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Design strategies to achieve degradation and ideally closed-loop recycling of organic semiconductors have attracted great interest in order to minimize the electronic waste (E-waste). In this work, three ester-incorporated monomers were synthesized by the names of Thiophene-Ester-Ethylene-Thiophene (TEET), Thiophene-Ester-Methylene-Thiophene (TEMT), and Thiophene-Ester-Thiophene (TET), which were co-polymerized via Stille polycondensation with a benzodithiophene (BnDT) pi-conjugated unit to yield a series of ester-incorporated polymers: PBnDT-TEET, PBnDT-TEMT, and PBnDT-TET. While the ester-only linker can maintain some extended conjugation in PBnDT-TET, the other two ester linkers having conjugation breaking units result in isolated conjugated segments in PBnDT-TEET and PBnDT-TEMT, evidenced by UV-Vis and CV results. This yields an improved photovoltaic performance of PBnDT-TET compared to PBnDT-TEET. While all three polymers can degrade under methanolysis, the alternating co-polymer PBnDT-TEET demonstrates the highest recyclability potential with a single dimethyl ester-functionalized product with an excellent 92% isolated yield, which can then be repolymerized to obtain the repolymerized PBnDT-TEET with a 36% yield. This work provides a framework towards achieving recyclable organic semiconductors to reduce E-waste. Although the incorporation of ester linkers allowed for closed-loop recycling, the low solar cell efficiency of PBnDT-TEET highlights the significant challenges in achieving both recycling and high device performance.

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Drug conjugates have emerged as a pivotal research focus in the field of targeted cancer therapy. They represent a widely explored prodrug strategy that significantly enhances the therapeutic index of drugs while minimizing side effects. The stability and selective cleavage of the linker within drug conjugates are critical for the therapeutic efficacy and targeted treatment achieved by these conjugates. In this review, we have categorized the linkers based on their cleavage mode and summarized the chemical properties, advantages, and limitations of various types of cleavable linkers. Particularly, examples have been provided to illustrate their specific potential for development.

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Heartland virus (HRTV) is a single-stranded negative-sense RNA virus that infects human beings. Because there are no antiviral medications available to treat HRTV infection, supportive care management is used in cases of severe disease. Therefore, it has spurred research into developing a multi-epitope vaccine capable of providing effective protection against HRTV infection. A multi-epitope vaccine was created using a combination of immuno-informatics, molecular docking and molecular dynamics simulation in this investigation. The HRTV proteome was utilized to predict B-cell, T-cell (HTL and CTL), and IFN-epitopes. Following prediction, highly antigenic, non-allergenic and immunogenic epitopes were chosen, including 6 CTL, 8 HTL, and 5 LBL epitopes that were connected to the final peptide by AAY, GPGPG, and KK linkers, respectively. An adjuvant was introduced to the vaccine's N-terminal through the EAAAK linker to increase its immunogenicity. Following the inclusion of linkers and adjuvant, the final construct has 359 amino acids. The presence of B-cell and IFN-γ-epitopes validates the construct's acquired humoral and cell-mediated immune responses. To ensure the vaccine's safety and immunogenicity profile, its allergenicity, antigenicity, and various physicochemical characteristics were assessed. Docking was used to assess the binding affinity and molecular interaction between the vaccination and TLR-3. In silico cloning was used to confirm the construct's validity and expression efficiency. The results of these computer assays demonstrated that the designed vaccine is highly promising in terms of developing protective immunity against HRTV; nevertheless, additional in vivo and in vitro investigations are required to validate its true immune-protective efficiency.

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Transition metal (Tm) chelation is an effective strategy to achieve optimal binding enthalpy (∆H) of H2-adsorption in the linkers of covalent organic frameworks (COFs). The first principle-based DFT method has been used to determine the H2 adsorption in nine organic linkers chelated with eight transition metal atoms from Cr to Zn. The obtained range of H2 binding enthalpy of the pure and chelated complexes is -7 to -20 kJ/mol, which is required for onboard H2 storage. The Linker-3 chelated with Ni (II) metal exhibits the most favorable binding enthalpy of approximately -18.72 kJ/mol for the single adsorbed H2 molecule, which falls within the physisorption range. Some of the complexes have shown the heat of adsorption between physisorption and chemisorption, i.e., in that case, H2 binds via Kubas interactions. However, physisorption-based complexes are preferable to others because physisorption is a reversible process with rapid kinetics. This study reveals that the dispersion, polarization, and electrostatic interactions mainly contribute to the binding enthalpy of H2 adsorption. Molecular surface potential analysis verified the origin of induced dipole moment in the H2 molecule, which enhances the hydrogen adsorption in transition metal chelated COFs.

