Irreversible Covalent Bond Research Articles

Rapid in situ forming PEG hydrogels for mucosal drug delivery.

In situ gelling polymeric biomaterials have proven useful as drug delivery vehicles to enable sustained release at sites of disease or injury. However, if delivered to mucosal tissues, such as the eyes, nose, gastrointestinal, and cervicovaginal tract, these gels must also possess the ability to adhere to an epithelium coated in mucus. Towards this end, we report a new rapid in situ gelling polyethylene glycol-based hydrogel. Unlike other chemistries that enable rapid gel formation which form via irreversible covalent bonds, we use a bio-reducible linker allowing the gels to be naturally degraded over several days once administered. We identified a set of 6 lead formulations, which rapidly form into disulfide-linked PEG hydrogels in 30 seconds or less. These rapidly forming PEG hydrogels were also able to conform and adhere to mucosal tissues via PEG-mucin entanglements and hydrogen bonding. Controlled release of protein-based cargoes from the PEG gels was achieved over several hours whereas 40 nm nanoparticle-based cargos were retained over 24 hours. We also found these rapid in situ forming PEG gels were well-tolerated by mammalian cells. These studies support further testing and development of rapid in situ forming PEG gels for drug delivery to improve therapeutic retention and efficacy at mucosal sites.

Ordered Carbonaceous Framework Synthesized from Hexaazatrinaphthylene with Enediyne Groups via Solid-State Bergman Cyclization Reaction.

Porous materials synthesized through bottom-up approaches, such as metal-organic frameworks and covalent organic frameworks, have attracted attention owing to their design flexibility for functional materials. However, achieving the chemical and thermal stability of these materials for various applications is challenging considering the reversible coordination bonds and irreversible covalent bonds in their frameworks. Thus, ordered carbonaceous frameworks (OCFs) emerge as a promising class of bottom-up materials with good periodicity, thermal and chemical stability, and electrical conductivity. However, a few OCFs have been reported owing to the limited range of precursor molecules. Herein, we designed a hexaazatrinaphthylene-based molecule with enediyne groups as a precursor molecule for synthesizing an OCF. The solid-state Bergman cyclization of enediyne groups at a low temperature formed a microporous polymer and an OCF, exhibiting redox activity and demonstrating their potential for electrochemical applications. The microporous polymer was used as an active material in sodium-ion batteries, while the OCF was used as an electrochemical capacitor. These findings illustrate the utility of the Bergman cyclization reaction for synthesizing microporous polymers and OCFs with a customizable functionality for broad applications.

Foldamer-Based Mechanoresponsive Materials: Molecular Nanoarchitectonics to Advanced Functions.

Artificial molecules that respond to external stimuli such as light, heat, chemical signals, and mechanical force have garnered significant interest due to their tunable functions, variable optical properties, and mechanical responses. Particularly, mechanoresponsive materials featuring molecules that respond to mechanical stress or show force-induced optical changes have been intriguing due to their extraordinary functions. Despite the promising potential of many such materials reported in the past, practical applications have remained limited, primarily because their functions often depend on irreversible covalent bond rupture. Foldamers, oligomers that fold into well-defined secondary structures, offer an alternative class of mechanoactive motifs. These molecules can reversibly sustain mechanical stress and efficiently dissipate energy by transitioning between folded and unfolded states. This review focuses on the emerging properties of foldamer-based mechanoresponsive materials. We begin by highlighting the mechanical responses of foldamers in their molecular form, which have been primarily investigated using single-molecule force spectroscopy and other analytical methods. Following this, we provide a detailed survey of the current trends in foldamer-appended polymers, emphasizing their emerging mechanical and mechanochromic properties. Subsequently, we present an overview of the state-of-the-art advancements in foldamer-appended polymers, showcasing significant reports in this field. This review covers some of the most recent advances in this direction and draws a perspective for further development.

