Peptide‐Coated Platinum Nanoparticles with Selective Toxicity against Liver Cancer Cells

Peptide‐stabilized platinum nanoparticles (PtNPs) were developed that have significantly greater toxicity against hepatic cancer cells (HepG2) than against other cancer cells and non‐cancerous liver cells. The peptide H‐Lys‐Pro‐Gly‐d Lys‐NH₂ was identified by a combinatorial screening and further optimized to enable the formation of water‐soluble, monodisperse PtNPs with average diameters of 2.5 nm that are stable for years. In comparison to cisplatin, the peptide‐coated PtNPs are not only more toxic against hepatic cancer cells but have a significantly higher tumor cell selectivity. Cell viability and uptake studies revealed that high cellular uptake and an oxidative environment are key for the selective cytotoxicity of the peptide‐coated PtNPs.     

Black Phosphorus: Bioactive Nanomaterials with Inherent and Selective Chemotherapeutic Effects

Black phosphorus nanosheets (BPs) are demonstrated to be highly bioactive anti‐cancer agents because of their inherent and selective chemotherapeutic effects. Fast intracellular biodegradation of BPs and acute elevation of phosphate anions were observed from different types of cancer cells due to the stronger intracellular oxidative stress and accelerated energy metabolism, but normal cells are not affected. Selective biodegradation of BPs induced G2/M phase arrest and subsequent apoptosis‐ and autophagy‐mediated cell death in cancer cells but not normal cells. The selectivity was superior to that of the traditional chemotherapeutic agent, doxorubicin (DOX). In vivo assessment confirmed the efficiency of BPs in suppressing tumor growth. This study provides insights into nanostructured bioactive anti‐cancer agents and reveals a new direction for nanomedicine research.     

Lewis Acid–Base Interaction‐Controlled ortho‐Selective C−H Borylation of Aryl Sulfides

An iridium/bipyridine‐catalyzed ortho ‐selective C−H borylation of aryl sulfides was developed. High ortho ‐selectivity was achieved by a Lewis acid–base interaction between a boryl group of the ligand and a sulfur atom of the substrate. This is the first example of a catalytic and regioselective C−H transformation controlled by a Lewis acid–base interaction between a ligand and a substrate. The C−H borylation reaction could be conducted on a gram scale, and with a bioactive molecule as a substrate, demonstrating its applicability to late‐stage regioselective C−H borylation. A bioactive molecule was synthesized from an ortho ‐borylated product by converting the boryl and methylthio groups of the product.     

Hydroformylation of Alkenes in a Planetary Ball Mill: From Additive‐Controlled Reactivity to Supramolecular Control of Regioselectivity

The Rh‐catalyzed hydroformylation of aromatic‐substituted alkenes is performed in a planetary ball mill under CO/H₂ pressure. The dispersion of the substrate molecules and the Rh‐catalyst into the grinding jar is ensured by saccharides: methyl‐α‐d ‐glucopyranoside, acyclic dextrins, or cyclodextrins (CDs, cyclic oligosaccharides). The reaction affords the exclusive formation of aldehydes whatever the saccharide. Acyclic saccharides disperse the components within the solid mixture leading to high conversions of alkenes. However, they showed typical selectivity for α‐aldehyde products. If CDs are the dispersing additive, the steric hindrance exerted by the CDs on the primary coordination sphere of the metal modifies the selectivity so that the β‐aldehydes were also formed in non‐negligible proportions. Such through‐space control via hydrophobic effects over reactivity and regioselectivity reveals the potential of such solventless process for catalysis in solid state.     

Insights into Mechanochemical Reactions at Targetable and Stable,Sub‐ambient Temperatures

We provide insights into the effects of stable and verifiable, low‐temperature conditions on mechanochemical reactions. These are made possible by modifications made to a SPEX 8000 m Mixer/mill allowing reliable fine control of low‐temperature mechanochemical reactions. Using the reduction of 4‐tert‐butylcyclohexanone as a model system we find the diastereomeric product distribution bore a strong dependence on the selected temperature. The same reduction in methanol at room temperature shows similar stereoselectivity trends. In both cases decreasing temperature favors increases in selectivity, although the effect is more pronounced in the solvent‐free mechanochemical conditions. These results indicate that the cooled jar provides a heatsink to mitigate the exothermic character of the reaction. Stereoselectivity also showed a dependence on operating frequency, although the nature of this dependence remains unclear. Applications of our reactor extend far beyond what is presented herein.     

