Flexible Zirconium Metal‐Organic Frameworks as Bioinspired Switchable Catalysts

Flexible metal–organic frameworks (MOFs) are highly desirable in host–guest chemistry owing to their almost unlimited structural/functional diversities and stimuli‐responsive pore architectures. Herein, we designed a flexible Zr‐MOF system, namely PCN‐700 series, for the realization of switchable catalysis in cycloaddition reactions of CO₂ with epoxides. Their breathing behaviors were studied by successive single‐crystal X‐ray diffraction analyses. The breathing amplitudes of the PCN‐700 series were modulated through pre‐functionalization of organic linkers and post‐synthetic linker installation. Experiments and molecular simulations confirm that the catalytic activities of the PCN‐700 series can be switched on and off upon reversible structural transformation, which is reminiscent of sophisticated biological systems such as allosteric enzymes.     

Cyano‐Schmittel Cyclization through Base‐Induced Propargyl‐Allenyl Isomerization: Highly Modular Synthesis of Pyridine‐Fused Aromatic Derivatives

The cyano‐Schmittel cyclization of in situ‐generated cyano‐allenes has been carried out. The DFT calculation results suggest that the diradical pathway plays a major role in this cyclization. The reactions can be conveniently performed in a one‐pot manner through cascade Sonogashira coupling of terminal cyano‐ynes with organic halides, followed by base‐promoted propargyl‐allenyl isomerization/cyclization, leading to an efficient access to pyridine‐fused polycyclic architectures. In particular, a large variety of aryl or heteroaryl rings such as furans, thiophenes and pyridines can be incorporated into the follow‐up cyano‐Diels–Alder reactions, highlighting the great synthetic utility of this chemistry.     

Hypercrosslinked Phenolic Polymers with Well‐Developed Mesoporous Frameworks

A soft chemistry synthetic strategy based on a Friedel–Crafts alkylation reaction is developed for the textural engineering of phenolic resin (PR) with a robust mesoporous framework to avoid serious framework shrinkage and maximize retention of organic functional moieties. By taking advantage of the structural benefits of molecular bridges, the resultant sample maintains a bimodal micro‐mesoporous architecture with well‐preserved organic functional groups, which is effective for carbon capture. Moreover, this soft chemistry synthetic protocol can be further extended to nanotexture other arene‐based polymers with robust frameworks.     

Transition‐Metal‐Mediated and ‐Catalyzed C−F Bond Activation by Fluorine Elimination

The activation of carbon–fluorine (C?F) bonds is an important topic in synthetic organic chemistry. Metal‐mediated and ‐catalyzed elimination of β‐ or α‐fluorine proceeds under milder conditions than oxidative addition to C?F bonds. The β‐ or α‐fluorine elimination is initiated from organometallic intermediates having fluorine substituents on carbon atoms β or α to metal centers, respectively. Transformations through these elimination processes (C?F bond cleavage), which are typically preceded by carbon–carbon (or carbon–heteroatom) bond formation, have been increasingly developed in the past five years as C?F bond activation methods. In this Minireview, we summarize the applications of transition‐metal‐mediated and ‐catalyzed fluorine elimination to synthetic organic chemistry from a historical perspective with early studies and from a systematic perspective with recent studies.     

Aqueous Anion Receptors through Reduction of Subcomponent Self‐Assembled Structures

To prepare new functional covalent architectures that are difficult to synthesize using conventional organic methods, we developed a strategy that employs metal–organic assemblies as precursors, which are then reduced and demetalated. The host–guest chemistry of the larger receptor thus prepared was studied using NMR spectroscopy and fluorescence experiments. This host was observed to strongly bind aromatic polyanions in water, including the fluorescent dye molecule pyranine with nanomolar affinity, thus allowing for the design of an indicator‐displacement assay.     

