Bond Formation Research Articles

Quantum Simulations of Radiation Damage in a Molecular Polyethylene Analog.

An atomic-level understanding of radiation-induced damage in simple polymers like polyethylene is essential for determining how these chemical changes can alter the physical and mechanical properties of important technological materials such as plastics. Ensembles of quantum simulations of radiation damage in a polyethylene analog are performed using the Density Functional Tight Binding method to help bind its radiolysis and subsequent degradation as a function of radiation dose. Chemical degradation products are categorized with a graph theory approach, and occurrence rates of unsaturated carbon bond formation, crosslinking, cycle formation, chain scission reactions, and out-gassing products are computed. Statistical correlations between product pairs show significant correlations between chain scission reactions, unsaturated carbon bond formation, and out-gassing products, though these correlations decrease with increasing atom recoil energy. The results present relatively simple chemical descriptors as possible indications of network rearrangements in the middle range of excitation energies. Ultimately, the work provides a computational framework for determining the coupling between nonequilibrium chemistry in polymers and potential changes to macro-scale properties that can aid in the interpretation of future radiation damage experiments on plasticmaterials.

Discovery of ICOS-Targeted Small Molecules Using Affinity Selection Mass Spectrometry Screening.

Inducible T cell co-stimulator (ICOS) is a positive immune checkpoint receptor expressed on the surface of activated T cells, which could promote cell function after being stimulated with ICOS ligand (ICOS-L). Although clinical benefits have been reported in the ICOS modulation-based treatment for cancer and autoimmune disease, current modulators are restricted in biologics, whereas ICOS-targeted small molecules are lacking. To fill this gap, we performed an affinity selection mass spectrometry (ASMS) screening for ICOS binding using a library of 15,600 molecules. To the best of our knowledge, this is the first study that utilizes ASMS screening to discover small molecules targeting immune checkpoints. Compound 9 with a promising ICOS/ICOS-L inhibitory profile (IC50=29.38±3.41 μM) was selected as the template for the modification. Following preliminary structure-activity relationship (SAR) study and molecular dynamic (MD) simulation revealed the critical role of the ortho-hydroxy group on compound 9 in the ICOS binding, as it could stabilize the interaction via the hydrogen bond formation with residuals on the glycan, and the depletion could lead to an activity lost. This work validates a promising inhibitor for the ICOS/ICOS-L interaction, and we anticipate future modifications could provide more potent modulators for this interaction.

Application of Sulfonyl Fluorides in Organic Transformation

ulfonyl fluorides, due to their balanced potential reactivity and stability as well as their compatibility with biological systems, have become important synthetic intermediates and building blocks in the fields of organic synthesis, drug discovery, and materials science. Especially after the report of sulfur(VI) fluoride exchange (SuFEx) chemistry by Sharpless and others, research on sulfonyl fluoride compounds and related compounds has increased significantly.This review summarizes the applications of sulfonyl fluorides in organic synthesis over the past decade, different types of organic reactions including C–X bond formation (including C–C, C–N, C–F bond formation etc.), S–C bond formation, S–N bond formation, S–O bond formation, multicomponent “one-pot” synthesis, and cyclization were discussed.

Micelle-Assisted C(sp2)-H Functionalization for C-Se and C-X Bond Formation in the Aqueous Medium.

An environmentally sustainable, versatile, and cost-effective approach for C-Se and C-X (X = I, Br, and Cl) bond formation through C-H functionalization assisted by micellar catalysis in water is developed. The reaction utilizes a minimum amount of diorganyl diselenides and potassium halides for the respective functionalizations. The present protocol was suitable for scale-up synthesis, which directly provided the desired selenylated products without the need for chromatographic purification, in sufficient purity. The aqueous micellar catalysis system was reusable for up to 5 reaction cycles without compromising the reaction yield.

Cascade CO2 Insertion in Carbanion Ionic Liquids Driven by Structure Rearrangement.

