The program Mercury, developed by the Cambridge Crystallographic Data Centre, is designed primarily as a crystal structure visualization tool. A new module of functionality has been produced, called the Materials Module, which allows highly customizable searching of structural databases for intermolecular interaction motifs and packing patterns. This new module also includes the ability to perform packing similarity calculations between structures containing the same compound. In addition to the Materials Module, a range of further enhancements to Mercury has been added in this latest release, including void visualization and links to ConQuest, Mogul and IsoStar.

Mercury CSD 2.0 – new features for the visualization and investigation of crystal structures

The hydrogen bond is the most important of all directional intermolecular interactions. It is operative in determining molecular conformation, molecular aggregation, and the function of a vast number of chemical systems ranging from inorganic to biological. Research into hydrogen bonds experienced a stagnant period in the 1980s, but re-opened around 1990, and has been in rapid development since then. In terms of modern concepts, the hydrogen bond is understood as a very broad phenomenon, and it is accepted that there are open borders to other effects. There are dozens of different types of X-H.A hydrogen bonds that occur commonly in the condensed phases, and in addition there are innumerable less common ones. Dissociation energies span more than two orders of magnitude (about 0.2-40 kcal mol(-1)). Within this range, the nature of the interaction is not constant, but its electrostatic, covalent, and dispersion contributions vary in their relative weights. The hydrogen bond has broad transition regions that merge continuously with the covalent bond, the van der Waals interaction, the ionic interaction, and also the cation-pi interaction. All hydrogen bonds can be considered as incipient proton transfer reactions, and for strong hydrogen bonds, this reaction can be in a very advanced state. In this review, a coherent survey is given on all these matters.

The hydrogen bond in the solid state.

A new way of exploring packing modes and intermolecular interactions in molecular crystals is described, using Hirshfeld surfaces to partition crystal space. These molecular Hirshfeld surfaces, so named because they derive from Hirshfeld's stockholder partitioning, divide the crystal into regions where the electron distribution of a sum of spherical atoms for the molecule (the promolecule) dominates the corresponding sum over the crystal (the procrystal). These surfaces reflect intermolecular interactions in a novel visual manner, offering a previously unseen picture of molecular shape in a crystalline environment. Surface features characteristic of different types of intermolecular interactions can be identified, and such features can be revealed by colour coding distances from the surface to the nearest atom exterior or interior to the surface, or by functions of the principal surface curvatures. These simple devices provide a striking and immediate picture of the types of interactions present, and even reflect their relative strengths from molecule to molecule. A complementary two-dimensional mapping is also presented, which summarizes quantitatively the types of intermolecular contacts experienced by molecules in the bulk and presents this information in a convenient colour plot. This paper describes the use of these tools in the compilation of a pictorial glossary of intermolecular interactions, using identifiable patterns of interaction between small molecules to rationalize the often complex mix of interactions displayed by large molecules.

Novel tools for visualizing and exploring intermolecular interactions in molecular crystals.

The C-H‚‚‚O hydrogen bond is so well-established in structural chemistry that it seems difficult now to believe that when Sutor proposed the existence of this type of hydrogen bond in the early 1960s,1,2 her suggestion was drowned in scepticism, if not outright hostility.3 It was only two decades later, with Taylor and Kennard’s paper, that the subject was properly revived.4 Shortly thereafter, an Account appeared from this laboratory describing the role of the C-H‚‚‚O interaction in crystal engineering.5 Subsequently, one felt confident enough to term these erstwhile “interactions” hydrogen bonds, in a second Account.6 A recent invitation to contribute another Account and the many recent efforts in this direction by my students and postdoctorals have led to the present paper. It is clearly no longer necessary to justify the relevance of C-H‚‚‚O hydrogen bonds, so widely invoked are they in small-molecule and biological crystallography. The presence of O-atoms in a large majority of organic molecules means that this hydrogen bond is widespread, even if not identified in many cases. However, other questions concerning these weak hydrogen bonds could be posed: (1) What is their upper distance limit? (2) Are very short, bent bonds significant? (3) Why do C-H‚‚‚O bonds sometimes disturb the strong O-H‚‚‚O and N-H‚‚‚O network? Alternatively, why do hydrogen bond donors and acceptors not always pair in descending order of strength? (4) How important is cooperativity for weak hydrogen bonds? (5) Are C-H‚‚‚O hydrogen bonds responsible for crystal packing, or are they the forced consequences of packing? (6) Are weak hydrogen bonds robust enough for supramolecular synthesis and crystal engineering? (7) Does the C-H‚‚‚O hydrogen bond have any biological significance? These difficult questions cannot be answered fully. This Account attempts to address some of them, but better answers can only follow from further work.

