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A survey of protein databases indicates that the majority of enzymes exist in oligomeric forms, with about half of those found in the UniProt database being homodimeric. Understanding why many enzymes are in their dimeric form is imperative. Recent developments in experimental and computational techniques have allowed for a deeper comprehension of the cooperative interactions between the subunits of dimeric enzymes. This review aims to succinctly summarize these recent advancements by providing an overview of experimental and theoretical methods, as well as an understanding of cooperativity in substrate binding and the molecular mechanisms of cooperative catalysis within homodimeric enzymes. Focus is set upon the beneficial effects of dimerization and cooperative catalysis. These advancements not only provide essential case studies and theoretical support for comprehending dimeric enzyme catalysis but also serve as a foundation for designing highly efficient catalysts, such as dimeric organic catalysts. Moreover, these developments have significant implications for drug design, as exemplified by Paxlovid, which was designed for the homodimeric main protease of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The need for an environmental risk assessment for engineered nanomaterials (ENM) necessitates the knowledge about their environmental emissions. Material flow models (MFA) have been used to provide predicted environmental emissions but most current nano-MFA models consider neither the rapid development of ENM production nor the fact that a large proportion of ENM are entering an in-use stock and are released from products over time (i.e., have a lag phase). Here we use dynamic probabilistic material flow modeling to predict scenarios of the future flows of four ENM (nano-TiO2, nano-ZnO, nano-Ag and CNT) to environmental compartments and to quantify their amounts in (temporary) sinks such as the in-use stock and ("final") environmental sinks such as soil and sediment. In these scenarios, we estimate likely future amounts if the use and distribution of ENM in products continues along current trends (i.e., a business-as-usual approach) and predict the effect of hypothetical trends in the market development of nanomaterials, such as the emergence of a new widely used product or the ban on certain substances, on the flows of nanomaterials to the environment in years to come. We show that depending on the scenario and the product type affected, significant changes of the flows occur over time, driven by the growth of stocks and delayed release dynamics. [ABSTRACT FROM AUTHOR]

The introduction of nitrogen vacancies has been shown to be an effective way to tune the plasmonic properties of refractory titanium nitrides. However, its underlying mechanism remains debated due to the lack of high-quality single-crystalline samples and a deep understanding of electronic properties. Here, a series of epitaxial titanium nitride films with varying nitrogen vacancy concentrations (TiN x ) were synthesized. Spectroscopic ellipsometry measurements revealed that the plasmon energy could be tuned from 2.64 eV in stoichiometric TiN to 3.38 eV in substoichiometric TiN x . Our comprehensive analysis of electrical and plasmonic properties showed that both the increased electronic states around the Fermi level and the decreased carrier effective mass due to the modified electronic band structures are responsible for tuning the plasmonic properties of TiN x . Our findings offer a deeper understanding of the tunable plasmonic properties in epitaxial TiN x films and are beneficial for the development of nitride plasmonic devices.

Although the concerted [3 + 2] mechanism of osmium-catalyzed asymmetric dihydroxylation has been generally accepted, the unusual nonlinear Hammett relationship induced by amine-type ligands remains unexplained. To understand this, we carried out a density functional theory (DFT) study for the osmylation of substituted styrenes by the following: OsO 4 , OsO 4 -pyridine, OsO 4 -4-cyanopyridine, OsO 4 -4-pyrrolidinopyridine, and OsO 4 -quinuclidine. Calculations using the M06 functional successfully reproduce the experimentally observed nonlinear relationships. The transition states exhibit considerable singlet-diradical character, which causes the nonlinear Hammett relationship. Regardless of the presence or absence of an amine-type ligand, an electron donation from styrene to OsO 4 is observed, indicating no mechanistic change. Calculations indicate that the electronic interaction between the amine-type ligand and styrene also influences the reaction rate.

Described herein is the development of a visible-light-induced photoredox 1,6-enyne reductive cyclization via selective reduction of a triple bond instead of an activated double bond. The selective 1,6-enyne radical cyclization/carbon═carbon double bond cleavage provided a straightforward route to structurally valuable α , β -unsaturated γ-lactams. TEMPO-trap experiments, control experiments, and DFT calculations have offered evidence supporting the possible catalytic cycle.

