Parallel Versus Antiparallel β-Sheet Structure in Cyclic Peptide Hybrids Containing γ- or δ-Cyclic Amino Acids

Cyclic peptides with disc-shaped structures have emerged as potent building blocks for the preparation of new biomaterials in fields ranging from biological to material science. In this work, we analyze in depth the self-assembling properties of a new type of cyclic peptides based on the alternation of α-residues and cyclic δ-amino acids (α,δ-CPs). To examine the preferred stacking properties adopted by cyclic peptides bearing this type of amino acids, we carried out a synergistic in vitro/in silico approximation by using simple dimeric models and then extended to nanotubes. Although these new cyclic peptides (α,δ-CPs) can interact either in a parallel or antiparallel fashion, our results confirm that although the parallel β-sheet is more stable, it can be switched to the antiparallel stacking by choosing residues that can establish favorable cross-strand interactions. Moreover, the subsequent comparison by using the same methodology but applied to α,γ-CPs models, up to the moment assumed as antiparallel-like d,l -α-CPs, led to unforeseen conclusions that put into question preliminary conjectures about these systems. Surprisingly, they tend to adopt a parallel β-sheet directed by the skeleton interactions. These results imply a change of paradigm with respect to cyclic peptide designs that should be considered for dimers and nanotubes.     

Sulfinyl-Mediated Stereoselective Functionalization of Acyclic Conjugated Dienes

The chemo- and stereocontrolled functionalization of conjugated sulfinyl dienes in a cascade process that involves a conjugate addition, diastereoselective protonation and a [2,3]-sigmatropic rearrangement is reported. Enantioenriched 1,4-diol and 1,4-aminoalcohol derivatives are obtained in a very straightforward manner. Further functionalization of these structures, including highly stereoselective epoxidation, dihydroxylation and the stereodivergent synthesis of several polyols in a controlled fashion is described.     

Development of a Neutral Diketopyrrolopyrrole Phosphine Oxide for the Selective Bioimaging of Mitochondria at the Nanomolar Level

Development of novel bioimaging materials that exhibit organelle specific accumulation continues to be at the forefront of research interests and efforts. Among the various subcellular organelles, mitochondria, which are found in the cytoplasm of eukaryotic cells, are of particular interest in relation to their vital function. To date, most molecular probes that target mitochondria utilise delocalised lipophilic cations such as triphenylphosphonium and pyridinium. However, the use of such charged motifs is known to be detrimental to the working function of the mitochondrial transmembrane potential and there remains a strong case for development of neutral mitochondrial fluorescent probes. Herein, we demonstrate for the first time the exploitation of diketopyrrolopyrrole-based chemistries for the realisation of a neutral fluorescent probe that exhibits organelle specific accumulation within the mitochondria at the nanomolar level. The synthesised probe, which bears a neutral triphenylphosphine oxide moiety, exhibits a large Stokes shift and high fluorescence quantum yield in water, both highly sought-after properties in the development of bioimaging agents. In vitro studies reveal no interference with cell metabolism when tested for the human MCF7 breast cancer cell and nanomolar subcellular organelle colocalisation with commercially available mitochondrial staining agent Mitotracker Red. In light of its novelty, neutral structure and the preferential accumulation at nanomolar concentrations we anticipate this work to be of significant interest for the increasingly larger community devoted to the realisation of neutral mitochondrial selective systems and more widely to those engaged in the rational development of superior organic architectures in the biological field.     

