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Chiral quantum dots (QDs) are promising materials applied in many areas, such as chiral molecular recognition and spin selective filter for charge transport, and can be prepared by facile ligand exchange approaches. However, ligand exchange leads to an increase in surface defects and reduces the efficiencies of radiative recombination and charge transport, which restricts further applications. Here, we investigate the light-induced photoluminescence (PL) enhancement in chiral L- and D-cysteine CdSe QD thin films, providing a strategy to increase the PL. The PL intensity of chiral CdSe QD films can be significantly enhanced over 100 times by continuous UV laser irradiation, indicating a strong passivation of surface defects upon laser irradiation. From the comparative measurements of the PL intensity evolutions in vacuum, dry oxygen, air, and humid nitrogen atmospheres, we conclude that the mechanism of PL enhancement is photo-induced surface passivation with the assistance of water molecules. [ABSTRACT FROM AUTHOR]

Ammonium and carboxylic moieties play a central role in proton-mediated processes of molecular recognition, charge transfer or chemical change in (bio)materials. Whereas both chemical groups constitute acid–base pairs in organic salt-bridge structures, they may as well host excess protons in acidic environments. The binding of excess protons often precedes proton transfer reactions and it is therefore of fundamental interest, though challenging from a quantum chemical perspective. As a benchmark for this process, we investigate proton storage in the amphoteric compound 5-aminovaleric acid (AV), within an intramolecular proton bond shared by its primary amine and carboxylic acid terminal groups. Infrared ion spectroscopy is combined with ab initio Molecular Dynamics (AIMD) calculations to expose and rationalize the spectral signatures of protonated AV and its deuterated isotopologues. The dynamic character of the proton bond confers a fluxional structure to the molecular framework, leading to wide-ranging bands in the vibrational spectrum. These features are reproduced with remarkable accuracy by AIMD computations, which serves to lay out microscopic insights into the excess proton binding scenario. [ABSTRACT FROM AUTHOR]

A one-pot synthetic protocol to access a diverse library of diamide–diester macrocycles from the same starting materials is reported. The molecular symmetry can be readily tuned based on the reaction sequence, while the core structure can be varied using amino acids and aromatic building blocks. The first class of macrocycles with C2 axes in their molecular plane were obtained in 24 h with 40–70% yield, while another class with C2 axes perpendicular to the plane were synthesized in 18 h in 10–30% yield. The phenyl- and serine-derived macrocycles of the first class could bind acetate, chloride, and phosphate ions. These macrocycles can be functionalized with hydrophobic groups and potentially be used as ion transporters. [ABSTRACT FROM AUTHOR]

The development of complex molecular scaffolds with defined folding properties represents a central challenge in chemical research. Proteins are natural scaffolds defined by a hierarchy of structural complexity and have evolved to manifest unique functional characteristics; for example, molecular recognition capabilities that facilitate the binding of target molecules with high affinity and selectivity. Utilizing these features, proteins have been used as a starting point for the design of synthetic foldamers and enhanced biocatalysts, as well as bioactive reagents in drug discovery. In this account, we describe the strategies used in our group to stabilize protein folds, ranging from the constraint of bioactive peptide conformations to chemical protein engineering. We discuss the evolution of peptides into peptidomimetics to inhibit protein–protein and protein–nucleic acid interactions, and the selective chemical modification of proteins to enhance their properties for biotechnological applications. The reported peptide- and proteomimetic structures cover a broad range of molecular sizes and they highlight the importance of structure stabilization for the design of functional biomimetics. 1 Introduction 2 Constraining the Conformation of Peptides 3 Peptide-Based Covalent Protein Modifiers 4 Chemical Protein Engineering 5 Conclusions [ABSTRACT FROM AUTHOR]

The aim of this work is the development of a biomimetic strategy involving a molecular recognition mechanism using aptamers immobilized on a solid support for the analysis of the mycotoxin zearalenone (ZEA) and two of its derivatives in human urine: alpha-zearelenol (α-ZEL) and beta-zearelenol (β-ZEL). Three oligonucleotide sequences reported in the literature as being specific to ZEA were thus covalently grafted onto activated sepharose, and a thorough study of the percolation and washing conditions was performed to promote the selective retention of the three targeted compounds. With the optimized extraction procedure, a strong and selective retention was obtained for ZEA and to a lesser extent α-ZEL and β-ZEL, with extraction recoveries of 88±9%, 77±15%, and 45±12% respectively, in standard solutions. Application of this procedure to spiked human urine strongly highlighted the efficiency of the clean-up effect resulting from the use of this selective sorbent. Limits of quantification of the whole analytical procedure including extraction on oligosorbent and LC-MS analysis were 0.18 and 0.24 ng mL−1, for ZEA and α-ZEL, respectively, thus demonstrating clearly the potential of the developed method for monitoring human dietary exposure to these compounds. [ABSTRACT FROM AUTHOR]

Angiotensin II (Ang II) is a peptide hormone that causes vasoconstriction and an increase in blood pressure. Due to its relationship with cardiovascular diseases, it is an important biomarker in blood serum. In this study, Ang II imprinted nanoparticles were synthesized by miniemulsion polymerization reaction for the determination of Ang II from human serum. Hydroxyethyl methacrylate (HEMA) based Ang II imprinted (Ang II‐MIPnp) and non‐imprinted nanoparticles (NIPnp) were synthesized, characterized by zeta size analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transform infrared spectrophotometer (FTIR‐ATR). The average particle size of the NPs was recorded as 50 nm. Ang II molecules were successfully removed from the Ang II‐MIPnp with a 98% success rate using 0.5 M NaCl solution to obtain template‐specific cavities. Then, the adsorption studies were achieved. The binding capacity was found as 4500 pg. g−1 at 700 pg. mL−1 Ang II concentration. The selectivity studies showed that Ang II‐MIPnp can recognize Ang II molecules 2.76 times and 3.23 times selectivity than Ang I and Vsp respectively. Reusability studies shows that the synthesized nanomaterial is reusable. [ABSTRACT FROM AUTHOR]