Selective Emergence of the Halogen Bond in Ground and Excited States of Noble‐Gas–Chlorine Systems

Molecular‐beam scattering experiments and theoretical calculations prove the nature, strength, and selectivity of the halogen bonds (XB) in the interaction of halogen molecules with the series of noble gas (Ng) atoms. The XB, accompanied by charge transfer from the Ng to the halogen, is shown to take place in, and measurably stabilize, the collinear conformation of the adducts, which thus becomes (in contrast to what happens for other Ng‐molecule systems) approximately as bound as the T‐shaped form. It is also shown how and why XB is inhibited when the halogen molecule is in the ³Π_u excited state. A general potential formulation fitting the experimental observables, based on few physically essential parameters, is proposed to describe the interaction accurately and is validated by ab initio computations.     

Biased Lewis Pairs: A General Catalytic Approach to Ether‐Ester Block Copolymers with Unlimited Ordering of Sequences

Polymerizing epoxides after cyclic esters remains a major challenge, though their block copolymers have been extensively studied and used for decades. Reported here is a simple catalytic approach based on a metal‐free Lewis pair that addresses the challenge. When the Lewis acid is used in excess of a base, selective (transesterification‐free) polymerization of epoxides occurs in the presence of esters, while selectivity toward cyclic esters is achieved by an oppositely biased catalyst. Hence, one‐pot block copolymerization can be performed in both ester‐first and ether‐first orders with selectivity being switchable at any stage, yielding ether‐ester‐type block copolymers with unlimited ordering of sequences as well as widely variable compositions and architectures. The selectivity can also be switched back and forth several times to generate a multiblock copolymer. Experimental and calculational results indicate that the selectivity originates mainly from the state of catalyst‐activated hydroxy species.     

Copper‐Catalyzed C(sp3)−H Amidation: Sterically Driven Primary and Secondary C−H Site‐Selectivity

Undirected C(sp³)?H functionalization reactions often follow site‐selectivity patterns that mirror the corresponding C?H bond dissociation energies (BDEs). This often results in the functionalization of weaker tertiary C?H bonds in the presence of stronger secondary and primary bonds. An important, contemporary challenge is the development of catalyst systems capable of selectively functionalizing stronger primary and secondary C?H bonds over tertiary and benzylic C?H sites. Herein, we report a Cu catalyst that exhibits a high degree of primary and secondary over tertiary C?H bond selectivity in the amidation of linear and cyclic hydrocarbons with aroyl azides ArC(O)N₃. Mechanistic and DFT studies indicate that C?H amidation involves H‐atom abstraction from R‐H substrates by nitrene intermediates [Cu](κ²‐N,O‐NC(O)Ar) to provide carbon‐based radicals R^. and copper(II)amide intermediates [Cu^II]‐NHC(O)Ar that subsequently capture radicals R^. to form products R‐NHC(O)Ar. These studies reveal important catalyst features required to achieve primary and secondary C?H amidation selectivity in the absence of directing groups.     

Synthetic Channel Specifically Inserts into the Lipid Bilayer of Gram‐Positive Bacteria but not that of Mammalian Erythrocytes

A series of tubular molecules with different lengths have been synthesized by attaching Trp‐incorporated peptides to the pillar[5]arene backbone. The tubular molecules are able to insert into the lipid bilayer to form unimolecular transmembrane channels. One of the channels has been revealed to specifically insert into the bilayer of the Gram‐positive bacteria. In contrast, this channel cannot insert into the membranes of the mammalian rat erythrocytes even at the high concentration of 100 μm . It was further demonstrated that, as a result of this high membrane selectivity, the channel exhibits efficient antimicrobial activity for the Gram‐positive bacteria and very low hemolytic toxicity for mammalian erythrocytes.     