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Targeted tumour therapy has proved to be an efficient alternative to overcome the limitations of conventional chemotherapy. The upregulation of the bombesin receptor 2 (BB2) in several malignancies and the advantages offered by peptide drug conjugates over antibody drug conjugates in terms of production and tumour targeting motivated us to synthesise and test bombesin conjugates armed with the tubulin binder monomethyl auristatin E. The widely used Val-Cit-PABC was initially included as cathepsin cleavable self-immolative linker for the release of the free drug. However, the poor stability of the Val-Cit-conjugates in mouse plasma encouraged us to consider the optimised alternatives Glu-Val-Cit-PABC and Glu-Gly-Cit-PABC. Conjugate BN-EVcM1, featuring Glu-Val-Cit-PABC, combined suitable stability (t(½) in mouse and human plasma: 8.4 h and 4.6 h, respectively), antiproliferative activity in vitro (IC50 = 29.6 nM on the human prostate cancer cell line PC-3) and the full release of the free payload within 24 h. Three conjugates, namely BN-EGcM1, BN-EVcM1 and BN-EVcM2, improved the accumulation of MMAE in PC-3 human prostate cancer xenograft mice models, compared to the administration of the free drug. Among them, BN-EVcM1 also stood out for the significantly extended survival of mice in in vivo acute efficacy studies and for the significant inhibition of the growth of a PC-3 tumour in mice in both acute and chronic efficacy studies.

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Porous materials perform molecular sorting, separation and transformation by interaction between their framework structures and the substrates. Proteins also interact with molecules to effect chemical transformations, but rely on the precise sequence of the amino acid building units along a common polypeptide backbone to maximise their performance. Design strategies that positionally order sidechains over a defined porous framework to diversify the internal surface chemistry would enhance control of substrate processing. Here we show that different sidechains can be ordered over a metal-organic framework through recognition of their distinct chemistries during synthesis. The sidechains are recognised because each one forces the common building unit that defines the backbone of the framework into a different conformation in order to form the extended structure. The resulting sidechain ordering affords hexane isomer separation performance superior to that of the same framework decorated only with sidechains of a single kind. The separated molecules adopt distinct arrangements within the resulting modified pore geometry, reflecting their strongly differentiated environments precisely created by the ordered sidechains. The development of frameworks that recognise  and  order multiple sidechain functionality by conformational control offers tailoring of the internal surfaces within families of porous materials to direct interactions at the molecular level.

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Molecular imaging is a non-invasive imaging method that is widely used for visualization and detection of biological events at cellular or molecular levels. Stimuli-responsive linkers that can be selectively cleaved by specific biomarkers at desired sites to release or activate imaging agents are appealing tools to improve the specificity, sensitivity, and efficacy of molecular imaging. This review summarizes the recent advances of stimuli-responsive linkers and their application in molecular imaging, highlighting the potential of these linkers in the design of activatable molecular imaging probes. It is hoped that this review could inspire more research interests in the development of responsive linkers and associated imaging applications.

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Using light as an external stimulus to control (bio)chemical processes offers many distinct advantages, most importantly it allows for the spatiotemporal control simply through operating the light source. Photocleavable protecting groups (PPGs) are a cornerstone class of compounds that are used to achieve photocontrol over (bio)chemical processes. PPGs are able to release a payload of interest upon light irradiation. The successful application of PPGs hinges on their efficiency of payload release, captured in the uncaging Quantum Yield (QY). Heterolytic PPGs efficiently release low pKa payloads, but their efficiency drops significantly for payloads with higher pKa values, such as alcohols. For this reason, alcohols are usually attached to PPGs via a carbonate linker. The self-immolative nature of the carbonate linker results in concurrent release of CO2 with the alcohol payload upon irradiation. We introduce herein novel PPGs containing sulfites as self-immolative linkers for photocaged alcohol payloads, for which we discovered that the release of the alcohol proceeds with higher uncaging QY than an identical payload released from a carbonate-linked PPG. Furthermore, we demonstrate that uncaging of the sulfite-linked PPGs results in the release of SO2 and show that the sulfite linker improves water solubility as compared to the carbonate based systems.

