Is there any point in making co-crystals?

Citation: Aakeroy, C. (2015). Is there any point in making co-crystals? Acta Crystallographica Section B-Structural Science Crystal Engineering and Materials, 71, 387-391. doi:10.1107/s2052520615010872Many aspects of co-crystals, including their synthesis, characterization and possible applications, are receiving considerable attention from academia and industry alike. The question is, can this interdisciplinary activity be translated into new fundamental insight and new solid forms of high-value materials with improved performances

Altering physical properties of pharmaceutical co-crystals in a systematic manner

Systematic structure-property studies on a series of co-crystals of potential cancer drugs with aliphatic dicarboxylic acids were undertaken. This study reveals that systematic changes to the molecular nature of the co-crystallizing agent combined with control over the way individual building blocks are organized within the crystalline lattice makes it possible to establish predictable links between molecular structure and macroscopic physical properties, such as melting behaviour and aqueous solubility. However, it is not possible to find any notable correlation between physical properties-chemical compositions in the absence of structural consistency

The quest for a molecular capsule assembled via halogen bonds

A halogen-bonded capsule is obtained via directed assembly of a rigid tetra(3-pyridyl) cavitand and a flexible tetra(4-iodotetrafluorophenyl) calix[4]arene. The pyridyl nitrogen atoms from one cavitand molecule interact with the iodine atoms of a single calixarene molecule through short and directional I…N halogen bonds. The flexibility of the ethylenedioxy moieties on the calixarene platform results in positional flexibility of the iodotetrafluorobenzene sites which, coupled with a supramolecular chelating effect, allow for an effective partner-induced geometric fitting between four nitrogen atoms on the cavitand and four iodine atoms on the calixarene

Controlling molecular tautomerism through supramolecular selectivity

We have isolated the stable as well as the metastable tautomers of 1-deazapurine in the solid state by exploiting principles of supramolecular selectivity in the context of cocrystal design

Competing hydrogen-bond donors: phenols vs. cyanooximes

Based on a systematic structural study of co-crystals of a ditopic probe molecule, (Z)-N,4-dihydroxybenzimidoyl cyanide, decorated with an –OH group and a cyanooxime moiety, it has been shown that in a competitive molecular recognition event, the former is the better hydrogen-bond donor. This structural behaviour is reflected by calculated electrostatic potential surfaces of the competing donors, which highlights that electrostatic charge can offer a reliable tool for predicting primary hydrogen-bond preferences

Interdependence of structure and physical properties in co-crystals of azopyridines

To establish how intermolecular interactions influence the supramolecular assembly of azopyridines, a total of five co-crystals of 3,3′ and 4,4′-azopyridine; 3,3′-azpy:succinic acid (3,3′-azpy:SA), 3,3′-azpy:adipic acid (3,3′-azpy:AA), 3,3′-azpy:suberic acid (3,3′-azpy:SuA), 3,3′-azpy:sebacic acid (3.3′-azpy:SeA), and 4,4′-azpy:suberic acid (4,4′-azpy:SuA) were synthesized. In all co-crystals of 3,3′-azopyridine, there are infinite 1-D zig-zag tapes composed of alternating 3,3′-azpy and diacids held together by COOHN(py) hydrogen bonds. Neighbouring chains are arranged into 2-D sheets via secondary inter-chain C–H•••O interactions between azopyridine ring hydrogen atoms and carbonyl oxygen atoms in an in-phase manner. However, in the co-crystal of 4,4′-azopyridine:suberic acid, the adjacent chains form 2-D sheets in an out-of-phase motif via two types of inter-chain C–H•••O interactions, i.e. between azopyridine ring hydrogen atoms and carbonyl oxygen as well as hydroxyl oxygen atoms. The structural consistency within the 3,3′-azopyridine co-crystals has made it possible to establish a correlation between melting point of the homomeric molecular solids and co-crystals of the corresponding carboxylic acids

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

In order to study the structure-directing competition between hydrogen- and alogen-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