Controlling the number of C-H bond activation is a long-standing challenge in organic synthesis. Recently, Yu's group demonstrated that in Pd-catalyzed alanine's arylation, pyridine-type ligands favor a mono-C-H bond activation, while quinoline-type ligands favor a di-C-H bond activation. To disclose the underlying principles, a theoretical study (density functional theory (DFT)) has been carried out. Our study indicates that a mono-ligand model, which is generally adopted in the community, does not reproduce the experimentally observed mono-/di-selectivity, while a bi-ligand model can rationalize the experimental observations well, including the observed diastereoselectivity in diarylation. The electron-rich pyridine-type ligands with less steric congestion can promote the C-H bond activation reaction of alanine derivatives. The quinoline-type ligands have a better π back-donation interaction with the metal, which makes a more active C-H bond activation than the pyridine-type ligands for this reaction. This bi-ligand model, which is a necessity, allows the understanding and future design of a dual ligand effect in C-H bond activation.

Addition of halomethyl radicals to form bioactive molecules has recently become an efficient strategy. The reaction has a bottleneck, however, which is the effective and selective generation of the proper halomethyl • CH n X 3- n radical by combining CH n X 4- n with a carbon radical. Understanding the reactivity and selectivity of carbon radicals in the hydrogen atom transfer (HAT) and halogen atom transfer (XAT) reactions of CH n X 4- n is key to the development of such an attractive method. With the help of the emerging data-driven strategy, DFT calculations were used to explore various correlations. For selectivity, the relative energy barriers between HAT and XAT reactions (Δ G ⧧ H - Δ G ⧧ X ) correlate reasonably well with the three parameters Δ G H , Δ G X , and IP, and the correlation studies reveal that the calculated IP inver and the experimental ΔBDE can be used to conveniently predict the selectivity. Predicted selectivities are consistent with experimental determinations. This work not only provides a possibility for selecting carbon radicals with the known or easily obtained physicochemical data but also demonstrates that the informatic workflow such as generating data and identifying correlations has potential applications in mining reaction rules.

Ultrafast time-resolved strong field ionization-photofragmentation (SFI-PF) has emerged as a useful method for investigation of dynamics of molecular cations. Here we perform a SFI-PF study on the electronic states of toluene cations. By measuring the ion yields as a function of delay time, we obtain the transients of both parent and daughter ions, which show ultrafast decays and out-of-phase oscillations. The results provide the first experimental evidence of D 1 -D 0 ultrafast relaxation of toluene cations occurring in about 530 fs and indicate coincident resonance between the vibrational states in D 1 and D 0 leading to oscillations with a period of about 2.05 ps. Our study should shed some light on the ultrafast photochemistry involving complex molecular cations.

Euphopias A-C ( 1 - 3 ), three rearranged jatrophane-type diterpenoids with tricyclo[8.3.0.0 2,7 ]tridecane ( 1 and 2 ) and tetracyclo[11.3.0.0 2,10 .0 3,7 ]hexadecane ( 3 ) cores, were isolated from Euphorbia helioscopia . Comprehensive spectroscopic analyses, quantum-chemical calculations, and X-ray diffractions were used to identify their structures. Compounds 1 - 3 could significantly inhibit NLRP3 inflammasome activation and block NLRP3 inflammasome-induced pyroptosis. Additionally, a mechanistic study revealed that 2 could ameliorate mitochondria damage, thereby interrupting NLRP3 inflammasome activation.

Benzene cation is a prototypical complex system that exhibits ultrafast conical intersections of different electronic states located close to the Franck-Condon region, yet little information is available about the dynamics of the cationic excited states. Here we utilize femtosecond time-resolved strong field ionization-photo fragmentation (SFI-PF) method to prepare and probe the electronic states of benzene cations. The transient of both the parent ion and the daughter ions are obtained, which present distinct behaviors at different pulse energies of the SFI laser. The results provide the first experimental evidence of B 2 E 2g -X 2 E 1g ultrafast relaxation of benzene cation, which occurs in about 250-270 fs. Our study should pave the way to revealing the ultrafast photochemistry of complex molecular cations.

An in situ forming hydrogel has emerged as a promising wound dressing recently. As physically cross-linked hydrogels are normally unstable, most in situ forming hydrogels are chemically cross-linked. However, big concerns have remained regarding the slow gelation and the potential toxicity of residual functional groups from cross-linkers or the polymer matrix. Herein, we report a sprayable in situ forming hydrogel composed of poly( N -isopropylacrylamide 166 - co - n -butyl acrylate 9 )-poly(ethylene glycol)-poly( N -isopropylacrylamide 166 - co - n -butyl acrylate 9 ) copolymer (P(NIPAM 166 - co -nBA 9 )-PEG-P(NIPAM 166 - co -nBA 9 ), denoted as PEP) and silver-nanoparticles-decorated reduced graphene oxide nanosheets (Ag@rGO, denoted as AG) in response to skin temperature. This thermoresponsive hydrogel exhibits intriguing sol-gel irreversibility at low temperatures for the stable dressing of a wound, which is attributed to the inorganic/polymeric dual network and abundant coordination interactions between Ag@rGO nanosheets and PNIPAM. The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus (MRSA) of this PEP-AG hydrogel wound dressing are confirmed in vitro and in vivo , which could transparently promote the healing of a MRSA-infected skin defect.