Ebselen: A Review on its Synthesis, Derivatives, Anticancer Efficacy and Utility in Combating SARS-COV-2.

Ebselen is a selenoorganic chiral compound with antioxidant properties comparable to glutathione peroxidase. It is also known as 2-phenyl-1,2-benzisoselenazol-3(2H)-one. In studies examining its numerous pharmacological activities, including antioxidant, anticancer, antiviral, and anti- Alzheimer's, ebselen has demonstrated promising results. This review's primary objective was to emphasize the numerous synthesis pathways of ebselen and their efficacy in fighting cancer. The data were collected from multiple sources, including Scopus, PubMed, Google Scholar, Web of Science, and Publons. The starting reagents for the synthesis of ebselen are 2-aminobenzoic acid and N-phenyl benzamide. It was discovered that ebselen has the ability to initiate apoptosis in malignant cells and prevent the formation of new cancer cells by scavenging free radicals. In addition, ebselen increases tumor cell susceptibility to apoptosis by inhibiting TNF-α mediated NF-kB activation. Ebselen can inhibit both doxorubicin and daunorubicin-induced cardiotoxicity. Allopurinol and ebselen administered orally can be used to suppress renal ototoxicity and nephrotoxicity. Due to excessive administration, diclofenac can induce malignancy of the gastrointestinal tract, which ebselen can effectively suppress. Recent research has demonstrated ebselen to inhibit viral function by binding to cysteinecontaining catalytic domains of various viral proteases. It was discovered that ebselen could inhibit the catalytic dyad function of Mpro by forming an irreversible covalent bond between Se and Cys145, thereby altering protease function and inhibiting SARS-CoV-2. Ebselen may also inhibit the activation of endosomal NADPH oxidase of vascular endothelial cells, which is believed to be required for thrombotic complications in COVID-19. In this review, we have included various studies conducted on the anticancer effect of ebselen as well as its inhibition of SARS-CoV-2.

Mussel-Inspired Antimicrobial and Antifouling Coating Constructed by the Combination of Zwitterionic Copolymers and Silver Nanoparticles.

Biofouling and bacterial infections are significant challenges in biomedical devices. In this study, a biocompatible dual-functional coating with antimicrobial and antifouling properties is developed by co-depositing the zwitterionic copolymer and silver nanoparticles via a dopamine-assisted strategy. Inspired by mussel adhesion, the coating exhibits substrate-independent adhesion as a result of the formation of irreversible covalent bonds. The zwitterionic copolymer in the dual coating plays a crucial role in improving surface wettability and reducing protein adsorption and platelet and bacterial adhesion, thereby improving its antifouling property significantly. The silver nanoparticles reduced by self-polymerized polydopamine without the addition of any chemical reductants can effectively improve the antimicrobial activity. Furthermore, as the zwitterion content in the zwitterion polymer increases, the antibacterial and antifouling properties of the coating can be further advanced. The simple and effective approach presented here provides a promising pathway for constructing potent antibacterial and antifouling surfaces, demonstrating great potential for clinical applications in implanted materials.

Detoxifying Cyanides Using Cyanase Enzyme Complexes Composed of Carbonic Anhydrase via Irreversible Covalent Bonds.

Cyanase is a possible solution to reduce the environmental impact of cyanide. However, the enzyme's dependence on HCO3- limits its industrial applications. To overcome this problem, carbonic anhydrase is utilized in this study. Three types of Catcher/Tag systems were introduced into the cyanase (psCYN) from Pseudomonas stutzeri and the carbonic anhydrase (hmCA) from Hydrogenovibrio marinus to construct enzyme complexes via irreversible covalent bonds. Initially, a cyanase complex with the aid of scaffolding proteins was designed. The results of cyanase complexes using scaffolding proteins were similar to or inferior to those of the two free enzymes. To address this, the two enzymes were manipulated to form a direct bioconjugation without the need for scaffolding proteins. The two enzymes forming a direct conjugation showed activity more than 2.5 times higher than that of cyanase alone. In conclusion, this outcome will contribute to solving problems related to residual cyanides in food and the environment.

