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Abstract As emerging alternatives to natural enzymes, nanoscale materials featuring enzyme‐like catalytic behaviors (nanozymes) exhibit some attractive merits including robust activity, low cost, and easy‐to‐regulate performance. These merits have enabled them to be intensively used in the biomedical field in recent years. To remedy the lack of catalytic selectivity in most nanozymes, deoxyribonucleic acid (DNA) chains with specific recognition functions are utilized to integrate with nanozymes to produce various nanozyme–DNA combinations via adsorption/desorption. In the formed combinations, the DNA component provides the molecular/ionic recognition role, and the nanozyme part offers response with catalytically amplified signals, enabling them to detect analytes and biomarkers selectively and sensitively. To highlight this interesting topic, here we made a critical review of the interactions between nanozymes and DNA and their applications in biosensing and disease diagnosis. First, strategies for the conjugation of DNA chains onto nanozyme surface were introduced briefly. Then, the interactions between DNA and nanozymes were summarized in detail, where flexible modulations of nanozyme activity by DNA adsorption/desorption as well as various factors were analyzed, and potential impacts caused by nanozymes on the recognition characteristics of DNA chains were pointed out. After that, typical applications of DNA‐mediated nanozyme modulation in toxic ion sensing, health risk factor monitoring, and biomedical diagnosis were introduced. In the end, prospects of the combination of nanozymes and DNA chains were presented, and future challenges of the emerging field were also discussed, to attract more interest and effort to advance this promising area.

Abstract Nanoparticles (NPs) are promising therapeutic delivery agents, with the number and manner of presentation of cell‐binding ligands on the NP affecting the eventual fate of the therapeutic. Whenever NPs are conjugated with biomolecules, a heterogeneous population of decorated NPs will be produced and these subpopulations of particle‐ligand structures need to be characterized for a reliable interpretation of NP‐based data. An optical microscopy method is reported to quantitatively evaluate the conjugation on a single‐particle basis in samples consisting of gold NPs (GNPs) decorated with holo‐transferrin fluorescently labeled with Alexa647 (Tf). Widefield fluorescence and extinction microscopy are employed on NP‐ligand constructs, alongside a correlative analysis that spatially co‐localizes diffraction‐limited sources of fluorescence with the optical extinction by individual GNPs. A photobleaching step analysis estimates the number of fluorophores contributing to the detected emission rate. The method quantifies the number of fluorescent biomolecules attached per GNP, the numbers of unconjugated GNPs and unbound Tf present within the mixed population, and the size and intraparticle clustering propensity of conjugated GNPs. A high variability is found in the number of Tf ligands per GNP within the GNP population, when analyzed at the single‐particle level, unraveling a non‐trivial statistical distribution not accessible in ensemble‐averaged approaches.

Optoelectronic properties of linear π-conjugated polymers/oligomers are of great importance for the fabrication of organic photonic and electronic devices. To this end, the π-conjugated polymers/oligomers need to meet both optoelectronic and key structural properties in order to fulfill their implementation as active components. In particular, they need to possess low bandgap and high thermal, conformational, and photochemical stabilities. So far, several strategies have been developed to attain such requirements including the covalent and non-covalent rigidification concepts of the π-conjugated systems. On the basis of these findings, we describe herein the theoretical studies of novel series of covalently bridged derivatives demonstrating the benefits of the strategy. Comparison of these derivatives with compounds previously described in the literature highlights enhanced optoelectronic properties and behaviors that would be beneficial for the construction and development of new linear π-conjugated polymers., (© 2024 Wiley-VCH GmbH.)

The photosensitive unit and conjugation play a significant role in   photocatalytic performance of covalent organic frameworks (COFs). In this work, a series of COFs that introduced the phenyl phenanthridine as photosensitive unit with different planarity of linkages were synthesized and the common regulation between them for photocatalysis hydrogen evolution reaction (HER) was also studied. The results indicate that DHTB-PPD, with 2/3 planarity linkages (β-ketoenamine/imine is 2/3) and the phenyl phenanthridine as building blocks, shows the narrowest bandgap and the strongest charge separation efficiency. Therefore, it shows the highest H 2 production rate of 12.13 mmol g -1  h -1 . The optimal photocatalytic efficiency of DTHB-PPD can be attributed to the combined effect of the photosensitive unit and the long-range ordering of the COF skeleton. According to The Density Functional Theory (DFT), the O site on β-ketoamine is the most possible H 2 generation site, but the photocatalytic efficiency of TP-PPD, with the highest skeletal conjugation and the highest proportion of β-ketoamine is not the most efficient photocatalyst, indicating that the long-range ordering of COFs is important on photocatalytic performance. Thus, these findings provide valuable guidance for the structural design of COFs photocatalysts., (© 2024 Wiley-VCH GmbH.)

Inspired by nature, scientists have harnessed the natural protein translation machinery to produce intricate and precise protein‐based polymers (PBPs)—composed of natural amino acid monomers and assembled on the nano‐to‐macro scale—for drug and gene delivery, to sense the environment, to produce valuable molecules, and to grow cells and tissues. Beyond the chemical repertoire of natural amino acids, the conjugation of chemically diverse molecules to recombinant PBPs can increase the ability of the latter to mimic or modify the remarkable properties of natural biomaterials and to impart new functions. In this review, recent progress in the production and application of recombinant PBP‐conjugates is described. First, the various approaches for protein conjugation or crosslinking are briefly discussed and then the utility of this approach for imparting new or improved properties and functions onto PBPs composed of elastin‐, resilin‐, silk‐, or collagen‐based sequences is demonstrated. Finally, emerging knowledge of and technologies for PBP‐conjugate production with the potential to expand the use of such precise and chemically diverse polymers in biomedicine is discussed.