The CO2 chemisorption in state-of-the-art sorbents based on oxide/hydroxide/amine moieties is driven by strong chemical bonding formation in the carbonate/bicarbonate/carbamate products, which in turn leads to high energy input in sorbent regeneration. In addition, the CO2 uptake capacity was limited by the active sites' utilization efficiency, with each active site incorporating one CO2 molecule or less. In this work, a new concept and generation of sorbent was developed to achieve cascade insertion of multiple CO2 molecules by leveraging structure rearrangement as the driving force, leading to in situ generation of extra CO2-binding sites and significantly reduced energy input for CO2 release. The designed ionic liquids (ILs) containing carbanions with conjugated and asymmetric structure, deprotonated (methylsulfonyl)acetonitrile ([MSA]) anion, allowed the cascade insertion of two CO2 molecules via consecutive C-C and O-C bond formations. The proton transfer and structure rearrangement of the carboxylic acid intermediates played critical roles in stabilizing the first integrated CO2 and generating extra electron-rich oxygen sites for the insertion of the second CO2. The structure variation and reaction pathway were confirmed by operando spectroscopy, magnetic resonance spectroscopy (NMR), mass spectroscopy, and computational chemistry. The energy input in sorbent regeneration could be further reduced by harnessing the phase-changing behavior of the carbanion salts in ether solutions upon reacting with CO2, avoiding the energy consumption in heating the solvent. The fundamental insights obtained herein provide a promising approach to greatly improve the CO2 sorption performance via sophisticated molecular-scale structural engineering of the sorbents.

A Dehydrocoupling Approach Towards Titanocene Iminophosphane Complexes

Dehydrocoupling reactions represent a powerful tool for element‐element bonds formation upon H2 elimination. It was shown that transition metals (in low oxidation states or in the form of hydrides) can be coupled with two equivalents of primary pnictanes (R–PnH2; Pn = P, Sb) providing direct access to otherwise elusive η2‐dipnictene (R–Pn=Pn–R) complexes. Herein, we report on the reactivity of the common group IV metallocene precursors Cp2Ti(btmsa) and Cp2Zr(btmsa)(pyridine) (btmsa = C2(SiMe3)2) towards primary pnictanes (R–PnH2 (Pn = P or N) and secondary aminophosphanes (R’P(H)–N(H)R). We found that Cp2Ti(btmsa) reacts with secondary aminophosphanes (R’P(H)–N(H)R) to give η2‐iminophosphane titanocene complexes. The molecular and electronic structure of the new compounds were thoroughly investigated spectroscopically, crystallographically and computationally.

Noncanonical Functions of Ketosynthase Domains in Type I Polyketide Synthases.

Modular type I polyketide synthases (PKSs) are remarkable molecular machines that can synthesize structurally complex polyketide natural products with a wide range of biological activities. In these molecular machines, ketosynthase (KS) domains play a central role, typically by catalyzing decarboxylative Claisen condensation for polyketide chain extension. Noncanonical KS domains with catalytic functions rather than Claisen condensation have increasingly been evidenced, further demonstrating the capability of type I PKSs for structural diversity. This review provides an overview of the reactions involving unusual KS activities, including PKS priming, acyl transfer, Dickmann condensation, Michael addition, aldol-lactonization bicyclization, C-N bond formation and decarbonylation. Insights into these reactions can deepen the understanding of PKS-based assembly line chemistry and guide the efforts for rational engineering of polyketide-related molecules.

Naphthalene Diimide and Bis-Heteroleptic Ru(II) Complex-Based Hybrid Molecule with 3-in-1 Functionalities.

Multipurpose applications of a newly developed homobimetallic Ru(II) complex, Ru-NDI[PF6]4, which incorporates 1,10-phenanthroline and triazole-pyridine ligands and linked via a (-CH2-)3 spacer to the reputed anion-π interacting NDI system, are described. Solution-state studies of the bimetallic complex, including EPR, PL, UV-vis, and NMR experiments, reveal two sequential one-electron transfers to the NDI unit, generating NDI⋅- and NDI2- in the presence of F- selectively. This process inhibits the primary electron transfer from Ru(II) to the NDI unit, thereby allowing the 3MLCT-based emission of the complex to be recovered, resulting in a corresponding ten-fold increase in luminescence intensity. DFT and TD-DFT computational studies further elucidate the experimentally observed absorption spectra of the complex. Secondly, CT-DNA binding studies with the complex are performed using various spectroscopic analyses such as UV-vis, PL, and CD. Comparative DNA binding studies employing EB and molecular docking reveal that the binding with CT-DNA occurs through both intercalative and groove binding modalities. Thirdly, the photocatalytic activities of the complex towards C-C, C-N, and C-O bond formation in organic cross-coupling reactions, including the amidation of α-keto acids to amines and the oxidation of alcohol to aldehydes, are also demonstrated.