Pyrolysis-Free Covalent Organic Polymers Directly for Oxygen Electrocatalysis.

ConspectusOxygen electrode catalysis is crucial for the efficient operation of clean energy devices, such as proton exchange membrane fuel cells (PEMFCs) and Zn-air batteries (ZABs). However, sluggish oxygen electrocatalysis kinetics in these infrastructures put forward impending requirements toward seeking efficient oxygen-electrode catalytic materials with a clear active-site configuration and geometrical morphology to study in depth the structure-property relationship of materials. Although transition-metal-nitrogen-carbon (M-N-C) electrocatalysts have shown great prospects currently and potential in oxygen electrocatalysis as promising platinum group metal-free catalysts, the universal pyrolysis operation in the preparation process often inevitably brings about randomness and diversity of active sites, for which it is difficult to determine the structure-activity relationship, understand the catalytic mechanism, and further improve facilities performance.Covalent organic polymers (COPs) are a class of molecular geometric constructs linked by irreversible kinetic covalent bonds through reticular chemistry. Unique structural tailorability, diverse design principles, and inherent well-defined construction in pristine COPs naturally provide a great platform to study the structure-property relationship of active sites and exhibit unique features for application. In this Account, we afford an overview of our recent attempts toward the utilization of COP materials as free-pyrolysis oxygen electrode catalysts, enabling accurate construction of oxygen electrodes with clear active site and geometrical morphology characteristics in PEMFC and ZAB devices yet without enduring any high-temperature pyrolysis treatments. Starting from the needs of modern electrocatalysis, we discussed the unique properties for the design and development of pyrolysis-free pristine COPs as high-performance oxygen electrode catalytic materials in terms of intrinsic electronic structure properties and membrane-electrode-assembly (MEA) application distinguished from pyrolysis M-N-C catalysts. First, the pyrolysis-free COP catalysts provide a viable molecular model catalyst platform, which is conducive to mechanism comprehension for the relationship between catalyst activity and structure. Second, the simple and low-energy consumption synthesis process for pyrolysis-free catalysts lays the foundation for the large-scale production of catalysts, oxygen electrodes, and even the entire stack assembly without considering numerous complicated factors as traditional pyrolytic catalysts. Besides, most traditional COPs are difficult to dissolve and solution process due to their cross-linked skeleton. Our newly developed COP materials with solution processability bring about new opportunities to the process and assemble oxygen electrodes into device. These properties are unparalleled and have not been systematically reviewed and analyzed by any research reports so far. Here, we have clarified the specific advantage and potential of pyrolysis-free COP materials as oxygen electrodes applied in PEMFC and ZAB devices in response to the latest progress and requirements of current electrocatalytic research.

One-Pot Cyclization to Large Peptidomimetic Macrocycles by In Situ-Generated β-Turn-Enforced Folding.

Macrocycles have been targets of extensive synthetic efforts for decades because of their potent molecular recognition and self-assembly capabilities. Yet, efficient syntheses of macrocyclic molecules via irreversible covalent bonds remain challenging. Here, we report an efficient approach to large peptidomimetic macrocycles by using the in situ-generated β-turn structural motifs afforded in the amidothiourea moieties from the early steps of the reaction of 2 molecules of bilateral amino acid-based acylhydrazine with 2 molecules of diisothiocyanate. Four chiral and achiral peptidomimetic large macrocycles were successfully synthesized in high yields of 45-63% in a feasible one-pot reaction under sub-molar concentration conditions and were purified by simple filtration. X-ray crystallographic characterization of three macrocycles reveals an important feature that their four β-turn structures, each maintained by four 10-membered intramolecular hydrogen bonds, alternatively network the four aromatic arms. This affords an interesting conformation switching mode upon anion binding. Binding of SO42- to 1L or 1D that contains 4 alanine residues (with the lowest steric hinderance among the macrocycles) leads to an inside-out structural change of the host macrocycle, as confirmed by the X-ray crystal structure of 1L-SO42- and 1D-SO42- complexes, accompanied by an inversion of the CD signals. On the basis of the strong sulfate affinity of the macrocycles, we succeeded in the removal of sulfate anions from water via a macrocycle-mediated liquid-liquid extraction method. Our synthetic protocol can be easily extended to other macrocycles of varying arms and/or chiral amino acid residues; thus, a variety of structurally and functionally diverse macrocycles are expected to be readily made.