Investigations of the nature and degree of antiaromaticity of cycloheptatrienyl anion derivatives using both experimental and computational tools are presented. The ground state of cycloheptatrienyl anion in the gas phase is triplet, planar and Baird-aromatic. In DMSO, it assumes a singlet distorted allylic form with a paratropic ring current. The other derivatives in both phases assume either allylic or diallylic conformations depending on the substituent pattern. A combination of experimental and computational methods was used to determine the pK a values of 16 derivatives in DMSO, which ranged from 36 to -10.7. We revealed that the stronger stabilization of the anionic system, which correlates with acidity, does not necessarily imply a lower degree of antiaromaticity in terms of magnetic properties. Conversely, the substitution pattern first affects the geometry of the ring through the bulkiness of the substituents and their better conjugation with a more distorted system. Consequently, the distortion reduces the cyclic conjugation in the π-system and thereby decreases the paratropic current in a magnetic field, which manifests itself as a decrease in the NICS. The triplet-state geometries and magnetic properties are nearly independent on the substitution pattern, which is typical for simple aromatic systems., (© 2024 Wiley-VCH GmbH.)

The role of monoclonal antibodies as vehicles to deliver payloads has evolved as a powerful tool in cancer therapy in recent years. The clinical development of therapeutic antibody conjugates with precise payloads holds great promise for targeted therapeutic interventions. The use of affinity-peptide mediated functionalization of native off-the-shelf antibodies offers an effective approach to selectively modify IgG antibodies with a drug-antibody ratio (DAR) of 2. Here, we report the traceless, peptide-directed attachment of two hydroxylamines to native IgGs followed by chemoselective potassium acyltrifluoroborate (KAT) ligation with quinolinium acyltrifluoroborates (QATs), which provide enhanced ligation rates with hydroxylamines under physiological conditions. By applying KAT ligation to the modified antibodies, conjugation of small molecules, proteins, and oligonucleotides to off-the-shelf IgGs proceeds efficiently, in good yields, and with simultaneous cleavage of the affinity peptide-directing moiety., (© 2024 Wiley‐VCH GmbH.)

An innovative switchable design strategy for modulating the electronic structures of quinones is proposed herein, leading to remarkably enhanced intrinsic redox potentials by restoring conjugated but nonaromatic backbone architectures. Computational validation of two fundamental hypotheses confirms the recovery of backbone conjugation and optimal utilization of the inductive effect in switched quinones, which affords significantly improved redox chemistry and overall performance compared to reference quinones. Geometric and electronic analyses provide strong evidence for the restored backbone conjugation and nonaromaticity in the switched quinones, while highlighting the reinforcement of the inductive effect and suppression of the resonance effect. This strategic approach facilitates the development of an exceptional quinone, viz. 2,6-naphthoquinone, with outstanding performance parameters (338.9 mAh g -1 and 912.9 mWh g -1 ). Furthermore, 2,6-anthraquinone with superior cyclic stability, demonstrates comparable performance (257.4 mAh g -1 and 702.8 mWh g -1 ). These findings offer valuable insights into the design of organic cathode materials with favorable redox chemistry in secondary batteries., (© 2023 Wiley‐VCH GmbH.)

In one-dimensional polycyclic aromatic hydrocarbons (PAHs) containing five- and six-membered rings fused together, one key question is whether the structures possess a quinoidal or aromatic diradical character. Here, we generate such PAHs by reversible oxidation of PAH-extended tetrathiafulvalenes (TTFs). Extended TTFs were thus prepared and studied for their geometrical properties (crystallography), redox properties, and UV/Vis/NIR/EPR characteristics as a function of charge state. The EPR measurements of radical cations showed unique features for each PAH-TTF. The dications, formally composed of fluoreno[3,2-b]fluorene and diindeno[1,2-b:1',2'-i]anthracene cores, were experimentally found to exhibit singlet ground states. For the latter, calculations reveal the closed shell, quinoid singlet state to be isoenergetic with the open shell singlet diradical. Each charge state exhibited unique optical properties with radical cations absorbing strongly in the NIR region with signatures from π-dimers for the large core. The experimental results were paralleled and supported by detailed computations, including spin density distribution calculations, EPR simulations, and nucleus independent chemical shift (NICS) xy scans., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Covalent organic frameworks (COFs) are a type of crystalline porous polymer composed of light elements through strong covalent bonds. COFs have attracted considerable attention due to their unique designable structures and excellent material properties. Currently, COFs have shown outstanding potential in various fields, including gas storage, pollutant removal, catalysis, adsorption, optoelectronics, and their research in the sensing field is also increasingly flourishing. In this review, we focus on COF-based sensors. Firstly, we elucidate the fundamental principles of COF-based sensors. Then, we present the primary application areas of COF-based sensors and their recent advancements, encompassing gas, ions, organic compounds, and biomolecules sensing. Finally, we discuss the future trends and challenges faced by COF-based sensors, outlining their promising prospects in the field of sensing., (© 2023 Wiley-VCH GmbH.)

Macrocycles with bent π-conjugation motif are extremely rare in nature and synthetically daunting and anticancer haouamines and spirohexenolides were representative of such rare natural products with synthetically challenging bent π-conjugation within a macrocycle. While the total synthesis of haouamines has been elegantly achieved, spirohexenolides remains an unmet synthetic challenge due to the highly strained bent 1,3,5-triene conjugation within C15 macrocycle. Inspired by the chemical synthesis of cycloparaphenylenes (CPPs) and haouamines, herein we devise a synthetic strategy to overcome the highly strained bent 1,3,5-triene conjugation within the macrocycle and achieve the first, asymmetric total synthesis of spirohexenolides A (>20 mg) and B (>50 mg). Our synthesis features strategic design of ring-closing metathesis (RCM) macrocyclization followed by double dehydration to achieve the C15 macrocycle with the deformed nonplanar 1,3,5-triene conjugation. In addition, we have developed a new enantioselective construction of highly functionalized spirotetronate fragment (northeast moiety) through RCM and Ireland-Claisen rearrangement. Our in vitro bioassay studies reveal that both spirohexenolides are cytotoxic against a panel of human cancer cells with IC 50 1.2-13.3 μM and spirohexenolide A is consistently more potent (up to 3 times) than spirohexenolide B, suggesting the importance of alcohol for their bioactivity and for medicinal chemistry development., (© 2023 Wiley-VCH GmbH.)

