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Motivated by the multiferroic effects and quantum magnetization plateaus in the skew chain antiferromagnets T 2 V 2 O 7 (T = Ni, Co), we have conducted a detailed density function theoretical study on Co 2 V 2 O 7. The results show that the nearest-neighbor interchain interaction (J 3 / k B = − 35.57 K) is not much greater than the intrachain interactions (J 1 / k B = − 19.54 K and J 2 / k B = 27.55 K), showing the absence of interchain dimerization of the Co ions. This indicates that the "dimer+monomer" model used for Ni 2 V 2 O 7 [Cao et al., Phys. Rev. B 106, 184409 (2022)] is no longer applicable to Co 2 V 2 O 7. Finally, the exact diagonalization of spin Hamiltonian, including anisotropic exchanges, produces the experimentally observed 1/2 and 3/4 magnetization plateaus. [ABSTRACT FROM AUTHOR]

Motivated by the multiferroic effects and quantum magnetization plateaus in the skew chain antiferromagnets T 2 V 2 O 7 (T = Ni, Co), we have conducted a detailed density function theoretical study on Co 2 V 2 O 7. The results show that the nearest-neighbor interchain interaction (J 3 / k B = − 35.57 K) is not much greater than the intrachain interactions (J 1 / k B = − 19.54 K and J 2 / k B = 27.55 K), showing the absence of interchain dimerization of the Co ions. This indicates that the "dimer+monomer" model used for Ni 2 V 2 O 7 [Cao et al., Phys. Rev. B 106, 184409 (2022)] is no longer applicable to Co 2 V 2 O 7. Finally, the exact diagonalization of spin Hamiltonian, including anisotropic exchanges, produces the experimentally observed 1/2 and 3/4 magnetization plateaus. [ABSTRACT FROM AUTHOR]

A proof-of-concept study is undertaken to demonstrate the utility of the machine learning combined with the thermodynamic perturbation theory (MLPT) to test the accuracy of electronic structure methods in finite-temperature thermodynamic calculations. As a test example, formic acid dimer is chosen, which is one of the systems included in the popular benchmark set S22 [Jurečka et al., Phys. Chem. Chem. Phys. 8, 1985–1993 (2006)]. Starting from the explicit molecular dynamics and thermodynamic integration performed at the PBE + D2 level, the MLPT is used to obtain fully anharmonic dimerization free and internal energies at the reference quality CCSD(T) level and 19 different density functional approximations, including GGA, meta-GGA, non-local, and hybrid functionals with and without dispersion corrections. Our finite-temperature results are shown to be both qualitatively and quantitatively different from those obtained using the conventional benchmarking strategy based on fixed structures. The hybrid functional HSE06 is identified as the best performing approximate method tested, with the errors in free and internal energies of dimerization being 36 and 41 meV, respectively. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulations are conducted to systematically investigate the insertion of spherical nanoparticles (NPs) in polymer brushes as a function of their size, strength of their interaction with the polymers, polymer grafting density, and polymer chain length. For attractive interactions between the NPs and the polymers, the depth of NPs' penetration in the brush results from a competition between the enthalpic gain due to the favorable polymer–NP interaction and the effect of osmotic pressure resulting from displaced polymers by the NP's volume. A large number of simulations show that the average depth of the NPs increases by increasing the strength of the interaction strength. However, it decreases by increasing the NPs' diameter or increasing the polymer grafting density. While the NPs' effect on the polymer density is local, their effect on their conformations is long-ranged and extends laterally over length scales larger than the NP's size. This effect is manifested by the emergence of laterally damped oscillations in the normal component of the chains' radius of gyration. Interestingly, we found that for high enough interaction strength, two NPs dimerize in the polymer brush. The dimer is parallel to the substrate if the NPs' depth in the brush is shallow. However, the dimer is perpendicular to the substrate if the NPs' are deep in the brush. These results imply that polymer brushes can be used as a tool to localize and self-assemble NPs in polymer brushes. [ABSTRACT FROM AUTHOR]

Plants sense abscisic acid (ABA) using chemical-induced dimerization (CID) modules, including the receptor PYR1 and HAB1, a phosphatase inhibited by ligand-activated PYR1. This system is unique because of the relative ease with which ligand recognition can be reprogrammed. To expand the PYR1 system, we designed an orthogonal * module, which harbors a dimer interface salt bridge; X-ray crystallographic, biochemical and in vivo analyses confirm its orthogonality. We used this module to create PYR1*MANDI/HAB1* and PYR1*AZIN/HAB1*, which possess nanomolar sensitivities to their activating ligands mandipropamid and azinphos-ethyl. Experiments in Arabidopsis thaliana and Saccharomyces cerevisiae demonstrate the sensitive detection of banned organophosphate contaminants using living biosensors and the construction of multi-input/output genetic circuits. Our new modules enable ligand-programmable multi-channel CID systems for plant and eukaryotic synthetic biology that can empower new plant-based and microbe-based sensing modalities.

Excited‐state intramolecular proton transfer (ESIPT) chromophores have attracted considerable attention as promising gain media for organic lasers, particularly in amplified spontaneous emission (ASE) due to their advantageous characteristics. These include an intrinsic four‐level photocycle, significant separation between absorption and emission spectra, and enhanced emission efficiency facilitated by aggregate‐induced emission. This study investigates the amplification of π‐conjugation in hydroxyphenyl‐benzothiazole (HBT)‐based ESIPT materials via dimerization to intensify ESIPT processes, surge absorption cross‐section, enhance optical gain, and induce a redshift in emission spectra. Computational study shows that the ESIPT processes of the new dimers proceed through single proton transfer where the second proton transfer is not accessible. While the ESIPT photocycle does not extend to both HBT moieties of the dimers, the dimers foster more efficient ESIPT processes in both solution and solid states than their parent HBT, resulting in substantial Stokes shifts (>233 nm). Moreover, both dimers exhibit enhanced solid‐state photoluminescence quantum yields, reaching up to ≈55%, and low solid‐state ASE threshold values (≈6.8 µJ cm−2) in the red region. Remarkably, the new dimers demonstrate excellent thermal and photostability with notably reduced spectral overlap compared to their parent, highlighting the potential utility of the approaches to developing new organic solid‐state laser materials. [ABSTRACT FROM AUTHOR]

Many stimuli‐responsive materials harness the reversible association of supramolecular binding motifs to enable advanced functionalities such as self‐healing, switchable adhesion, or mechanical adaptation. Despite extensive research into the structure–property relationships of these materials, direct correlations between molecular‐level changes in supramolecular binding and macroscopic material behaviors have mostly remained elusive. Here, we show that this challenge can be overcome with supramolecular binding motifs featuring integrated binding indicators. We demonstrate this using a novel motif that combines a hydrogen‐bonding ureido‐4‐pyrimidinone (UPy) with two strategically placed pyrene fluorophores. Dimerization of this motif promotes pyrene excimer formation, facilitating the straightforward optical quantification of supramolecular assembly under various conditions. We exploit the new motif as a supramolecular cross‐linker in poly(methyl acrylate)s to probe the extent of (dis)assembly as a function of cross‐linker content, processing history, and applied stimuli. We demonstrate that the stimuli‐induced dissociation of hydrogen‐bonding linkages strongly depends on the initial cross‐link density, which also dictates whether the force‐induced dissociation in polymer films correlates with the applied stress or strain. Thus, beyond introducing a robust tool for the in situ study of dynamic (dis)assembly mechanisms in supramolecular systems, our findings provide new insights into the mechanoresponsive behavior of such materials. [ABSTRACT FROM AUTHOR]