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Aiming to create an innovative series of anti-colorectal cancer agents, we designed in this work hybrid triarylmethane compounds. Three hybrid triarylmethanes and their corresponding N-oxide analogues were successfully synthesized using an efficient procedure that involved connecting two triarylmethane molecules, through mono-, bi-, and triethylene glycol fragments. In our pursuit to develop more soluble molecules, we synthesized a hybrid triarylmethane featuring a lysine-based spacer through a convergent strategy involving 7 steps. All hybrid compounds were assessed for their antiproliferative activity on human HT-29 and HCT116 colorectal cancer (CRC) cell lines. Three pyridine N-oxide analogs demonstrated notable antiproliferative potential among the set of tested compounds, with IC50 values ranging from 18 to 24 µM on both human CRC cell lines analyzed. A cytotoxicity study conducted on murine fibroblasts revealed that these three active compounds were not toxic at the IC50 values, indicating their suitability for further drug development. A docking study was conducted on two representative compounds, one for each series and protein kinase B (AKT) was identified as a potential target of their in anti-cancer effects. A computational drug-likeness study predicted favourable oral and intestinal absorption efficiency.

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The fluorination of the central ring of 1,3,5-benzene-tris-(meta-benzoate) (referred to as BTMB) leads to a twisted tritopic linker which reacts with copper(II) ions to assemble into octahedral (pseudospherical) metal-organic cages (MOCs) with paddle wheel units at their vertices. In this work, the different sphere packings of these MOCs are explored in detail together with their material properties, which closely resemble those of copper-based metal organic frameworks (MOFs). Theoretical investigations of the linkers are carried out to analyze the energetic barrier imposed by the fluorine substituents to form the observed atropisomers.

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This study investigates the wash resistance of polyester fabrics functionalized with chitosan, a biopolymer known for its biocompatibility, non-toxicity, biodegradability and environmentally friendly properties. The interaction of chitosan with synthetic polymers, such as polyester, often requires surface treatment due to the weak natural affinity between the two materials. To improve the interaction and stability of chitosan on polyester, alkaline hydrolysis of the polyester fabric was used as a surface treatment method. The effectiveness of using cross-linking agents 1,2,3,4-butane tetracarboxylic acid (BTCA) and hydroxyethyl methacrylate (HEMA) in combination with ammonium persulphate (APS) to improve the stability of chitosan on polyester during washing was investigated. The wash resistance of polyester fabrics functionalized with chitosan was tested after 1, 5 and 10 washes with a standard ECE detergent. Staining tests were carried out to evaluate the retention of chitosan on the fabric. The results showed that polyester fabrics functionalized with chitosan without cross-linkers exhibited better wash resistance than the fabrics treated with crosslinkers.

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OBJECTIVES: To evaluate the effect of proanthocyanidin-functionalized hydroxyapatite nanoparticles (nHAp_PA) used as pretreatment at different concentrations on the microtensile bond strength (µTBS) and endogenous enzymatic activity (MMPs) on pH-cycled dentin after 24 h and 6 months of artificial aging. MATERIALS AND METHODS: Fifty human sound dentin blocks were randomly assigned to 5 groups (n = 10): (i) negative control (no treatment); (ii) positive control (pH-cycling); (iii) pH-cycling + 2% nHAp_PA for 60s; (iv) pH-cycling + 6.5% nHAp_PA for 60s; (v) pH-cycling + 15% nHAp_PA for 60s. A self-etch adhesive was used for bonding procedures before resin composite build-ups. Specimens were tested with the µTBS test after 24 h and 6 months of laboratory storage. The proteolytic activity in each group was evaluated with gelatin zymography and in situ zymography. Data were statistically analyzed (p < 0.05). RESULTS: At 24 h, the µTBS of the experimental groups were significantly higher than the controls (p ≤ 0.001), and no differences were observed between different concentrations (p > 0.05). Artificial aging significantly decreased bond strength in all groups (p ≤ 0.008); however, nHAp_PA 2% still yielded higher bonding values than controls (p ≤ 0.007). The groups pretreated with nHAp_PA exhibited lower MMP-9 and MMP-2 activities compared to the positive control group and almost the same enzymatic activity as the negative control group. In situ zymography showed that after 6 months of aging, nHAp_PA 2% and nHAp_PA 6,5% decreased enzymatic activity as well as the negative control. CONCLUSIONS: Dentin pretreatment with nHAp_PA increased the bonding performance of a self-etch adhesive and decreased MMP-2 and MMP-9 activities after 6 months.