A modular approach for the synthesis of isolable crystalline Schlenk hydrocarbon diradicals from m-phenylene bridged electron-rich bis-triazaalkenes as synthons is reported. EPR spectroscopy confirms their diradical nature and triplet electronic structure by revealing a half-field signal. A computational analysis confirms the triplet state to be the ground state. As a proof-of-principle for the modular methodology, the 4,6-dimethyl-m-phenylene was further utilized as a coupling unit between two alkene motifs. The steric conjunction of the 4,6-dimethyl groups substantially twists the substituents at the nonbonding electron bearing centers relative to the central coupling m-phenylene motif. As a result, the spin delocalization is decreased and the exchange coupling between the two unpaired spins, hence, significantly reduced. Notably, 108 years after Schlenk's m-phenylene-bis(diphenylmethyl) synthesis as a diradical, for the first time we were able to isolate its derivative with the same spacer, i.e. m-phenylene, between two radical centers in a crystalline form., (© 2023 Wiley-VCH GmbH.)

Post-synthetic modification (PSM) imparts additional functionality to metal-organic frameworks (MOFs) that is often difficult to access using solvothermal synthesis. As such, expanding the repertory of PSM reactions available to the practitioner is of increased importance for the generation of materials tailored for desired applications. Herein, a method is described for the protecting group-free installation of diverse functional groups within the pores of a MIL-53(Al) analogue via disulfide bond formation. The majority of the reactions proceed with thiol-to-disulfide conversions ranging from high to nearly quantitative. The disulfide bonds are stable in various solvents and can be cleaved in the presence of a reducing agent., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

In general, electrocyclizations follow the Woodward-Hoffmann's rules of conservation of orbital symmetry. These rules have been extensively verified in low-order processes, both in thermal and photochemical reactions, up to eight π-electrons. However, when the number of π-electrons in the system increases, some deviations of that general rules can be found. This focused review highlights the main features of reported higher-order electrocyclizations involving 10, 12, 14, 16 and 18 π-electrons. Some of these examples constitute useful intermediates in the synthesis of biologically active compounds. When computational studies were not included in the reported examples, DFT calculations have been performed to be included in this review. Analysis of the respective pericyclic topologies shows the importance of computational tools for understanding the selectivity observed experimentally., (© 2023 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

The first case of successful suppression of the coordination of a lithium atom with a dialkylamino group by the effective conjugation of the latter with the aromatic core has been discovered. This effect controls regioselectivity of the bromine-lithium exchange in 4,6,7,9-tetrabromo-1,3-dimethyl-2,3-dihydro-1H-perimidine, which leads to products with the most effective conjugation. As a result, the product of this quadruple exchange demonstrates no tendency of the coordination of the NMe groups to neighboring lithium atoms despite the absence of steric restrictions. Experimental results are explained by means of quantum chemical calculations: geometry optimization, natural bond analysis and scans using the modredundant scheme., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Bacteria represent a class of living cells that are very attractive carriers for the transport and delivery of nano- and microsized particles. The use of cell-based carriers, such as for example bacteria, may allow to precisely direct nano- or microsized cargo to a desired site, which would greatly enhance the selectivity of drug delivery and allow to mitigate side effects. One key step towards the use of such nano-/microparticle - bacteria hybrids is the immobilization of the cargo on the bacterial cell surface. To fabricate bacteria - nano-/microparticle biohybrid microsystems, a wide range of chemical approaches are available that can be used to immobilize the particle payload on the bacterial cell surface. This article presents an overview of the various covalent and noncovalent chemistries that are available for the preparation of bacteria - nano-/microparticle hybrids. For each of the different chemical approaches, an overview will be presented that lists the bacterial strains that have been modified, the type and size of nanoparticles that have been immobilized, as well as the methods that have been used to characterize the nanoparticle-modified bacteria., (© 2022 Wiley-VCH GmbH.)

Heavier tetrylenes attract attention for their potential in synthesis, catalysis and small molecule activation. The coordination by N-heterocyclic carbenes (NHCs) and cyclic (alkyl)(amino)carbenes (CAACs) results in substantial structural and electronic differences although typically only one of these yields stable derivatives for one and the same tetrylene. We now report both NHC- and CAAC-coordination to a bridged bis(germylene) motif. The NHC-coordinated bis(germylene) exhibits pyramidal germanium centers with lone pairs of electrons, while with CAAC an unprecedented stable bis(germene) with two Ge=C bonds is isolated. Spectroscopic and crystallographic evidence as well as DFT calculations confirm the effects of σ,π-conjugation between the two germanium centers in both cases. The coordination of NHC is reversible as the reaction with BPh 3 liberates the transient bis(germylene) and thus provides an alternative low-temperature route towards polymers with Ge=Ge bonds., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Site-specific conjugation approaches are of great importance in drug discovery, notably for the synthesis of biochemical probes or molecular conjugates for targeted delivery. Herein, we report a mild ionic liquid (IL)-mediated thiolation technique that relies on the use of 1,3-ethyl-methyl imidazolium acetate, [C 2 mim][OAc] as a solvent and precursor to generate activated IL, as well as a solvent for the conjugation reaction. First, a focused library of active ILs was prepared for functionalizing/conjugating cysteine-containing small molecules and unprotected peptides. Interestingly, a bifunctional active IL could also be successfully employed as a linker for the conjugation of peptides lacking Cys. This study sets the ground for further investigation of the use of active ILs for modifying, labeling or conjugating larger and more complex therapeutic modalities such as proteins and antibodies., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