Receptors for carboxylate anions have many possible biomedical applications, including mimicry of the vancomycin group of antibiotics. However, binding carboxylates in water, the biological solvent, is highly challenging due to the hydrophilicity of these polar anions. Here we report, for the first time, the recognition of simple carboxylates such as acetate and formate in water by synthetic receptors with charge‐neutral binding sites. The receptors are solubilised by polyanionic side‐chains which, remarkably, do not preclude anion binding. The tricyclic structures feature two identical binding sites linked by polyaromatic bridges, capable of folding into closed, twisted conformations. This folding is hypothesised to preorganise the structures for anion recognition, mimicking the process which generates many protein binding sites. The architecture is suitable for elaboration into enclosed structures with potential for selective recognition of biologically relevant carboxylates. [ABSTRACT FROM AUTHOR]

An efficient strategy for high‐performance chiral materials is to design and synthesize host molecules with left‐ and right‐ (M‐ and P‐)twisted conformations and to control their twisted conformations. For this, a quantitative analysis is required to describe the chiroptical inversion, chiral transfer, and chiral recognition in the host‐guest systems, which is generally performed using circular dichroism (CD) and/or proton nuclear magnetic resonance (1H NMR) spectroscopies. However, the mass‐balance model that considers the M‐ and P‐twisted conformations has not yet been established. In this study, we derived the novel equations based on the mass‐balance model for the 1 : 1 host‐guest systems. Then, we further applied them to analyze the 1 : 1 host‐guest systems for the achiral calixarene‐based capsule molecule, achiral dimeric zinc porphyrin tweezer molecule, and chiral pillar[5]arene with the chiral and/or achiral guest molecules by using the data obtained from the CD titration, variable temperature CD (VT−CD), and 1H NMR experiments. The thermodynamic parameters (ΔH and ΔS), equilibrium constants (K), and molar CD (Δϵ) in the 1 : 1 host‐guest systems could be successfully determined by the theoretical analyses using the derived equations. [ABSTRACT FROM AUTHOR]

The importance of anions in various processes has led to a search for molecules that can effectively recognize and interact with these anions. This study explores how the tetraglycine [(Gly)4] peptide in its zwitterionic, neutral, and terminally capped forms acts as a receptor for H2PO4− and HSO4− anions within the framework of supramolecular host‐guest chemistry. Using molecular dynamics (MD) simulations, we obtained the conformations of the receptor‐anion complexes. Density functional theory (DFT), quantifies the complexes' interaction energies in both gas and solvent phases. Proton transfer within the zwitterionic complex with H2PO4− anion alters peptide charge distribution, affecting its conformation and binding site arrangement, as analysed by quantum mechanics/molecular mechanics (QM/MM) methods. Symmetry‐adapted perturbation theory (SAPT) and noncovalent interactions analysis highlight the role of electrostatic interactions in these receptor‐anion complexes. It emphasizes the key interactions such as N−H⋅⋅⋅⋅O and O−H⋅⋅⋅O=C between the peptide backbone and anions and elucidates the molecular recognition mechanism driven by crucial noncovalent interactions. The termination of the peptide's end groups modulates anion binding sites from the backbone to the charged N‐terminal, resulting in distinct binding sites. Our findings provide insights for designing peptides tailored to function as anion receptors in diverse supramolecular chemistry applications. [ABSTRACT FROM AUTHOR]

In this review, a summary of the precursors, processing conditions, and exogenous additions involved in the synthesis of ethyl carbamate (EC) in fermented alcoholic beverages is provided. The discussion then shifts to the inhibitory effect of molecularly imprinted polymers (MIPs) on EC development, with a focus on the molecular mechanism behind MIP effective recognition and elimination of EC. MIPs work well to extract EC and its precursors from alcoholic fermented drinks. To provide a comprehensive explanation of the structure-activity connections and molecular recognition mechanisms, the inhibition of EC is covered in detail. More information is provided on the health risks posed by MIPs, and it is imperative that green MIPs be developed in order to make up for their shortcomings in food processing applications. Additionally covered are the potential drawbacks and alluring possibilities of MIPs for EC inhibition. [ABSTRACT FROM AUTHOR]

Comprehensive Summary The construction of luminescent two‐dimensional (2D) imine‐linked covalent organic frameworks (COFs) is a formidable challenge due to the strong interlayer stacking and bond rotations that typically suppress intramolecular charge transfer (ICT), leading to nonradiative energy dissipation. Herein, three COFs with tailored interlayer distances and bond rotations are designed to modulate the ICT behaviours. The targeted COF (TPAZ‐TPE‐COF) achieved a significantly enhanced photoluminescence quantum yield (PLQY) of 21.22% in the solid state by restricting bond rotation and enlarging the layer distance. This represents a 3.5‐fold and 530.5‐fold improvement over TPAZ‐PYTA‐COF (6.15%), which has a shortened interlayer space, and TPAZ‐PATA‐COF (0.04%), which exhibits strong bond rotations, respectively. Importantly, TPAZ‐TPE‐COF also exhibits exceptional sensing performance for iron ions, with a detection limit at the ppb level. Both experimental and theoretical analyses reveal that the prominent luminescent performance of TPAZ‐TPE‐COF is assigned to the effective suppression of nonradiative pathways, especially those arising from interlayer stacking and bond vibrations. These findings pave the way for deliberate construction of imine‐linked 2D COFs with high PL intensity, thereby expanding the portfolio of luminescent COFs with potential applications in sensing and optoelectronics. [ABSTRACT FROM AUTHOR]