Ascorbic Acid: An Efficient Organocatalyst for the Synthesis of 2‐Amino‐1,3,4‐oxadiazoles and Thiadiazoles via C−X Bond Formation

AbstractA new protocol for the synthesis of 2‐amino‐substituted 1,3,4‐oxadiazoles and 1,3,4‐thiadiazoles, were developed using semicarbazide or thiosemicarbazide along with the various aldehydes, followed by C−X (X=O, S) bond formation using ascorbic acid as a catalyst. This rapid, efficient, accessible, and robust/scalable sequential synthesis works with aromatic, aliphatic, and cinnamic aldehydes to provide a wide range of diazole derivatives with a 2‐amino substituent without the use of any transition metals. The synthesised molecules were characterised by 1H and 13C NMR analysis.

A multifunctional metal–organic complex fluorescent probe for highly sensitive detection of lysine, CrO42-/Cr2O72-, Fe3+ and nitro-aromatic compounds

Water contamination caused by organic and inorganic compounds represents an urgent global issue. It is meaningful to detect these compounds. A metal–organic complex (Zn-HTBA) was investigated as a multifunctional fluorescent probe which showed exceptional fluorescence characteristics. The Zn- HTBA can specifically detect lysine in water through fluorescence enhancement, and the detection limit was 0.17 μM. The Zn-HTBA also selectively detect CrO42-/Cr2O72- and Fe3+ with the detection limits of 0.014/0.022 and 0.12 μM through fluorescence quenching. In addition, the Zn-HTBA was found to sensitively detect nitroaromatic compounds in ethanol through fluorescence quenching. The possible detection mechanisms were studied in detail through UV–Vis, PXRD, XPS, etc. The mechanism of Zn-HTBA to detect CrO42-/Cr2O72-, Fe3+ and 2-nitrotoluene was energy competition, and the mechanism of Zn-HTBA to detect lysine was the formation of hydrogen bonds.

Silyl- and Germyl-Substituted Boranes: Synthesis and Investigation as Potential Atomic Layer Deposition Precursors.

Boranes featuring bulky hypersilyl or supersilyl groups and/or sterically unencumbered trimethylgermyl substituents were synthesized for investigation as potential precursors for atomic layer deposition (ALD) of elemental boron. The envisaged ALD process would employ a boron trihalide coreactant, exploiting the formation of strong silicon-halogen and germanium-halogen bonds as a driving force. The alkali metal silyl and germyl compounds hypersilyl lithium, {(Me3Si)3Si}Li(THF)3 (1), supersilyl sodium, (tBu3Si)Na(THF)n (2, n = 2-3), and trimethylgermyl lithium, {Me3GeLi(THF)2}2 (3), were used for the synthesis of the silyl- and germyl-substituted boranes in this work. Compounds 1 and 2 were synthesized as previously reported, and compound 3 was isolated from the reaction of trimethylgermane with tert-butyl lithium. Compounds 2 and 3 were crystallographically characterized. Reaction of B(NMe2)Cl2 with 2 equiv of 1 afforded previously reported {(Me3Si)3Si}2B(NMe2) (4), whereas reactions of B(NMe2)Cl2 or {B(NMe2)F2}2 with excess 2 only afforded the monosilyl boranes (tBu3Si)B(NMe2)X {X = Cl (5) and F (6)}. Reaction of 5 with 0.5 equiv of {Me3GeLi(THF)2}2 (3) provided the first example of a mixed silyl/germyl-substituted borane, (tBu3Si)(Me3Ge)B(NMe2) (7). Attempts to synthesize (Me3Ge)2B(NMe2) from the 1:1 reaction of B(NMe2)Cl2 with {Me3GeLi(THF)2}2 afforded a mixture of two major products, one of which was identified as the tri(germyl)(amido)borate {(Me3Ge)3B(NMe2)}Li(THF)2 (8); compound 8 was isolated from the 1:1.5 reaction. Reaction of more sterically encumbered B(TMP)Cl2 with 1 equiv of {Me3GeLi(THF)2}2 afforded the di(germyl)(amido)borane (Me3Ge)2B(TMP) (9). Boranes 4, 7, and 9 and borate 8 were crystallographically characterized. The thermal stability and volatility of boranes 4, 7, and 9 was evaluated, the solution reactivity of 4 and 7 with boron trihalides was assessed, and ALD was attempted using 4 in combination with BCl3 and BBr3 at 150 and 300 °C.