Effect of SpyTag/SpyCatcher cyclization on reactivation of covalently immobilized biocatalysts

SpyTag and SpyCatcher can rapidly conjugate covalently to form an irreversible covalent bond. Fusing SpyTag and SpyCatcher to the termini of a protein of interest enables the generation of SpyRing structure, which is often helpful for the stability of protein. In this paper, green fluorescent protein (GFP), L-phenylserine aldolase (LPA) and SRGFP, SRLPA (their SpyRing cyclized form) were covalently bound to glyoxyl-agarose (Gx) beads to prepare immobilized enzymes (Gx-GFP, Gx-LPA, Gx-SRGFP and Gx-SRLPA) with different protein loadings, and the effects of the SpyRing structure on solid-phase refolding were investigated. When the immobilized enzyme was inactivated in high concentrations of N, N-dimethylformamide (DMF) and 9 M guanidine hydrochloride, then reactivated with refolding buffer, the results showed that proteins with the SpyRing structure had a higher renaturation yield than their wild-type counterparts in all three replication cycles. The highest renaturation yields of Gx-SRGFP and Gx-SRLPA were over 90 % and 70 % respectively, which were approximately 15 % and 30 % higher than those of Gx-GFP and Gx-LPA. It suggests that the introduction of the SpyRing structure facilitates the reactivation of immobilized biocatalysts and provides a reference for the regeneration and recycling of industrial biocatalysts.

Synthesis and metalation of polycatechol nanohoops derived from fluorocycloparaphenylenes.

Due to their unique topology and distinct physical properties, cycloparaphenylenes (CPPs) are attractive building blocks for new materials synthesis. While both noncovalent interactions and irreversible covalent bonds have been used to link CPP monomers into extended materials, a coordination chemistry approach remains less explored. Here we show that nucleophilic aromatic substitution reactions can be leveraged to rapidly introduce donor groups (-OR, -SR) onto polyfluorinated CPP rings. Demethylation of methoxide-substituted CPPs produces polycatechol nanohoop ligands that are readily metalated to produce well-defined, multimetallic CPP complexes. As catechols are recurring motifs throughout coordination chemistry and dynamic covalent chemistry, the polycatechol nanohoops reported here open the door to new strategies for the bottom-up synthesis of atomically precise CPP-based materials.

Balanced Coexistence of Reversible and Irreversible Covalent Bonds in a Conductive Triple Polymeric Network Enables Stretchable Hydrogels with High Toughness and Adhesiveness.

The application of soft hydrogels to stretchable devices has attracted increasing attention in deformable bioelectronics owing to their unique characteristic, "modulus matching between materials and organs". Despite considerable progress, their low toughness, low conductivity, and absence of tissue adhesiveness remain substantial challenges associated with unstable skin-interfacing, where body movements undesirably disturb electrical signal acquisitions. Herein, we report a material design of a highly tough strain-dissipative and skin-adhesive conducting hydrogel fabricated through a facile one-step sol-gel transition and its application to an interactive human-machine interface. The hydrogel comprises a triple polymeric network where irreversible amide linkage of polyacrylamide with alginate and dynamic covalent bonds entailing conjugated polymer chains of poly(3,4-ethylenedioxythiophene)-co-(3-thienylboronic acid) are simultaneously capable of high stretchability (1300% strain), efficient strain dissipation (36,209 J/m2), low electrical resistance (590 Ω), and even robust skin adhesiveness (35.0 ± 5.6 kPa). Based on such decent characteristics, the hydrogel was utilized as a multifunctional layer for successfully performing either electrophysiological cardiac/muscular on-skin sensors or an interactive stretchable human-machine interface.

