3,4-Dichlorophenol (1) crystallizes in the tetragonal space groupI4₁/awith a short axis of 3.7926 (9) Å. The structure is unique in that both type I and type II Cl...Cl interactions are present, these contact types being distinguished by the angle ranges of the respective C—Cl...Cl angles. The present study shows that these two types of contacts are utterly different. The crystal structures of 4-bromo-3-chlorophenol (2) and 3-bromo-4-chlorophenol (3) have been determined. The crystal structure of (2) is isomorphous to that of (1) with the Br atom in the 4-position participating in a type II interaction. However, the monoclinicP2₁/cpacking of compound (3) is different; while the structure still has O—H...O hydrogen bonds, the tetramer O—H...O synthon seen in (1) and (2) is not seen. Rather than a type I Br...Br interaction which would have been mandated if (3) were isomorphous to (1) and (2), Br forms a Br...O contact wherein its electrophilic character is clearly evident. Crystal structures of the related compounds 4-chloro-3-iodophenol (4) and 3,5-dibromophenol (5) were also determined. A computational survey of the structural landscape was undertaken for (1), (2) and (3), using a crystal structure prediction protocol in space groupsP2₁/candI4₁/awith the COMPASS26 force field. While both tetragonal and monoclinic structures are energetically reasonable for all compounds, the fact that (3) takes the latter structure indicates that Br prefers type II over type I contacts. In order to differentiate further between type I and type II halogen contacts, which being chemically distinct are expected to have different distance fall-off properties, a variable-temperature crystallography study was performed on compounds (1), (2) and (4). Length variations with temperature are greater for type II contacts compared with type I. The type II Br...Br interaction in (2) is stronger than the corresponding type II Cl...Cl interaction in (1), leading to elastic bending of the former upon application of mechanical stress, which contrasts with the plastic deformation of (1). The observation of elastic deformation in (2) is noteworthy; in that it finds an explanation based on the strengths of the respective halogen bonds, it could also be taken as a good starting model for future property design. Cl/Br isostructurality is studied with the Cambridge Structural Database and it is indicated that this isostructurality is based on shape and size similarity of Cl and Br, rather than arising from any chemical resemblance.

Two drug-drug co-crystals of the anti-tuberculosis drugs isoniazid (INH), pyrazinamide (PYR) and 4-aminosalicylic acid (PAS) are reported. The first is the 1 : 1 molecular complex of INH and PAS. The second is the monohydrate of the 1 : 1 complex of PYR and PAS. The crystal structures of both co-crystals are characterized by a number of hydrogen bonded synthons. Hydrogen bonding of the COOH⋯N_pyridine type is found in both cases. In the INH : PAS co-crystal, there are two symmetry independent COOH⋯N_pyridine hydrogen bonds. In one of these, the H-atom is located on the carboxylic group and is indicative of a co-crystal. In the second case, partial proton transfer occurs across the hydrogen bond, and the extent of proton transfer depends on the temperature. This is more indicative of a salt. Drug-drug co-crystals may have some bearing in the treatment of tuberculosis.

Co-crystals of 4,4′-bipyridine and 4-hydroxybenzoic acid (1 ∶ 2) show synthon polymorphism with the former being more stable. A 2 ∶ 1 co-crystal is pseudopolymorphic within the same structural landscape with the structural roles of the two bipyridine N-atoms being distinct, as evidenced by mimicry by 4-phenylpyridine.