The C-h···o hydrogen bond: structural implications and supramolecular design.

Crystal polymorphism is encountered in all areas of research involving solid substances. Its occurrence introduces complications during manufacturing processes and adds another dimension to the complexity of designing materials with specific properties. Research on polymorphism is fraught with unique difficulties due to the subtlety of polymorphic transformations and the inadvertent formation of pseudopolymorphs. In this report, a summary of thermodynamic, kinetic and structural considerations of polymorphism is presented. A wide variety of techniques appropriate to the study of organic crystalline polymorphism and pseu-dopolymorphism is then surveyed, ranging from simple crystal density measurement to observation of polymorphic transformations using variable-temperature synchrotron X-ray diffraction methods. Application of newer methodology described in this report is yielding fresh insights into the nature of the crystallization process, holding promise for a deeper understanding of the phenomenon of polymorphism and its practical control.

Crystalline Polymorphism of Organic Compounds

Whereas much of organic chemistry has classically dealt with the preparation and study of the properties of individual molecules, an increasingly significant portion of the activity in chemical research involves understanding and utilizing the nature of the interactions between molecules. Two representative areas of this evolution are supramolecular chemistry and molecular recognition. The interactions between molecules are governed by intermolecular forces whose energetic and geometric properties are much less well understood than those of classical chemical bonds between atoms. Among the strongest of these interactions, however, are hydrogen bonds, whose directional properties are better understood on the local level (that is, for a single hydrogen bond) than many other types of non-bonded interactions. Nevertheless, the means by which to characterize, understand, and predict the consequences of many hydrogen bonds among molecules, and the resulting formation of molecular aggregates (on the microscopic scale) or crystals (on the macroscopic scale) has remained largely enigmatic. One of the most promising systematic approaches to resolving this enigma was initially developed by the late M. C. Etter, who applied graph theory to recognize, and then utilize, patterns of hydrogen bonding for the understanding and design of molecular crystals. In working with Etter's original ideas the power and potential utility of this approach on one hand, and on the other, the need to develop and extend the initial Etter formalism was generally recognized. It with that latter purpose that we originally undertook the present review.

Patterns in Hydrogen Bonding: Functionality and Graph Set Analysis in Crystals

Wahrend sich die klassische Organische Chemie bisher weitgehend mit der Synthese individueller Molekule und der Untersuchung ihrer Eigenschaften beschaftigte, gewinnen nunmehr zunehmend Forschungsaktivitaten an Bedeutung, die sich mit dem Verstandnis und dem Ausnutzen von Wechselwirkungen zwischen Molekulen befassen. Zwei fur diese Entwicklung reprasentative Gebiete sind die supramolekulare Chemie und die molekulare Erkennung. Die Wechselwirkungen zwischen Molekulen werden durch intermolekulare Krafte bestimmt, deren energetische und geometrische Eigenschaften viel weniger gut verstanden sind als die von klassischen chemischen Bindungen zwischen Atomen. Zu den starksten dieser Wechselwirkungen gehoren die H-Brucken, deren gerichtete Eigenschaften auf lokalem Niveau (d. h. fur nur eine H-Brucke) besser als die vieler anderer Typen nichtbindender Wechselwirkungen verstanden werden. Trotzdem ist noch weithin ungeklart, wie man vorgehen muste, um die Konsequenzen der Bildung vieler H-Brucken zwischen Molekulen und den daraus folgenden Aufbau von molekularen Aggregaten (im mikroskopischen Bereich) oder von Kristallen (im makroskopischen Bereich) zu charakterisieren, zu verstehen und vorherzusagen. Einer der vielversprechendsten systematischen Ansatze, um dieses Problem zu losen, wurde ursprunglich von der inzwischen verstorbenen M. C. Etter entwickelt. In den letzten Jahren wurden ihre Ideen von anderen ubernommen und angewendet. Diese Arbeiten bewiesen einerseits die Bedeutung und die potentielle Nutzlichkeit der ursprunglichen Ideen und Ansatze, zeigten andererseits aber auch die Notwendigkeit auf, Etters Formalismus zu erweitern. Gerade letzteres war der Ausloser fur die hier vorgestellten Arbeiten.