The dimerization of small molecule acceptors (SMAs) holds significant potential by combining the advantages of both SMAs and polymer acceptors in realizing high power conversion efficiency (PCE) and operational stability in organic solar cells (OSCs). However, advancements in the selection and innovation of dimeric linkers are still challenging in enhancing their performance. In this study, three new dimeric acceptors, namely DY‐Ar‐4, DY‐Ar‐5, and DY‐Ar‐6 are synthesized, by linking two Y‐series SMA subunits via an “end‐to‐end” strategy using flexible spacers (octyl, decyl, and dodecyl, respectively). The influence of spacer lengths on device performance is systematically investigated. The results indicate that DY‐Ar‐5 exhibits more compact and ordered packing, leading to an optimal morphology. OSCs based on PM6: DY‐Ar‐5 achieves a maximum PCE of 15.76%, attributes to enhance and balance carrier mobility, and reduce carrier recombination. This dimerization strategy using suitable non‐conjugated linking units provides a rational principle for designing high‐performance non‐fullerene acceptors. [ABSTRACT FROM AUTHOR]

The opening of the mitochondrial permeability transition pore (PTP), a Ca2+‐dependent pore located in the inner mitochondrial membrane, triggers mitochondrial outer membrane permeabilization (MOMP) and induces organelle rupture. However, the underlying mechanism of PTP‐induced MOMP remains unclear. Mitochondrial carrier homolog 2 (MTCH2) mediates MOMP process by facilitating the recruitment of tBID to mitochondria. Here, we show that MTCH2 binds to cyclophilin D (CyPD) and promotes the dimerization of F‐ATP synthase via interaction with subunit j. The interplay between MTCH2 and subunit j coordinates MOMP and PTP to mediate the occurrence of mitochondrial permeability transition. Knockdown of CyPD, MTCH2 and subunit j markedly sensitizes cells to RSL3‐induced ferroptosis, which is prevented by MitoTEMPO, suggesting that mitochondrial permeability transition mediates ferroptosis defense. [ABSTRACT FROM AUTHOR]

The inhibitor of κB (IκB) kinase (IKK) is a central regulator of NF-κB signaling. All IKK complexes contain hetero- or homodimers of the catalytic IKKβ and/or IKKα subunits. Here, we identify a YDDΦxΦ motif, which is conserved in substrates of canonical (IκBα, IκBβ) and alternative (p100) NF-κB pathways, and which mediates docking to catalytic IKK dimers. We demonstrate a quantitative correlation between docking affinity and IKK activity related to IκBα phosphorylation/degradation. Furthermore, we show that phosphorylation of the motif's conserved tyrosine, an event previously reported to promote IκBα accumulation and inhibition of NF-κB gene expression, suppresses the docking interaction. Results from integrated structural analyzes indicate that the motif binds to a groove at the IKK dimer interface. Consistently, suppression of IKK dimerization also abolishes IκBα substrate binding. Finally, we show that an optimized bivalent motif peptide inhibits NF-κB signaling. This work unveils a function for IKKα/β dimerization in substrate motif recognition. The inhibitor of kB kinase (IKK) is a central regulator of NF-kB signalling. Here the authors identify a motif conserved in substrates of canonical and alternative NF-kB pathways which mediates docking to catalytic IKK dimers: they show that phosphorylation of the conserved tyrosine suppresses the docking interaction. [ABSTRACT FROM AUTHOR]

WNT signaling is fundamental in development and homeostasis, but how the Frizzled receptors (FZDs) propagate signaling remains enigmatic. Here, we present the cryo-EM structure of FZD4 engaged with the DEP domain of Dishevelled 2 (DVL2), a key WNT transducer. We uncover a distinct binding mode where the DEP finger-loop inserts into the FZD4 cavity to form a hydrophobic interface. FZD4 intracellular loop 2 (ICL2) additionally anchors the complex through polar contacts. Mutagenesis validates the structural observations. The DEP interface is highly conserved in FZDs, indicating a universal mechanism by which FZDs engage with DVLs. We further reveal that DEP mimics G-protein/β-arrestin/GRK to recognize an active conformation of receptor, expanding current GPCR engagement models. Finally, we identify a distinct FZD4 dimerization interface. Our findings delineate the molecular determinants governing FZD/DVL assembly and propagation of WNT signaling, providing long-sought answers underlying WNT signal transduction. Here the authors report the cryo-EM structure of Frizzeled 4 in complex with the DEP domain of Dishevelled 2. The study unveils the key mechanism of WNT signalling activation, the recruitment of dishevelled to Frizzled receptor. [ABSTRACT FROM AUTHOR]

In the title compound, bis[aqua(2,2′-bipyridine) fluoridotin (II)] hexafluoridotin(IV), [SnF(C10H8N2)(H2O)]2[SnF6], an ionic mixed-valent tin(II)–tin(IV) compound, the bivalent tin atom is the center atom of the cation and the tetravalent tin atom is the center atom of the anion. With respect to the first coordination sphere, the cation is monomeric, with the tin(II) atom having a fourfold seesaw coordination with a fluorine atom in an equatorial position, a water molecule in an axial position and the two nitrogen atoms of the chelating 2,2′-bipyridine ligand in the remaining axial and equatorial positions. The bond lengths and angles of this hypervalent first coordination sphere are described by 2c–2e and 3c–4e bonds, respectively, all of which are based on the orthogonal 5p orbitals of the tin atom. In the second coordination sphere, which is based on an additional, very long tin–fluorine bond that leads to dimerization of the cation, the tin atom is trapezoidal–pyramidally coordinated. The tetravalent tin atom of the centrosymmetric anion has an octahedral coordination. The differences in its tin–fluorine bond lengths are attributed to hydrogen bonding, as the two of the four fluorine atoms are each involved in two hydrogen bonds, linking anions and cations together to form strands. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG), the only near-infrared (NIR) dye approved for clinical use, has received increasing attention as a theranostic agent wherein diagnosis (fluorescence) is combined with therapy (phototherapy), but suffers rapid hepatic clearance, poor photostability, and limited accumulation at tumor sites. Here we report that dimerized ICG can self-assemble to form zwitterionic nanoparticles (ZN-dICG), which generate fluorescence self-quenching but exhibit superior photothermal and photodynamic properties over ICG. The zwitterionic moieties confer ZN-dICG an ultralow critical micelle concentration and high colloidal stability with low non-specific binding in vivo. In addition, ZN-dICG can respond to the over-generated reactive oxygen species (ROSs) and dissociate to restore NIR fluorescence of ICG, amplifying the sensitivity via albumin binding for low-background imaging of tumors. Following systemic administration, ZN-dICG accumulated in tumors of xenograft-bearing mice for imaging primary and metastatic tumors, and induced tumor ablation under laser irradiation. The discovery of ZN-dICG would contribute to the design of translational phototheranostic platform with high biocompatibility. Indocyanine green (ICG) has been extensively studied as a phototheranostic agent that combines imaging with phototherapies, but it suffers from rapid hepatic clearance, poor photostability, and limited accumulation at tumor sites. Here, we report a strategy to construct ICG dimers (ICG-tk-ICG) by conjugating two ICG molecules via a thioketal bond, which can self-assemble into zwitterionic nanoparticles (ZN-dICG) at ultralow critical micelle concentrations, exhibiting superior photothermal and photodynamic properties over ICG. ZN-dICG responds to the over-generated ROS in tumors and dissociates to restore the NIR fluorescence of ICG, enhancing the sensitivity via albumin binding for low-background imaging of tumors. This study offers a supramolecular strategy that may potentiate the clinical translation of ICG in imaging-guided cancer phototherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Redox flow battery shows promise for grid-scale energy storage. Aqueous organic redox flow batteries are particularly popular due to their potentially low material cost and safe water-based electrolyte. Commonly, redox active molecules used in this field feature aromatic rings, and increasing π -aromatic conjugation has been a popular strategy to achieve high energy density, high power density, and reduced crossover in new material design. However, this approach can inadvertently hinder redox activity depending on redox mechanism. This study reveals the underlying π - π stacking effect in extended aromatic redox active compounds, where aromatic radical intermediates are involved in the redox process. We report a molecular design strategy to mitigate the negative effect of π - π stacking by altering solvation dynamics and introducing molecular steric hindrance. [ABSTRACT FROM AUTHOR]

