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. In total, these findings suggest that if students can be guided to engage more successfully with the in-class activities, they are likely to be more successful in carrying out the higher order learning required on the final exam. In addition to the analyses of student performance and engagement in the in-class activities, the implementation of the flipped classroom structure and suggestions for how student engagement in higher order learning might be improved in future iterations of the class are described herein.

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.

Small Structural Variations Have Large Effects on the Assembly Properties and Spin State of Room Temperature High Spin Fe(II) Iminopyridine Cages.

Small changes in steric bulk at the terminus of bis-iminopyridine ligands can effect large changes in the spin state of self-assembled Fe(II)-iminopyridine cage complexes. If the added bulk is properly matched with ligands that are either sufficiently flexible to allow twisted octahedral geometries at the Fe centers or can assemble with unusual mer configurations at the metals, room temperature high spin Fe(II) cages can be synthesized. These complexes maintain their high spin state in solution at low temperatures and have been characterized by X-ray crystallographic and computational methods. The high spin M2L3 meso-helicate and M4L6 cage complexes display longer N-Fe bond distances and larger interligand N-Fe-N bond angles than their diamagnetic counterparts, and these structural changes invert the ligand selectivity in narcissistic self-sorting and accelerate subcomponent exchange rates. The paramagnetic cages can be easily converted to diamagnetic cages by subcomponent exchange under mild conditions, and the intermediates of the exchange process can be visualized in situ by NMR analysis.

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.

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

A strained, "springloaded" Fe2L3 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 ML3 fragments with pendant, "hanging" NH2 groups are selectively formed instead. Slight variations in diamine structure have large effects on the product outcome: less rigid diamines convert the mesocate to more favored self-assembled cage complexes under mild conditions and allow observation of heterocomplex intermediates in the displacement pathway. The mesocate allows control of equilibrium processes and direction of product outcomes via small, iterative changes in added subcomponent structure and provides a method of accessing metal-ligand cage structures not normally observed in multicomponent Fe-iminopyridine self-assembly.

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 tBuOOH, 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 tBuOOH, the unfavorability of the self-assembled ketone cages forces the reaction to form the tbutyl peroxide and alcohol-containing oxidation products, respectively. In addition, the oxidation is diastereoselective, with only single isomers of the cage assemblies formed, despite the presence of as many as 10 stereocenters in the final product. The self-assembled structures exploit self-complementary hydrogen bonding and geometrical constraints to direct the postassembly reactions to outcomes not observed in free solution. This selectivity is reminiscent of the fine control of post-translational modification seen in biomacromolecules.

Electronic Effects on Narcissistic Self-Sorting in Multicomponent Self-Assembly of Fe-Iminopyridine meso-Helicates.

Small changes in the electron donating ability of coordinating groups have substantial effects on the multicomponent self-assembly of Fe (II)-iminopyridine-based meso-helicate complexes. Both the nature of the internal diamine core and the terminal formylpyridine reactants control the rate of the assembly process, the thermodynamic favorability of the meso-helicate products, and the selective incorporation of different aldehyde termini into the assembly. Steric congestion at the coordinating ligands can prevent assembly altogether, and favorable incorporation of electron-rich aldehyde termini is observed, even though the rate of reaction is accelerated by the use of electron-poor aldehyde reactants. NMR and electrospray ionization mass spectrometry analyses were employed to determine the synergistic nature of narcissistic self-sorting in this system, which depends on both the rigidity of the central core and the electronic donor ability of the aldehyde terminus. These experiments illustrate that significant control of self-sorting and self-assembly is possible upon extremely small variations in ligand structure, rigidity, and donor ability.

Structural switching in self-assembled metal-ligand helicate complexes via ligand-centered reactions.

Ligand centered reactions are capable of conferring structural switching between a metastable, self-assembled Fe-iminopyridine aggregate and a stable M2L3 helicate. The reactivity is directed and accelerated by the stability of the final product structure. Under aerobic conditions, both substitution and oxidation occurs at the ligand, exploiting atmospheric oxygen as the oxidant. In the absence of air, reaction occurs more slowly, forming the less stable substitution product. Control ligands show a preference for simple substitution, but the self-assembly directs both substitution and oxidation. The metastable nature of the initial aggregate species is essential for the reaction: while the aggregate is "primed" for reaction, other analogous helicate structures are "locked" by self-assembly, preventing reactivity.

High fidelity sorting of remarkably similar components via metal-mediated assembly.

Subtle differences in ligand coordination angle and rigidity lead to high fidelity sorting between individual components displaying identical coordination motifs upon metal-mediated self-assembly. Narcissistic self-sorting can be achieved between highly similar ligands that vary minimally in rigidity and internal coordination angle upon combination with Fe(ii) ions and 2-formylpyridine. Selective, sequential cage formation can be precisely controlled in a single flask from a mix of three different core ligands (and 33 total components) differing only in the hybridization of one group that is uninvolved in the metal coordination process.