Nitrogen-rich based conjugated microporous polymers for highly efficient adsorption and removal of COVID-19 antiviral drug chloroquine phosphate from environmental waters

Chloroquine phosphate (CQP) has been suggested as an important and effective clinical reliever medication for the 2019 coronavirus (COVID-19). Nevertheless, its excessive use will inevitably cause irreparable damage to the entire ecosystem, thereby posing a considerable environmental safety concern. Hence, the development of highly-efficient methods of removing CQP from water pollution sources, e.g., effluents from hospitals and pharmaceutical factories is significant. This study reported the fabrication of novel CN bond linked conjugated microporous polymers (CMPs) (BPT–DMB–CMP) with multiple nitrogen-rich anchoring sites for the quick and efficient removal of CQP from aqueous solutions. The irreversible covalent CN bond linked in the internal framework of BPT–DMB–CMP endowed it with good chemical stability and excellent adsorbent regeneration. With its predesigned functional groups (i.e., rich NH bonds, triazine rings, and benzene rings) and large area surface (1,019.89 m2·g−1), BPT–DMB–CMP demonstrated rapid adsorption kinetics (25 min) and an extraordinary adsorption capacity (334.70 mg·g−1) for CQP, which is relatively higher than that of other adsorbents. The adsorption behavior of CQP on BPT–DMB–CMP corresponded with Liu model and mixed-order model. Based on the density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and adsorption comparisons test, the halogen bonding, and hydrogen bonding cooperates with π − π, C H···π interactions and size-matching effect in the CQP adsorption system on BPT–DMB–CMP. The excellent practicability for the removal of CQP from real wastewater samples verified the prospect of practical application of BPT–DMB–CMP. BPT–DMB–CMP exhibited the application potentials for the adsorption of other antiviral drugs. This work opens up an efficient, simple, and high adsorption capacity way for removal CQP.

Switching of Photocatalytic Tyrosine/Histidine Labeling and Application to Photocatalytic Proximity Labeling.

Weak and transient protein interactions are involved in dynamic biological responses and are an important research subject; however, methods to elucidate such interactions are lacking. Proximity labeling is a promising technique for labeling transient ligand–binding proteins and protein–protein interaction partners of analytes via an irreversible covalent bond. Expanding chemical tools for proximity labeling is required to analyze the interactome. We developed several photocatalytic proximity-labeling reactions mediated by two different mechanisms. We found that numerous dye molecules can function as catalysts for protein labeling. We also identified catalysts that selectively modify tyrosine and histidine residues and evaluated their mechanisms. Model experiments using HaloTag were performed to demonstrate photocatalytic proximity labeling. We found that both ATTO465, which catalyzes labeling by a single electron transfer, and BODIPY, which catalyzes labeling by singlet oxygen, catalyze proximity labeling in cells.

Ionic Compatibilization of Polymers.

The small specific entropy of mixing of high molecular weight polymers implies that most blends of dissimilar polymers are immiscible with poor physical properties. Historically, a wide range of compatibilization strategies have been pursued, including the addition of copolymers or emulsifiers or installing complementary reactive groups that can promote the in situ formation of block or graft copolymers during blending operations. Typically, such reactive blending exploits reversible or irreversible covalent or hydrogen bonds to produce the desired copolymer, but there are other options. Here, we argue that ionic bonds and electrostatic correlations represent an underutilized tool for polymer compatibilization and in tailoring materials for applications ranging from sustainable polymer alloys to organic electronics and solid polymer electrolytes. The theoretical basis for ionic compatibilization is surveyed and placed in the context of existing experimental literature and emerging classes of functional polymer materials. We conclude with a perspective on how electrostatic interactions might be exploited in plastic waste upcycling.

