Trans/cis isomerization of Xaa-Pro bonds is key for the structure and function of several enzymes. In recent years, numerous versatile peptidic catalysts have been developed that bear Xaa-Pro amide bonds. Due to the many degrees of freedom within even short peptides, the design and optimization of peptidic catalysts by rational structural modifications is difficult. We envisioned that control over the trans/cis amide bond ratio may provide a tool to optimize the catalytic performance of peptidic catalysts. Here, we investigated the influence of the amide bond conformation on the stereoselectivity of H-Pro-Pro-Xaa-NH-type peptidic catalysts in conjugate addition reactions. The middle Pro residue within the tripeptides was replaced with analogues of varying ring sizes (azetidine carboxylic acid, Aze, and piperidine carboxylic acid, Pip) to produce different trans/cis ratios in different solvents. The studies revealed a direct correlation between the trans/cis amide bond ratio and the enantio- and diastereoselectivity of structurally related peptidic catalysts. These insights led to the identification of H-d-Pro-Pip-Glu-NH as a highly reactive and stereoselective amine-based catalyst that allows C-C bond formations to be performed in the presence of as little as 0.05 mol %, which is the lowest catalyst loading yet achieved for organocatalyzed reactions that rely on an enamine-based mechanism.

The periplasmic cytochrome cd1 nitrite reductase NirS occurring in denitrifying bacteria such as the human pathogen Pseudomonas aeruginosa contains the essential tetrapyrrole cofactors haem c and haem d1. Whereas the haem c is incorporated into NirS by the cytochrome c maturation system I, nothing is known about the insertion of the haem d1 into NirS. Here, we show by co-immunoprecipitation that NirS interacts with the potential haem d1 insertion protein NirN in vivo. This NirS–NirN interaction is dependent on the presence of the putative haem d1 biosynthesis enzyme NirF. Further, we show by affinity co-purification that NirS also directly interacts with NirF. Additionally, NirF is shown to be a membrane anchored lipoprotein in P. aeruginosa. Finally, the analysis by UV–visible absorption spectroscopy of the periplasmic protein fractions prepared from the P. aeruginosa WT (wild-type) and a P. aeruginosa ΔnirN mutant shows that the cofactor content of NirS is altered in the absence of NirN. Based on our results, we propose a potential model for the maturation of NirS in which the three proteins NirS, NirN and NirF form a transient, membrane-associated complex in order to achieve the last step of haem d1 biosynthesis and insertion of the cofactor into NirS.

Despite impressive advances in the construction of metal–organic frameworks (MOFs), the formation of networks from peptidic ligands is difficult, though they are sought after for their modularity and biocompatibility. Herein we present a peptide–metal framework that consists of helical oligo­proline ligands and Zn/K (or Zn/Rb). The crystalline network contains pleated nanosheets with the metal ions aligned in strings. This unprecedented architecture derives from under-appreciated London dispersion interactions between the oligo­proline ligands that play in concert with the metal coordination to create the network. Hence, the secondary structure of the peptidic ligand represents an additional control element for the creation of new MOF architectures. We anticipate that our results will instruct the design of further peptidic MOFs and enable the generation of versatile biocompatible materials.

Chiral secondary amines are valuable catalysts for reactions that proceed through an enamine intermediate. Here, we explored the importance of the pyramidalization direction of the enamine-N on the reactivity of chiral enamines with a combination of computational, NMR spectroscopic, and kinetic experiments. Studies with peptidic catalysts that bear cyclic amines with different ring sizes revealed that endo-pyramidalized enamines are significantly more reactive compared to exo-pyramidalized analogs. The results show that the pyramidalization direction can have a greater effect than n/p* orbital overlap on the reactivity of chiral enamines. The data enabled the development of a catalyst with higher reactivity compared to the parent catalyst. Scheme 1 (a) Secondary amine catalyzed addition reaction of aldehydes to electrophiles. (b) Anti-attack of enamine. (c) Equilibrium between endo and exo pyramidalized enamines. Scheme 2 (a) Conjugate addition reaction of butanal to nitrostyrene catalyzed by 2a, 2 and 2b. (b) In situ IR monitoring of the formation of g-nitroaldehyde, and (c) Arrhenius plot and activation energy of the peptide catalyzed reactions.This journal is

Many stereoselective peptide catalysts have been established. They consist, like nature’s catalysts, of amino acids but have significantly lower molecular weights than enzymes. Whereas enzymes operate with exquisite chemoselectivity in...

Despite intense interest in amine-catalyzed stereoselective reactions, high catalyst loadings of ≥10 mol % are still common and either due to low reactivity or catalyst deactivation. Yet, few deactivation pathways are well understood. Here, we unraveled the deactivation of secondary amines by undesired aldol reaction. Mechanistic studies with peptide and prolinol silyl ether catalysts showed the generality of this so-far underappreciated catalyst deactivation pathway. The insights enabled conjugate addition reactions between aldehydes and nitroolefins on a multigram scale in the absence of solventconditions that are attractive as environmentally benign processeswith excellent product yields and stereoselectivities in the presence of as little as 0.1 mol % of a chemoselective peptidic catalyst.

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Supramolecular copolymers formed by the noncovalent synthesis of multiple components expand the complexity of functional molecular systems. However, varying the composition and microstructure of copolymers through tuning the interactions between building blocks remains a challenge. Here, we report a remarkable discovery of the temperature-dependent supramolecular copolymerization of the two chiral monomers 4,4′,4″-(1,3,5triazine-2,4,6-triyl)tribenzamide (S-T) and 4,4′,4″-(benzene-1,3,5-triyl)tribenzamide (S-B). We first demonstrate in the homopolymerization of the two individual monomers that a subtle change from the central triazine to benzene in the chemical structure of the monomers significantly affects the properties of the resulting homopolymers in solution. Homopolymers formed by S-T exhibit enhanced stability in comparison to S-B. More importantly, through a combination of spectroscopic analysis and theoretical simulation, we reveal the complex process of copolymerization: S-T aggregates into homopolymers at elevated temperature, and upon slow cooling S-B gradually intercalates into the copolymers, to finally give copolymers with almost 80% alternating bonds at 10 °C. The formation of the predominantly alternating copolymers is plausibly contributed by preferred heterointeractions between triazine and benzene cores in S-T and S-B, respectively, at lower temperatures. Overall, this work unravels the complexity of a supramolecular copolymerization process where an intermediate heterointeraction (higher than one homointeraction and lower than the other homointeraction) presents and proposes a general method to elucidate the microstructures of copolymers responsive to temperature changes.