Using Flipped Classroom Modules to Facilitate Higher Order Learning in Undergraduate Organic Chemistry.

In an ongoing effort to incorporate active learning and promote higher order learning outcomes in undergraduate organic chemistry, a hybrid ("flipped") classroom structure has been used to facilitate a series of collaborative activities in the first two courses of the lower division organic chemistry sequence. An observational study of seven classes over a five-year period reveals there is a strong correlation between performance on the in-class activities and performance on the final exam across all classes; however, a significant number of students in these courses continue to struggle on both the in-class activities and final exam. The Activity Engagement Survey (AcES) was administered in the most recent course offering included in this study, and these preliminary data suggest that students who achieved lower scores on the in-class activities had lower levels of emotional and behavioral/cognitive engagement and were less likely to work in collaborative groups.

Imaging active site chemistry and protonation states: NMR crystallography of the tryptophan synthase α-aminoacrylate intermediate.

NMR-assisted crystallography-the integrated application of solid-state NMR, X-ray crystallography, and first-principles computational chemistry-holds significant promise for mechanistic enzymology: by providing atomic-resolution characterization of stable intermediates in enzyme active sites, including hydrogen atom locations and tautomeric equilibria, NMR crystallography offers insight into both structure and chemical dynamics. Here, this integrated approach is used to characterize the tryptophan synthase α-aminoacrylate intermediate, a defining species for pyridoxal-5'-phosphate-dependent enzymes that catalyze β-elimination and replacement reactions. For this intermediate, NMR-assisted crystallography is able to identify the protonation states of the ionizable sites on the cofactor, substrate, and catalytic side chains as well as the location and orientation of crystallographic waters within the active site.

Cofactor-Mediated Nucleophilic Substitution Catalyzed by a Self-Assembled Holoenzyme Mimic.

A self-assembled FeL cage is capable of co-encapsulating multiple carboxylic acid containing guests in its cavity, and these acids can act as cofactors for cage-catalyzed nucleophilic substitutions. The kinetics of the substitution reaction depend on the size, shape, and binding affinity of each of the components, and small structural changes in guest size can have large effects on the reaction. The host is quite promiscuous and is capable of binding multiple guests with micromolar binding affinities while retaining the ability to effect turnover and catalysis.

A Self-Assembled Cage with Endohedral Acid Groups both Catalyzes Substitution Reactions and Controls Their Molecularity.

A self-assembled Fe L cage complex internally decorated with acid functions is capable of accelerating the thioetherification of activated alcohols, ethers and amines by up to 1000-fold. No product inhibition is seen, and effective supramolecular catalysis can occur with as little as 5 % cage. The substrates are bound in the host with up to micromolar affinities, whereas the products show binding that is an order of magnitude weaker.

Tandem Reactivity of a Self-Assembled Cage Catalyst with Endohedral Acid Groups.

Self-assembly of a carboxylic acid-containing ligand into an FeL iminopyridine cage allows endohedral positioning of the acid groups while maintaining a robust cage structure. The cage is an effective supramolecular catalyst, providing up to 1000-fold rate enhancement of acetal solvolysis. This enhanced reactivity allows a tandem deprotection/cage-to-cage interconversion that cannot be achieved with other acid catalysts.

A Springloaded Metal-Ligand Mesocate Allows Access to Trapped Intermediates of Self-Assembly.

A strained, "springloaded" FeL iminopyridine mesocate shows highly variable reactivity upon postassembly reaction with competitive diamines. The strained assembly is reactive toward transimination in minutes at ambient temperature and allows observation of kinetically trapped intermediates in the self-assembly pathway. When diamines are used that can only form less favored cage products upon full equilibration, trapped ML fragments with pendant, "hanging" NH groups are selectively formed instead.

Controlled self-sorting in self-assembled cage complexes.

In this frontier article we highlight recent advances in subcomponent self-sorting in self-assembled metal-ligand cage complexes, with a focus on selective discrimination between ligands that contain highly similar metal-coordinating groups. Effects such as varying ligand length, coordination angle and backbone flexibility, as well as the introduction of secondary weak forces such as hydrogen bonds can be exploited to favor either narcissistic or social self-sorting. We highlight these creative solutions, and emphasize the challenges that remain in the development of functional self-assembled heterocomplexes.

Stereoselective Postassembly CH Oxidation of Self-Assembled Metal-Ligand Cage Complexes.

Self-assembled Fe-iminopyridine cage complexes containing doubly benzylic methylene units such as fluorene and xanthene can be selectively oxidized at the ligand backbone with BuOOH, with no competitive oxidation observed at the metal centers. The self-assembled cage structure controls the reaction outcome, yielding oxidation products that are favored by the assembly, not by the reactants or functional groups. Whereas uncomplexed xanthene and fluorene control ligands are solely oxidized to the ketone equivalents with BuOOH, the unfavorability of the self-assembled ketone cages forces the reaction to form the butyl peroxide and alcohol-containing oxidation products, respectively.