A supramolecular sorting hat: stereocontrol in metal-ligand self-assembly by complementary hydrogen bonding.

A combination of self-complementary hydrogen bonding and metal-ligand interactions allows stereocontrol in the self-assembly of prochiral ligand scaffolds. A unique, non-tetrahedral M4L6 structure is observed upon multicomponent self-assembly of 2,7-diaminofluorenol with 2-formylpyridine and Fe(ClO4)2. The stereochemical outcome of the assembly is controlled by self-complementary hydrogen bonding between both individual ligands and a suitably sized counterion as template. This hydrogen-bonding-mediated stereoselective metal-ligand assembly allows the controlled formation of nonsymmetric discrete cage structures from previously unexploited ligand scaffolds.

A combined experimental and theoretical study of dinitrosyl iron complexes containing chelating bis(diphenyl)phosphinoX (X = benzene, propane and ethylene): X-ray crystal structures and properties influenced by the presence or absence of π-bonds in chelating ligands.

Recent discoveries involving the roles of nitric oxide in humans have stimulated intense interest in transition metal nitrosyl complexes. A series of dinitrosyl iron complexes with the formula [(DPPX)Fe(NO)2], {DPPX = 1,2-bis(diphenylphosphino)benzene (1), 1,3-bis(diphenylphosphino)propane (2), and cis-1,2-bis(diphenylphosphino)ethylene (3)} has been prepared and characterized through a combination of FT-IR, NMR, UV-vis, X-ray crystallography, and electrochemical techniques. Infrared spectroscopy showed NO shifts to the region of 1723 and 1674 cm-1 for complexes 1 and 3, and 1708 and 1660 cm-1 for 2, indicating that ligand 2 acts as a stronger σ-donor. The X-ray crystallographic data showed that 1 and 3 possess the rare repulso conformation while 2 has the attracto conformation. CV studies on compounds 1, 2 and 3 display two quasi-reversible oxidations with the E°1/2 values at 0.101 and 0.186 V, 0.121 and 0.184 V, and 0.019 and 0.342 V, respectively. The larger ΔE value for compound 2 compared with that of 1 and 3 is attributed to the lack of π-bonds between the two phosphorus atoms. Theoretical calculations using density functional theory were carried out on the synthesized compounds and model compounds and the results are consistent with the experimental data. The calculated HOMO-LUMO gaps for compounds 1, 2 and 3 are 3.736, 4.060, and 3.669 eV, respectively, which supports the stronger back-donation for compound 2 than that of compounds 1 and 3.

Hoxa-5 acts in segmented somites to regulate cervical vertebral morphology.

The vertebrate axial skeleton (vertebral column and ribs) is derived from embryonic structures called somites. Mechanisms of somite formation and patterning are largely conserved along the length of the body axis, but segments acquire different morphologies in part through the action of Hox transcription factors. Although Hox genes' roles in axial skeletal patterning have been extensively characterized, it is still not well understood how they interact with somite patterning pathways to regulate different vertebral morphologies. Here, we investigated the role of Hoxa-5 in after somite segmentation in chick. Hoxa-5 mRNA is expressed in posterior cervical somites, and within them is restricted mainly to a sub-domain of lateral sclerotome. RNAi-based knockdown leads to cartilage defects in lateral vertebral elements (rib homologous structures) whose morphologies vary within and outside of the Hoxa-5 expression domain. Both knockdown and misexpression suggest that Hoxa-5 acts via negative regulation of Sox-9. Further, Hoxa-5 misexpression suggests that spatial and/or temporal restriction of Hoxa-5 expression is necessary for proper vertebral morphology. Finally, the restriction of Hoxa-5 expression to lateral sclerotome, which we hypothesize is important for its patterning function, involves regulation by signaling pathways that pattern somites, Fgf-8 and Shh.

The Preparation, Structural Characteristics, and Physical Chemical Properties of Metal-Nitrosyl Complexes.

The preparation and characterization of a representative group of novel non-heme metal nitrosyl complexes that have been synthesized over the last decade are discussed here. Their structures are examined and classified based on metal type, the number of metal centers present, and the type of ligand that is coordinated with the metal. The ligands can be phosphorus, nitrogen, or sulfur based (with a few exceptions) and can vary depending on the presence of chelation, intermolecular forces, or the presence of other ligands. Structural and bonding characteristics are summarized and examples of reactivity regarding nitrosyl ligands are given. Some of the relevant physical chemical properties of these complexes, including IR, EPR, NMR, UV-vis, cyclic voltammetry, and X-ray crystallography are examined.