Muster aus H‐Brücken: ihre Funktionalität und ihre graphentheoretische Analyse in Kristallen

Intermolecular Effects in Crystals of 11-(Trifluoromethyl)-15,16-dihydrocyclopenta[a]phenanthren-17-one

The modes of hydrogen bonding of arginine, asparagine, and glutamine side chains and of urea have been examined in small-molecule crystal structures in the Cambridge Structural Database and in crystal structures of protein-nucleic acid and protein-protein complexes. Analysis of the hydrogen bonding patterns of each by graph-set theory shows three patterns of rings (R) with one or two hydrogen bond acceptors and two donors and with eight, nine, or six atoms in the ring, designated R2(2)(8), R2(2)(9), and R1(2)(6). These three patterns are found for arginine-like groups and for urea, whereas only the first two patterns R2(2)(8) and R2(2)(9) are found for asparagine- and glutamine-like groups. In each case, the entire system is planar within 0.7 A or less. On the other hand, in macromolecular crystal structures, the hydrogen bonding patterns in protein-nucleic acid complexes between the nucleic acid base and the protein are all R2(2)(9), whereas hydrogen bonding between Watson-Crick-like pairs of nucleic acid bases is R2(2)(8). These two hydrogen bonding arrangements [R2(2)(9)] and R2(2)(8)] are predetermined by the nature of the groups available for hydrogen bonding. The third motif identified, R1(2)(6), involves hydrogen bonds that are less linear than in the other two motifs and is found in proteins.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/pro.5560040109

Hydrogen bonding motifs of protein side chains: descriptions of binding of arginine and amide groups.

The propensity of C-F groups to form C-F ⋯ H-C interactions with C-H groups on other molecules has been analyzed. Crystal structures of molecules containing only carbon, hydrogen, and fluorine, but no oxygen, nitrogen, or other hydrogen-bond-forming elements, were chosen for an initial study in which the intermolecular interactions in crystal-structure determinations of polycyclic aromatic hydrocarbons and their analogous fluoro derivatives were analyzed. It is found that C-F ⋯ H-C interactions occur, but they are weak, as judged by the intermolecular distances and the angles involved. In a study of crystal structures of molecules containing other elements in addition to carbon, hydrogen, and fluorine, it was found that when an oxygen atom is in a neighboring position on an interacting molecule, a C-O group is more likely than a C-F group to form a linear interaction to the hydrogen atom of a C-H group. Thus, in spite of the high electronegativity of the fluorine atom, a C-F group competes unfavorably with a C-O−, C-OH, or C=O group to form a hydrogen bond to an O-H, N-H, or C-H group. It is found, however, particularly for polycyclic aromatic hydrocarbons with substituted CF3 groups that, in the absence of other functional groups that can form stronger interactions, C-F ⋯ H-C interactions may serve to align molecules and give a different crystal packing from that in the pure hydrocarbon (where fluorine is replaced by hydrogen). Thus, C-F ⋯ H-X (X = C, N, O) interactions are very weak, much weaker than C=O ⋯ H-X interactions, but they cannot be ignored in predictions of modes of molecular packing in complexes and in crystals.

Liat Shimoni

Papers

Patterns in Hydrogen Bonding: Functionality and Graph Set Analysis in Crystals

Muster aus H‐Brücken: ihre Funktionalität und ihre graphentheoretische Analyse in Kristallen

Intermolecular Effects in Crystals of 11-(Trifluoromethyl)-15,16-dihydrocyclopenta[a]phenanthren-17-one

Hydrogen bonding motifs of protein side chains: descriptions of binding of arginine and amide groups.

The Geometry of Intermolecular Interactions in Some Crystalline Fluorine-Containing Organic Compounds