The Arabidopsis CROWDED NUCLEI (CRWN) family proteins form a lamina-like meshwork beneath the nuclear envelope with multiple functions, including maintenance of nuclear morphology, genome organization, DNA damage repair and transcriptional regulation. CRWNs can form homodimers/heterodimers through protein‒protein interactions; however, the exact molecular mechanism of CRWN dimer formation and the diverse functions of different CRWN domains are not clear. In this report, we show that the N-terminal coiled-coil domain of CRWN1 facilitates its homodimerization and heterodimerization with the coiled-coil domains of CRWN2–CRWN4. We further demonstrated that the N-terminus but not the C-terminus of CRWN1 is sufficient to rescue the defect in nuclear morphology of the crwn1 crwn2 mutant to the WT phenotype. Moreover, both the N- and C-terminal fragments of CRWN1 are necessary for its normal function in the regulation of plant development. Collectively, our data shed light on the mechanism of plant lamina network formation and the functions of different domains in plant lamin-like proteins. [ABSTRACT FROM AUTHOR]

The Cossee–Arlman mechanism of nickel-catalyzed oligomerization and dimerization with various N∩N-type ligands was studied using the DFT method. For the L1 ligands (L1 = 2,9-disubstituted 1,10-phenanthroline), the dimerization energy barriers for R = Me and R = Ph are about 17.9 and 15.8 kcal mol−1, respectively. However, the presence of Ph substituents at positions 2 and 9 of the L1 ligand reduces the free energy barriers for the dimerization and trimerization processes by approximately 2.1 and 8.1 kcal mol−1, respectively. Therefore, the Ph substituents prevent the removal of β-H from 1-butene, thus promoting the formation of 1-hexene. This result is consistent with experimental observations. In the case of the L2 ligands (L2 = substituted 2-benzoxazole-pyridines) with R1 = H and R2 = H or Me, and R3 = H, the calculated dimerization energy barriers for the systems (H-H) and (H-Me) are about 12.8 and 20.5 kcal mol−1, respectively. The energy barrier for the system with R1 = H and R2 = R3 = Me (Me-Me) is about 20.9 kcal mol−1. Thus, the activity of these systems towards the formation of 1-butene can be arranged as (H-H) > (H-Me) > (Me-Me). As for L3 ligands (L3 = 2-benzimidazolylpyridine derivatives), six systems with R1 = H, Me, tBu; R2 = H, Me, were studied. The calculated dimerization energy barrier values indicate that the (H-H), (H-Me), and (H-tBu) systems (10.8, 11.1, and 10.9 kcal mol−1, respectively) are more active than the (Me-H), (Me-Me) and (Me-tBu) systems (18.8, 19.1 and 19.0 kcal mol−1, respectively). Finally, for the L4 ligand (L4 = 2-benzoimidazol-8-alkylquinoline derivatives), nine systems were studied, divided into three groups: A system (R1 = H and R2 = H or Me or Et), B system R1 = Me with identical R2 substituents, and C system (R1 = Et with identical R2 substituents). Based on the values of the calculated energy barriers for dimerization and trimerization, the B system shows higher activity than the other systems. [ABSTRACT FROM AUTHOR]

Most albumin in blood plasma is thought to be monomeric with some 5% covalently dimerized. However, many reports in the recent biophysics literature find that albumin is reversibly dimerized or even oligomerized. We review data on this from X‐ray crystallography and diverse biophysical techniques. The number‐average molecular weight of albumin would be increased by dimerization, affecting size‐dependent filtration processes of albumin such as at the glycocalyx of the capillary endothelium and the podocyte slit‐diaphragm of the renal glomerulus. If correct, and depending on characteristics of the process, such as Kd, reversible dimerization of albumin in plasma would have major implications for normal physiology and medicine. We present quantitative models of the impact of dimerization on albumin molecular forms, on the number‐average molecular weight of albumin, and estimate the effect on the colloid osmotic pressure of albumin. Dimerization reduces colloid osmotic pressure as total albumin concentration increases below that expected in the absence of dimerization. Current models of albumin filtration by the renal glomerulus would need revision to account for the dynamic size of albumin molecules filtered. More robust biophysical data are needed to give a definitive answer to the questions posed and we suggest possible approaches to this. [ABSTRACT FROM AUTHOR]

Exploration of expanded porphyrins with unprecedented reactivities has remained important. Here [22]pentaphyrins(2.0.1.1.0) were synthesized as a constitutional isomer of sapphyrin by acid‐catalyzed cyclization of 1,14‐dibromo‐5,10‐diaryltripyrrin with 1,2‐di(pyrro‐2‐ly)ethenes. These pentaphyrins display roughly planar structures and varying aromaticities depending upon the vinylene structures. The 19,20‐ditolyl pentaphyrin gave an N‐fused product and an unprecedented pyrrole‐rearranged product, depending upon the oxidation conditions. Remarkably, upon the metalation with CuCl, the N‐fused product and the pyrrole‐rearranged product afforded an inner β‐β coupled face‐to‐face CuII complex dimer and an outer β‐β coupled lateral CuII complex dimer, respectively, in fairly good yields. Further, [22]pentaphyrin(2.0.1.1.0) fused with a NiII porphyrin was effectively dimerized upon oxidation with MnO2 to give a 16–16' directly linked dl‐dimer. [ABSTRACT FROM AUTHOR]