Andrographolide Encapsulation in Metal‐organic Frameworks (MOFs) via Solvent‐free Process at High Pressure

Andrographolide (ADG) encapsulation was carried out on MOFs MIL‐53(Al) and ZIF‐8 by high‐pressure (0.3 GPa) contact. This methodology is not only environment‐friendly but also energy/time‐saving and gives rise to ADG‐MOFs with physical features equivalent to those of materials obtained by common liquid phase encapsulation. The loaded MOFs were characterized through TEM, SEM, XRD, TGA, FT‐IR, BET, and NMR. The observed decrease in the intensity of ADG XRD peaks is due to the adsorption of ADG into the MOFs. TGA showed the decomposition step of ADG in the range of 200‐300 °C in both loaded MOFs. FT‐IR also showed intense signals of the ADG in the synthesized materials. The dissolution profile of ADG in MIL‐53(Al) in PBS (pH = 7.4) was carried out showing that the drug was released up to 96% after 75 h. NMR confirmed the interactions between ADG molecules and ZIF‐8 groups and the formation of a hydrogen bond between the carboxylic group of ADG and the hydroxyl group of MIL‐53(Al). Coefficient partition studies determined that both MOFs did not improve the hydrophilicity of the ADG, due to the loading of the drug preferably occurring by interactions in the hydrophobic areas within the pores of the MOFs.

One‐Pot Synthesis of Fused Isoxazolo[4′,5′:3,4]pyrrolo[2,1‐b] Quinazolines as Potent EGFR Targeting Anticancer Agents

AbstractIn response to the need for scaffolds for medical applications, synthetic chemists have developed simple and efficient methods for optimal synthesis. To investigate the synthesis of fused isoxazoles in the presence of [3+2] cycloaddition followed by C−N bond formation reaction between 3‐((4‐iodo‐3‐phenylisoxazol‐5‐yl)methyl)quinazolin‐4(3H)‐one and various nitrile oxides was carried out by previously reported conditions. The cancer activities of the synthesized compounds were then tested in vitro against two cancer cell lines, MCF‐7 and A‐549. Three of the compounds, 3‐(3,5‐dichlorophenyl) isoxazolo[4′,5′:3,4]pyrrolo[2,1‐b]quinazolin‐9(11H)‐one, 3‐(4‐fluorophenyl)isoxazolo[4′,5′:3,4]pyrrolo[2,1‐b]quinazolin‐9(11H)‐one, and 3‐(4‐(trifluoromethyl)phenyl)isoxazolo[4′,5′:3,4] pyrrolo[2,1‐b] quinazolin‐9(11H)‐one has shown superior activity against the non‐small‐cell lung cancer cell line (A‐549) than the standards 5‐fluorouracil and erlotinib. Later, in vitro EGFR results revealed that a more potent compound was more effective than the conventional medicine, erlotinib. In silico investigations of more potent compounds and erlotinib on the EGFR protein indicated that more potent compounds had comparable binding energies and inhibition constants to erlotinib.

Activation of Alkenes via Chalcogen Bond: Chalcogen•••π Bond Catalyzed the Diels‐Alder Reaction of 2‐Vinylindoles

