aIn order to study the structure-directing competition between hydrogen-and halogen-bond donors we 5 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 singlecrystal 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 10 6 co-crystals of 4,4'-azobipyridine, both hydrogen bonds (O-HN) and halogen bonds (C-XN) are present as comparable 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, i.e. -174 and -172 kJ/mol respectively, 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 15 influence over the structural balance between hydrogen-and halogen-bond donors.

A fundamental principle of supramolecular chemistry 1 de scribes a molecule as being built from atoms connected by covalent bonds, whereas a supermolecule is constructed from molecules using intermolecular interactions such as hydrogen bonds, 2 halogen bonds, 3 and πÀπ interactions as the connectors. 1,4 One of the biggest challenges in supramolecular synthesis arises due to the reversible nature of these interactions which effectively restricts noncovalent synthesis to one-pot processes. 5 An added complication with using relatively weak chemical bonds as primary synthetic tools is, of course, that the outcome of the supramolecular reaction can be quite unpredictable, which explains the ongoing quest for more robust synthons that can be combined into reliable and reproducible noncovalent synthesis. Hydrogen bonds remain the most commonly utilized tools in the assembly of co-crystals due to their relatively high strength and directionality, 2,6 and many successful studies have been reported where overall assembly of binary and ternary cocrystals is guided by a synthetic scheme based on hydrogen bonds of varying strengths in a predictable manner. However, for designing co-crystals of higher complexity, a strategy that relies solely on hydrogen bonds could soon fail because of unavoidable competition between the intended hydrogen-bond donors/acceptors which could lead to "synthon crossover". Supramolecular strategies, that can accommodate two or more different noncovalent interactions in such a way that they are unlikely to interfere with each other, would, in principle, alleviate this problem. A suitable accompaniment to a hydrogen-bond based strategy may be provided by halogen bonds, which are typically formed between activated iodine or bromine atoms (the halogen-bond donor) and an appropriate halogen-bond acceptor (electron-pair donor)

Magnetic levitation (MagLev) provides a simple method for the separation of crystal polymorphs that differ in density (Δρ) by greater than 0.001 g cm−3. Density‐based separations of multiple crystalline forms were shown for four organic compounds: 5‐methyl‐2‐[(2‐nitro‐ phenyl)amino]‐3‐thiophenecarbonitrile, sulfathiazole, carbamazepine, and trans‐ cinnamic acid.

It has been shown, using a foundation of new structural data, that the relative strength and capability of iodo-and bromo-based molecules to act as halogen-bond donors in a competitive supramolecular arena accurately reflect a ranking of halogen-bond donors based upon electrostatic molecular potentials. Furthermore, to obtain the critical structural information, a protocol (comprising a lowering of molecular symmetry and the addition of strong and directional hydrogen bonds) for engineering crystals without positional disorder was successfully developed.

Hydrogen bonds and halogen bonds can be used as synthetic vectors without structural interference as long as the primary molecular recognition events are designed around a careful combination of geometric and electrostatic complementarity. In addition, a one-step procedure for the synthesis of tectons equipped with powerful hydrogen- and halogen-bond donors is presented.