Limited by the two mutually exclusive physicochemical processes of separation and recombination of photogenerated carriers, achieving photoluminescence and photocatalysis simultaneously is extremely challenging but essential for ever‐growing complex issues and specialized scenarios. Here we proposed a biomimetic isolation‐conduction strategy induced by an arene‐perfluoroarene (A−P) interaction for enabling photoluminescence and photocatalytic hydrogen evolution reaction (HER) activity in the co‐assembly of aromatic monomers and octafluoronapthalene (OFN). Inspired by the isolation‐conduction effect of periodic isolation of myelin sheaths on the axons of vertebrate nerve fibers by node of Ranvier, we use OFN as a molecular isolator embedded in the aromatic monomers array to block the singlet‐to‐triplet pathway, while the enlarged intermolecular dipoles resulting from the A−P interactions facilitate the conduction of photogenerated carriers in the isolated regions. The resultant co‐assembly exhibits an enhanced monomeric green emission compared to the corresponding monocomponent self‐assembly with weak red emission. Meanwhile, it also has an enhanced photocatalytic HER performance with a rate of 2.45 mmol g−1 h−1, which is 15.2 times more than the self‐assembled one. On this basis, a sequential fluoric wastewater reuse system that includes real‐time fluorescence detection/removal of perfluorooctanoic acids and photocatalytic HER device is constructed. [ABSTRACT FROM AUTHOR]

AbstractThe 4,5-diamine-2,6-dimercaptopyrimidine (DAD) molecule contains an aromatic N-heterocyclic center with two amino and two thiol groups, providing an attractive multifunctional ligand to be explored in coordination chemistry and molecular recognition studies. It reacts with [Ru(bipy)2Cl2] in the presence of air, yielding a [Ru(bipy)2DAD]2+ complex, which converts into the corresponding Ru(II)-diimine form, leaving the pyrimidine N-atoms and thiol groups available for participating in intermolecular association through selective hydrogen bonding. This expectation has been confirmed by resonance Raman spectroscopy in solution and the solid state through the detailed analysis of the vibrational peaks of the Ru(II)-bipy and Ru(II)-DAD chromophores under resonance Raman condition. Accordingly, it was observed that the DAD vibrational profiles are sensitive to molecular interactions in the solid state and the presence of species, such as creatinine, thus expressing a typical molecular recognition behavior. [ABSTRACT FROM AUTHOR]

Multimeric aptamer strategies are often adopted to improve the binding affinity of an aptamer toward its target molecules. In most cases, multimeric aptamers are constructed by connecting pre‐identified monomeric aptamers derived from in vitro selection. Although multimerization provides an added benefit of enhanced binding avidity, the characterization of different aptamer pairings adds more steps to an already lengthy procedure. Therefore, an aptamer engineering strategy that directly selects for multimeric aptamers is highly desirable. Here, an in vitro selection strategy is reported on using a pre‐structured DNA library that forms dimeric aptamers. Rather than using a library containing a single random region, which is nearly ubiquitous in existing aptamer selections, the library contains two random regions separated by a flexible poly‐thymidine linker. Following sixteen rounds of selection against the SARS‐CoV‐2 spike protein, a relevant model target protein due to the COVID‐19 pandemic, the top aptamers displayed superb affinity with KD values as low as 150 pM. Further analysis reveals that each random region functions as a distinct binding moiety and works together to achieve higher affinity. The demonstrated strategy provides an accelerated method to obtain high‐affinity aptamers, which may prove useful in future aptamer diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

The advancement of synthetic host–guest chemistry has played a pivotal role in exploring and quantifying weak non-covalent interactions, unraveling the intricacies of molecular recognition in both chemical and biological systems. Macrocycles, particularly calix[4]resorcinarene-based cavitands, have demonstrated significant utility in receptor design, facilitating the creation of intricately organized architectures. Within the realm of macrocycles, these cavitands stand out as privileged scaffolds owing to their synthetic adaptability, excellent topological structures, and unique recognition properties. So far, extensive investigations have been conducted on various applications of calix[4]resorcinarene-based cavitands. In this review, we will elaborate on their diverse functions, including catalysis, separation and purification, polymeric materials, sensing, battery materials, as well as drug delivery. This review aims to provide a holistic understanding of the multifaceted roles of calix[4]resorcinarene-based cavitands across various applications, shedding light on their contributions to advancing the field of supramolecular chemistry. [ABSTRACT FROM AUTHOR]

Targeted therapy is an attractive approach for treating infectious diseases. Affibody molecules have similar capability to antibodies that facilitate molecular recognition in both diagnostic and therapeutic applications. Targeting major outer membrane protein (MOMP) for treating infection of Chlamydia trachomatis , one of the most common sexually transmitted pathogens, is a promising therapeutic approach. Previously, we have reported a MOMP-specific affibody (ZMOMP:461) from phage display library. Here, we first fused it with modified Pseudomonas exotoxin (PE38KDEL) and a cell-penetrating peptide (CPP) to develop an affitoxin, Z461X-CPP. We then verified the addition of both toxin and CPPs that did not affect the affinitive capability of ZMOMP:461 to MOMP. Upon uptake by C trachomatis –infected cells, Z461X-CPP induced cell apoptosis in vitro. In an animal model, Z461X significantly shortened the duration of C trachomatis infection and prevented pathological damage in the mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C trachomatis infection. [ABSTRACT FROM AUTHOR]