Chalcogen bond catalysis is a promising catalytic strategy, characterized by its environmental friendliness, relatively inexpensive cost, and similar reactivity to transition metal catalysis. Experimental results suggest that the S•••π and Se•••π bonds can efficiently drive the vinyl‐indole‐based Diels‐Alder reaction (Angew. Chem. Int. Ed. 2021, 60, 9395‐9400). In this work, chalcogen bond catalysis in the Diels‐Alder reaction between 2‐vinylindoles has been investigated based on density functional theory. For this reaction, the Te•••π bond catalysis is as an alternative catalytic strategy. The Diels‐Alder reaction catalyzed by chalcogen bond is stepwise and involves two steps: the carbon–carbon bond formation process and the cyclization process. The cyclization process is the rate‐determining step. From the perspective of energy decomposition analysis, the electrostatic interaction is the main factor to cause Se•••π bond catalysis, the polarization interaction is the main factor to cause Te•••π bond catalysis. Additionally, this catalytic reaction involves the endo pathway and exo pathway. The Gibbs free energy barrier values of the endo pathway are lower than those of the exo pathway, which facilitates the formation of the endo product. This study will provide a valuable perspective on the application of chalcogen bond in the activation of alkenes.

Molecular dynamics study of the effect of composition on elastic properties of silicon oxynitride films

Abstract Understanding mechanical properties of silicon oxynitride (a-SiON), a key insulating material, is vital for electronic device design and reliability. Though the effects of fabrication conditions on a-SiON have been studied, the underlying relationship between its atomic-scale structure and mechanical properties remains unclear. This study investigates the relationship between elasticity and atomic-scale structures in a-SiON by molecular dynamics simulations with a universal graph neural network interatomic potential. The bulk modulus increases from 49 to 140 GPa with higher N content. N atoms form N2 molecules under O-rich conditions, hindering bulk modulus increase, and form an Si3N4-like network under O-poor conditions, enhancing bulk modulus. Formation energy calculations indicate N2 formation is preferable under O-rich conditions. Meanwhile, under O-poor conditions, Si-N bond formation is preferable, which reinforces a-SiON by increasing bond density. The findings suggest realizing O-poor conditions is crucial for highly elastic insulating films.

Mechanisms of Social Attachment Between Children and Pet Dogs.

An increasing body of evidence indicates that owning a pet dog is associated with improvements in child health and well-being. Importantly, the degree of the social bond between child and dog may mediate the beneficial outcomes of dog ownership. The formation of social bonds is an intrinsically dyadic, interactive process where each interactor's behavior influences the other's behavior. For this reason, it is critical to evaluate the biological mechanisms of attachment in both children and their pet dogs as a socially bonded pair. Here, we review the physical, mental, and emotional outcomes that are associated with pet dog ownership or interaction in children. We then discuss the evidence that suggests that the strength of a social bond between a child and their pet dog matters for maximizing the beneficial outcomes associated with pet dog ownership, such as possible stress-buffering effects. We review the existing literature on the neural and endocrinological mechanisms of social attachment for inter-species social bonds that form between human children and dogs, situating this emerging knowledge within the context of the mechanisms of intra-species bonds in mammals. Finally, we highlight the remaining open questions and point toward directions for future research.

Dual Cocatalysts on Covalent Organic Framework as Charge Transfer Mediator Facilitating Photocatalytic Water Oxidation

AbstractCovalent organic frameworks (COFs) have been regarded as promising photocatalytic materials. However, the sluggish diffusion of photoinduced charges in a single‐component COF remains the obstacles that have to be overcome. Here, we demonstrate a synthesis of a COF bearing dual cocatalysts Co3O4 and Re complex as photocatalyst for water oxidation. The dual cocatalysts are coordinated on the COF, and enable the spatial separation of photoinduced charges. The generated electrons were attracted to Re moiety, while the holes were localized on Co3O4 cocatalyst for water oxidation to produce O2 product. The synergy of dual cocatalysts of COF promote the charge separation and redox reaction. Moreover, hydroxyl radicals generated from the hydration of COF contribute to O−O bond formation, which is the key step of O2 formation. Accordingly, an excellent O2 production rate of 400 μmol g−1 h−1 under visible light irradiation was obtained. This work may pave the way to the development of highly efficient COF photocatalysts for solar energy conversion.