Copper chaperones of the ATX1 family are found in a wide range of organisms where these essential soluble carriers strictly control the transport of monovalent copper across the cytoplasm to various targets in diverse cellular compartments thereby preventing detrimental radical formation catalyzed by the free metal ion. Notably, the ATX1 family in plants contains two distinct forms of the cellular copper carrier. In addition to ATX1 having orthologs in other species, they also contain the copper chaperone CCH. The latter features an extra C-terminal extension whose function is still unknown. The secondary structure of this extension was predicted to be disordered in previous studies, although this has not been experimentally confirmed. Solution NMR studies on purified CCH presented in this study disclose that this region is intrinsically disordered regardless of the chaperone's copper loading state. Further biophysical analyses of the purified metallochaperone provide evidence that the C-terminal extension stabilizes chaperone dimerization in the copper-free and copper-bound states. A variant of CCH lacking the C-terminal extension, termed CCHΔ, shows weaker dimerization but similar copper binding. Computational studies further corroborate the stabilizing role of the C-terminal extension in chaperone dimerization and identify key residues that are vital to maintaining dimer stability. [ABSTRACT FROM AUTHOR]

HIV-1 transcript function is controlled in part by twinned transcriptional start site usage, where 5' capped RNAs beginning with a single guanosine (1G) are preferentially packaged into progeny virions as genomic RNA (gRNA) whereas those beginning with three sequential guanosines (3G) are retained in cells as mRNAs. In 3G transcripts, one of the additional guanosines base pairs with a cytosine located within a conserved 5' polyA element, resulting in formation of an extended 5' polyA structure as opposed to the hairpin structure formed in 1G RNAs. To understand how this remodeling influences overall transcript function, we applied in vitro biophysical studies with in-cell genome packaging and competitive translation assays to native and 5' polyA mutant transcripts generated with promoters that differentially produce 1G or 3G RNAs. We identified mutations that stabilize the 5' polyA hairpin structure in 3G RNAs, which promote RNA dimerization and Gag binding without sequestering the 5' cap. None of these 3G transcripts were competitively packaged, confirming that cap exposure is a dominant negative determinant of viral genome packaging. For all RNAs examined, conformations that favored 5' cap exposure were both poorly packaged and more efficiently translated than those that favored 5' cap sequestration. We propose that structural plasticity of 5' polyA and other conserved RNA elements place the 5' leader on a thermodynamic tipping point for low-energetic (~3 kcal/mol) control of global transcript structure and function. [ABSTRACT FROM AUTHOR]

The Light-oxygen-voltage-sensing domain (LOV) superfamily, found in enzymes and signal transduction proteins, plays a crucial role in converting light signals into structural signals, mediating various biological mechanisms. While time-resolved spectroscopic studies have revealed the dynamics of the LOV-domain chromophore's electronic structures, understanding the structural changes in the protein moiety, particularly regarding light-induced dimerization, remains challenging. Here, we utilize time-resolved X-ray liquidography to capture the light-induced dimerization of Avena sativa LOV2. Our analysis unveils that dimerization occurs within milliseconds after the unfolding of the A'α and Jα helices in the microsecond time range. Notably, our findings suggest that protein-protein interactions (PPIs) among the β-scaffolds, mediated by helix unfolding, play a key role in dimerization. In this work, we offer structural insights into the dimerization of LOV2 proteins following structural changes in the A'α and Jα helices, as well as mechanistic insights into the protein-protein association process driven by PPIs. Here, the authors provide mechanistic insight into light-induced dimerization of a Light-Oxygen-Voltage (LOV) domain using time-resolved X-ray liquidography, furthering our understanding LOV domain photoactivation and protein-protein interaction-driven oligomerization. [ABSTRACT FROM AUTHOR]

12-oxophytodienoate reductase 3 (OPR3) is a key enzyme in the biosynthesis of jasmonoyl-L-isoleucine, the receptor-active form of jasmonic acid and crucial signaling molecule in plant defense. OPR3 was initially crystallized as a self-inhibitory dimer, implying that homodimerization regulates enzymatic activity in response to biotic and abiotic stresses. Since a sulfate ion is bound to Y364, mimicking a phosphorylated tyrosine, it was suggested that dimer formation might be controlled by reversible phosphorylation of Y364 in vivo. To investigate OPR3 homodimerization and its potential physiological role in more detail, we performed analytical gel filtration and dynamic light scattering on wild-type OPR3 and three variants (R283D, R283E, and Y364P). The experiments revealed a rapid and highly sensitive monomer–dimer equilibrium for all OPR3 constructs. We crystallized all constructs with and without sulfate to examine its effect on the dimerization process and whether reversible phosphorylation of Y364 triggers homodimerization in vivo. All OPR3 constructs crystallized in their monomeric and dimeric forms independent of the presence of sulfate. Even variant Y364P, lacking the putative phosphorylation site, was crystallized as a self-inhibitory homodimer, indicating that Y364 is not required for dimerization. Generally, the homodimer is relatively weak, and our results raise doubts about its physiological role in regulating jasmonate biosynthesis. [ABSTRACT FROM AUTHOR]

An efficient cyclization for the synthesis of 1,2,4,5-tetra-substituted benzenes via copper catalyzed dimerization of γ,δ-unsaturated ketones has been described. This one-pot procedure employs the γ,δ-unsaturated ketones as the sole substrate with multiple C–C bond formation. This protocol features broad substrate scope and provides a facile and robust method to construct polysubstituted benzene derivatives under mild conditions. [ABSTRACT FROM AUTHOR]

In this Synpacts article, we describe the concept of cyclodimerization in the biosynthesis and biomimetic synthesis of natural products and unnatural products. We also discuss key details of our discovery and development of a biomimetic-like, selective, homo- and heterochiral cyclodimerization strategy for the construction of nonnatural dimeric carbazole frameworks by employing a formal [3+2] annulation. Our work also demonstrated a novel reactivity of 1-(indol-2-yl)pent-4-yn-3-ols, and their potential as new synthetic building blocks in organic synthesis. 1 Introduction: Chiral Cyclodimerization Reactions 2 Biomimetic Syntheses of Natural Products through Chiral Cyclodimerizations 3 Bioinspired Synthesis of Nonnatural Dimeric Carbazoles through Selective Chiral Cyclodimerizations 4 Future Perspectives and Conclusions [ABSTRACT FROM AUTHOR]

A series of non‐spherical metallic Au and bimetallic core@shell AuAg nanoparticles (NPs) have been synthesized for SERS improvements. The bimetallic core@shell AuAg NPs were obtained through a controlled overgrowth of an Ag shell onto the surface of two types of non‐spherical Au NPs, used as seeds, Au nanooctaheda (Au NOc) and Au nanotriangles (Au NTs). This Ag overgrowth was able to produce bimetallic core@shell structures such as nanocubes and nanopyramids, respectively. Transmission electron microscopy (TEM) was used to determine the particle size and particle morphology for metallic and bimetallic NPs, and energy‐dispersive X‐ray (EDX) elemental mapping analysis confirmed the core@shell structure of the bimetallic NPs. The plasmonic absorption bands exhibited for each nanosystem were observed by UV–vis spectroscopy. The concentration of Au and Ag in the bimetallic systems was determined by inductively coupled plasma mass spectrometry (ICP‐MS). After synthesis and characterization, p‐aminothiophenol (PATP) was used as a model analyte to investigate the surface‐enhanced Raman spectroscopy (SERS) capabilities of the synthesized metallic and bimetallic nanosystems. In PATP, a dimerization reaction to 4,4′‐dimercaptoazobenzene (DMAB) is produced when it is adsorbed onto the surface of certain noble metals. This SERS analysis was performed at 10−4 M of PATP and by using two different laser wavelengths (532 and 785 nm) in all cases. In this context, we were able to detect the dimerization reaction of PATP to DMAB only for the bimetallic structures and under the 532 nm laser line. Moreover, we have found that the dimerization capacity also depends on the nanoparticle morphology. [ABSTRACT FROM AUTHOR]