Autophagy is a ubiquitous process of organelle interaction in eukaryotic cells, in which various organelles or proteins are recycled and operated through the autophagy pathway to ensure nutrient and energy homeostasis. Although numerous fluorescent probes have been developed to image autophagy, these environment‐responsive probes suffer from inherent deficiencies such as inaccuracy and limited versatility. Here, we present a modular macrocyclic amphiphile Förster Resonance Energy Transfer (FRET) platform (SC6A12C/NCM, SN), constructed through the amphiphilic assembly of sulfonatocalix[6]arene (SC6A12C) with N‐cetylmorpholine (NCM) for lysosome targeting. The hydrophobic fluorophore BPEA (FRET donor) was entrapped within the inner hydrophobic phase and showed strong fluorescence emission. Attributed to the broad‐spectrum encapsulation of SC6A12C, three commercially available organelle probes (Mito‐Tracker Red, ER Tracker Red, and RhoNox‐1) were selected as SC6A12C guests (FRET acceptors). During autophagy process, the formation of intracellular host–guest complexes leads to strong FRET signal, allowing us to visualize the fusion of mitochondria, endoplasmic reticulum, and Golgi apparatus with lysosomes, respectively. This study provides a versatile and accessible platform for imaging organelle autophagy. [ABSTRACT FROM AUTHOR]

G‐quadruplexes (G4 s), as non‐canonical DNA structures, attract a great deal of research interest in the molecular biology as well as in the material science fields. The use of small molecules as ligands for G‐quadruplexes has emerged as a tool to regulate gene expression and telomeres maintenance. Meso‐tetrakis‐(N‐methyl‐4‐pyridyl) porphyrin (TMPyP4) was shown as one of the first ligands for G‐quadruplexes and it is still widely used. We report an investigation comprising molecular docking and dynamics, synthesis and multiple spectroscopic and spectrometric determinations on simple cationic porphyrins and their interaction with different DNA sequences. This study enabled the synthesis of tetracationic porphyrin derivatives that exhibited binding and stabilizing capacity against G‐quadruplex structures; the detailed characterization has shown that the presence of amide groups at the periphery improves selectivity for parallel G4 s binding over other structures. Taking into account the ease of synthesis, 5,10,15,20‐tetrakis‐(1‐acetamido‐4‐pyridyl) porphyrin bromide could be considered a better alternative to TMPyP4 in studies involving G4 binding. [ABSTRACT FROM AUTHOR]

Although biocatalysis has garnered widespread attention in both industrial and academic realms, the enzymatic synthesis of chiral oxetanes remains an underdeveloped field. Halohydrin dehalogenases (HHDHs) are industrially relevant enzymes that have been engineered to accomplish the reversible transformation of epoxides. In this study, a biocatalytic platform was constructed for the stereoselective kinetic resolution of chiral oxetanes and formation of 1,3‐disubstituted alcohols. HheC from Agrobacterium radiobacter AD1 was engineered to identify key variants capable of catalyzing the dehalogenation of γ‐haloalcohols (via HheC M1‐M3) and ring opening of oxetanes (via HheC M4‐M5) to access both (R)‐ and (S)‐configured products with high stereoselectivity and remarkable catalytic activity, yielding up to 49 % with enantioselectivities exceeding 99 % ee and E>200. The current strategy is broadly applicable as demonstrated by expansion of the substrate scope to include up to 18 examples for dehalogenation and 16 examples for ring opening. Additionally, the functionalized products are versatile building blocks for pharmaceutical applications. To shed light on the molecular recognition mechanisms for the relevant variants, molecular dynamic (MD) simulations were performed. The current strategy expands the scope of HHDH‐catalyzed chiral oxetane ring construction, offering efficient access to both enantiomers of chiral oxetanes and 1,3‐disubstituted alcohols. [ABSTRACT FROM AUTHOR]

The document titled "Contents list" from Chemical Society Reviews provides a comprehensive overview of various research articles in the field of chemistry. Topics covered include covalent organic frameworks for environmental pollution control, chemical strategies for antisense antibiotics, and light-driven nitrogen fixation routes for green ammonia production. The journal showcases exceptional research on solar energy, photovoltaics, and advanced catalysis, offering valuable insights into cutting-edge developments in the field. [Extracted from the article]

The development of methodology for attaching ligand binding sites to proteins of interest has accelerated biomedical science. Such protein tags have widespread applications as well as properties that significantly limit their utility. This review describes the mechanisms and applications of supramolecular systems comprising the synthetic receptors cucurbit[7]uril (Q7) or cucurbit[8]uril (Q8) and their polypeptide ligands. Molecular recognition of peptides and proteins occurs at sites of 1–3 amino acids with high selectivity and affinity via several distinct mechanisms, which are supported by extensive thermodynamic and structural studies in aqueous media. The commercial availability, low cost, high stability, and biocompatibility of these synthetic receptors has led to the development of myriad applications. This comprehensive review compiles the molecular recognition studies and the resulting applications with the goals of providing a valuable resource to the community and inspiring the next generation of innovation. [ABSTRACT FROM AUTHOR]