Silver Films with Hierarchical Chirality

Physical fabrication of chiral metallic films usually results in singular or large‐sized chirality, restricting the optical asymmetric responses to long electromagnetic wavelengths. The chiral molecule‐induced formation of silver films prepared chemically on a copper substrate through a redox reaction is presented. Three levels of chirality were identified: primary twisted nanoflakes with atomic crystal lattices, secondary helical stacking of these nanoflakes to form nanoplates, and tertiary micrometer‐sized circinates consisting of chiral arranged nanoplates. The chiral Ag films exhibited multiple plasmonic absorption‐ and scattering‐based optical activities at UV/Vis wavelengths based on their hierarchical chirality. The Ag films showed chiral selectivity for amino acids in catalytic electrochemical reactions, which originated from their primary atomic crystal lattices.     

Rhodium‐Catalyzed meta‐C−H Functionalization of Arenes

Rhodium‐catalyzed ortho ‐C−H functionalization is well known in the literature. Described herein is the Xphos‐supported rhodium catalysis of meta ‐C−H olefination of benzylsulfonic acid and phenyl acetic acid frameworks with the assistance of a para ‐methoxy‐substituted cyano phenol as the directing group. Complete mono‐selectivity is observed for both scaffolds. A wide range of olefins and functional groups attached to arene are tolerated in this protocol.     

Chiral Phosphoric Acids in Metal–Organic Frameworks with Enhanced Acidity and Tunable Catalytic Selectivity

Chiral phosphoric acids are incorporated into indium‐based metal–organic frameworks (In‐MOFs) by sterically preventing them from coordination. This concept leads to the synthesis of three chiral porous 3D In‐MOFs with different network topologies constructed from three enantiopure 1,1′‐biphenol‐phosphoric acid derived tetracarboxylate linkers. More importantly, all the uncoordinated phosphoric acid groups are periodically aligned within the channels and display significantly enhanced acidity compared to the non‐immobilized acids. This facilitates the Brønsted acid catalysis of asymmetric condensation/amine addition and imine reduction. The enantioselectivities can be tuned (up to >99 % ee) by varying the substituents to achieve a nearly linear correlation with the concentrations of steric bulky groups in the MOFs. DFT calculations suggest that the framework provides a chiral confined microenvironment that dictates both selectivity and reactivity of chiral MOFs.     

Stereospecific α‐Sialylation by Site‐Selective Fluorination

Sialic acids are ubiquitous components of mammalian cell membranes and key regulators of cellular recognition events. Located at the non‐reducing termini of bioactive gangliosides, these essential building blocks are fused to the polysaccharide core via a characteristic α‐linkage, and rarely occur in the monomeric form. Effective chemical strategies to enable α‐sialylation are urgently required to construct well‐defined tools for glycomics. To complement existing chemoenzymatic strategies, an α‐selective process has been devised based on the site‐selective introduction of fluorine at C3 (more than 20 examples, up to 90 % yield). Predicated on localized particle charge inversion (C?H^δ+→C?F^δ?), fluorine insertion simultaneously augments the anomeric effect, enhances electrophilicity at C2 and mitigates elimination. A stereochemical induction model is postulated that spans the S_N continuum and validates the role of the C?F bond in orchestrating α‐selectivity.     

Isolable Silylene Ligands Can Boost Efficiencies and Selectivities in Metal‐Mediated Catalysis

A significant number of isolable silylenes are currently known. They have quickly developed from laboratory curiosities to useful ligands in metal‐mediated homogeneous catalysis. This includes their utilization in various catalytic transformations, such as C?C cross‐coupling, cyclotrimerization, hydroformylation, borylation, deuteration, hydrosilylation, amination, hydrogenation, and transfer semi‐hydrogenation reactions. Recent studies suggest that the silylene ligands surpass the steering properties of their phosphine and N‐heterocyclic carbene (NHC) analogues and provide excellent chemo‐, regio‐, and stereoselectivites. Mechanistic studies suggest that their promoted performance of metal‐mediated catalytic transformations results from a strong σ‐donor character along with cooperative effects of their Si^II centers. This Minireview covers the most recent advances in the field.     