The fabrication of van der Waals heterostructures mainly extends to two-dimensional (2D) materials that are exfoliated from their bulk counterparts, which is greatly limited by high-volume manufacturing. Here, we demonstrate multilayered PtS 2 /PtSe 2 heterojunctions covering a large area on the SiO 2 /Si substrate with a maximum size of 2″ in diameter, offering throughputs that can meet the practical application demand. Theoretical simulation was carried out to understand the electronic properties of the PtS 2 /PtSe 2 heterojunctions. Zero-bias photoresponse in the heterojunctions is observed under laser illumination of different wavelengths (405-2200 nm). The PtS 2 /PtSe 2 heterojunctions exhibit broad band photoresponse and high quantum efficiency at infrared wavelengths with lower bounds for the external quantum efficiencies being 1.2% at 1064 nm, 0.2% at 1550 nm, and 0.05% at 2200 nm, and also relatively fast response time at the dozens of millisecond level. The large area, broad band 2D heterojunction photodetector demonstrated in this work further corroborates the great potential of 2D materials in the future low-energy optoelectronics.

2-Iodoxybenzoic acid (IBX) is an important species for the oxidation of alcohols to aldehydes or ketones. An often-cited mechanism involving a hypervalent twist as the rate-determining step (RDS) is inconsistent with kinetic isotope effect (KIE) experiments. The computations with larger basis sets reveal that the reductive elimination involving the C-H bond cleavage is the RDS (rate-determining step). Further computational/experimental studies suggest that the reactivity can be improved by adjusting the trans influence with Lewis acids.

The presence of a direct band gap and high carrier mobility in few-layer black phosphorus (BP) offers opportunities for using this material for infrared (IR) light detection. However, the poor air stability of BP and its large contact resistance with metals pose significant challenges to the fabrication of highly efficient IR photodetectors with long lifetimes. In this work, we demonstrate a graphene-BP heterostructure photodetector with ultrahigh responsivity and long-term stability at IR wavelengths. In our device architecture, the top layer of graphene functions not only as an encapsulation layer but also as a highly efficient transport layer. Under illumination, photoexcited electron-hole pairs generated in BP are separated and injected into graphene, significantly reducing the Schottky barrier between BP and the metal electrodes and leading to efficient photocurrent extraction. The graphene-BP heterostructure phototransistor exhibits a long-term photoresponse at near-infrared wavelength (1550 nm) with an ultrahigh photoresponsivity (up to 3.3 × 10 3 A W -1 ), a photoconductive gain (up to 1.13 × 10 9 ), and a rise time of about 4 ms. Considering the thickness-dependent band gap in BP, this material represents a powerful photodetection platform that is able to sustain high performance in the IR wavelength regime with potential applications in remote sensing, biological imaging, and environmental monitoring.

Asymmetric total synthesis of structurally intriguing and highly oxygenated lancifodilactone G acetate (7) has been achieved for the first time in 28 steps from a cheap commodity chemical, 2-(triisopropylsiloxy)-1,3-butadiene.

The need for an environmental risk assessment for engineered nanomaterials (ENM) necessitates the knowledge about their environmental concentrations. Despite significant advances in analytical methods, it is still not possible to measure the concentrations of ENM in natural systems. Material flow and environmental fate models have been used to provide predicted environmental concentrations. However, almost all current models are static and consider neither the rapid development of ENM production nor the fact that many ENM are entering an in-use stock and are released with a lag phase. Here we use dynamic probabilistic material flow modeling to predict the flows of four ENM (nano-TiO2, nano-ZnO, nano-Ag and CNT) to the environment and to quantify their amounts in (temporary) sinks such as the in-use stock and ("final") environmental sinks such as soil and sediment. Caused by the increase in production, the concentrations of all ENM in all compartments are increasing. Nano-TiO2 had far higher concentrations than the other three ENM. Sediment showed in our worst-case scenario concentrations ranging from 6.7 μg/kg (CNT) to about 40 000 μg/kg (nano-TiO2). In most cases the concentrations in waste incineration residues are at the "mg/kg" level. The flows to the environment that we provide will constitute the most accurate and reliable input of masses for environmental fate models which are using process-based descriptions of the fate and behavior of ENM in natural systems and rely on accurate mass input parameters.