This study reports a method for enhancing the functions and properties of traditional organic macrocyclic hosts by fully encapsulating them within a large M9L6 cage to form host‐in‐host complexes. Within the cage host, the macrocyclic organic hosts with electron‐rich aromatic rings, such as cyclotriveratrylene and calix[8]arene, adopt specific orientations enhancing their inherent molecular recognition abilities. Due to the high crystallinity of the M9L6 cage, the guest encapsulation behavior of the host‐in‐host complexes can be observed by X‐ray structural analysis. [ABSTRACT FROM AUTHOR]

We developed a pyridine–acetylene–phenol macrocycle in which a fluorine atom was introduced in place of a hydroxy group, as a host for the selective binding to epimers of glucose. The fluorine atom was expected to work as a negatively charged infill repelling oxygen atoms of saccharides and prevent the efficient formation of a hydrogen‐bond network with a glucoside, whose cross‐section size is larger than those of the corresponding epimers, especially of a mannoside. UV–Vis and fluorescence titration experiments revealed that this host showed a higher affinity for a mannoside than a glucoside. 1H NMR and molecular modeling suggested that the fluorine atom acts as a moderate infill weakening the binding to a glucoside. This result indicates that selectivity for guest molecules can be modified by replacing a hydroxy group and a hydrogen atom in host molecules with a fluorine atom. [ABSTRACT FROM AUTHOR]

ABSTRACT Transcriptional enhanced associate domain (Tead)–mediated Hippo signaling pathway regulates diverse physiological processes; its dysfunction has been implicated in an increasing number of human gynecological cancers. The transcriptional coactivator with PDZ‐binding motif (Taz) binds to and then activates Tead through forming a three‐helix bundle (THB) at their complex interface. The THB is defined by a double‐helical hairpin from Tead and a single α‐helix from Taz, serving as the key interaction hotspot between Tead and Taz. In the present study, the helical hairpin was derived from Tead protein to generate a hairpin segment, which is a 25‐mer polypeptide consisting of a longer helical arm‐1 and a shorter helical arm‐2 as well as a flexible loop linker between them. Dynamics simulation and energetics characterization revealed that the hairpin peptide is intrinsically disordered when splitting from its protein context, thus incurring a large entropy penalty upon binding to Taz α‐helix. A disulfide bridge was introduced across the two helical arms of hairpin peptide to obtain a strong binder termed TAZ‐hTrap, which can maintain in a considerably structured, native‐like conformation in unbound state, and the entropy penalty was minimized by disulfide stapling to effectively improve its affinity toward the α‐helix. These computational findings can be further substantiated by circular dichroism and fluorescence polarization at molecular level, and viability assay also observed a potent cytotoxic effect on diverse human gynecological tumors at cellular level. In addition, we further demonstrated that the TAZ‐hTrap has a good selectivity for its cognate Taz over other noncognate proteins that share a high conservation with the Taz α‐helix. [ABSTRACT FROM AUTHOR]

Protein phosphorylation is a crucial process in various cellular functions, and its irregularities have been implicated in several diseases, including cancer. Antibodies are commonly employed to detect protein phosphorylation in research. However, unlike the extensive studies on recognition mechanisms of the phosphate group by proteins such as kinases and phosphatases, only a few studies have explored antibody mechanisms. In this study, we produced and characterized two rabbit monoclonal antibodies that recognize a monophosphorylated Akt peptide. Through crystallography, thermodynamic mutational analyses, and molecular dynamics simulations, we investigated the unique recognition mechanism that enables higher binding affinity and selectivity of the antibodies compared to other generic proteins with lower binding affinity to phosphorylated epitopes. Our results demonstrate that molecular dynamics simulations provide novel insights into the dynamic aspects of molecular recognition of posttranslational modifications by proteins beyond static crystal structures, highlighting how specific atomic level interactions drive the exceptional affinity and selectivity of antibodies. [ABSTRACT FROM AUTHOR]

In this study, unconventional C—Hlg···H–C (Hlg = Cl, Br, and I) interactions involving sp, sp2, and sp3 organic halides were investigated at the RI-MP2/aug-cc-pVQZ level of theory. Energy Decomposition Analyses (EDA) and Natural Bonding Orbital (NBO) studies showed that these intermolecular contacts are mainly supported by orbital and dispersion contributions, which counteracted the unfavorable/slightly favorable electrostatics due to the halogen–hydrogen σ-hole facing. In addition, the Bader's Quantum Theory of Atoms in Molecules (QTAIM) and the Noncovalent Interaction plot (NCIplot) visual index methodologies were used to further characterize the interactions discussed herein. We expect that the results reported herein will be useful in the fields of supramolecular chemistry, crystal engineering, and rational drug design, where the fine tuning of noncovalent interactions is crucial to achieve molecular recognition or a specific solid-state architecture. [ABSTRACT FROM AUTHOR]

Metal nanoclusters (MNCs) are emerging as a novel class of luminescent nanomaterials with unique properties, bridging the gap between individual atoms and nanoparticles. Among these, DNA-templated MNCs have gained significant attention due to the synergistic combination of MNCs' properties (such as exceptional resistance to photostability, size-tunable emission, and excellent optical characteristics) with the inherent advantages of DNA, including programmability, functional modification, molecular recognition, biocompatibility, and water solubility. The programmability and biocompatibility of DNA offer precise control over the size, shape, and composition of MNCs, leading to tunable optical, electrical, and magnetic properties. This review delves into the complex relationship between DNA sequence, structure, and the resulting MNC properties. By adjusting parameters such as DNA sequence, length, and conformation, the size, morphology, and composition of the corresponding MNCs can be fine-tuned, enabling insights into how DNA structure influences the optical, electrical, and magnetic properties of MNCs. Finally, this review highlights the remarkable versatility and latest advancements of DNA-templated MNCs, particularly in biosensing and imaging, and explores their future potential to revolutionize biomedical applications. [ABSTRACT FROM AUTHOR]