This study reports an effective peripheral decoration of organic donor-acceptor diads with B(C 6 F 5 ) 3 for stabilizing electrogenerated radical ions. By employing a common p-type organic semiconductor benzothienobenzothiophene (BTBT) as the donor, tetracoordinate boron complexes showed improved solution electrochemiluminescence (ECL) intensity, reaching a 156-fold increase compared to that of the parent diad. The unprecedented Lewis-pairing-induced ECL enhancement is attributed to the multiple roles of B(C 6 F 5 ) 3 : 1) redistributing frontier orbitals, 2) facilitating electrochemical excitation, and 3) restricting molecular motions. Furthermore, B(C 6 F 5 ) 3 converted the molecular arrangement of BTBT from conventional 2D herringbones into 1D π-stacks. This robust, highly ordered columnar nanostructure allowed red-shifting of the crystalline film ECL with electrochemical doping through the electronic coupling pathways of BTBT. Our approach will facilitate the development of elaborate metal-free ECL systems., (© 2023 Wiley-VCH GmbH.)

There is an urgent need for new treatment options for carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae), which is a common cause of life-threatening hospital- and community-acquired infections. Prophylactic or therapeutic vaccination may offer an approach to control these infections, however, none has yet been approved for human use. Here, we report the chemical synthesis of an outer core tetra- and pentasaccharide derived from the lipopolysaccharide of K. pneumoniae. The oligosaccharides were equipped with an aminopentyl linker, which facilitated conjugation to the carrier proteins CRM 197 and BSA. Mice immunized with the glycoconjugate vaccine candidates elicited antibodies that recognized isolated LPS as well as various strains of K. pneumoniae. The successful preparation of the oligosaccharides relied on the selection of monosaccharide building blocks equipped with orthogonal hydroxyl and amino protecting groups. It allowed the differentiation of three types of amines of the target compounds and the installation of a crowded 4,5-branched Kdo moiety., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Covalent organic frameworks have recently shown high potential for photocatalytic hydrogen production. However, their structure-property-activity relationship has not been sufficiently explored to identify a research direction for structural design. Herein, we report the design and synthesis of four benzotrithiophene (BTT)-based covalent organic frameworks (COFs) with different conjugations of building units, and their photocatalytic activity for hydrogen production. All four BTT-COFs had slipped parallel stacking patterns with high crystallinity and specific surface areas. The change in the degree of conjugation was found to rationally tune the rate of photocatalytic hydrogen evolution. Based on the experimental and calculation results, the tunable photocatalytic performance could be mainly attributed to the electron affinity and charge trapping of the electron accepting units. This study provides important insights for designing covalent organic frameworks for efficient photocatalysts., (© 2022 Wiley-VCH GmbH.)

Large π-conjugated systems are key in the area of molecular materials. Herein, we prepare via Au I -catalyzed cyclization a series of fully π-conjugated anthracene-fused oligo-BODIPYs. Their structural and optoelectronic properties were studied by several techniques, ranging from X-ray, UV/Vis, and cyclic voltammetry to transient absorption spectroscopy. As a complement, their electronic structures were explored by means of Density Functional Theory (DFT) calculations. Depending on the size and shape of the π-conjugated skeleton, unique features-such as face-to-face supramolecular organization, NIR absorption and fluorescence as well as strong electron accepting character-were noted. All in all, the aforementioned features render them valuable for technological applications., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Mono-alkene-inserted [n]cycloparaphenylenes 1 [(ene)-[n]CPP] with n=6, 8, and 10, mono-ortho-phenylene-inserted [6]CPP 2, and di-alkene-insertved [n]CPP 3 [(ene) 2 -[n]CPP] with n=4, 6, and 8 were synthesized by fusing CPP precursors and alkene or ortho- phenylene groups through coupling reactions. Single-crystal X-ray diffraction analyses reveal that the strips formed by the π-surfaces of 1 and 2 exhibited a Möbius topology in the solid state. While the Möbius topology in the parent 1 and 2 in solution was lost due to the free rotation of the paraphenylene unit even at low temperatures, ene-[6]CPP 4 with eight 1-pyrrolyl groups preserved the Möbius topology even in solution. Despite a twist, 1 has in-plane conjugation and possesses a unique size dependence of the electronic properties: namely, the opposite size dependency of the HOMO-LUMO energy relative to conventional π-conjugated molecules., (© 2022 Wiley-VCH GmbH.)

Reported here is the first catalytic atroposelective electrophilic amination of indoles, which delivers functionalized atropochiral N-sulfonyl-3-arylaminoindoles with excellent optical purity. This reaction was furnished by 1,6-nucleophilic addition to p-quinone diimines. Control experiments suggest an ionic mechanism that differs from the radical addition pathway commonly proposed for 1,6-addition to quinones. The origin of 1,6-addition selectivity was investigated through computational studies. Preliminary studies show that the obtained 3-aminoindoles atropisomers exhibit anticancer activities. This method is valuable with respect to enlarging the toolbox for atropochiral amine derivatives., (© 2022 Wiley-VCH GmbH.)