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Synthetic peptides are important as drugs and in research. Currently, the method of choice for producing these compounds is solid-phase peptide synthesis. Here, we describe the scope and limitations of Fmoc solid-phase peptide synthesis. Furthermore, we provide a detailed protocol for Fmoc peptide synthesis.

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Dimer acceptors in organic solar cells (OSCs) offer distinct advantages, including a well-defined molecular structure and excellent batch-to-batch reproducibility. Their high glass transition temperature (Tg) aids in achieving an optimal kinetic morphology, thereby enhancing device stability. Currently, most of dimer acceptor materials are linked with conjugated units in order to obtain high power conversion efficiencies (PCEs). In this study, different from previous works on conjugation-linked dimer acceptors, a novel series of dimer acceptors are synthesized (named T1, T4, T6, and T12), each linked with different flexible alkyl linkers, and investigated their PCEs, device stability, and flexibility robustness. When blended with PM6, the T6-based device achieves a PCE of 17.09%, comparable to the fully conjugated T0-based device's PCE of 17.12%. The molecular dynamics simulations and density functional theory calculations suggested that flexible conjugation-broken linkers (FCBLs) promote intermolecular electronic couplings, thereby maintaining good electron mobilities of dimer acceptors. Notably, the T6-based device exhibits impressive long-term stability with a T80 lifetime of 1427 h, while in the T0-based device, T80 is only 350 h. The present work has thus established the relationship between the length of flexible alkyl linkers in such dimer acceptors and the performance and stability of OSCs, which is important to further designing new materials for the fabrication of efficient and stable OSCs.

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A series of novel vindoline-piperazine conjugates were synthesized by coupling 6 N-substituted piperazine pharmacophores at positions 10 and 17 of Vinca alkaloid monomer vindoline through different types of linkers. The in vitro antiproliferative activity of the 17 new conjugates was investigated on 60 human tumor cell lines (NCI60). Nine compounds presented significant antiproliferative effects. The most potent derivatives showed low micromolar growth inhibition (GI50) values against most of the cell lines. Among them, conjugates containing [4-(trifluoromethyl)benzyl]piperazine (23) and 1-bis(4-fluorophenyl)methyl piperazine (25) in position 17 of vindoline were outstanding. The first one was the most effective on the breast cancer MDA-MB-468 cell line (GI50 = 1.00 µM), while the second one was the most effective on the non-small cell lung cancer cell line HOP-92 (GI50 = 1.35 µM). The CellTiter-Glo Luminescent Cell Viability Assay was performed with conjugates 20, 23, and 25 on non-tumor Chinese hamster ovary (CHO) cells to determine the selectivity of the conjugates for cancer cells. These compounds exhibited promising selectivity with estimated half-maximal inhibitory concentration (IC50) values of 2.54 µM, 10.8 µM, and 6.64 µM, respectively. The obtained results may have an impact on the design of novel vindoline-based anticancer compounds.

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Covalent organic frameworks (COFs) have emerged as versatile materials with many applications, such as carbon capture, molecular separation, catalysis, and energy storage. Traditionally, flexible building blocks have been avoided due to their potential to disrupt ordered structures. Recent studies have demonstrated intriguing properties and enhanced structural diversity achievable with flexible components by judicious selection of building blocks. This study presents a novel series of ionic COFs (ICOFs) consisting of tetraborate nodes and flexible linkers. These ICOFs use borohydrides to irreversibly deprotonate the alcohol monomers to achieve a high polymerization degree. Structural analysis confirms the dia topologies. Reticulation is explored using various monomers and metal counter-ions. Also, these frameworks exhibit excellent stability in alcohols and coordinating solvents. The materials are tested as single-ion conductive solid-state electrolytes. ICOF-203-Li displays one of the lowest activation energies reported for ion conduction. This tetraborate chemistry is anticipated to facilitate further structural diversity and functionality in crystalline polymers.