Signaling proteins in eukaryotes usually comprise a catalytic domain coupled to one or several interaction domains, such as SH2 and SH3 domains. An additional class of proteins critically involved in cellular communication are adapter or scaffold proteins, which fulfill their purely non-enzymatic functions by organizing protein–protein interactions. Intriguingly, certain signaling enzymes, e.g., kinases and phosphatases, have been demonstrated to promote particular cellular functions by means of their interaction domains only. In this review, we will refer to such a function as "the adapter function of an enzyme". Though many stories can be told, we will concentrate on several proteins executing critical adapter functions in cells of the immune system, such as Bruton´s tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), and SH2-containing inositol phosphatase 1 (SHIP1), as well as in cancer cells, such as proteins of the rat sarcoma/extracellular signal-regulated kinase (RAS/ERK) mitogen-activated protein kinase (MAPK) pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors. Thereby, we are highlighting the need to develop pharmacological approaches, such as proteolysis-targeting chimeras (PROTACs), that eliminate the entire protein, and thus both enzymatic and adapter functions of the signaling protein. We also review how genetic knock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins. [ABSTRACT FROM AUTHOR]

[Display omitted] Hypothesis: Graphene quantum dots (GQDs) with various functional groups are hypothesized to inhibit the α-synuclein (αS) dimerization, a crucial step in Parkinson's disease pathogenesis. The potential of differently functionalized GQDs is systematically explored. Experiments: All-atom replica-exchange molecular dynamics simulations (accumulating to 75.6 μs) in explicit water were performed to study the dimerization of the αS non-amyloid component region and the influence of GQDs modified with various functional groups. Conformation ensemble, binding behavior, and free energy analysis were conducted. Findings: All studied GQDs inhibit β-sheet and backbone hydrogen bond formation in αS dimers, leading to looser oligomeric conformations. Charged GQDs severely impede the growth of extended β-sheets by providing extra contact surface. GQD binding primarily disrupts αS inter-peptide interactions through π-π stacking, CH-π interactions, and for charged GQDs, additionally through salt-bridge and hydrogen bonding interactions. GQD-COO– showed the most optimal inhibitory effect, binding mode, and intensity, which holds promise for the development of nanomedicines targeting amyloid aggregation in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Context: 1,3-Dithiole-2-thione-4,5-dithiolate (dmit) ligands are known for their conductive and optical properties. Dmit compounds have been assessed for use in sensor devices, information storage, spintronics, and optical material applications. Associations with various metallic centers endow dmit complexes with magnetic, optical, conductive, and antioxidant properties. Optical doping can facilitate the fabrication of magnetic conductor materials from ground-state nonmagnetic cations. While most studied complexes involve transition-metal centers due to their diverse chemistry, compounds with representative elements are less explored in the literature. This study investigated the structural and electronic properties of bisdmit complexes with representative Bi(III), Sb(III), and Zn(II) cations. AIMD calculations revealed two new geometries for Bi(III) and Zn(II) complexes, diverging from the isolated geometry typically used in quantum chemical calculations. The coordination of acetonitrile molecules to the cationic centers of the complexes resulted in unstable structures, while the dimerization of the complexes was stable. SA-CASSCF/NEVPT2 calculations were applied to the structures of the isolated complexes and stable dimers, confirming the multireference character of the electronic structure of the three systems and the multiconfigurational character of the Bi(III) complex. The electronic spectra simulated by the STEOM-DLPNO-CCSD calculations accurately reproduced the experimental UV‒Vis spectra indicating the participation of the isolated Bi(III) dmit complex and its dimeric form in solution. Methodology: AIMD calculations of the dmit salts were conducted using the GFN2-xTB method with 60 explicit acetonitrile molecules as the solvent at 300 K for a total simulation time of 50.0 ps, with printing intervals of 0.5 fs. The final geometries were optimized employing the PBEh-3c compound method, incorporating implicit conductor-like polarizable continuum model (CPCM) solvation for acetonitrile. Local energy decomposition (LED) analysis at the DLPNO-CCSD(T)/Def2-TZVP level of theory was utilized to investigate the stability of the complex geometries identified by AIMD. The electronic structures of the complexes were assessed using the SA-CASSCF/NEVPT2/Def2-TZVP method to confirm the multiconfigurational and multireference nature of their electronic structures. Electronic spectra were analyzed using the STEOM-DLPNO-CCSD/Def2-TZVP method, with CPCM used to simulate an acetonitrile medium. [ABSTRACT FROM AUTHOR]

The swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused significant disruptions in porcine breeding and raised concerns about potential human infection. The nucleocapsid (N) protein of SADS-CoV plays a vital role in viral assembly and replication, but its structure and functions remain poorly understood. This study utilized biochemistry, X-ray crystallography, and immunization techniques to investigate the N protein’s structure and function in SADS-CoV. Our findings revealed distinct domains within the N protein, including an RNA-binding domain, two disordered domains, and a dimerization domain. Through biochemical assays, we confirmed that the N-terminal domain functions as an RNA-binding domain, and the C-terminal domain is involved in dimerization, with the crystal structure analysis providing visual evidence of dimer formation. Immunization experiments demonstrated that the disordered domain 2 elicited a significant antibody response. These identified domains and their interactions are crucial for viral assembly. This comprehensive understanding of the N protein in SADS-CoV enhances our knowledge of its assembly and replication mechanisms, enabling the development of targeted interventions and therapeutic strategies. IMPORTANCE SADS-CoV is a porcine coronavirus that originated from a bat HKU2-related coronavirus. It causes devastating swine diseases and poses a high risk of spillover to humans. The coronavirus N protein, as the most abundant viral protein in infected cells, likely plays a key role in viral assembly and replication. However, the structure and function of this protein remain unclear. Therefore, this study employed a combination of biochemistry and X-ray crystallography to uncover distinct structural domains in the N protein, including RNA-binding domains, two disordered domains, and dimerization domains. Additionally, we made the novel discovery that the disordered domain elicited a significant antibody response. These findings provide new insights into the structure and functions of the SADS-CoV N protein, which have important implications for future studies on SADS-CoV diagnosis, as well as the development of vaccines and anti-viral drugs. [ABSTRACT FROM AUTHOR]