Recent Advances in Radical‐Mediated C—C Bond Fragmentation of Non‐Strained Molecules

The carbon‐carbon (C—C) σ‐bonds construct the fundamental frameworks of organic molecules. The direct functionalization of C—C bonds represents one of the most efficient and step‐economical transformations in synthetic chemistry. The past few decades have witnessed the fast development of transition‐metal mediated C—C bond activation. In contrast, the radical‐promoted C—C bond cleavage has received relatively less attention. As the occurrence of ring strain significantly facilitates the fission of cyclic C—C bonds via radical approaches, the strain relief‐driven C—C bond activation mostly relies on the three‐ and four‐membered rings. The C—C activation of non‐strained molecules such as medium‐ or large‐sized rings and linear alkanes remains challenging. In this review, we will focus on the recent advances in radical‐mediated C—C bond activation of non‐strained molecules. Herein, the alkoxy‐ and iminyl‐radical triggered scission of non‐strained C—C bonds and C—C cleavage via the strategy of remote functional group migration is summarized.     

Interpenetrated Cage Structures

This Review covers design strategies, synthetic challenges, host–guest chemistry, and functional properties of interlocked supramolecular cages. Some dynamic covalent organic structures are discussed, as are selected examples of interpenetration in metal–organic frameworks, but the main focus is on discrete coordination architectures, that is, metal‐mediated dimers. Factors leading to interpenetration, such as geometry, flexibility and chemical makeup of the ligands, coordination environment, solvent effects, and selection of suitable counter anions and guest molecules, are discussed. In particular, banana‐shaped bis‐pyridyl ligands together with square‐planar metal cations have proven to be suitable building blocks for the construction of interpenetrated double‐cages obeying the formula [M₄L₈]. The peculiar topology of these double‐cages results in a linear arrangement of three mechanically coupled pockets. This allows for the implementation of interesting guest encapsulation effects such as allosteric binding and template‐controlled selectivity. In stimuli‐responsive systems, anionic triggers can toggle the binding of neutral guests or even induce complete structural conversions. The increasing structural and functional complexity in this class of self‐assembled hosts promises the construction of intelligent receptors, novel catalytic systems, and functional materials.     

Synthesis of Extended π‐Systems through C–H Activation

Activation of aromatic C? H bonds by a transition metal catalyst has received significant attention in the synthetic chemistry community. In recent years, rapid and site‐selective extension of π‐electron systems by C–H activation has emerged as an ideal methodology for preparing organic materials with extended π‐systems. This Review focuses on recently reported π‐extending C–H activation reactions directed toward new optoelectronic conjugated materials.     

Design and Applications of Protein‐Cage‐Based Nanomaterials

Materials science is beginning to focus on biotemplation, and in support of that trend, it is realized that protein cages—proteins that assemble from multiple monomers into architectures with hollow interiors—can instill a number of unique advantages to nanomaterials. In addition, the structural and functional plasticity of many protein‐cage systems permits their engineering for specific applications. In this review, the most commonly used viral and non‐viral protein cages, which exhibit a wide diversity of size, functionality, and chemical and thermal stabilities, are described. Moreover, how they have been exploited for nanomaterial and nanotechnology applications is summarized.     

Rare‐Earth‐Metal Methylidene Complexes

Transition‐metal carbene complexes have been known for about 50 years and widely applied as reagents and catalysts in organic transformations. In contrast, the carbene chemistry of the rare‐earth metals is much less developed, but has attracted the research interest in the recent years. In this field rare‐earth‐metal alkylidene, especially methylidene, compounds are an emerging class of compounds with a high synthetic potential for organometallic chemistry and maybe in the future also for organic chemistry.     

Protein Organic Chemistry and Applications for Labeling and Engineering in Live‐Cell Systems

The modification of proteins with synthetic probes is a powerful means of elucidating and engineering the functions of proteins both in vitro and in live cells or in vivo. Herein we review recent progress in chemistry‐based protein modification methods and their application in protein engineering, with particular emphasis on the following four strategies: 1) the bioconjugation reactions of amino acids on the surfaces of natural proteins, mainly applied in test‐tube settings; 2) the bioorthogonal reactions of proteins with non‐natural functional groups; 3) the coupling of recognition and reactive sites using an enzyme or short peptide tag–probe pair for labeling natural amino acids; and 4) ligand‐directed labeling chemistries for the selective labeling of endogenous proteins in living systems. Overall, these techniques represent a useful set of tools for application in chemical biology, with the methods 2–4 in particular being applicable to crude (living) habitats. Although still in its infancy, the use of organic chemistry for the manipulation of endogenous proteins, with subsequent applications in living systems, represents a worthy challenge for many chemists.     

