Themed collection Functional Co-crystals

Welcome to this CrystEngComm themed issue on functional co-crystals.

Progression from drug to co-crystal to medicine.

Head-to-tail photodimerization of thiophene is achieved in a co-crystal while a co-crystal with an acid dimer and heterosynthon is also described.

The melamine barbital co-crystal is an optically stable NLO material, engineered from the pharmaceutically active barbital molecule, showing SHG efficiency higher than that of KDP.

Post-synthesis (de)hydration techniques were used here to explore further hydrated forms of ionic co-crystals (ICCs) of nicotinamide with CaCl₂.

Twelve multi-component molecular crystals of the active pharmaceutical ingredient (API) piroxicam (PX) are described contrasting those with basic N-heterocycles with those formed with strong haloanilic acids. The effect on the solubility of this API is discussed, with evidence of enhanced solubility in the multi-component crystals formed.

The O⋯O, O⋯H and O⋯N interactions dominantly hold all the crystal packing.

Basing our reasoning on the only known and available crystalline structure of a hybrid co-crystal of caffeic acid, we extended our study to the analysis of the behaviour of another humic substance, the protocatechuic acid.

Role of local crystal environment on proton location was modelled using DFT calculations. Alteration in the strength of the hydrogen bonding can convert a system from a salt to a co-crystal.

Haloprogin is a widely used antifungal agent. Here we report the first polymorphs and halogen-bonded co-crystals ever described.

Reaction of brivaracetam (BRV) and seletracetam (SEL) with MgCl₂ and CaCl₂ yields ionic co-crystals with improved physico-chemical properties with respect to pure drugs.

Crystallization of a meta-bis(iminoylnitroxide) with dichloromethane (DCM) gives co-crystal in which DCM planarizes the diradical, enabling pi-stacks with 1-D antiferromagnetic exchange between radical units.

The antibacterial drug sulfacetamide was screened with pharmaceutically acceptable coformers to discover solid forms with low solubility. Cocrystals with INIC and CAF exhibited 0.64 and 0.68 times the IDR of the parent drug. SACT–CAF cocrystal with lower solubility and good stability is a potential candidate to increase the drug residence time at the site of action for improved therapeutic efficacy.

Current approaches for knowledge-based co-crystal design are explained and exemplified, followed by presentation of emerging methodologies which build on these concepts.

Three pairs of molecular complexes based around 4-iodoaniline and 3,5-dinitrobenzoic acid are reported. Within each pair, one complex is colourless and one red; the influences on the colour are discussed including the role of molecular disorder and proton transfer.

Systematic structure–property studies on a series of co-crystals of potential cancer drugs with aliphatic dicarboxylic acids were undertaken.

Discovery, characterisation and scale-up of novel α-lipoic acid co-crystals using continuous crystallisation in a COBC is demonstrated.

Tuning phase transformation temperatures through the use of solid solutions.

The arrangement of the title compound (crystal I) was regulated via different solvates and cocrystals (crystals II–V) for fluorescence modulation.

Acids and bases were crystallized so that their ΔpK_a spans the ‘uncertainty’ region for the formation of salt versus co-crystals.

Crystal engineering principles were used to produce the homochiral R- and S-chains of naproxen (NPX) by cocrystallization with bipyridine (BPY) and piperazine (PIZ).

A 1 : 1 cocrystal of flufenamic acid with theophylline shows improved solubility and dissolution rate when compared to flufenamic acid and the recently reported cocrystal with nicotinamide, which also helps to inhibit the hygroscopic nature of theophylline and is stable under slurry conditions.

Hydrogen bonding patterns for a cocrystal and a series of salts of an orally active antimalarial drug candidate are presented, together with thermal stability and solubility data as part of a programme aimed at early identification of new crystal forms of the active compound.