Tunable Oxygen Activation for Catalytic Organic Oxidation: Schottky Junction versus Plasmonic Effects

The charge state of the Pd surface is a critical parameter in terms of the ability of Pd nanocrystals to activate O₂ to generate a species that behaves like singlet O₂ both chemically and physically. Motivated by this finding, we designed a metal–semiconductor hybrid system in which Pd nanocrystals enclosed by {100} facets are deposited on TiO₂ supports. Driven by the Schottky junction, the TiO₂ supports can provide electrons for metal catalysts under illumination by appropriate light. Further examination by ultrafast spectroscopy revealed that the plasmonics of Pd may force a large number of electrons to undergo reverse migration from Pd to the conduction band of TiO₂ under strong illumination, thus lowering the electron density of the Pd surface as a side effect. We were therefore able to rationally tailor the charge state of the metal surface and thus modulate the function of Pd nanocrystals in O₂ activation and organic oxidation reactions by simply altering the intensity of light shed on Pd–TiO₂ hybrid structures.     

Mechanistic Insights into the Interface‐Directed Transformation of Thiols into Disulfides and Molecular Hydrogen by Visible‐Light Irradiation of Quantum Dots

Quantum dots (QDs) offer new and versatile ways to harvest light energy. However, there are few examples involving the utilization of QDs in organic synthesis. Visible‐light irradiation of CdSe QDs was found to result in virtually quantitative coupling of a variety of thiols to give disulfides and H₂ without the need for sacrificial reagents or external oxidants. The addition of small amounts of nickel(II) salts dramatically improved the efficiency and conversion through facilitating the formation of hydrogen atoms, thereby leading to faster regeneration of the ground‐state QDs. Mechanistic studies reveal that the coupling reaction occurs on the QD surfaces rather than in solution and offer a blueprint for how these QDs may be used in other photocatalytic applications. Because no sacrificial agent or oxidant is necessary and the catalyst is reusable, this method may be useful for the formation of disulfide bonds in proteins as well as in other systems sensitive to the presence of oxidants.     

Constraining Cyclic Peptides To Mimic Protein Structure Motifs

Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well‐defined three‐dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable protein‐like structures in water. However, short peptides can be induced to fold into protein‐like bioactive conformations (strands, helices, turns) by cyclization, in conjunction with the use of other molecular constraints, that helps to fine‐tune three‐dimensional structure. Such constrained cyclic peptides can have protein‐like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three‐dimensional structures of strand, turn or helical segments of peptides and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic peptidomimetics that refine peptide structure and confer biological properties.     

Mechanically Interlocked Single‐Wall Carbon Nanotubes

Extensive research has been devoted to the chemical manipulation of carbon nanotubes. The attachment of molecular fragments through covalent‐bond formation produces kinetically stable products, but implies the saturation of some of the C? C double bonds of the nanotubes. Supramolecular modification maintains the structure of the SWNTs but yields labile species. Herein, we present a strategy for the synthesis of mechanically interlocked derivatives of SWNTs (MINTs). In the key rotaxane‐forming step, we employed macrocycle precursors equipped with two π‐extended tetrathiafulvalene SWNT recognition units and terminated with bisalkenes that were closed around the nanotubes through ring‐closing metathesis (RCM). The mechanically interlocked nature of the derivatives was probed by analytical, spectroscopic, and microscopic techniques, as well as by appropriate control experiments. Individual macrocycles were observed by HR STEM to circumscribe the nanotubes.     

An Aluminophosphate Molecular Sieve with 36 Crystallographically Distinct Tetrahedral Sites

The structure of the new medium‐pore aluminophosphate molecular sieve PST‐6 is determined by the combined use of rotation electron diffraction tomography, synchrotron X‐ray powder diffraction, and computer modeling. PST‐6 was prepared by calcination of another new aluminophosphate material with an unknown structure synthesized using diethylamine as a structure‐directing agent, which is thought to contain bridging hydroxy groups. PST‐6 has 36 crystallographically distinct tetrahedral sites in the asymmetric unit and is thus crystallographically the most complex zeolitic structure ever solved.     

Highly Enantioselective Construction of Tricyclic Derivatives by the Desymmetrization of Cyclohexadienones

The asymmetric synthesis of tricyclic compounds by the desymmetrization of cyclohexadienones is presented. The reaction tolerated a large variety of substituents at different positions of the cyclohexadienone, and heterocyclic rings of different sizes were accessible. Density functional theory calculations showed that the reaction proceeds through an asynchronous [4+2] cycloaddition.     

Optical Control of Acetylcholinesterase with a Tacrine Switch

Photochromic ligands have been used to control a variety of biological functions, especially in neural systems. Recently, much effort has been invested in the photocontrol of ion channels and G‐protein coupled receptors found in the synapse. Herein, we describe the expansion of our photopharmacological approach toward the remote control of an enzyme. Building on hallmark studies dating from the late 1960s, we evaluated photochromic inhibitors of one of the most important enzymes in synaptic transmission, acetylcholinesterase (AChE). Using structure‐based design, we synthesized several azobenzene analogues of the well‐known AChE inhibitor tacrine (THA) and determined their effects on enzymatic activity. One of our compounds, AzoTHA, is a reversible photochromic blocker of AChE in vitro and ex vivo with high affinity and fast kinetics. As such, AzoTHA can be used to control synaptic transmission on the neuromuscular endplate based on the light‐dependent clearance of a neurotransmitter.     

Characterizing Methyl‐Bearing Side Chain Contacts and Dynamics Mediating Amyloid β Protofibril Interactions Using 13Cmethyl‐DEST and Lifetime Line Broadening

Many details pertaining to the formation and interactions of protein aggregates associated with neurodegenerative diseases are invisible to conventional biophysical techniques. We recently introduced ¹⁵N dark‐state exchange saturation transfer (DEST) and ¹⁵N lifetime line‐broadening to study solution backbone dynamics and position‐specific binding probabilities for amyloid β (Aβ) monomers in exchange with large (2–80 MDa) protofibrillar Aβ aggregates. Here we use ¹³C_methyl DEST and lifetime line‐broadening to probe the interactions and dynamics of methyl‐bearing side chains in the Aβ‐protofibril‐bound state. We show that all methyl groups of Aβ40 populate direct‐contact bound states with a very fast effective transverse relaxation rate, indicative of side‐chain‐mediated direct binding to the protofibril surface. The data are consistent with position‐specific enhancements of ¹³C_methyl‐${R{{{\rm tethered}\hfill \atop 2\hfill}}}$ values in tethered states, providing further insights into the structural ensemble of the protofibril‐bound state.     

Aldehyde‐Assisted Ruthenium(II)‐Catalyzed CH Oxygenations

Versatile ruthenium(II) complexes allow for site‐selective C? H oxygenations with weakly‐coordinating aldehydes. The challenging C? H functionalizations proceed with high chemoselectivity by rate‐determining C? H metalation. The new method features an ample substrate scope, which sets the stage for the step‐economical preparation of various bioactive heterocycles.