Molecules with intense near-IR (NIR) emission are beneficial for modern applications such as night vision, bio-imaging etc. However, elaborate synthetic manipulations make them demanding to accomplish. Herein, we present a simple yet exciting strategy to obtain novel Janus butterfly-shaped terrylene diimide derivatives with carbazole wings having absorption and intense emission in the NIR. Especially, unsymmetrically substituted terrylene diimides (TDIs) have been observed to have impressive emission quantum yields (up to 93 %), highest for this class of compounds. Minimal structural distortion as evidenced from structural characterization has been shown to correlate with these observations. Also, a novel two-tiered TDI-carbazole having an intense emission at 897 nm is also reported. Our strategy demonstrates that efficient near-IR luminophores can be achieved via precise functionalization., (© 2022 Wiley-VCH GmbH.)

The present review focuses on recent examples of tetracoordinate boryl groups greatly influencing reactions in organic synthesis. Electron-rich tetracoordinate boryl groups stabilize or activate reactive intermediates such as cations, radicals and π-conjugation systems, and interaction of the intermediates with carbon-boron or heteroatom-boron bonds is the origin of such substituent effects. Unique substituent effects of tetracoordinate boryl groups often promote desired reactions and affect results of reactions such as yield and selectivity of products., (© 2022 Wiley-VCH GmbH.)

Distorting linear polyaromatic hydrocarbons (PAHs) out of planarity affects their physical properties and breaks their symmetry to induce inherent chirality. However, the chirality cannot be achieved in large distorted PAHs-based macrocycles due to a low racemization barrier for isomerization. Herein, we report the precise synthesis and tuning size-dependent (chir)optical properties of a new class of chiral PAHs-containing conjugated macrocycles (cyclo[n]paraphenylene-2,6-anthrylene, [n]CPPAn 2,6 ; n=6-8). Their inherent chiralities were squeezed out in small anthrylene-based macrocycles. Efficient resolutions for chiral enantiomers with (P)/(M)-helicity of small [6-7]CPPAns were achieved by HPLC. Interestingly, these macrocycles showed enriched size-dependent physical, chiral, and (chir)optical properties. Theoretical calculations indicate that these macrocycles have high strain energy (E strain =60.8 to 73.4 kcal/mol) and very small E gap (∼3.0 eV). Notably, these enantiomers showed strong chiroptical properties and dissymmetry factors (|g abs | and |g lum |∼0.01 for an enantiomer of [6]CPPAn 2,6 ), which can give them potential applications in optically active materials., (© 2022 Wiley-VCH GmbH.)

A series of mitochondria-targeted triphenylphosphonium conjugated C-3 modified betulin were synthesized and evaluated against tumor cells. As a result, a new derivative 13 i, the conjugate of 3-O-(3'-acetylphenylacetate)-betulin with triphenylphosphonium, was identified as the one with the best anti-tumor effect. Conjugate 13 i significantly inhibited HCT116 cells with IC 50 at 0.66 μM. While betulin, C-3 modified betulin, and the triphenylphosphonium moiety showed no inhibition of HCT116 cell proliferation at 20 μM. More importantly, 13 i exhibited a more cytotoxic effect against the tumor cell HCT116 than normal cell NCM460. Mode of action studies demonstrated that 13 i induced the G2/M phase cell cycle arrest and apoptosis in HCT116 cells through the mitochondrial pathway. Structure-activity relationship analysis revealed that integration of triphenylphosphonium moiety into the C-28 of betulin can greatly improve cytotoxicity. Appropriate modification on C-3 of the conjugate would improve the selectivity., (© 2021 Wiley-VCH GmbH.)

Bis(dioxaborin) compounds containing π-conjugated systems have been studied as n-type semiconductors for organic field-effect transistors (OFETs). In this study, with the aim of investigating the effect of the extension of the π-conjugation on the n-type semiconducting properties and stability of bis(dioxaborin) compounds, we synthesized new compounds containing 2,2'-bithiophene derivatives extended with an olefin or an acetylene spacer. The absorption maxima of the compounds containing olefin spacers were greatly red-shifted compared with those of the original compound without a π-spacer. The newly synthesized compounds exhibited high electron affinity, and the olefin spacers effectively reduced the on-site Coulomb repulsion in the two-electron reduction of the compounds. An OFET fabricated using one of these compounds having a layer-by-layer crystal structure exhibited n-type semiconductor behavior with a low threshold voltage, most likely due to the small on-site Coulomb repulsion. The electron-transporting properties were investigated by theoretical calculations based on the Marcus theory., (© 2021 Wiley-VCH GmbH.)

The functionalization of C-H bonds, ubiquitous in drugs and drug-like molecules, represents an important synthetic strategy with the potential to streamline the drug-discovery process. Late-stage aromatic C-N bond-forming reactions are highly desirable, but despite their significance, accessing aminated analogues through direct and selective amination of C-H bonds remains a challenging goal. The method presented herein enables the amination of a wide array of benzoic acids with high selectivity. The robustness of the system is manifested by the large number of functional groups tolerated, which allowed the amination of a diverse array of marketed drugs and drug-like molecules. Furthermore, the introduction of a synthetic handle enabled expeditious access to targeted drug-delivery conjugates, PROTACs, and probes for chemical biology. This rapid access to valuable analogues, combined with operational simplicity and applicability to high-throughput experimentation has the potential to aid and considerably accelerate drug discovery., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Recognition-driven modification has been emerging as a novel approach to modifying biomolecular targets of interest site-specifically and efficiently. To this end, protein modular adaptors (MAs) are the ideal reaction model for recognition-driven modification of DNA as they consist of both a sequence-specific DNA-binding domain (DBD) and a self-ligating protein-tag. Coupling DNA recognition by DBD and the chemoselective reaction of the protein tag could provide a highly efficient sequence-specific reaction. However, combining an MA consisting of a reactive protein-tag and its substrate, for example, SNAP-tag and benzyl guanine (BG), revealed rather nonselective reaction with DNA. Therefore new substrates of SNAP-tag have been designed to realize sequence-selective rapid crosslinking reactions of MAs with SNAP-tag. The reactions of substrates with SNAP-tag were verified by kinetic analyses to enable the sequence-selective crosslinking reaction of MA. The new substrate enables the distinctive orthogonality of SNAP-tag against CLIP-tag to achieve orthogonal DNA-protein crosslinking by six unique MAs., (© 2021 Wiley-VCH GmbH.)