Selective Inhibitors of FKBP51 Employ Conformational Selection of Dynamic Invisible States

The recently discovered SAFit class of inhibitors against the Hsp90 co‐chaperone FKBP51 show greater than 10 000‐fold selectivity over its closely related paralogue FKBP52. However, the mechanism underlying this selectivity remained unknown. By combining NMR spectroscopy, biophysical and computational methods with mutational analysis, we show that the SAFit molecules bind to a transient pocket in FKBP51. This represents a weakly populated conformation resembling the inhibitor‐bound state of FKBP51, suggesting conformational selection rather than induced fit as the major binding mechanism. The inhibitor‐bound conformation of FKBP51 is stabilized by an allosteric network of residues located away from the inhibitor‐binding site. These residues stabilize the Phe67 side chain in a dynamic outward conformation and are distinct in FKBP52, thus rationalizing the basis for the selectivity of SAFit inhibitors. Our results represent a paradigm for the selective inhibition of transient binding pockets.     

Selectivity of Chemical Conversions: Do Light‐Driven Photoelectrocatalytic Processes Hold Special Promise?

One of the great challenges in chemistry is the development of innovative catalytic processes. In this context, significant opportunities are currently opening up for technologies based on electrocatalysis and photoelectrocatalysis, as these can drive various valuable catalytic redox transformations under very mild conditions. However, many catalytic processes lead to various different products of different value, and the technological attractiveness of catalytic processes depends to a large extent on their selectivity towards a specific desired product. In this Viewpoint, I propose and explore the idea that, due to the distinct features of interfacial energetics at illuminated semiconductors, light‐driven photoelectrocatalytic processes at well‐designed semiconductors represent a particularly attractive platform for the development of highly efficient systems for selective catalytic conversions. The investigations of selectivity and synthetic aspects of photoelectrocatalysis should gain momentum, especially as they also promise commercially viable applications on a more immediate time scale as compared to, for example, the light‐driven production of hydrogen.     

Palladium‐Mediated Arylation of Lysine in Unprotected Peptides

A mild method for the arylation of lysine in an unprotected peptide is presented. In the presence of a preformed biarylphosphine‐supported palladium(II)–aryl complex and a weak base, lysine amino groups underwent C−N bond formation at room temperature. The process generally exhibited high selectivity for lysine over other amino acids containing nucleophilic side chains and was applicable to the conjugation of a variety of organic compounds, including complex drug molecules, with an array of peptides. Finally, this method was also successfully applied to the formation of cyclic peptides by macrocyclization.     

Entropically Favoured Assembly of Pyrazine‐Based Helical Fibers into Superstructures: Achiral/ Chiral Guest‐Induced Chirality Transformation

The development of synthetic helical structures undergoing stimuli‐responsive chirality transformations is important for an understanding of the role of chirality in natural systems. However, controlling supramolecular chirality in entropically driven assemblies in aqueous media is challenging. To develop stimuli‐responsive assemblies, we designed and synthesized pyrazine derivatives with l ‐alanine groups as chiral building blocks. These systems undergo self‐assembly in aqueous media to generate helical fibers and the embedded alanine groups transfer their chirality to the assembled structures. Furthermore, these helical fibers undergo a Ni²⁺‐induced chirality transformation. The study demonstrates the role of intermolecular hydrogen bonding, π–π stacking, and the hydrophobic effect in the Ni²⁺‐mediated transition of helical fibers to supercoiled helical ensembles which mimic the formation of superstructures in biopolymers.     

Enantioselective Synthesis of Spiroindenes by Enol‐Directed Rhodium(III)‐Catalyzed C?H Functionalization and Spiroannulation

Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol‐directed C(sp²)‐H functionalization and oxidative annulation with alkynes to give spiroindenes containing all‐carbon quaternary stereocenters. High selectivity between two possible directing groups, as well as control of the direction of rotation in the isomerization of an O‐bound rhodium enolate into the C‐bound isomer, appear to be critical for high enantiomeric excesses.     

Design and Enantioselective Construction of Axially Chiral Naphthyl‐Indole Skeletons

The first enantioselective construction of a new class of axially chiral naphthyl‐indole skeletons has been established by organocatalytic asymmetric coupling reactions of 2‐naphthols with 2‐indolylmethanols (up to 99 % yield, 97:3 e.r.). This approach not only affords a new type of axially chiral heterobiaryl backbone, but also provides a new catalytic enantioselective strategy for constructing axially chiral biaryl scaffolds by making use of the C3‐electrophilicity of 2‐indolylmethanols.