Transformations of Modified Morita‐Baylis‐Hillman Adducts from Isatins Catalyzed by Lewis Bases

The development of synthetic protocols to access architectures with broad structural and functional diversity from readily available starting materials is very attractive in both organic and medicinal chemistry fields. Toward this objective, the multifunctional isatin‐derived Morita‐Baylis‐Hillman (MBH) adducts provide opportunities to construct a variety of complex scaffolds containing a “privileged” oxindole motif through several catalytic pathways. By forming the ammonium or phosphonium salts with Lewis bases, isatin‐derived MBH adducts can undergo allylic substitutions with a range of nucleophiles, usually in a S_N2′‐S_N2′ pattern. Besides, assisted by Brønsted bases, the corresponding onium salts can be converted into the allylic ylide intermediates, which can undergo various annulation reactions or even 1,3‐difunctionalizations. Moreover, recent cooperative catalysis of Lewis bases and transition metal complexes further puts forward the application of isatin‐derived MBH adducts. This tutorial review covers the significant transformations of isatin‐derived MBH adducts, mostly in an asymmetric version, catalyzed by various Lewis bases over the past decade.     

Silicon‐Based Bulky Group‐Induced Remote Control and Conformational Preference in the Synthesis and Application of Isolable Atropisomeric Amides with Secondary Alcohol or Amine Moieties

Remote stereocontrol through conformational transmission along a carbon chain is highly important in synthetic systems and molecular architectures. In this work, the interactional reactivity between a remote silicon‐based bulky group and an O‐/N‐containing functional group has been revealed and determined by lateral lithiation–substitution, desilylation, as well as desilylation–olefination with benzaldehyde. The results suggest considerable information transmission and steric hindrance that can be exploited for the controllable synthesis of atropisomeric molecules. Based on the remote steric effect of a functional group across the aromatic ring of an amide, the construction of isolable atropisomeric amides with functional groups, such as alcohol, amine, and olefin was successfully achieved. All these new atropisomers were obtained in reasonable yield in pure diastereomeric form, and the specific configuration of representative products was confirmed by X‐ray crystallography.     

Supramolecular Diblock Copolymers Featuring Well‐defined Telechelic Building Blocks

We report supramolecular AB diblock copolymers comprised of well‐defined telechelic building blocks. Helical motifs, formed via reversible addition‐fragmentation chain‐transfer (RAFT) or anionic polymerization, are assembled with coil‐forming and sheet‐featuring blocks obtained via atom‐transfer radical polymerization (ATRP) or ring‐opening metathesis polymerization (ROMP). Interpolymer hydrogen bonding or metal‐coordination achieves dynamic diblock architectures featuring hybrid topologies of coils, helices, and/or π‐stacked sheets that, on a basic level, mimic protein structural motifs in fully synthetic systems. The intrinsic properties of each block (e.g., circular dichroism and fluorescence) remain unaffected in the wake of self‐assembly. This strategy to develop complex synthetic polymer scaffolds from functional building blocks is significant in a field striving to produce architectures reminiscent of biosynthesis, yet fully synthetic in nature. This is the first plug‐and‐play approach to fabricate hybrid π‐sheet/helix, π‐sheet/coil, and helix/coil architectures via directional self‐assembly.     

Indole‐N‐Carboxylic Acids and Indole‐N‐Carboxamides in Organic Synthesis

Indoles are ubiquitous structures that are found in natural products and biologically active molecules. The synthesis of indoles and indole‐involved synthetic methodologies in organic chemistry have been receiving considerable attention. Indole‐N‐carboxylic acids and derived indole‐N‐carboxamides are intriguing compounds, which have been widely used in organic synthesis, especially in multicomponent reactions and C?H functionalization of indoles. This Minireview summarizes the advances of reactions involving indole‐N‐carboxylic acids and indole‐N‐carboxamides in organic chemistry, and discusses the synthetic potential and perspective of this field.     

Synergistically Directed Assembly of Aromatic Stacks Based Metal‐Organic Frameworks by Donor‐Acceptor and Coordination Interactions

A synergistically directed assembly approach to distinctive metal‐organic frameworks utilizing both donor‐acceptor (D‐A) interaction from aromatic systems and coordination interactions is presented. Based on such an approach, the coronene‐tpt (tpt = 2,4,6‐tri(4‐pyridyl)‐1,3,5‐triazine) stacks based coronene‐MOF‐1 — 4 have been successfully fabricated. Their structural discrepancies with coronene‐ absent control products, 1′ — 4′ , illustrate clearly the significance of coronene‐tpt based D‐A interactions in these architectures. All these coronene‐MOFs contain varied coronene‐tpt stacks as organic secondary building blocks (SBUs), which are closely interrelated with the coordination based framework structures. Moreover, porous coronene‐MOF‐1 and ‐2 exhibit high physicochemical stability and significant light hydrocarbons storage and separation performances.     