Chrysene is a readily available material for exploring new polycyclic aromatic hydrocarbons (PAHs). In this study, two chrysene based azahelicenes, nine-membered BA7 and ten-membered DA6, are constructed by intermolecular oxidative annulation of 6-aminochrysene and intramolecular annulation of N 6 ,N 12 -bis(1-chloronaphthalen-2-yl)chrysene-6,12-diamine, respectively. The hexylated BA7 and DA6 and their brominated products were undoubtedly characterized by single crystal XRD. Subsequent amination with bis(9-methyl-9H-carbazol-3-yl)amine (BMCA) electron donor afforded D-π-D-type semiconductors BA7-BMCA and DA6-BMCA with beneficial properties to act as hole transport materials for perovskite solar cell. Compared with 19.4 % champion power conversion efficiency (PCE) of BA7-BMCA based device, a higher PCE of 20.2 % for DA6-BMCA counterpart may be attributed to its S-shaped double helicene-like linker with extended π-conjugated system., (© 2021 Wiley-VCH GmbH.)

The synthesis, structures, and properties of [4]cyclonaphthodithiophene diimides ([4]C-NDTIs) are described. NDTIs as important n-type building blocks were catenated in the α-positions of thiophene rings via an unusual electrochemical-oxidation-promoted macrocyclization route. The thiophene-thiophene junction in [4]C-NDTIs results in an ideal pillar shape. This interesting topology, along with appealing electronic and optical properties inherited from the NDTI units, endows the [4]C-NDTIs with both near-infrared (NIR) light absorptions, strong excitonic coupling, and tight encapsulation of C 60 . Stable orientations of the NDTI units in the nanopillars lead to stable inherent chirality, which enables detailed circular dichroism studies on the impact of isomeric structures on π-conjugation. Remarkably, the [4]C-NDTIs maintain the strong π-π stacking abilities of NDTI units and thus adopt two-dimensional (2D) lattice arrays at the molecular level. These nanopillar molecules have great potential to mimic natural photosynthetic systems for the development of multifunctional organic materials., (© 2021 Wiley-VCH GmbH.)

Polycyclic aromatic hydrocarbons (PAHs) are widely used in organic electronic devices. The electronic, magnetic, and optical properties of PAHs can be tuned by structural modifications to the aromatic backbone to introduce an inherent distortion from planarity, such as bending or twisting. However, it remains difficult to isolate and control the effects of such distortions. Here, we sought to understand how backbone twisting and bending affect the electronic properties of acenes, as models for larger PAHs. We found that, even when highly distorted from planarity (30° per ring), acenes maintain their aromatic character and π orbital delocalization with minor mixing of the σ and π orbitals. In addition, the energy gap between the HOMO and LUMO decreases with increasing twist, while the gap is hardly affected by bending, since the energy of both orbitals increase to a similar extent. For bent acenes in the triplet state, the spin becomes more localized with increasing bend, whereas twisting produces an evenly distributed spin delocalization. These findings can guide the synthesis of PAHs with tailored properties., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. European Journal of Organic Chemistry published by Wiley-VCH GmbH.)

Self-assembly processes guide disordered molecules or particles into long-range organized structures due to specific supramolecular interactions among the building entities. Herein, we report a unique evaporation-induced self-assembly (EISA) strategy for four different silica nanoparticle systems obtained through peptide functionalization of the particle surface. First, covalent peptide-silica coupling was investigated in detail, starting with the grafting of a single amino acid (L-serine) and expanded to specific small peptides (up to four amino acids) and transferred to different particle types (MCM-48-type MSNs, solid nanoparticles, and newly developed virus-like nanoparticles). These materials were investigated regarding their ability to undergo EISA, which was shown to be independent of particle type and amount of peptide anchored to their surface. This EISA-based approach provides new possibilities for the design of future advanced drug delivery systems, engineered hierarchical sorbents, and nanocatalyst assemblies., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

s-Indacene is a classical non-alternant hydrocarbon that contains 12 π-electrons in a cyclic π-conjugation system. Herein, we report its nitrogen-doped analogue, 1,5-diaza-s-indacene. 1,5-Diaza-s-indacenes were readily prepared from commercially available 2,5-dichlorobenzene-1,4-diamine through a two-step transformation consisting of a palladium-catalyzed Larock cyclization with diaryl acetylenes followed by hydrogen abstraction. The thus obtained 1,5-diaza-s-indacenes exhibited distinct antiaromaticity, as manifested in clear bond-length alternation, a forbidden HOMO-LUMO transition, and a paratropic ring current. As compared to the parent s-indacene, the 1,5-diaza-s-indacenes showed higher electron-accepting ability owing to the presence of imine-type nitrogen atoms. The 1,5-diaza-s-indacene core is effectively conjugated with the peripheral aryl groups, which enables fine-tuning of the absorption spectra and redox properties. The two possible localized forms of 1,5-diaza-s-indacene were compared in terms of their energetic aspects., (© 2021 Wiley-VCH GmbH.)

