentials are still vigorously debated and disputed, and the optimal choice of the reference state -- a necessary component of these potentials -- is an unsolved problem. PMFs are loosely justified by analogy to the reversible work theorem in statistical physics, or by a statistical argument based on a likelihood function. Both justifications are insightful but leave many questions unanswered. Here, we show for the first time that PMFs can be seen as approximations to quantities that do have a rigorous probabilistic justification: they naturally arise when probability distributions over different features of proteins need to be combined. We call these quantities reference ratio distributions deriving from the application of the reference ratio method. This new view is not only of theoretical relevance, but leads to many insights that are of direct practical use: the reference state is uniquely defined and does not require external physical insights; the approach can be generalized beyond pairwise distances to arbitrary features of protein structure; and it becomes clear for which purposes the use of these quantities is justified. We illustrate these insights with two applications, involving the radius of gyration and hydrogen bonding. In the latter case, we also show how the reference ratio method can be iteratively applied to sculpt an energy funnel. Our results considerably increase the understanding and scope of energy functions derived from known biomolecular structures

Magnetically-induced ferroelectricity in the (ND4)2[FeCl5(D2O)] molecular compound

The number of magnetoelectric multiferroic materials reported to date is scarce, as magnetic structures that break inversion symmetry and induce an improper ferroelectric polarization typically arise through subtle competition between different magnetic interactions. The (NH4)2[FeCl5(H2O)] compound is a rare case where such improper ferroelectricity has been observed in a molecular material. We have used single crystal and powder neutron diffraction to obtain detailed solutions for the crystal and magnetic structures of (NH4)2[FeCl5(H2O)], from which we determined the mechanism of multiferroicity. From the crystal structure analysis, we observed an order-disorder phase transition related to the ordering of the ammonium counterion. We have determined the magnetic structure below TN, at 2K and zero magnetic field, which corresponds to a cycloidal spin arrangement with magnetic moments contained in the ac-plane, propagating parallel to the c-axis. The observed ferroelectricity can be explained, from the obtained magnetic structure, via the inverse Dzyaloshinskii-Moriya mechanism