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A family of: 1:1 cocrystals 11-Aza:4-X-SalA have been prepared from the potent anti-malarial compound 11-azaartemisinin with 4-halosalicylic acids. When X = 4-Cl, 4-Br and 4-I, two conformational polymorphs can be isolated in each case. Monoclinic type-I was found previously for parent 11-Aza:SalA (1) and 11-Aza:4-Br-SalA (3a) which have polar 21 stacks of molecular pairs with no short halogen bond contacts between stacks. Orthorhombic type-II is found for 4-Cl (3b) and 4-I (4b) from solution growth. This has a translational stack of molecular pairs involving a conformational change of the acid-lactam hetero-synthon and supramolecular association of stacks via halogen bonds. Notably, phase pure polymorph type-I can be formed for 4-Cl (3a) and 4-I (4a) by hetero-seeding with 11-Aza:SalA, whist conversely phase pure type-II for 4-Br (2b) can be formed using homo-seeding from liquid assisted grinding (LAG) product. This work demonstrates both the viability of engineering polymorphic cocrystal forms using hetero-seeds and the involvement of halogen bonds in helping to discriminate quite different polymorphic types. [ABSTRACT FROM AUTHOR]

A family of: 1:1 cocrystals 11-Aza:4-X-SalA have been prepared from the potent anti-malarial compound 11-azaartemisinin with 4-halosalicylic acids. When X = 4-Cl, 4-Br and 4-I, two conformational polymorphs can be isolated in each case. Monoclinic type-I was found previously for parent 11-Aza:SalA (1) and 11-Aza:4-Br-SalA (3a) which have polar 21 stacks of molecular pairs with no short halogen bond contacts between stacks. Orthorhombic type-II is found for 4-Cl (3b) and 4-I (4b) from solution growth. This has a translational stack of molecular pairs involving a conformational change of the acid-lactam hetero-synthon and supramolecular association of stacks via halogen bonds. Notably, phase pure polymorph type-I can be formed for 4-Cl (3a) and 4-I (4a) by hetero-seeding with 11-Aza:SalA, whist conversely phase pure type-II for 4-Br (2b) can be formed using homo-seeding from liquid assisted grinding (LAG) product. This work demonstrates both the viability of engineering polymorphic cocrystal forms using hetero-seeds and the involvement of halogen bonds in helping to discriminate quite different polymorphic types.

The X‐ray structures of three new 1:1 pharmaceutical cocrystals of 11‐azaartemisinin (11‐Aza; systematic name: 1,5,9‐trimethyl‐14,15,16‐trioxa‐11‐azatetracyclo[10.3.1.04,13.08,13]hexadecan‐10‐one, C15H23NO4) with bromo‐substituted salicylic acids [namely, 5‐bromo‐ (5‐BrSalA, C7H5BrO3), 4‐bromo‐ (4‐BrSalA, C7H5BrO3) and 3,5‐dibromosalicylic acid (3,5‐Br2SalA, C7H4Br2O3)] are reported. All the structures are related to the parent 11‐Aza:SalA cocrystal (monoclinic P21) reported previously. The 5‐BrSalA analogue is isostructural with the parent, with lattice expansion along the c axis. The 4‐BrSalA and 3,5‐Br2SalA cocrystals retain the highly preserved 21 stacks of the molecular pairs, but these pack with a varying degree of slippage with respect to neighbouring stacks, altering the close contacts between them, and represent two potential alternative homostructural arrangements for the parent compound. Structure redeterminations of the bromosalicylic acids 5‐BrSalA, 4‐BrSalA and 3,5‐Br2SalA at 100 K show that the packing efficiency of the cocrystals need not be higher than the parent coformers, based on specific‐volume calculations, attributable to the strong O—H...O=C hydrogen bonds of 2.54 Å in the cocrystals. [ABSTRACT FROM AUTHOR]

The controlled formation of complex and functional 1‐, 2‐, and 3D hierarchical assemblies from molecular building blocks represents a key current challenge. Herein, we report the use of a seeded growth approach for a series of perylenediimide‐based molecules (PDIs 1–4) to access otherwise inaccessible self‐assembly pathways that yield complex hierarchical structures. The key to the new approach is to use hetero‐seeds which possess a different composition and morphology from that of the molecular building block. For example, a nanotube seed (from PDI 3) and a microribbon seed (from PDI 4) were found to initiate different self‐assembly pathways for PDI 1, which normally assembles to yield nanocoils. This led to the formation of unprecedented 3D scroll‐like and scarf‐like hierarchical nanostructures, respectively. Also, the hetero‐seeds from PDI 3 initiate hidden self‐assembly pathways of PDI 2 to generate 1D tubular heterojunctions. Significantly, this new strategy offers new opportunities to create emergent and functional hierarchical and complex structures from small molecule precursors. [ABSTRACT FROM AUTHOR]