The development of new linkages is one of the most efficient strategies to enrich the diversity of covalent organic frameworks (COFs). Particularly, functional linkages can endow COFs with additional tailored properties besides the building units, which further diversify COFs with desirable functions. Herein, we have developed a new arylamine linkage for the construction of COFs. Two new arylamine-linked COFs (AAm-TPB and AAm-Py) were prepared by condensing cost-effective dimethyl succinyl succinate (DMSS) with corresponding multitopic amines (TPB-NH 2 and Py-NH 2 ). Due to the abundant electroactive diphenylamine moieties in the COF skeletons resembling that of polyaniline (PANI), a state-of-the-art conductive polymer, the pseudocapacitive energy storage performance of AAm-TPB was further investigated. Remarkably, the AAm-TPB electrode exhibits a high capacitance of 271 F g -1 with a three-electrode setup at a discharge rate of 1 A g -1 , which represents one of the highest capacitances among the reported COF-based electrode materials., (© 2021 Wiley-VCH GmbH.)

Photoswitch triads comprising two dihydroazulene (DHA) units in conjugation with a central trans-azobenzene (AZB) unit were prepared in stepwise protocols starting from meta- and para-disubstituted azobenzenes. The para-connected triad had significantly altered optical properties and lacked the photoactivity of the separate photochromes. In contrast, for the meta-connected triad, all three photochromes could be photoisomerized to generate an isomer with two vinylheptafulvene (VHF) units and a cis-azobenzene unit. Ultrafast spectroscopy of the photoisomerizations revealed a fast DHA-to-VHF photoisomerization and a slower trans-to-cis AZB photoisomerization. This meta triad underwent thermal VHF-to-DHA back-conversion with a similar rate of all VHFs, independent of the identity of the neighboring units, and in parallel thermal cis-to-trans AZB conversion. The experimental observations were supported by computation (excitation spectra and orbital analysis of the transitions)., (© 2021 Wiley-VCH GmbH.)

The synthesis of persistent sila- and germacyclopentadienyl (silolyl- and germolyl-) radicals by careful stoichiometric reduction of the corresponding halides with potassium is reported. The radicals were characterized by EPR spectroscopy and trapping reactions. The reduction of tris(trimethylsilyl)silyl-substituted halides was successful while smaller substituents (i. e., t-Butyl, Ph) gave the corresponding dimers. The EPR spectroscopic parameter of the synthesized tetrolyl radicals indicate only small spin delocalization to the butadiene unit due to cross-hyperconjugation. Silolyl- and germolyl anions are unavoidable byproducts and are isolated in the form of their potassium salts and characterized by X-ray crystallography. The comparison of the molecular structures of two closely related potassium silolides provided an example for different coordination of the potassium cation to the silolyl anion (η 1 vs. η 5 coordination) that triggers the switch between delocalized and localized states., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Currently, most organic semiconducting materials (OSMs) are π-conjugated structures in one or two dimension (2D), where the lack of layer-layer π-conjugation connection greatly blocks their electron delocalization and transport. The 3D fully conjugated materials could solve this issue because they can provide efficient charge-transport pathways throughout the whole 3D skeleton, in which the suitable 3D building block is the key to the development of fully conjugated 3D OSMs. Cyclooctatetraene (COT) and its derivatives are good candidates due to their π-conjugation with 3D saddle-shaped architecture. In this Concept, we discuss the key features of saddle-shaped COT-based derivatives and their synthetic strategy, then we present the current development of using the COT derivatives as building blocks to construct the 3D fully conjugated organic small compound- and polymer-based OSMs. The properties and perspectives of these OSMs in photovoltaics, electro-catalysis and electrical conductivities are also discussed. These recent advances in the developing 3D fully conjugated materials could potentially open up a new frontier in the design of OSMs., (© 2021 Wiley-VCH GmbH.)

We report the synthesis and properties of acridino[2,1,9,8-klmna]acridine bisimide (AABI), a nitrogen-doped anthanthrene with two imide functionalities. AABI exhibits excellent electron affinity as evident by its low-lying LUMO level (-4.1 eV vs. vacuum). Single-electron reduction of one AABI derivative afforded the corresponding radical anion, which was stable under ambient conditions. Photoconductivity measurements suggest that the intrinsic electron mobility of an N-phenethyl AABI derivative obeys a band-transport model. Accordingly, an electron mobility of 0.90 cm 2  V -1  s -1 was attained with the corresponding single-crystal organic field-effect transistor (OFET) device. The vacuum-deposited OFET device consisting of a polycrystalline sample exhibited high electron mobility of up to 0.27 cm 2  V -1  s -1 even in air. This study demonstrates that dual incorporation of both imide substituents and imine-type nitrogen atoms is an effective strategy to create novel electron-deficient π-systems., (© 2021 Wiley-VCH GmbH.)

Heterogeneous molecular catalysts have attracted considerable attention as carbon dioxide reduction reaction (CO 2 RR) electrocatalysts. The π-electron system of conjugated ligands in molecular catalysts may play an important role in determining the activity. In this work, by enlarging π-conjugation through appending more aromatic substituents on the porphyrin ligand, altered π-electron system endows the as-prepared 5,10,15,20-tetrakis(4-(pyren-1-yl)phenyl)porphyrin Co II with high Faradaic efficiency (ca. 95 %) for CO production, as well as high turnover frequency (2.1 s -1 at -0.6 V vs. RHE). Density functional theory calculation further suggests that the improved electrocatalytic performance mainly originates from the higher proportion of Co d z 2 orbital and the CO 2 π* orbital in the HOMO of the (Co-porphyrin-CO 2 ) - intermediate with larger π-conjugation, which facilitates the CO 2 activation. This work provides strong evidence that π-conjugation perturbation is effective in boosting the CO 2 RR., (© 2021 Wiley-VCH GmbH.)