Background: Cisplatin is integral to ovarian cancer treatment, yet resistance to this drug often results in adverse patient outcomes. The association of circular RNA (circRNA) with cisplatin resistance in ovarian cancer has been observed, but the mechanisms governing this relationship require further elucidation. Methods: High-throughput sequencing was utilized to profile circRNA expression in cisplatin-resistant ovarian cancer cells. Gain-and-loss-of-function experiments assessed the impact on cisplatin sensitivity, both in vitro and in vivo. Fluorescence in situ hybridization was conducted to determine the cellular distribution of circRNAs, and RNA pulldown and immunoprecipitation experiments were performed to identify associated binding proteins. Results: The study revealed that circ_ARHGEF28 is overexpressed in certain cisplatin-resistant ovarian cancer tissues and cell lines, and is associated with reduced progression-free survival in patients. It was observed that circ_ARHGEF28 contributes to cisplatin resistance in ovarian cancer models, both in vitro and in vivo. Importantly, circ_ARHGEF28 was found to interact directly with MST1/2, inhibiting the SARAH coiled-coil binding domains and consequently deactivating the Hippo pathway. Conclusion: This investigation identifies circ_ARHGEF28 as a novel circRNA that contributes to cisplatin resistance in ovarian cancer by suppressing the Hippo pathway. Therapeutic strategies targeting circ_ARHGEF28 may offer a potential avenue to mitigate cisplatin resistance in ovarian cancer treatment. [ABSTRACT FROM AUTHOR]

We describe an approach for designing high-affinity small molecule–binding proteins poised for downstream sensing. We use deep learning–generated pseudocycles with repeating structural units surrounding central binding pockets with widely varying shapes that depend on the geometry and number of the repeat units. We dock small molecules of interest into the most shape complementary of these pseudocycles, design the interaction surfaces for high binding affinity, and experimentally screen to identify designs with the highest affinity. We obtain binders to four diverse molecules, including the polar and flexible methotrexate and thyroxine. Taking advantage of the modular repeat structure and central binding pockets, we construct chemically induced dimerization systems and low-noise nanopore sensors by splitting designs into domains that reassemble upon ligand addition. [ABSTRACT FROM AUTHOR]

Fibroblast activation protein (FAP) has emerged as a highly promising target for cancer diagnostic imaging and targeted radionuclide therapy. To exploit the therapeutic potential of suitably radiolabeled FAP inhibitors (FAPIs), this study presents the design and synthesis of a series of FAPI dimers to increase tumor uptake and retention. Preclinical evaluation and a pilot clinical PET imaging study were conducted to screen the lead compound with the potential for radionuclide therapy. Methods: Three new FAPI dimers were synthesized by linking two quinoline-based FAPIs with different spacers. The in vitro binding affinity and preclinical small animal PET imaging of the compounds were compared with their monomeric counterparts, FAPI-04 and FAPI-46. The lead compound, [68Ga]Ga -LNC1013, was then evaluated in a pilot clinical PET imaging study involving seven patients with gastrointestinal cancer. Results: The three newly synthesized FAPI homodimers had high binding affinity and specificity in vitro and in vivo. Small animal PET imaging and biodistribution studies showed that [68Ga]Ga-LNC1013 had persistent tumor retention for at least 4 h, also higher uptake than the other two dimers and the monomer counterparts, making it the lead compound to enter clinical investigation. In the pilot clinical PET imaging study, seven patients were enrolled. The effective dose of [68Ga]Ga-LNC1013 was 8.24E-03 mSv/MBq. The human biodistribution of [68Ga]Ga-LNC1013 demonstrated prominent tumor uptake and good tumor-to-background contrast. [68Ga]Ga-LNC1013 PET imaging showed potential in capturing primary and metastatic lesions and outperforming 18F-FDG PET in detecting pancreatic and esophageal cancers. The SUVmax for lesions with [68Ga]Ga-FAPI-46 decreased over time, whereas [68Ga]Ga-LNC1013 exhibited persistently high tumor uptake from 1 to 4 h post-injection. Conclusion: Dimerization is an effective strategy to produce FAPI derivatives with favorable tumor uptake, long tumor retention, and imaging contrast over its monomeric counterpart. We demonstrated that [68Ga]Ga-LNC1013, the lead compound without any piperazine moiety, had superior diagnostic potential over [68Ga]Ga-FAPI-46 and 18F-FDG, suggesting the future potential of LNC1013 for radioligand therapy of FAP-positive cancers. [ABSTRACT FROM AUTHOR]

Dimeric indole‐containing diketopiperazines (di‐DKPs) are a diverse group of natural products produced through cytochrome P450‐catalyzed C–C or C–N coupling reactions. The regio‐ and stereoselectivity of these reactions plays a significant role in the structural diversity of di‐DKPs. Despite their pivotal role, the mechanisms governing the selectivity in fungi are not fully understood. Employing bioinformatics analysis and heterologous expression experiments, five undescribed P450 enzymes (AmiP450, AcrP450, AtP450, AcP450, and AtuP450) responsible for the regio‐ and stereoselective dimerization of diketopiperazines (DKPs) in fungi are identified. The function of these P450s is consistent with phylogenetic analysis, highlighting their dominant role in controlling the dimerization modes. Combinatorial biosynthesis‐based pathway reconstitution of non‐native gene clusters expands the chemical space of fungal di‐DKPs and reveals that the regioselectivity is influenced by the substrate. Furthermore, multiple sequence alignment and molecular docking of these enzymes demonstrate a C‐terminal variable region near the substrate tunnel entrance in AtuP450 that is crucial for its regioselectivity. These findings not only reveal the secret of fungal di‐DKPs diversity but also deepen understanding of the mechanisms and catalytic specificity involved in P450‐catalyzed dimerization reactions. [ABSTRACT FROM AUTHOR]

Transition‐metal‐catalyzed [4+4] cycloaddition leading to cyclooctanoids has centered on dimerization between 1,3‐diene‐type substrates. Herein, we describe a [4σ+4π−1] and [4σ+4π] cycloaddition strategy to access 7/8‐membered fused carbocycles through rhodium‐catalyzed coupling between the 4σ‐donor (benzocyclobutenones) and pendant diene (4π) motifs. The two pathways can be controlled by adjusting the solvated CO concentration. A broad range (>40 examples) of 5–6–7 and 5–6–8 polyfused carbocycles was obtained in good yields (up to 90 %). DFT calculations, kinetic monitoring and 13C‐labeling experiments were carried out, suggesting a plausible mechanism. Notably, one 5–6–7 tricycle was found to be a very rare, potent, and selective ligand for the liver X receptor β (KD=0.64 μM), which is a potential therapeutic target for cholesterol‐metabolism‐related fatal diseases. [ABSTRACT FROM AUTHOR]

Ethylene dimerization is an industrial process that is currently carried out using homogeneous catalysts. Here we present a highly active heterogeneous catalyst containing minute amounts of atomically dispersed Pd. It requires no co‐catalyst(s) or activator(s) and significantly outperforms previously reported catalysts tested under similar reaction conditions. The selectivity to C4‐ and C6‐hydrocarbons was about 80 % and 10 % at 42 % ethylene conversion at 200 °C using an industrially relevant feed containing 50 vol % ethylene, respectively. Our kinetic and catalyst characterization experiments complemented by density functional theory calculations provide molecular insights into the local environment of isolated Pd(II)Ox species and their role in achieving high activity in the target reaction. When the developed catalyst was rationally integrated with a Mo‐containing olefin metathesis catalyst in the same reactor, the formed butenes reacted with ethylene to propylene with a selectivity of 98 % at about 24 % ethylene conversion. [ABSTRACT FROM AUTHOR]