A combined experimental/computational study on the amino acid ligand-assisted Pd-catalyzed C-H bond activation reveals a mechanism in which the amino acid acts as both a dianionic bidentate ligand and a proton acceptor. This new model explains the effects of amino acids on reactivity and selectivity and unveils the dual roles of amino acids: stabilizing monomeric Pd complexes and serving as the internal base for proton abstraction.

Density functional theory investigations have elucidated the mechanism and origins of meta-regioselectivity of Pd(II)-catalyzed C-H olefinations of toluene derivatives that employ a nitrile-containing template. The reaction proceeds through four major steps: C-H activation, alkene insertion, β-hydride elimination, and reductive elimination. The C-H activation step, which proceeds via a concerted metalation-deprotonation (CMD) pathway, is found to be the rate- and regioselectivity-determining step. For the crucial C-H activation, four possible active catalytic species-monomeric Pd(OAc)2, dimeric Pd2(OAc)4, heterodimeric PdAg(OAc)3, and trimeric Pd3(OAc)6-have been investigated. The computations indicated that the C-H activation with the nitrile-containing template occurs via a Pd-Ag heterodimeric transition state. The nitrile directing group coordinates with Ag while the Pd is placed adjacent to the meta-C-H bond in the transition state, leading to the observed high meta-selectivity. The Pd2(OAc)4 dimeric mechanism also leads to the meta-C-H activation product but with higher activation energies than the Pd-Ag heterodimeric mechanism. The Pd monomeric and trimeric mechanisms require much higher activation free energies and are predicted to give ortho products. Structural and distortion energy analysis of the transition states revealed significant effects of distortions of the template on mechanism and regioselectivity, which provided hints for further developments of new templates.

Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. Through the development of a drug delivery system that tethers doxorubicin onto the surface of gold nanoparticles with a poly(ethylene glycol) spacer via an acid-labile linkage (DOX-Hyd@AuNPs), we have demonstrated that multidrug resistance in cancer cells can be significantly overcome by a combination of highly efficient cellular entry and a responsive intracellular release of doxorubicin from the gold nanoparticles in acidic organelles. DOX-Hyd@AuNPs achieved enhanced drug accumulation and retention in multidrug resistant MCF-7/ADR cancer cells when it was compared with free doxorubicin. It released doxorubicin in response to the pH of acidic organelles following endocytosis, opposite to the noneffective drug release from doxorubicin-tethered gold nanoparticles via the carbamate linkage (DOX-Cbm@AuNPs), which was shown by the recovered fluorescence of doxorubicin from quenching due to the nanosurface energy transfer between the doxorubicinyl groups and the gold nanoparticles. DOX-Hyd@AuNPs therefore significantly enhanced the cytotoxicity of doxorubicin and induced elevated apoptosis of MCF-7/ADR cancer cells. With a combined therapeutic potential and ability to probe drug release, DOX-Hyd@AuNPs represent a model with dual roles in overcoming MDR in cancer cells and probing the intracellular release of drug from its delivery system.

Combination of two or more therapeutic strategies with different mechanisms can cooperatively prohibit cancer development. Combination of chemotherapy and small interfering RNA (siRNA)-based therapy represents an example of this approach. Hypothesizing that the chemotherapeutic drug and the siRNA should be simultaneously delivered to the same tumoral cell to exert their synergistic effect, the development of delivery systems that can efficiently encapsulate two drugs and successfully deliver payloads to targeted sites via systemic administration has proven to be challenging. Here, we demonstrate an innovative "two-in-one" micelleplex approach based on micellar nanoparticles of a biodegradable triblock copolymer poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(2-aminoethyl ethylene phosphate) to systemically deliver the siRNA and chemotherapeutic drug. We show clear evidence that the micelleplex is capable of delivering siRNA and paclitaxel simultaneously to the same tumoral cells both in vitro and in vivo. We further demonstrate that systemic administration of the micelleplex carrying polo-like kinase 1 (Plk1) specific siRNA and paclitaxel can induce a synergistic tumor suppression effect in the MDA-MB-435s xenograft murine model, requiring a thousand-fold less paclitaxel than needed for paclitaxel monotherapy delivered by the micelleplex and without activation of the innate immune response or generation of carrier-associated toxicity.