Safety and tolerability of Bruton's tyrosine kinase inhibitors in the treatment of Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM) is an indolent B-cell non-Hodgkin lymphoma (NHL) characterized by malignant B cells that produce IgM monoclonal protein. Like other indolent B-cell NHLs, treatment is indicated when patients are symptomatic with lymphadenopathy, splenomegaly or have detrimental cytopenias, but uniquely hyperviscosity and other complications related to gammopathy may present a need for treatment. Currently in Canada chemoimmunotherapy using bendamustine and rituximab (BR) is the favored therapeutic combination for treatment-naïve patients with WM due to a superior efficacy and toxicity profile compared to rituximab plus CHOP and a fixed duration schedule. The availability of Bruton’s tyrosine kinase inhibitors (BTKi) have transformed the treatment landscape for patients with WM, particularly in the relapsed setting. Ibrutinib, a once-daily BTKi, was approved by Health Canada (HC) for WM in 2016 based on two non-randomized studies showing high response rates in heavily pretreated rituximab-refractory patients with sustained efficacy (86% progression-free survival (PFS) at 18 months) and acceptable tolerability. Ibrutinib forms an irreversible covalent bond to the cysteine residue (C481) at the active binding site of BTK. Patients with mutated MYD88 (MYD88MUT), who represent over 90% of patients with WM, have a higher rate of response with ibrutinib than those without (MYD88WT). Aside from its impressive efficacy, its oral administration offers a major advantage in terms of convenience for patients and lower administrative costs for publicly funded health care systems such as in Canada. The toxicity of ibrutinib has become of greater concern with the ongoing emergence of trial data and real-world clinical experience with the drug. The indefinite duration of treatment results in extended exposure of a primarily elderly patient population to toxicities such as increased bleeding risk, atrial fibrillation, hypertension, and infection. Discontinuation of ibrutinib due to adverse events occurs at a higher rate in the real-world compared to clinical trials and has been associated with an inferior overall survival in WM. Fortunately, several BTKis have recently emerged. Both acalabrutinib and zanubrutinib also bind irreversibly to BTK at C481, but both have more selectivity for targeting BTK than ibrutinib. Data has demonstrated that tighter and more selective binding of BTK does translate into fewer adverse effects for patients. The most informative study to date in this regard is the randomized phase 3 clinical trial comparing ibrutinib to zanubrutinib, the ASPEN study. ASPEN is the largest multicentre phase 3 trial to date randomizing 201 patients with MYD88MUT WM to receive ibrutinib at 420 mg daily (n=99) vs. zanubrutinib 160 mg twice daily (n=102), with 37 patients being treatment-naïve and 164 being relapsed or refractory (R/R) with a median of 1 prior line of therapy (range 1-8). The median age at enrolment was 70 however more patients randomized to zanubrutinib than to ibrutinib were >75 years old (33% vs 22%, respectively). Although not statistically significant, a higher rate of complete response (CR)/very good partial response (VGPR) was observed for zanubrutinib vs ibrutinib (28% vs 19%, respectively). With a median follow up of 19.4 months the major response rates (77% vs. 78%) and PFS (85% vs. 84% at 18 months) were also not statistically different in patients receiving zanubrutinib vs. ibrutinib, respectively. However, zanubrutinib was associated with a trend towards less toxicity. In particular, the incidences of all grade atrial fibrillation, diarrhea, bruising, muscle spasms, peripheral edema, and pneumonia were over 10% higher among ibrutinib-treated patients. The incidence of neutropenia was higher for zanubrutinib-treated patients (> 10% difference), although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). Further, more ibrutinib-treated patients required dose reductions (23% vs. 14%) and discontinued treatment (9% vs. 4%) due to adverse events. An analysis of quality of life (QoL) instruments demonstrated a trend towards greater improvement in the zanubrutinib arm, particularly in the subgroup of patients who achieved VGPR. These QoL improvements were most notable in validated instrument subscales encompassing appetite, dyspnea, fatigue, physical functioning and role functioning. The ASPEN trial formed the basis for recent approval of zanubrutinib for WM by HC. Although provincial funding is not yet in place, clinicians in Quebec can access zanubrutinib through the Patient d’exception mechanism. As Canadian hematologists will be able to choose a BTKi for their patient with R/R WM, it is important to review the toxicities reported in trials. Toxicities of BTKis and their management will be discussed in this article.