A simple, solvent‐free arginine‐catalyzed aldol dimerization of levulinic acid was achieved via the simultaneous formation of a eutectic mixture. Dimers of levulinic acid are valued as biomass‐derived fine chemical precursors, with potential to upgrade to bio‐jet fuels or N‐containing functional chemicals. Typically, these dimers are produced as isomeric mixtures using high temperatures and a variety of solid inorganic catalysts or mineral acids. In this study, an organocatalytic and regioselective dimerization was achieved at 22 % conversion on either a bench or kilogram scale using mild temperatures and only L‐arginine as both a co‐solvent and catalyst. The intricate H‐bonding network comprising the eutectic solvent was harnessed to produce only one product, minimizing side reactivity and preserving the reactants for recycling. [ABSTRACT FROM AUTHOR]

Iodination of 2-(4-arylthiazole-2-yl)acetonitriles in DMF proceeds with the formation of previously undescribed 2,3-bis(4-aryl-1,3-thiazole-2-yl)but-2-enedicarbonitriles as a mixture of E- and Z-isomers. The latter were alternatively prepared by the reaction of cyanothioacetamide, α-bromoketones and iodine in DMF. Structure of the key compounds was proven by means of single crystal X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

This study presents a comprehensive analysis of the dimerization interfaces of fly GSTs through sequence alignment. Our investigation revealed GSTE1 as a particularly intriguing target, providing valuable insights into the variations within Delta and Epsilon GST interfaces. The X-ray structure of GSTE1 was determined, unveiling remarkable thermal stability and a distinctive dimerization interface. Utilizing circular dichroism, we assessed the thermal stability of GSTE1 and other Drosophila GSTs with resolved X-ray structures. The subsequent examination of GST dimer stability correlated with the dimerization interface supported by findings from X-ray structural analysis and thermal stability measurements. Our discussion extends to the broader context of GST dimer interfaces, offering a generalized perspective on their stability. This research enhances our understanding of the structural and thermodynamic aspects of GST dimerization, contributing valuable insights to the field. [ABSTRACT FROM AUTHOR]

Alternative splicing significantly enhances the diversity of the G protein-coupled receptor (GPCR) family, including the histamine H3 receptor (H3R). This post-transcriptional modification generates multiple H3R isoforms with potentially distinct pharmacological and physiological profiles. H3R is primarily involved in the presynaptic inhibition of neurotransmitter release in the central nervous system. Despite the approval of pitolisant for narcolepsy (Wakix®) and daytime sleepiness in adults with obstructive sleep apnea (Ozawade®) and ongoing clinical trials for other H3R antagonists/inverse agonists, the functional significance of the numerous H3R isoforms remains largely enigmatic. Recent publicly available RNA sequencing data have confirmed the expression of multiple H3R isoforms in the brain, with some isoforms exhibiting unique tissue-specific distribution patterns hinting at isoform-specific functions and interactions within neural circuits. In this review, we discuss the complexity of H3R isoforms with a focus on their potential roles in central nervous system (CNS) function. Comparative analysis across species highlights evolutionary conservation and divergence in H3R splicing, suggesting species-specific regulatory mechanisms. Understanding the functionality of H3R isoforms is crucial for the development of targeted therapeutics. This knowledge will inform the design of more precise pharmacological interventions, potentially enhancing therapeutic efficacy and reducing adverse effects in the treatment of neurological and psychiatric disorders. [ABSTRACT FROM AUTHOR]

The desulfurization of carbons modified with SO2 was studied as a dispersion in boiling cyclohexane (81°C) using activated carbon (mAC) and graphene oxide (mGO), modified by SO2. The steady‐state species in the carbon matrix after the catalytic reduction of SO2 was considered a trisulfane. For mAC, there was a burst of a sulfur species identified as S2 by UV spectrum with a maximum at 217 nm (εM at 217 nm = 2.56 × 103) that showed a second‐order decay of absorbance with kS2 = 47.29 M‐1·sec‐1 (ΔG354‡= 18.1 kcal·mol‐1). The product was postulated to be S4. No other consecutive reaction was observed because of the possible adsorption of S4 in the carbon matrix. The desulfurization of mGO was shown by XPS and the kinetics were a second‐order decay up to 16 min (kS2= 18.41 M‐1·sec‐1; ΔG354‡= 18.8 kcal·mol‐1) followed by a second‐order increase of absorbance with kS4 = 3.84 M‐1·sec‐1 (ΔG354‡= 19.9), where the product showed a double maximum at 260‐285 nm typical of S8. These results are consistent with a mechanism of consecutive thermodynamically favorable dimerizations of S2 and S4 and with the desulfurization mechanism that has been previously postulated. [ABSTRACT FROM AUTHOR]

Polymers with all mechanically interlocked rings, such as linear [n]catenanes, have great potential as functional materials due to possible higher degrees of freedom that may contribute to their flexibility but remain elusive. All the synthetic methods used to prepare such a polymer yield mixtures of products. In the absence of higher molecular weight linear [n]catenanes, emphasis on synthesizing low molecular weight oligomers is being pursued. Here, we have described the synthesis of a linear [5]catenane by post‐functionalizing a Co(III) templated [2]catenane having a pyridine‐diamide unit free for further metal ion coordination. Two molecules were synthesized with suitable threading groups: one, two terminal azide groups, and two, with two terminal alkyne groups to form two [3]pseudorotaxane utilizing Co(III) coordination. These units were then joined, forming a macrocycle, using click reaction, giving the desired metalated linear [5]catenane in 40 % yield. Removal of metal ions leads to linear [5]catenane. In addition, the formation of linear [3] and [2]catenane are also observed. All synthesized structures have been isolated by column chromatographic technique and characterized by 1H‐NMR, 13C‐NMR, and mass spectroscopy. [ABSTRACT FROM AUTHOR]

Here, we report the reactivity of copper(I) clusters toward sulfide ions; these sulfide copper(I) clusters have attracted much attention due to their relevance to biologically active centers and their fascinating structural and photophysical properties. Treatment of the CuI3RhIII2 pentanuclear complex, [Cu3{Rh(aet)3}2]3+ (aet=2‐aminoethanethiolate), in which a {CuI3}3+ cluster moiety is bound by two fac‐[Rh(aet)3] metalloligands, with NaSH in water produced the CuI6RhIII4 decanuclear complex, [Cu6S{Rh(aet)3}4]4+, accompanied by the dimerization of [Cu3{Rh(aet)3}2]3+ and the incorporation of a sulfide ion at the center. While similar treatment using the analogous CuI3IrIII2 complex with fac‐[Ir(aet)3] metalloligands, [Cu3{Ir(aet)3}2]3+, produced the isostructural CuI6IrIII4 decanuclear complex, [Cu6S{Ir(aet)3}4]4+, the use of the CuI3RhIII2 complex with fac‐[Rh(apt)3] metalloligands, [Cu3{Rh(apt)3}2]3+ (apt=3‐aminopropanethiolate), resulted in the removal of one of the three CuI atoms from {CuI3}3+ to afford the CuI2RhIII2 tetranuclear complex, [Cu2{Rh(apt)3}2]2+. [ABSTRACT FROM AUTHOR]