Kinases mediate cell signaling pathways by catalyzing protein phosphorylation. Irregularities in kinase activity are directly associated with disease conditions. Therefore, methods to identify substrates of a particular kinase are needed to understand signaling cascades in normal and diseased states. Photocrosslinking ATP analogs provide powerful tools to study kinases by covalently linking kinases with substrates. However, the involvement of UV light and nonspecific reactivity of current ATP-photocrosslinkers challenge kinase-substrate identification. We report here an affinity-based crosslinking ATP analog, ATP-methylacrylamide (ATP-MAc), that contains a cysteine-reactive acrylamide crosslinking group, which avoids the UV irradiation and non-specific reactivity of prior analogs. Using in vitro kinase assays, ATP-MAc acts as a kinase co-substrate and covalently crosslinks only kinases containing cysteines in the active site. ATP-MAc was also able to crosslink cellular proteins in lysates, documenting compatibility with cell-based studies., (© 2021 Wiley-VCH GmbH.)

The Pt II linker [ethylenediamineplatinum(II)] 2+ , coined Lx, has emerged as a novel non-conventional approach to antibody-drug conjugates (ADCs) and has shown its potential in preclinical in vitro and in vivo benchmark studies. A crucial improvement of the Lx conjugation reaction from initially <15 % to ca. 75-90 % conjugation efficiency is described, resulting from a systematic screening of all relevant reaction parameters. NaI, a strikingly simple inorganic salt additive, greatly improves the conjugation efficiency as well as the conjugation selectivity simply by exchanging the leaving chloride ligand on Cl-Lx-drug complexes (which are direct precursors for Lx-ADCs) for iodide, thus generating I-Lx-drug complexes as more reactive species. Using this iodide effect, we developed a general and highly practical conjugation procedure that is scalable: our lead Lx-ADC was produced on a 5 g scale with an outstanding conjugation efficiency of 89 %., (© 2020 Wiley-VCH GmbH.)

In search of the design rules for structural ordering of open-chain molecules, we have built a series of zig-zag shaped π-conjugated structures with ring-fused heteroaromatics as sharp turns and tolane-based linear fragments as light-emitting units. Using only a finite number of common building blocks, an efficient "double-elongation" strategy was implemented to construct a series of π-conjugated oligomers with precise length control (55-89 % yields). Our approach takes advantage of the modular nature of the bis(triazolo)benzene synthesis and the masked reactivity of the nitro group. A combination of photophysical and DFT computational studies revealed that the bis(triazolo)benzene-tolane repeat units behave as electronically decoupled light-absorbing/emitting units (λ max,em = 408-422 nm; Φ F = 20-25 % in THF). Such context-independent photophysical properties promise their potential applications in chemical sensing and switching., (© 2021 Wiley-VCH GmbH.)

A rotating phenyl ring is introduced between the two pyridinium rings, namely, 1,1'-bis[3-(trimethylamonium)propyl]-4,4'-(1,4-phenylene)bispyridinium tetrachloride ((APBPy)Cl 4 ), to form a switchable conjugation. In this design, the conjugation is switched "off" in the oxidized state and the two pyridinium rings behave independently during the redox process, yielding a concomitant transfer of two electrons at the same potential and, thus, simplifying the battery management. The conjugation is switched "on" in the reduced state and the charge can be effectively delocalized, lowering the Lewis basicity and improving its chemical stability. By pairing 0.50 m (APBPy)Cl 4 with a 2,2,6,6-tetramethylpiperidin-1-yl oxyl derivative as the positive electrolyte, a flow battery delivers a high standard cell voltage of 1.730 V and a high specific capacity of 20.0 Ah L -1 . The battery also shows an exceptionally high energy efficiency of 80.8% and a superior cycling stability at 80 mA cm -2 . This strategy proves itself a great success in engineering viologen as a two-electron storage mediator with high capacity and stability., (© 2021 Wiley-VCH GmbH.)

The synthesis of a cyclohexa-2,7-(4,5-diaryl)anthrylene ethynylene (1) was achieved for the first time by using 1,8-diaryl-3,6-diborylanthracene and 1,8-diaryl-3,6-diiodoanthracene as key synthetic intermediates. Macrocycle 1 possesses a planar conformation of approximately D 6h symmetry, because of the triple-bond linker between the anthracene units at the 2,7-positions. It was confirmed that macrocycle 1, bearing bulky substituents at the outer peripheral positions, behaves as a monomeric form in solution without π-stacking self-association. Macrocycle 1 has an inner-cavity size that allows specific inclusion of [9]cycloparaphenylene ([9]CPP), but not [8]CPP or [10]CPP, through an aromatic edge-to-face CH-π interaction., (© 2020 Wiley-VCH GmbH.)

The synthesis of unsubstituted oligo-para-phenylenes (OPP) exceeding para-hexaphenylene-in the literature often referred to as p-sexiphenyl-has long remained elusive due to their insolubility. We report the first preparation of unsubstituted para-nonaphenylenes (9PPs) by extending our precursor route to poly-para-phenylenes (PPP) to a discrete oligomer. Two geometric isomers of methoxylated syn- and anti-cyclohexadienylenes were synthesized, from which 9PP was obtained via thermal aromatization in thin films. 9PP was characterized via optical, infrared and solid-state 13 C NMR spectroscopy as well as atomic force microscopy and mass spectrometry, and compared to polymeric analogues. Due to the lack of substitution, para-nonaphenylene, irrespective of the precursor isomer employed, displays pronounced aggregation in the solid state. Intermolecular excitonic coupling leads to formation of H-type aggregates, red-shifting emission of the films to greenish. 9PP allows to study the structure-property relationship of para-phenylene oligomers and polymers, especially since the optical properties of PPP depend on the molecular shape of the precursor., (© 2020 The Authors. Published by Wiley-VCH GmbH.)