The unexpected and important role of alcohol stabilizer in thermal cis-trans isomerization of push-pull dyes in chloroform solution

The study demonstrates the influence of ethanol as a stabilizer in chloroform on the thermal cis-trans isomerization kinetics of photochromic compounds based on azobenzene and azopyridine derivatives. The significance of the addition of ethanol as a stabilizer in chloroform-based solutions on the isomerization reaction of the hydroxy- and the 6-hydroxylalkoxy-substituted azo compounds was investigated. The results have revealed that the presence of a polar stabilizer in a solvent can significantly reduce the reaction rate constant of the dark cis-trans isomerization due to the formation of hydrogen bonds at both ends of the azo-chromophore, thereby inhibiting the isomerization. Furthermore, a stabilizer can facilitate the reversion of azo-hydrazone tautomers of azophenols to their azobenzene form, resulting in a decrease in the reaction rate constant. The research presented in this paper can be essential for scientists who study the kinetics of the trans-cis and the cis-trans isomerization reactions of azo-chromophores. The results show that the use of solvents with polar stabilizers should be rather avoided, as their usage without information about stabilizers can lead to different experimental data. The authors should ensure that detailed information about stabilizers used in unstable solvents is included in the experimental section of their works (a detail currently often omitted in the literature).

Turmeric as a therapeutic agent against arsenic-induced metabolic dysregulation in rat models

Ethnopharmacological relevanceHealth hazards stemming from metalloid consumption, such as arsenic, pose a global concern. This study aimed to assess the protective effects of turmeric against arsenic-induced alterations in lipid profiles and energy metabolism in rats. MethodsThirty male rats were divided into three groups over a 90–180-day exposure period: Group 1 (Control) received standard rat chow; Group 2 received an arsenic diet; and Group 3 received arsenic plus turmeric supplemented diet. Blood and liver tissue samples were collected for lipid profiles, glucose levels, energy metabolism parameters, and PPAR-α mRNA expression using qRT-PCR. Statistical analysis was performed (p<0.05). ResultsResults indicated significant (p<0.05) increases in lipid profiles among arsenic-exposed rats after 180 days, elevating the risk of coronary artery diseases. Both arsenic and turmeric-exposed groups showed heightened total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) levels at 90 and 180 days, with nuanced differences suggesting dyslipidemia and atherosclerosis. Blood glucose observations revealed hypoglycemia initially in arsenic-exposed rats, progressing to hyperglycemia by 180 days. Arsenic significantly (p<0.05) inhibited pyruvate kinase, hexokinase, and isocitrate dehydrogenase activities in the liver after 180 days, while turmeric exposure showed no significant (p<0.05) changes. Additionally, both arsenic and turmeric groups exhibited downregulation of PPAR-α expression at 180 days. In-silico analysis identified curcumin as a promising component for anti-atherosclerosis and arsenic-related conditions due to its strong binding affinities and multiple hydrogen bond formations. ConclusionIn conclusion, long-term turmeric consumption may mitigate arsenic-induced oxidative damage associated with early hyperglycemia, diabetes mellitus, cardiovascular diseases, and atherosclerosis. These findings underscore turmeric’s potential therapeutic role against arsenic toxicity, suggesting avenues for future research and public health interventions.

Versatile Dual Reporter to Identify Ribosome Pausing Motifs Alleviated by Translation Elongation Factor P.

Protein synthesis is influenced by the chemical and structural properties of the amino acids incorporated into the polypeptide chain. Motifs containing consecutive prolines can slow the translation speed and cause ribosome stalling. Translation elongation factor P (EF-P) facilitates peptide bond formation in these motifs, thereby alleviating stalled ribosomes and restoring the regular translational speed. Ribosome pausing at various polyproline motifs has been intensively studied using a range of sophisticated techniques, including ribosome profiling, proteomics, and in vivo screening, with reporters incorporated into the chromosome. However, the full spectrum of motifs that cause translational pausing in Escherichia coli has not yet been identified. Here, we describe a plasmid-based dual reporter for rapid assessment of pausing motifs. This reporter contains two coupled genes encoding mScarlet-I and chloramphenicol acetyltransferase to screen motif libraries based on both bacterial fluorescence and survival. In combination with a diprolyl motif library, we used this reporter to reveal motifs of different pausing strengths in an E. coli strain lacking efp. Subsequently, we used the reporter for a high-throughput screen of four motif libraries, with and without prolines at different positions, sorted by fluorescence-associated cell sorting (FACS) and identify new motifs that influence the translational efficiency of the fluorophore. Our study provides an in vivo platform for rapid screening of amino acid motifs that affect translational efficiencies.