A Bioorthogonal Click Chemistry Toolbox for Targeted Synthesis of Branched and Well‐Defined Protein–Protein Conjugates

Bioorthogonal chemistry holds great potential to generate difficult‐to‐access protein–protein conjugate architectures. Current applications are hampered by challenging protein expression systems, slow conjugation chemistry, use of undesirable catalysts, or often do not result in quantitative product formation. Here we present a highly efficient technology for protein functionalization with commonly used bioorthogonal motifs for Diels–Alder cycloaddition with inverse electron demand (DA_inv). With the aim of precisely generating branched protein chimeras, we systematically assessed the reactivity, stability and side product formation of various bioorthogonal chemistries directly at the protein level. We demonstrate the efficiency and versatility of our conjugation platform using different functional proteins and the therapeutic antibody trastuzumab. This technology enables fast and routine access to tailored and hitherto inaccessible protein chimeras useful for a variety of scientific disciplines. We expect our work to substantially enhance antibody applications such as immunodetection and protein toxin‐based targeted cancer therapies.     

Synthetic Strategies for Constructing Two‐Dimensional Metal‐Organic Layers (MOLs): A Tutorial Review

Two‐dimensional (2D) metal‐organic layers (MOLs) are the 2D version of metal‐organic frameworks (MOFs) with nanometer thickness in one dimension. MOLs are also known as 2D‐MOFs, 2D coordination polymers, ultrathin MOF nanosheets (UMOFNs) or coordination nanosheets in literature. This new category of 2D materials has attracted a lot of interests because of the opportunity in combining molecular chemistry, surface/interface chemistry and material chemistry of low dimensional materials in these systems. Several synthetic strategies have been developed for the construction of 2D MOLs, but the general synthesis of MOLs still presents a challenge. This tutorial level review summarizes the recent progress in the fabrication of novel 2D MOLs and aims to highlight challenges in this field.     

Guest Binding via N−H⋅⋅⋅π Bonding and Kinetic Entrapment by an Inorganic Macrocycle

Modern supramolecular chemistry is overwhelmingly based on non‐covalent interactions involving organic architectures. However, the question of what happens when you depart from this area to the supramolecular chemistry of structures based on non‐carbon frameworks remains largely unanswered, and is an area that potentially provides new directions in molecular activation, host–guest chemistry, and biomimetic chemistry. In this work, we explore the unusual host–guest chemistry of the pentameric macrocycle [{P(μ‐N^tBu}₂NH]₅ with a range of anionic and neutral guests. The polar coordination site of this host promotes new modes of guest encapsulation via hydrogen bonding with the π systems of the unsaturated C≡C and C≡N bonds of acetylenes and nitriles as well as with the PCO^? anion. Halide guests can be kinetically locked within the structure by oxidation of the phosphorus periphery by oxidation to P^V. Our study underscores the future promise of p‐block macrocyclic chemistry.     

Preorganization—From Solvents to Spherands

This article assesses the importance of molecular preorganization to the rapidly developing field of complexation involving designed synthetic organic compounds. Since its birth as a science, organic chemistry has drawn heavily on biological chemistry as a vast storehouse of evolutionary structures, reactions, and control mechanisms that serve as inspiration for designed organic-compounds mimics. Biological systems, through highly structured complexation, accomplish complicated tasks. The receptor sites of enzymes, the genes, the antibodies, and ionophores possess high degree of preorganization. In other words, their functional groups act cooperatively as binding or catalytic sites which are largely collected and oriented prior to complexation.—The strength of the organic chemist derives from his ability to design organic compounds, organic reactions, synthetic sequences, and test systems to evaluate hypotheses. The design of highly structured complexs and the discovery of the rules that govern their behavior are described here. Research in this field is particularly rewarding because scientific and aesthetic content merge and become visible in the structures of many of the complexes.