Explaining Cu@Pt Bimetallic Nanoparticles Activity Based on NO Adsorption

Cu@Pt nanoparticles (NPs) are experimentally regarded as improved catalysts for NO_x storage/reduction, with higher activities and selectivities compared with pure Pt or Cu NPs, and with inverse Pt@Cu NPs. Here, a density functional theory-based study on such NP models with different sizes and shapes reveals that the observed enhanced stability of Cu@Pt compared with Pt@Cu NPs is due to energetic reasons. On both types of core@shell NPs, charge is transferred from Cu to Pt, strengthening the NP cohesion energy in Pt@Cu NPs, and spreading charge along the surface in Cu@Pt NPs. The negative surface Pt atoms in the latter diminish the NO bonding owing to an energetic rise of the Pt bands, as detected by the appliance of the d-band model, although other factors, such as atomic low coordination or the presence of an immediate subsurface Pt atom do as well. A charge density difference analysis discloses a donation/back-donation mechanism in the NO adsorption.     

Ambident Reactivity of Imidazolium Cations as Evidence of the Dynamic Nature of N-Heterocyclic Carbene-Mediated Organocatalysis

This work reveals ambident nucleophilic reactivity of imidazolium cations towards carbonyl compounds at the C2 or C4 carbene centers depending on the steric properties of the substrates and reaction conditions. Such an adaptive behavior indicates the dynamic nature of organocatalysis proceeding via a covalent interaction of imidazolium carbenes with carbonyl substrates and can be explained by generation of the H-bonded ditopic carbanionic carbenes.     

Which Stereoinductor Is Better for Asymmetric Functionalization of α-Amino Acids in a Nickel(II) Coordination Environment? Experimental and DFT Considerations

The results of extended comparative investigation of nickel(II) Schiff base complexes (containing various auxiliary chiral moieties) commonly used as a methodological platform for the asymmetric synthesis of tailor-made α-amino acids are provided. The following issues are addressed: 1) redox activity (determining the possibility for electrochemically induced reactions); 2) quantitative estimation of the reactivity of deprotonated complexes towards electrophiles; and 3) quantum-chemical estimation of noncovalent interactions in the metal coordination environment (which shed light on the origin of the stereochemical outcome observed for different stereoinductors). Possible mechanisms that determine the relationship between the stereochemical configuration of a molecule and its electronic structure are discussed. The DFT-calculated HOMO–LUMO energies and localization, as well as relative energies for the (S)- and (R)-alanine derivatives, that determine the stereoinduction efficiency in thermodynamically controlled reactions in nickel(II) coordination are provided. The computational data are supported by experimental results on the monobenzylation of glycine derivatives.     

Enantioselective Synthesis of Polycyclic Aromatic Hydrocarbon (PAH)-Based Planar Chiral Bent Cyclophanes by Rhodium-Catalyzed [2+2+2] Cycloaddition

The enantioselective synthesis of polycyclic aromatic hydrocarbon (PAH)-based planar chiral cyclophanes was achieved for the first time by the rhodium-catalyzed intramolecular regio- and enantioselective [2+2+2] cycloaddition of tethered diyne-benzofulvenes followed by stepwise oxidative transformations. The thus synthesized planar chiral bent cyclophanes, that possess bent p-terphenyl- and 9-fluorenone-cores, were converted to 9-fluorenol-based ones with excellent ee values of >99 % by diastereoselective 1,2-reduction. These 9-fluorenol-based cyclophanes exhibited high fluorescence quantum yields, which were significantly higher than that of an acyclic reference molecule (78–82 % vs. 48 %). The bending effect on the chiroptical property was also examined, which revealed that the anisotropy factors (g_abs values) for electronic circular dichroism (ECD) of these 9-fluorenol-based planar chiral bent cyclophanes increase as the tether length becomes shorter.     

Conformational Studies of Oligosaccharides

The conformation of a molecule strongly affects its function, as demonstrated for peptides and nucleic acids. This correlation is much less established for carbohydrates, the most abundant organic materials in nature. Recent advances in synthetic and analytical techniques have enabled the study of carbohydrates at the molecular level. Recurrent structural features were identified as responsible for particular biological activities or material properties. In this Minireview, recent achievements in the structural characterization of carbohydrates, enabled by systematic studies of chemically defined oligosaccharides, are discussed. These findings can guide the development of more potent glycomimetics. Synthetic carbohydrate materials by design can be envisioned.