Macrocycles are key tools for molecular recognition and self‐assembly. However, traditionally prevalent macrocyclic compounds exhibit specific cavities with diameters usually less than 1 nm, limiting their range of applications in supramolecular chemistry. The efficient synthesis of giant macrocycles remains a significant challenge because an increase in the monomer number results in cyclization‐entropy loss. In this study, we developed a low‐entropy‐penalty synthesis strategy for producing giant macrocycles in high yields. In this process, long and rigid monomers possessing two reaction modules were condensed with paraformaldehyde via Friedel–Crafts reaction. A series of giant macrocycles with cavities of sizes ranging from 2.0 to 4.7 nm were successfully synthesized with cyclization yields of up to 72%. Experimental results and theoretical calculations revealed that extending the monomer length rather than increasing the monomer numbers could notably reduce the cyclization‐entropy penalty and avoid configuration twists, thereby favoring the formation of giant macrocycles with large cavities. Significantly, the excellent self‐assembly capacity of these giant macrocycles promoted their assembly into organogels. The xerogels exhibited enhanced photoluminescence quantum efficiencies of up to 83.1%. Mechanism investigation revealed the excellent assembly capacity originated from the abundant π–π interactions sites of the giant macrocycles. The outstanding emission enhancement resulted from the restricted nonradiative decay processes of rotation/vibration and improved radiative decay process of fluorescence. This study provides an effective and general method for achieving giant macrocycles, thereby expanding the supramolecular toolbox for host–guest chemistry and assembly applications. Moreover, the intriguing assembly and photophysical properties demonstrate the feasibility of developing novel and unique properties by expanding the macrocycle size. [ABSTRACT FROM AUTHOR]

Catalysis plays a crucial role in modern chemistry, with macrocyclic compounds like calixarenes serving as key players in organic transformations through supramolecular chemistry. These macrocycles, synthesized from phenol and formaldehyde condensation, exhibit a variety of conformations, such as cone and partial‐cone, due to their flexible structures. Their effectiveness as catalysts arises from their lipophilic cavities and the ease of functionalization on both the upper and lower rims. Water‐soluble calixarenes, in particular, have gained attention for their ability to interact with hydrophobic cavities, facilitating molecular recognition in aqueous environments. A landmark achievement in this field was Shinkai's synthesis of water‐soluble calix[4]arene in 1984, which involved sulphonation using tert‐butyl groups, resulting in compounds known for their low toxicity and encapsulation capabilities. This review provides a comprehensive overview of the advancements in sulphonated calixarenes as catalysts, emphasizing their diverse applications and potential for future development. Key catalytic reactions and their substrate scopes are discussed, along with future perspectives on how these compounds can further revolutionize catalytic processes. [ABSTRACT FROM AUTHOR]

The three isomers of the tetraoxa[4]arene derivative, C24H16O4, which consist of two m-phenylenes and two phenylenes (meta 1, para 2, ortho 3), represent not only intriguing fundamental structures that induce molecular recognition toward non-porous adaptive crystals, but also attractive candidates for crystallographic polymorphism. In this study, we crystallized isomers 2 and 3, in comparison to isomer 1, in order to understand their stable orientations and the corresponding intermolecular interactions in the crystalline state. For example, m-phenylene derivative 1 exhibits polymorphism with both prismatic and block-shaped crystals. Therefore, we prepared p-phenylene derivative 2 and o-phenylene derivative 3, and their structures were fully characterized by SC-XRD, revealing two polymorphs of derivative 2, namely prismatic crystal 2-I and block-shaped crystal 2-II, along with changes to the crystal lattice parameters (2-Ia, 2-Ib, and 2-Ic) based on temperature dependence. In all of its crystal forms, derivative 2 adopts an O-shaped planar structure, where the p-phenylene units face each other. This suggests that the packing mode during the early stages of crystallization, rather than due to any remarkable changes in the molecular structure, directly affects the bulk crystal morphology. On the other hand, derivative 3 adopts a U-shaped vent structure and, to the best of our knowledge, does not form polymorphs. The Platon and Hirshfeld surface analyses indicated that the contributions to the crystal packing were C···C (av. 37.3% for 2-Ia, av. 38.2% for 2-II, and 18.7% for 3), C···H/H···C (av. 37.3% for 2-Ia, av. 38.2% for 2-II, and 18.7% for 3), and O···H/H···O (av. 17.8% for 2-Ia, av. 19.6% for 2-II, and 19.4% for 3), highlighting significant intermolecular CH···π interactions and pseudo-hydrogen bonding forms for derivative 2 and π···π interactions for derivative 3. [ABSTRACT FROM AUTHOR]

