Modifying the internal substituents of self-assembled cages controls their molecular recognition and optical properties.

Self-assembled Fe4L6 cage complexes with variable internal functions can be synthesized from a 2,7-dibromocarbazole ligand scaffold, which orients six functional groups to the cage interior. Both ethylthiomethylether and ethyldimethylamino groups can be incorporated. The cages show strong ligand-centered fluorescence emission and a broad range of guest binding properties. Coencapsulation of neutral organic guests is favored in the larger, unfunctionalized cage cavity, whereas the thioether cage has a more sterically hindered cavity that favors 1 : 1 guest binding. Binding affinities up to 106 M-1 in CH3CN are seen. The dimethylamino cage is more complex, as the internal amines display partial protonation and can be deprotonated by amine bases. This amine cage displays affinity for a broad range of neutral organic substrates, with affinities and stoichiometries comparable to that of the similarly sized thioether cage. These species show that simple variations in ligand backbone allow variations in the number and type of functions that can be displayed towards the cavity of self-assembled hosts, which will have applications in biomimetic sensing, catalysis and molecular recognition.

Moderated Basicity of Endohedral Amine Groups in an Octa-Cationic Self-Assembled Cage.

A self-assembled FeII4 L6 cage was synthesized with 12 internal amines in the cavity. The cage forms as the dodeca-ammonium salt, despite the cage carrying an overall 8+ charge at the metal centers, extracting protons from displaced water in the reaction. Despite this, the basicity of the internal amines is lower than their counterparts in free solution. The 12 amines have a sliding scale of basicity, with a ≈6 pKa unit difference between the first and last protons to be removed. This moderation of side-chain basicity in an active site is a hallmark of enzymatic catalysis.

Size- and Shape-Selective Catalysis with a Functionalized Self-Assembled Cage Host.

A self-assembled Fe4L6 cage with internally oriented carboxylic acid functions was shown to catalyze a variety of dissociative nucleophilic substitution reactions that proceed via oxocarbenium ion or carbocation intermediates. The catalytic behavior of the cage was compared to that of other small acid catalysts, which illustrated large differences in reactivity of the cage-catalyzed reactions, dependent on the structure of the substrate. For example, only a 5% cage confers a 1000-fold rate acceleration of the thioetherification of vinyldiphenylmethanol when compared to the rate with free carboxylic acid surrogates but only a 52-fold acceleration in the formation of small thioacetals. Multiple factors control the variable reactivity in the host, including substrate inhibition, binding affinity, and accessibility of reactive groups once bound. Simple effective concentration increases or the overall charge of the cage does not explain the variations in reactivity shown by highly similar reactants in the host: small differences in structure can have large effects on reactivity. Reaction of large spherical guests is highly dependent on substitution, whereas flat guests are almost unaffected by size and shape differences. The cage is a promiscuous catalyst but has strong selectivity for particular substrate shapes, reminiscent of enzymatic activity.

Supramolecular Catalysis of the oxa-Pictet-Spengler Reaction with an Endohedrally Functionalized Self-Assembled Cage Complex.

An endohedrally functionalized self-assembled Fe4 L6 cage complex can catalyze oxa-Pictet-Spengler cyclizations of tryptophols and various aldehyde derivatives, showing strong rate accelerations and size-selectivity. Selective molecular recognition of substrates controls the reactivity, and the cage is capable of binding and activating multiple different species along the multistep reaction pathway. The combination of a functionalized active site, size-selective reactivity, and multistep activation, all from a single host molecule, illustrates the biomimetic nature of the catalysis.

Developing the DELTA: Capturing Cultural Changes in Undergraduate Departments.

Departments are now recognized as an important locus for sustainable change on university campuses. Making sustainable changes typically requires a shift in culture, but culture is complex and difficult to measure. For this reason, cultural changes are often studied using qualitative methods that provide rich, detailed data. However, this imposes barriers to measuring culture and studying change at scale (i.e., across many departments). To address this issue, we introduce the Departmental Education and Leadership Transformation Assessment (DELTA), a new survey aimed at capturing cultural changes in undergraduate departments. We describe the survey's development and validation and provide suggestions for its utility for researchers and practitioners.

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

A self-assembled Fe4L6 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. Substrate binding modes vary widely, from simple 1:1 complexes to 1:2 complexes that can show either negative or positive cooperativity, depending on the guest. The molecularity of the dissociative substitution reaction varies, depending on the electrophile leaving group, acid cofactor, and nucleophile size: small changes in the nature of substrate can have large effects on reaction kinetics, all controlled by selective molecular recognition in the cage interior.

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

A self-assembled Fe4 L6 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. Most importantly, the cage host alters the molecularity of the reaction: whereas the reaction catalyzed by simple acids is a unimolecular, SN 1-type substitution process, the rate of the host-mediated process is dependent on the concentration of nucleophile. The molecularity of the cage-catalyzed reaction is substrate-dependent, and can be up to bimolecular. In addition, the catalysis can be prevented by a large excess of nucleophile, where substrate inhibition dominates, and the use of tritylated anilines as substrates causes a negative feedback loop, whereby the liberated product destroys the catalyst and stops the reaction.

Probing the Relevance of Chemical Identity Thinking in Biochemical Contexts.

The solving of problems in biochemistry often uses concepts from multiple disciplines such as chemistry and biology. Chemical identity (CI) is a foundational concept in the field of chemistry, and the knowledge, thinking, and practices associated with CI are used to answer the following questions: "What is this substance?" and "How is it different from other substances?" In this study, we examined the relevance of CI in biochemical contexts and first explored the ways in which practicing biochemists consider CI relevant in their work. These responses informed the development of creative exercises (CEs) given to second--semester biochemistry students. Analysis of the student responses to these CEs revealed that students incorporated precursors to CI thinking in more than half of their responses, which were categorized by seven previously identified themes of CI relevant to the presented biochemical contexts. The prevalence of these precursors in student responses to the CEs, coupled with the examples provided by practicing biochemists of contexts in which CI is relevant, indicate that CI thinking is relevant for both students training to be biochemists and practicing biochemists.

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

Self-assembly of a carboxylic acid-containing ligand into an Fe4L6 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. The combination of rate enhancements and sequestration of the reactive function confers both activity and selectivity on the process, mimicking enzymatic behavior.