Christer B. Aakeröy

Recent advances in crystal engineering

The articles published in the tenth anniversary issue of CrystEngComm are reviewed. The issue highlighted the state-of-the-art of crystal engineering and new trends and developing areas in crystal engineering. In particular, the following article emphasises developments in the areas of intermolecular interactions, notably hydrogen and halogen bonds; metal–organic frameworks or coordination polymers; polymorphism and solvates.

Building co-crystals with molecular sense and supramolecular sensibility

Molecular recognition is typically associated with molecules in solution, but such events are also responsible for organizing molecules in the solid state. Translating principles of molecular recognition to solid-state assembly of heteromeric molecular solids is of key importance to the development of versatile, reliable and practical supramolecular synthesis. In this article we provide an overview of some modular and transferable strategies for the synthesis of binary and ternary supermolecules and co-crystals based upon a hierarchy of intermolecular interactions, notably hydrogen bonds.

Crystal engineering : Strategies and architectures

The area broadly described as crystal engineering is currently expanding at a brisk pace. Imaginative schemes for supramolecular synthesis, and correlations between molecular structure, crystal packing and physical properties are presented in the literature with increasing regularity. In practice, crystal engineering can be many different things; synthesis, statistical analysis of structural data, ab initio calculations etc. Consequently, we have been provided with a new playing field where chemists from traditionally unconnected parts of the spectrum have exchanged ideas, defined goals and made creative contributions to further progress not only in crystal engineering, but also in other disciplines of chemistry. Crystal engineering is delineated by the nature and structural consequences of intermolecular forces, and the way in which such interactions are utilized for controlling the assembly of molecular building blocks into infinite architectures. Although it is important to acknowledge that a crystal structure is the result of a subtle balance between a multitude of non-covalent forces, this article will focus on design strategies based upon the hydrogen bond and will present a range of approaches that have relied on the directionality and selectivity of such interactions in the synthesis of predictable one-, two- and three-dimensional motifs.

A VERSATILE ROUTE TO POROUS SOLIDS: ORGANIC-INORGANIC HYBRID MATERIALS ASSEMBLED THROUGH HYDROGEN BONDS

Square-planar and octahedral complexes of NiII and PtII link through head-to-head hydrogen bonds to form porous frameworks with large cavities that are suitable for inclusion of guest molecules. A series of four different complexes with pyridine-based ligands (in the center of the picture) are described, which contain either counterions or small molecules in channels. A=hydrogen-bond acceptor, D=hydrogen-bond donor, M=metal ion.

Using Cocrystals To Systematically Modulate Aqueous Solubility and Melting Behavior of an Anticancer Drug

Five cocrystals of an anticancer compound have been assembled using a well-defined hydrogen-bond-based supramolecular approach that produced the necessary structural consistency in the resulting solids. These cocrystals contain aliphatic even-numbered dicarboxylic acids of increasing chain length, and as a result, the physical properties of the cocrystals can be related to the molecular structure of the acid. The melting points of the five cocrystals show an excellent correlation with the melting points of the individual acids, and it has also been shown that aqueous solubility can be increased by a factor of 2.5 relative to that of the individual drug. Consequently, cocrystals can offer a range of solid forms from which can be chosen an active ingredient where a particular physical property can be dialed in, provided that the cocrystals show considerable structural consistency and that systematic changes are made to the participating cocrystallizing agents.

The C-H...Cl hydrogen bond: Does it exist?

The extensive occurrence of C–H···Cl hydrogen bonds has been established through a systematic statistical analysis of the Cambridge Crystallographic Database; chloride anions are shown to be better hydrogen-bond accepor systems than neutral chloride-containing molecules, and a similar situation pertains for the other halides. As a result of this study, we propose that the conceptual van der Waals cut-off criterion be dropped for establishing the presence of weak intermolecular and intramolecular interactions, and be replaced by a distance/angle criterion determined by the empirical approach outlined here.

Supramolecular Hierarchy among Halogen-Bond Donors

Through a combination of structural chemistry, vibrational spectroscopy, and theory, we have systematically examined the relative structure-directing importance of a series of ditopic halogen-bond (XB) donors. The molecular electrostatic potential surfaces of six XB donors were evaluated, which allowed for a charge-based ranking. Each molecule was then co-crystallized with 21 XB acceptors and the results have made it possible to map out the supramolecular landscape describing the competition between I/Br-ethynyl donors, perfluorinated I/Br donors, and I/Br-phenyl based donors. The results offer practical guidelines for synthetic crystal engineering driven by robust and directional halogen bonds.

Competing hydrogen-bond and halogen-bond donors in crystal engineering

In order to study the structure-directing competition between hydrogen- and halogen-bond donors we have synthesized two ligands, 3,3′-azobipyridine and 4,4′-azobipyridine, and co-crystallized them with a series of bi-functional donor molecules comprising an activated halogen-bond donor (I or Br) as well as a hydrogen-bond donor (acid, phenol or oxime) on the same backbone. Based on the subsequent single-crystal analysis, 5 of 6 co-crystals of 3,3′-azobipyridine are assembled using hydrogen bonds as the primary driving force accompanied by weaker secondary (C–X⋯O) interactions. However, in 5 out of the 6 co-crystals of 4,4′-azobipyridine, both hydrogen bonds (O–H⋯N) and halogen bonds (C–X⋯N) are present as structure-directing interactions leading to 1-D chains. Since the charges on the acceptor sites in 3,3′- and 4,4′-azobipyridine are very similar, the observed difference in binding behaviour highlights the importance of binding-site location on the acceptor molecules (anti-parallel in 3,3′-azobipyridine and co-linear in 4,4′-azobipyridine) as a direct influence over the structural balance between hydrogen- and halogen-bond donors.

Organic salts of L-tartaric acid: materials for second harmonic generation with a crystal structure governed by an anionic hydrogen-bonded network

Twelve hydrogen-bonded hydrogen-L-tartrate salts, capable of second harmonic generation (SHG), have been synthesized {the crystal structure of piperazinium(2+) bis-hydrogen-L-tartrate, [H2NC4H8NH2][C4H5O6]2, is reported} the structural significance of hydrogen bonding and its use as a tool in crystal engineering is discussed.

Heteromeric intermolecular interactions as synthetic tools for the formation of binary co-crystals

The crystal structure of 4-nitrobenzamide pyrazinecarboxamide (1 ∶ 1) contains two homomeric amide⋯amide dimers, which is in sharp contrast with the structural motifs displayed by the vast majority of binary co-crystals (illustrated here with five new examples), where the driving force for the supramolecular assembly is one or more strong heteromeric intermolecular interactions.