No abstract

Nanoindentation is applied to the two polymorphs of aspirin to examine and differentiate their interaction anisotropy and shear instability. Aspirin provides an excellent test system for the technique because: (i) polymorphs I and II exhibit structural similarity in two dimensions, thereby facilitating clear examination of the differences in mechanical response in relation to well-defined differences between the two crystal structures; (ii) single crystals of the metastable polymorph II have only recently become accessible; (iii) shear instability has been proposed for II. Different elastic moduli and hardness values determined for the two polymorphs are correlated with their crystal structures, and the interpretation is supported by measured thermal expansion coefficients. The stress-induced transformation of the metastable polymorph II to the stable polymorph I can be brought about rapidly by mechanical milling, and proceeds via a slip mechanism. This work establishes that nanoindentation provides ''signature'' responses for the two aspirin polymorphs, despite their very similar crystal structures. It also demonstrates the value of the technique to quantify stability relationships and phase transformations in molecular crystals, enabling a deeper understanding of polymorphism in the context of crystal engineering.

Aspirin: No end to the headaches? The two known crystalline arrangements of aspirin are so closely related that aspirin crystals form intergrowth structures containing domains of form I and domains of form II. The ratio and distribution of the domains is variable among aspirin samples, raising questions for the definition of the term polymorph in this case.

The crystal structures of the complete series of n-alkyl carboxylic acids from hexanoic to pentadecanoic acid have been determined following in situ crystallisation. The structures reveal that the melting point alternation across the series is correlated with alternating crystal density. All even acids crystallise from the liquid as the C modification, while the odd acids exhibit a transition from the C 0 to the C 00 modification between undecanoic and tridecanoic acid. In each structure, molecules form hydrogen-bonded dimers arranged into bilayers, with a rectangular packing arrangement in the plane perpendicular to the dimer long axes. The packing density within bilayers is comparable in each case and the alternating crystal density can be attributed solely to alternating packing density between bilayers. The carboxyl groups are identically disposed in all structures, but adjacent dimers are offset to differing degrees parallel to their long axes to reduce in-plane OÁ Á ÁO repulsions, giving rise to angles between n-alkyl chains. The extent of the lateral offset diminishes in general across the series as the nalkyl chains exert an increasing driving force towards parallel alignment. The systematic alternation in the packing density between bilayers arises as a result of different orientations adopted by the terminal C-C bonds with respect to the methyl group interface. Several of the key structural features may be rationalised using a simple two-dimensional model that describes the packing of modified parallelograms and trapezoids, representing the even and odd acids, respectively. Extension of the model into three dimensions permits complete rationalisation of the structures.y Electronic supplementary information (ESI) available: crystallographic data for C 6 -C 15 in tabular and .cif format, full details of temperature calibration and density measurement, packing coefficients and lattice binding energies, formal definitions of the orthogonal cells, details of all projections and measurements of all geometric parameters referred to in the text. See

Sesterterpenoids are a rare terpene class harboring untapped chemodiversity and bioactivities. Their structural diversity originates primarily from the scaffold-generating sesterterpene synthases (STSs). In fungi, all six known STSs are bifunctional, containing C-terminal trans-prenyltransferase (PT) and N-terminal terpene synthase (TPS) domains. In plants, two colocalized PT and TPS gene pairs from Arabidopsis thaliana were recently reported to synthesize sesterterpenes. However, the landscape of PT and TPS genes in plant genomes is unclear. Here, using a customized algorithm for systematically searching plant genomes, we reveal a suite of physically colocalized pairs of PT and TPS genes for the biosynthesis of a large sesterterpene repertoire in the wider Brassicaceae. Transient expression of seven TPSs from A. thaliana, Capsella rubella, and Brassica oleracea in Nicotiana benthamiana yielded fungal-type sesterterpenes with tri-, tetra-, and pentacyclic scaffolds, and notably (−)-ent-quiannulatene, an enantiomer of the fungal metabolite (+)-quiannulatene. Protein and structural modeling analysis identified an amino acid site implicated in structural diversification. Mutation of this site in one STS (AtTPS19) resulted in premature termination of carbocation intermediates and accumulation of bi-, tri-, and tetracyclic sesterterpenes, revealing the cyclization path for the pentacyclic sesterterpene (−)-retigeranin B. These structural and mechanistic insights, together with phylogenetic analysis, suggest convergent evolution of plant and fungal STSs, and also indicate that the colocalized PT-TPS gene pairs in the Brassicaceae may have originated from a common ancestral gene pair present before speciation. Our findings further provide opportunities for rapid discovery and production of sesterterpenes through metabolic and protein engineering.sesterterpene biosynthesis | plant natural products | cyclization mechanism | convergent evolution | Brassicaceae S esterterpenoids are a largely unexplored class of terpenes with only around 1,000 members isolated from nature so far, representing a mere <2% of the reported terpene family members (>70,000). These compounds are structurally diverse and have a wide spectrum of biological activities, ranging from antiinflammatory, anticancer, cytotoxic, and antimicrobial bioactivities to phytotoxicity and plant defense (1). Recent work on sesterterpenoids has suggested that this terpene class could be an important new source of anticancer drugs (2, 3). The majority of sesterterpenoids characterized to date are from marine sponges and terrestrial fungi, with only ∼60-70 being of plant origin. Many of these plant sesterterpenes were isolated from the mint family (Lamiaceae) and have been implicated in plant defense (4-7). Although large transcriptome datasets for the mint family have been generated (8), very limited genome sequences for the Lamiaceae are currently available (9, 10).Like other classes of terpenes, the structural diversity of sesterterpenes largely originates from the...