We report the synthesis and characterization of sulfated pillar[5]arene hosts (P5S2‐P5S10) that differ in the number of sulfate substituents. All five P5Sn hosts display high solubility in water (73–131 mM) and do not undergo significant self‐association according to 1H NMR dilution experiments. The x‐ray crystal structures of P5S6, P5S6 ⋅ Me6HDA, P5S8 ⋅ Me6HDA, and P5S10 ⋅ Me6HDA reveal one intracavity molecule of Me6HDA and several external molecules of Me6HDA which form a network of close methonium ⋅ ⋅ ⋅ sulfate interactions. The thermodynamic parameters of complexation between P5Sn and the panel of guests was measured by direct or competitive isothermal titration calorimetry. We find that the binding free energy toward a guest becomes more negative as the number of sulfate substituents increase. Conversely, the binding free energy of a specific sulfated pillar[5]arene toward a homologous series of guests becomes more negative as the number of NMe groups increases. The ability to tune the host ⋅ guest affinity by changing the number of sulfate substituents will be valuable in supramolecular polymers, separation materials, and latching applications. [ABSTRACT FROM AUTHOR]

Glycan‐mediated molecular recognition events are essential for life. NMR is widely used to monitor glycan binding to lectins in solution using isolated glycans and lectins. In this context, we herein explore diverse NMR methodologies, from both the receptor and ligand perspectives, to monitor glycan‐lectin interactions under experimental conditions mimicking the native milieu inside cells and on cell surface. For the NMR experiments inside cells, galectin‐7 is employed as model, since most galectins are soluble and carry out their functions in the cellular micro‐environment. Using Danio Rerio oocytes, the 1H‐15N HMQC NMR spectrum of a folded galectin has been observed inside cell for the first time, using a glycomimetic ligand (TDG) to overcoming the natural tendency of galectins to bind to numerous galactose‐containing receptors within cells. Alternatively, most lectins, other than galectins, are displayed on the cell surface, providing a multivalent presentation to bind their glycan partners in cis (at the same cell) or in trans (on other cells). In this case, ligand‐based STD‐NMR experiments have been successfully applied to account for the interactions of natural glycans and glycomimetics with Siglec‐10. These methodologies provide the proof‐of‐concept to open the door to the NMR analysis of the recognition of glycans in native‐like settings. [ABSTRACT FROM AUTHOR]

We have developed a family of dinuclear complexes using 2,7‐disubstituted 1,8‐naphthalenediol ligands that bind by molecular recognition to two neighboring phosphate diesters of the DNA backbone with the dinuclear CuII and NiII complexes exhibiting a severe cytotoxicity for human cancer cells. To increase the binding affinity, we intended to synthesize the corresponding dinuclear FeIII complex. Surprisingly, we obtained a tetranuclear FeIII perylene‐based complex instead of the expected dinuclear FeIII naphthalene‐based complex. In order to establish a rational and reproducible synthesis, we carefully analyzed this reaction. This revealed a multistep oxidative cascade reaction including the pre‐coordination of FeII ions in the N3‐binding pockets, the Lewis‐acid assisted MOM‐deprotection of the pre‐ligand by the pre‐oriented FeII ions, two oxidative aromatic C−C coupling reactions, oxidation of the perylene‐based backbone and of FeII to FeIII. The careful analysis of bond lengths, HOMA indices (harmonic oscillation model of aromaticity), FTIR and UV‐Vis‐NIR spectra supported by DFT calculations reveals the presence of an aromatic 18‐electron oxidized perylenequinone ligand backbone. In summary, a multistep cascade reaction involving in total a 10‐electron oxidation has been established for the straight‐forward synthesis of an unprecedented perylenequinone‐based ligand system. [ABSTRACT FROM AUTHOR]

Cage‐type structures based on coordination and dynamic covalent chemistry have the characteristics of facile and efficient preparation but poor stability. Chemically stable organic cages, generally involving fragment coupling and multi‐step reactions, are relatively difficult to synthesize. Herein, we offer a general and modular strategy to customize covalent organic cages with diverse skeletons and sizes. First, one skeleton (S) module with three extension (E) modules and three reaction (R) modules are connected by one‐ or two‐step coupling to get the triangular monomer bearing three reaction sites. Then one‐pot Friedel‐Crafts condensation of the monomer and linking module of paraformaldehyde produces the designed organic cages. The cage forming could be regulated by the geometrical configuration of monomeric blocks. The S−E−R angles in the monomer is crucial; only 120° (2,4‐dimethoxyphen as reaction module) or 60° (2,5‐dimethoxyphen as reaction module) angle between S−E−R successfully affords the resulting cages. By the rational design of the three modules, a series of organic cages have been constructed. In addition, the host‐guest properties show that the representative cages could strongly encapsulate neutral aromatic diimide guests driven by solvophobic interactions in polar solvents, giving the highest association constant of (2.58±0.18)×105 M−1. [ABSTRACT FROM AUTHOR]

GTP-binding proteins are essential molecular switches that regulate a wide range of cellular processes. Their function relies on the specific recognition and binding of guanine within their binding pockets. This study aims to elucidate the molecular determinants underlying this recognition. A large-scale data mining of the Protein Data Bank yielded 298 GTP-binding protein complexes, which provided a structural foundation for a systematic analysis of the intermolecular interactions that are responsible for the molecular recognition of guanine in proteins. It was found that multiple modes of non-bonded interactions including hydrogen bonding, cation–π interactions, and π–π stacking interactions are employed by GTP-binding proteins for binding. Subsequently, the strengths of non-bonded interaction energies between guanine and its surrounding protein residues were quantified by means of the double-hybrid DFT method B2PLYP-D3/cc-pVDZ. Hydrogen bonds, particularly those involving the N2 and O6 atoms of guanine, confer specificity to guanine recognition. Cation–π interactions between the guanine ring and basic residues (Lys and Arg) provide significant electrostatic stabilization. π–π stacking interactions with aromatic residues (Phe, Tyr, and Trp) further contribute to the overall binding affinity. This synergistic interplay of multiple interaction modes enables GTP-binding proteins to achieve high specificity and stability in guanine recognition, ultimately underpinning their crucial roles in cellular signaling and regulation. Notably, the NKXD motif, while historically considered crucial for guanine binding in GTP-binding proteins, is not universally required. Our study revealed significant variability in hydrogen bonding patterns, with many proteins lacking the NKXD motif but still effectively binding guanine through alternative arrangements of interacting residues. [ABSTRACT FROM AUTHOR]