Detachable all-carbon-linked 3D covalent organic framework films for semiconductor/COF heterojunctions by continuous flow synthesis

Detachable all-carbon-linked 3D covalent organic framework films for semiconductor/COF heterojunctions by continuous flow synthesis

Stimuli-responsive destructible polymeric hydrogels based on irreversible covalent bond dissociation

Covalently crosslinked stimuli-destructible hydrogels with the ability of irreversible bond dissociation have attracted great attentions due to their biodegradability, stability against hydrolysis, and controlled solubility upon insertion of desired triggers.

Lazertinib: on the Way to Its Throne.

Lazertinib is an oral, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that forms an irreversible covalent bond to the Cys797 residue in the ATP-binding site of the EGFR kinase domain and exhibits a high selectivity for sensitizing and T790M EGFR mutations. In January 2021, it was first approved for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) patients with EGFR T790M who had previously received EGFR TKI therapy based on LASER201, a phase I/II trial. At a recommended dose of 240 mg, lazertinib achieved an encouraging anti-tumor activity in both extra- and intracranial lesions. With a high half-maximal inhibitory concentration for EGFR wildtype tumors, it is anticipated to pose a lower risk of skin and cardiac adverse events compared to osimertinib. Lazertinib is currently being investigated as a monotherapy in first-line treatment and in combination with amivantamab under various settings. In this review, we systematically summarize the preclinical and clinical data of lazertinib and discuss future perspectives on the treatment of EGFR-mutant NSCLC.

Discrete Self‐Assembled Metallo‐Foldamers with Heteroleptic Sequence Specificity

AbstractDiscrete and structurally diverse foldamer sequences are constructed in both natural and abiotic systems primarily using inert connectivity with irreversible organic covalent bonds, serving to preserve the identity of the sequence. The formation of sequences under thermodynamic control using labile coordination bonds would be attractive for synthetic ease and modular capability, but this presents issues regarding sequence preservation. Here is presented an approach integrating palladium(II) metal ions into the sequence itself, with fidelity maintained through use of complementary pairings of ligand arrangements at the metal centre. This is accomplished using sites of different denticity and/or hydrogen bonding capability. In this fashion, discrete and ordered metallo‐sequences are formed as thermodynamic products in a single step, and these then fold into defined conformations due to π–π interactions between electron‐rich and ‐poor aromatic regions of the combined componentry.

Discrete Self-Assembled Metallo-Foldamers with Heteroleptic Sequence Specificity.

Discrete and structurally diverse foldamer sequences are constructed in both natural and abiotic systems primarily using inert connectivity with irreversible organic covalent bonds, serving to preserve the identity of the sequence. The formation of sequences under thermodynamic control using labile coordination bonds would be attractive for synthetic ease and modular capability, but this presents issues regarding sequence preservation. Here is presented an approach integrating palladium(II) metal ions into the sequence itself, with fidelity maintained through use of complementary pairings of ligand arrangements at the metal centre. This is accomplished using sites of different denticity and/or hydrogen bonding capability. In this fashion, discrete and ordered metallo-sequences are formed as thermodynamic products in a single step, and these then fold into defined conformations due to π-π interactions between electron-rich and -poor aromatic regions of the combined componentry.