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KRAS-mutant cancers, due to their protein targeting complexity, present significant therapeutic hurdles. The identification of the macropinocytic phenotype in these cancers has emerged as a promising alternative therapeutic target. Our study introduces MPD1, an macropinocytosis-targeting peptide-drug conjugates (PDC), which is developed to treat KRAS mutant cancers. This PDC is specifically designed to trigger a positive feedback loop through its caspase-3 cleavable characteristic. However, we observe that this loop is hindered by DNA-PK mediated DNA damage repair processes in cancer cells. To counter this impediment, we employ AZD7648, a DNA-PK inhibitor. Interestingly, the combined treatment of MPD1 and AZD7648 resulted in a 100% complete response rate in KRAS-mutant xenograft model. We focus on the synergic mechanism of it. We discover that AZD7648 specifically enhances macropinocytosis in KRAS-mutant cancer cells. Further analysis uncovers a significant correlation between the increase in macropinocytosis and PI3K signaling, driven by AMPK pathways. Also, AZD7648 reinforces the positive feedback loop, leading to escalated apoptosis and enhanced payload accumulation within tumors. AZD7648 possesses broad applications in augmenting nano-sized drug delivery and preventing DNA repair resistance. The promising efficacy and evident synergy underscore the potential of combining MPD1 with AZD7648 as a strategy for treating KRAS-mutant cancers.

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Based on multiple ligands strategy, a series of multivariate metal organic frameworks (MTV-MOFs) named as PCN-224-DCDPSx were prepared using one-pot solvothermal method to extract and remove sulfonamide antibiotics (SAs). The pore structure and adsorption performance can be further regulated by modulating the doping ratios of medium-tetra(4-carboxylphenyl) porphyrin and 4,4'-dicarboxydiphenyl sulfones. The MTV-MOFs of PCN-224-DCDPS1.0 possesses very large specific surface area (1625 m2/g). Using PCN-224-DCDPS1.0 as sorbent, a dispersive solid-phase extraction method was developed to extract and preconcentrate SAs from water, eggs, and milk prior to high performance liquid chromatography analysis. The limits of detection of method were determined between 0.17 and 0.27 ng/mL with enrichment factors ranging 214-327. The adsorption can be finished within 30 s, and the recovery rate remains above 80 % after 10 repeated uses. The adsorption capacities of sorbent were determined from 300 to 621 mg/g for sulfadiazine, sulphapyridine, sulfamethoxydiazine, sulfachlorpyridazine, sulfabenzamide, and sulfadimethoxine. The adsorption mechanisms were investigated and can be attributed to π-π interactions, hydrogen bonds, and electrostatic interactions. This work represents a method for preparation of MTV-MOFs and uses as sorbent for extraction and enrichment of trace pollutants from complex samples.

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Considering the increasing demand for high-resolution light-emitting diodes (LEDs), it is important that direct fine patterning technologies for LEDs be developed, especially for quantum-dot LEDs (QLEDs). Traditionally, the patterning of QLEDs relies on resin-based photolithography techniques, requiring multiple steps and causing performance deterioration. Nondestructive direct patterning may provide an easy and stepwise method to achieve fine-pixelated units in QLEDs. In this study, two isomeric tridentate cross-linkers (X8/X9) are presented and can be blended into the hole transport layer (HTL) and the emissive layer (EML) of QLEDs. Because of their photosensitivity, the in situ cross-linking process can be efficiently triggered by ultraviolet irradiation, affording high solvent resistance and nondestructive direct patterning of the layers. Red QLEDs using the cross-linked HTL demonstrate an impressive external quantum efficiency of up to 22.45%. Through lithographic patterning enabled by X9, line patterns of HTL and EML films exhibit widths as narrow as 2 and 4 µm, respectively. Leveraging the patterned HTL and EML, we show the successful fabrication of pixelated QLED devices with an area size of 3 × 3 mm2, alongside the successful production of dual-color pixelated QLED devices. These findings showcase the promising potential of direct patterning facilitated by engineered cross-linkers for the cost-effective fabrication of pixelated QLED displays.

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Molecularly imprinted polymers (MIPs) as artificial synthetic receptors are in high demand for food analysis due to their inherent molecular recognition abilities. It is common practice to employ functional monomers with basic or acidic groups that can interact with analyte molecules via hydrogen bonds, covalent bonds, and other interactions (π-π, dipole-ion, hydrophobic, and Van der Waals). Therefore, selecting the appropriate functional monomer and cross-linker is crucial for determining how precisely they interact with the template and developing the polymeric network's three-dimensional structure. This study summarizes the advancements made in MIP's functional monomers and cross-linkers for food analysis from 2018 to 2023. The subsequent computational design of MIP has been thoroughly explained. The discussion has concluded with a look at the difficulties and prospects for MIP in food analysis.

Benefits of MIP in food analysis have been discussed.Different functional monomers of MIPs have been discussed.Different cross-linkers of MIPs have been discussed.Theoretical interactions between functional monomers and templates for MIP design have been discussed.