Congenital heart defects (CHDs) rank among the most common birth defects, presenting diverse phenotypes. Genetic and environmental factors are critical in molding the process of cardiogenesis. However, these factors' interactions are not fully comprehended. Hence, this study aimed to identify and characterize differentially expressed genes involved in CHD development through bioinformatics pipelines. We analyzed experimental datasets available in genomic databases, using transcriptome, gene enrichment, and systems biology strategies. Network analysis based on genetic and phenotypic ontologies revealed that EP300, CALM3, and EGFR genes facilitate rapid information flow, while NOTCH1, TNNI3, and SMAD4 genes are significant mediators within the network. Differential gene expression (DGE) analysis identified 2513 genes across three study types, (1) Tetralogy of Fallot (ToF); (2) Hypoplastic Left Heart Syndrome (HLHS); and (3) Trisomy 21/CHD, with LYVE1, PLA2G2A, and SDR42E1 genes found in three of the six studies. Interaction networks between genes from ontology searches and the DGE analysis were evaluated, revealing interactions in ToF and HLHS groups, but none in Trisomy 21/CHD. Through enrichment analysis, we identified immune response and energy generation as some of the relevant ontologies. This integrative approach revealed genes not previously associated with CHD, along with their interactions and underlying biological processes. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Carbohelicenes have garnered considerable attention for their inherent chirality and structural flexibility. Increasing multi‐helicity and incorporating non‐six‐membered rings to substitute benzenoid rings within helicenes are effective strategies for introducing unique photoelectric properties. Despite the disclosure of numerous helicenes, the inaccessible precursors and the lack of synthetic routes pose a challenge in achieving desired helicene structures fused with non‐benzenoid rings. Herein, we report the synthesis of multiple non‐benzenoid carbohelicenes fused with fluorene unit(s) through intramolecular cyclodehydrogenation of 9,10‐di(naphthalen‐1‐ yl)anthracene on Au(111) surface. Two potential cyclodehydrogenation manners between naphthyl and anthracene lead to the formation of fluorene‐fused [5]helicene and [4]helicene moiety. Consequently, a total of four stable products were observed. The atomic topographies of products are characterized by bond‐resolving scanning tunneling microscopy. The chiral helicity of targeted products can be switched by tip manipulation. Density‐functional‐theory calculations unveils the reaction pathway of four products. The comparative analysis of their respective energy barriers exhibits a correlation with the experimentally determined yields. Furthermore, we synthesize the polymer chains incorporating non‐benzenoid carbohelicenes via the Ullmann reaction of 2,6‐dibromo‐9,10‐di(1‐naphthyl)anthracene precursors. Our work proposes a synthetic methodology for several novel helicene‐like structures fused with fluorene units and the polymer bearing helicene subunits, thus highlighting the immense potential of these compounds in the application fields of luminescent electronic devices. [ABSTRACT FROM AUTHOR]

This compound is a synthetic macrocycle comprising three pivaloyl‐protected resorcinarene units connected by six pentylene chains. We conducted a conformational study using 1H‐NMR, X‐ray diffraction (XRD), and computational analyses. The macrocycle adopts two conformers, one open, the other closed. The ratio of the open to closed forms depended on the solvent used. Only the open form existed in [D8]toluene, both forms coexisted in [D6]benzene, and the closed form was the major conformer in [D1]chloroform. The benzene‐solvated open form observed in the solid state suggests that cavity solvation by solvent molecules directs the open form. The open form was the major or only conformer in [D10]o‐ and [D10]m‐xylene and [D12]mesitylene, whereas the closed form was the major conformer in [D6]acetone. The open and closed forms were equally populated in [D10]p‐xylene, suggesting that the size, shape, and dimensions of the solvent molecules most likely influenced the conformation of the protected trisresocinarene. [ABSTRACT FROM AUTHOR]

Protein surfaces have pivotal roles in interactions between proteins and other biological molecules. However, the structural dynamics of protein surfaces have rarely been explored and are poorly understood. Here, the surface of a single‐stranded DNA (ssDNA) binding protein (SSB) with four DNA binding domains that bind ssDNA in binding site sizes of 35, 56, and 65 nucleotides per tetramer is investigated. Using oligonucleotides as probes to sense the charged surface, NaCl induces a two‐state structural transition on the SSB surface even at moderate concentrations. Chelation of sodium ions with charged amino acids alters the network of hydrogen bonds and/or salt bridges on the surface. Such changes are associated with changes in the electrostatic potential landscape and interaction mode. These findings advance the understanding of the molecular mechanism underlying the enigmatic salt‐induced transitions between different DNA binding site sizes of SSBs. This work demonstrates that monovalent salt is a key regulator of biomolecular interactions that not only play roles in non‐specific electrostatic screening effects as usually assumed but also may configure the surface of proteins to contribute to the effective regulation of biomolecular recognition and other downstream events. [ABSTRACT FROM AUTHOR]