Amino Acid Residues Determine the Response of Flexible Metal-Organic Frameworks to Guests.

Flexible metal-organic frameworks (MOFs) undergo structural transformations in response to physical and chemical stimuli. This is hard to control because of feedback between guest uptake and host structure change. We report a family of flexible MOFs based on derivatized amino acid linkers. Their porosity consists of a one-dimensional channel connected to three peripheral pockets. This network structure amplifies small local changes in linker conformation, which are strongly coupled to the guest packing in and the shape of the peripheral pockets, to afford large changes in the global pore geometry that can, for example, segment the pore into four isolated components. The synergy among pore volume, guest packing, and linker conformation that characterizes this family of structures can be determined by the amino acid side chain, because it is repositioned by linker torsion. The resulting control optimizes noncovalent interactions to differentiate the uptake and structure response of host-guest pairs with similar chemistries.

The Anisotropic Responses of a Flexible Metal-Organic Framework Constructed from Asymmetric Flexible Linkers and Heptanuclear Zinc Carboxylate Secondary Building Units.

A new porous and flexible metal-organic framework (MOF) has been synthesized from the flexible asymmetric linker N-(4-carboxyphenyl)succinamate (CSA) and heptanuclear zinc oxo-clusters of formula [Zn7O2(carboxylate)10DMF2] involving two coordinated terminal DMF ligands. The structural response of this MOF to the removal or exchange of its guest molecules has been probed using a combination of experimental and computational approaches. The topology of the material, involving double linker connections in the a and b directions and single linker connections along the c axis, is shown to be key in the material's anisotropic response. The a and b directions remain locked during guest removal, whereas the c axis linker undergoes large changes significantly reducing the material's void space. The changes to the c axis linker involve a combination of a hinge motion on the linker's rigid side and conformational rearrangements on its flexible end, which were probed in detail during this process despite the presence of crystallographic disorder along this axis, which prevented accurate characterization by experimental methods alone. Although inactive during guest removal, the flexible ends of the a and b axis linkers are observed to play a prominent role during DMF to DMSO solvent exchange, facilitating the exchange reaction arising in the cluster.

Decontamination of Chia and Flax Seed Inoculated with Salmonella and Surrogate, Enterococcus faecium NRRL B-2354, Using a Peracetic Acid Sanitizing Solution: Antimicrobial Efficacy and Impact on Seed Functionality.

Raw chia and flax seeds are increasingly associated with Salmonella contamination. However, intervention technologies for these seeds that maintain them in a raw state, without causing clumping because of mucilage production upon moisture exposure, are limited. In this study, a commercial ethanol and paracetic acid sanitizing solution meeting these criteria was evaluated for efficacy against Salmonella and Enterococcus faecium NRRL B-2354, a known Salmonella surrogate for thermal intervention technologies. Samples (100 g each) of chia and flax seeds ( n = 5) were inoculated with either a cocktail of Salmonella Newport, Senftenberg, Oranienburg, Saintpaul, Typhimurium DT104, and Cubana or E. faecium NRRL B-2354. After overnight acclimatization, samples were treated with 4 mL of sanitizing solution per sample and then held at ambient temperature (20 to 25°C) for 1 h before bacterial enumeration. Separate 1-kg-treated batches were evaluated for germination ability (4 replicates of 100-g samples), as well as nutrient content and rancidity ( n = 3), compared with untreated control. Following the posttreatment holding time, these batches were dried back to original moisture content at 70°C to evaporate residual sanitizing solution, thereby stopping treatment. The sanitizing solution was found to be an effective intervention method for chia and flax seeds, reducing Salmonella to below the level of detection by more than 4 and more than 5 average log CFU/g, respectively. Germination was not significantly affected ( P ≥ 0.05) for chia seed. For both seeds, nutrition and rancidity were not significantly affected ( P ≥ 0.05). Furthermore, E. faecium NRRL B-2354 was found to be an appropriate Salmonella surrogate for treatment of chia and flax seeds with this sanitizing solution, showing comparable but higher resistance to treatment with the sanitizing solution than the Salmonella cocktail.

Report on the sixth blind test of organic crystal structure prediction methods.

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and `best practices' for performing CSP calculations. All of the targets, apart from a single potentially disordered Z' = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms.

Are the Crystal Structures of Enantiopure and Racemic Mandelic Acids Determined by Kinetics or Thermodynamics?

Mandelic acids are prototypic chiral molecules where the sensitivity of crystallized forms (enantiopure/racemic compound/polymorphs) to both conditions and substituents provides a new insight into the factors that may allow chiral separation by crystallization. The determination of a significant number of single crystal structures allows the analysis of 13 enantiopure and 30 racemic crystal structures of 21 (F/Cl/Br/CH3/CH3O) substituted mandelic acid derivatives. There are some common phenyl packing motifs between some groups of racemic and enantiopure structures, although they show very different hydrogen-bonding motifs. The computed crystal energy landscape of 3-chloromandelic acid, which has at least two enantiopure and three racemic crystal polymorphs, reveals that there are many more possible structures, some of which are predicted to be thermodynamically more favorable as well as slightly denser than the known forms. Simulations of mandelic acid dimers in isolation, water, and toluene do not differentiate between racemic and enantiopure dimers and also suggest that the phenyl ring interactions play a major role in the crystallization mechanism. The observed crystallization behavior of mandelic acids does not correspond to any simple "crystal engineering rules" as there is a range of thermodynamically feasible structures with no distinction between the enantiopure and racemic forms. Nucleation and crystallization appear to be determined by the kinetics of crystal growth with a statistical bias, but the diversity of the mandelic acid crystallization behavior demonstrates that the factors that influence the kinetics of crystal nucleation and growth are not yet adequately understood.