MiRNAs are viable therapeutic targets for cancer therapy, but the targeted delivery of miRNA or its anti-miRNA antisense oligonucleotides (AMOs) remains a challenge. We report here a PEGylated LPH (liposome-polycation-hyaluronic acid) nanoparticle formulation modified with cyclic RGD peptide (cRGD) for specific and efficient delivery of AMO into endothelial cells, targeting α(v)β₃ integrin present on the tumor neovasculature. The nanoparticles effectively delivered anti-miR-296 AMO to the cytoplasm and downregulated the target miRNA in human umbilical vein endothelial cells (HUVECs), which further efficiently suppressed blood tube formulation and endothelial cell migration, owing to significant upregulation of hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), whereas nanoparticles without cRGD modification showed only little AMO uptake and miRNA silencing activity. In vivo assessment of angiogenesis using Matrigel plug assay also demonstrated that cRGD modified LPH nanoparticles have potential for antiangiogenesis in miRNA therapeutics. With the delivery of anti-miR-296 AMO by targeted nanoparticles, significant decrease in microvessel formulation within Matrigel was achieved through suppressing the invasion of CD31-positive cells into Matrigel and prompting HGS expression in angiogenic endothelial cells.

A series of optically pure β-amino ketones have been synthesized in high enantioselectivities (ee > 99%) by Rh-DuanPhos-catalyzed asymmetric hydrogenation of readily prepared β-keto enamides. Further reduction of these β-amino ketones with hydrogen and Pd/C leads to the formation of a variety of protected enantiomerically pure γ-aryl amines (ee > 99%), which are key building blocks in many bioactive molecules.

Surface modification is often needed in tissue engineering to enhance the interaction between cells and synthetic materials and improve the cytocompatibility and cellular functions. In this study, block copolymers of poly(L-lactic acid) and poly(ethyl ethylene phosphate) (PLLA-b-PEEP) were synthesized and used to modify the PLLA surface via a spin-coating process, to understand whether surface modification with polyphosphoester-based polymer will be osteoinductive for potential bone tissue engineering applications. X-ray photoelectron spectra measurements revealed that phosphorus atomic compositions after surface modification increased from 2.09% to 4.39% with increasing PEEP length of PLLA-b-PEEP from 58 to 224 units, which also led to a more hydrophilic surface property compared with unmodified PLLA. The initial osteoblast attachment and proliferation on the modified surfaces were significantly enhanced. Moreover, cellular alkaline phosphatase activity and mineral calcium depositions were also promoted by PEEP modification. The gene expression determined by reverse transcription polymerase chain reaction further revealed that type I collagen and osteocalcin expression were upregulated in osteoblasts cultured on the modified surfaces, indicating that PEEP modification might be potentially osteoinductive and favorable for further application in bone tissue engineering.

A series of novel amphiphilic triblock copolymers of poly(ethyl ethylene phosphate) and poly(-caprolactone) (PEEP-PCL-PEEP) with various PEEP and PCL block lengths were synthesized and characterized. These triblock copolymers formed micelles composed of a hydrophobic core of poly(-caprolactone) (PCL) and a hydrophilic shell of poly(ethyl ethylene phosphate) (PEEP) in aqueous solution. The micelle morphology was spherical, determined by transmission electron microscopy. It was found that the size and critical micelle concentration values of the micelles depended on both hydrophobic PCL block length and PEEP hydrophilic block length. The in vitro degradation characteristics of the triblock copolymers were investigated in micellar form, showing that these copolymers were completely biodegradable under enzymatic catalysis of Pseudomonas lipase and phosphodiesterase I. These triblock copolymers were used for paclitaxel (PTX) encapsulation to demonstrate the potential in drug delivery. PTX was successfully loaded into the micelles, and the in vitro release profile was found to be correlative to the polymer composition. These biodegradable triblock copolymer micelles are potential as novel carriers for hydrophobic drug delivery.

Novel biodegradable hydrogels by photo-cross-linking macromers based on polyphosphoesters and poly(ethylene glycol) (PEG) are reported. Photo-cross-linkable macromers were synthesized by ring-opening polymerization of the cyclic phosphoester monomer 2-(2-oxo-1,3,2-dioxaphospholoyloxy) ethyl methacrylate (OPEMA) using PEG as the initiator and stannous octoate as the catalyst. The macromers were characterized by 1H NMR, Fourier transform infrared spectroscopy, and gel permeation chromatography measurements. The content of polyphosphoester in the macromer was controlled by varying the feed ratio of OPEMA to PEG. Hydrogels were fabricated by exposing aqueous solutions of macromers with 0.05% (w/w) photoinitiator to UV light irradiation, and their swelling kinetics as well as degradation behaviors were evaluated. The results demonstrated that cross-linking density and pH values strongly affected the degradation rates. The macromers was compatible to osteoblast cells, not exhibiting significant cytotoxicity up to 0.5 mg/mL. "Live/dead" cell staining assay also demonstrated that a large majority of the osteoblast cells remained viable after encapsulation into the hydrogel constructs, showing their potential as tissue engineering scaffolds.