In this manuscript, we demonstrate a visible‐light driven dimerization of para‐quinone methides using eosin Y catalyst via a reductive homocoupling process. This mild and operationally simple methodology was found to be compatible with a variety of differently substituted para‐quinone methides and a broad range of tetra‐arylethane derivatives were obtained in moderate to good yields (47%–87%). [ABSTRACT FROM AUTHOR]

Naturally occurring gain-of-function (GOF) mutants have been identified in patients for a variety of cytokine receptors. Although this constitutive activation of cytokine receptors is strongly associated with malignant disorders, ligand-independent receptor activation is also a useful tool in synthetic biology e.g. to improve adoptive cellular therapies with genetically modified T-cells. Balanced Interleukin (IL-)7 signaling via a heterodimer of IL-7 receptor (IL-7Rα) and the common γ-chain (γc) controls T- and B-cell development and expansion, whereas uncontrolled IL-7 signaling can drive acute lymphoid leukemia (ALL) development. The ALL-driver mutation PPCL in the transmembrane domain of IL-7Rα is a mutational insertion of the four amino acids proline-proline-cysteine-leucine and leads to ligand-independent receptor dimerization and constitutive activation. We showed here in the cytokine-dependent pre-B-cell line Ba/F3 that the PPCL-insertion in a synthetic version of the IL-7Rα induced γc-independent STAT5 and ERK phosphorylation and also proliferation of the cells and that booster-stimulation by arteficial ligands additionally generated non-canonical STAT3 phosphorylation via the synthetic IL-7Rα-PPCL-receptors. Transfer of the IL-7Rα transmembrane domain with the PPCL insertion into natural and synthetic cytokine receptor chains of the IL-6, IL-12 and Interferon families also resulted in constitutive receptor signaling. In conclusion, our data suggested that the insertion of the mutated PPCL IL-7Rα transmembrane domain is an universal approach to generate ligand-independent, constitutively active cytokine receptors. [ABSTRACT FROM AUTHOR]

The Gag‐Pol polyprotein in human immunodeficiency virus type I (HIV‐1) encodes enzymes that are essential for virus replication: protease (PR), reverse transcriptase (RT), and integrase (IN). The mature forms of PR, RT and IN are homodimer, heterodimer and tetramer, respectively. The precise mechanism underlying the formation of dimer or tetramer is not yet understood. Here, to gain insight into the dimerization of PR and RT in the precursor, we prepared a model precursor, PR‐RT, incorporating an inactivating mutation at the PR active site, D25A, and including two residues in the p6* region, fused to a SUMO‐tag, at the N‐terminus of the PR region. We also prepared two mutants of PR‐RT containing a dimer dissociation mutation either in the PR region, PR(T26A)‐RT, or in the RT region, PR‐RT(W401A). Size exclusion chromatography showed both monomer and dimer fractions in PR‐RT and PR(T26A)‐RT, but only monomer in PR‐RT(W401A). SEC experiments of PR‐RT in the presence of protease inhibitor, darunavir, significantly enhanced the dimerization. Additionally, SEC results suggest an estimated PR‐RT dimer dissociation constant that is higher than that of the mature RT heterodimer, p66/p51, but slightly lower than the premature RT homodimer, p66/p66. Reverse transcriptase assays and RT maturation assays were performed as tools to assess the effects of the PR dimer‐interface on these functions. Our results consistently indicate that the RT dimer‐interface plays a crucial role in the dimerization in PR‐RT, whereas the PR dimer‐interface has a lesser role. [ABSTRACT FROM AUTHOR]

Infected cell protein 0 (ICP0) is an immediate‐early regulatory protein of herpes simplex virus 1 (HSV‐1) that possesses E3 ubiquitin ligase activity. ICP0 transactivates viral genes, in part, through its C‐terminal dimer domain (residues 555–767). Deletion of this dimer domain results in reduced viral gene expression, lytic infection, and reactivation from latency. Since ICP0's dimer domain is associated with its transactivation activity and efficient viral replication, we wanted to determine the structure of this specific domain. The C‐terminus of ICP0 was purified from bacteria and analyzed by X‐ray crystallography to solve its structure. Each subunit or monomer in the ICP0 dimer is composed of nine β‐strands and two α‐helices. Interestingly, two adjacent β‐strands from one monomer "reach" into the adjacent subunit during dimer formation, generating two β‐barrel‐like structures. Additionally, crystallographic analyses indicate a tetramer structure is formed from two β‐strands of each dimer, creating a "stacking" of the β‐barrels. The structural protein database searches indicate the fold or structure adopted by the ICP0 dimer is novel. The dimer is held together by an extensive network of hydrogen bonds. Computational analyses reveal that ICP0 can either form a dimer or bind to SUMO1 via its C‐terminal SUMO‐interacting motifs but not both. Understanding the structure of the dimer domain will provide insights into the activities of ICP0 and, ultimately, the HSV‐1 life cycle. [ABSTRACT FROM AUTHOR]

The entanglement generation of two two‐level giant atoms coupled to a photonic waveguide, which is formed by a Su–Schrieffer–Heeger (SSH) type coupled‐cavity array is studied. Here, each atom is coupled to the waveguide through two coupling points.The two‐atom separate‐coupling case is studied, and 16 coupling configurations are considered for the coupling‐point distributions between the two atoms and the waveguide. Quantum master equations are derived to govern the evolution of the two atoms and characterize atomic entanglement by calculating the concurrence of the two‐atom states. It is found that the two giant‐atom entanglement depends on the coupling configurations and the coupling‐point distance of the giant atoms. In particular, the entanglement dynamics of the two giant atoms in 14 coupling configurations depend on the dimerization parameter of the SSH waveguide. According to the self‐energies of the two giant atoms, it is found that ten of these 16 coupling configurations can be divided into five pairs. It is also showed that the delayed sudden birth of entanglement between the two giant atoms is largely enhanced in these five pairs of coupling configurations. This work will promote the study of quantum effects and coherent manipulation in giant‐atom topological‐waveguide‐QED. [ABSTRACT FROM AUTHOR]

Pulsed underwater direct current discharge is considered as a tool for a one-step process for ferrite synthesis and organic dye removal. The formation of cobalt, nickel and titanium ferrites during the discharge firing process was confirmed by methods of dynamic light scattering and X-ray phase analysis. The transformation of dye molecules (fluorescein, methylene green) during the combined action of plasma and ferrites was detected by UV absorption spectroscopy. The contributions of the separate action of plasma and ferrites to the process of dye removal from the solution were investigated. It was found that the synthesized structures have a high sorption capacity. It was found that fluorescein can be used as an indicator for the presence of nickel ferrites. [ABSTRACT FROM AUTHOR]

Metabotropic glutamate receptors (mGluRs) are dimeric class C G-protein-coupled receptors that operate in glia and neurons. Glutamate affinity and efficacy vary greatly between the eight mGluRs. The molecular basis of this diversity is not understood. We used single-molecule fluorescence energy transfer to monitor the structural rearrangements of activation in the mGluR ligand binding domain (LBD). In saturating glutamate, group II homodimers fully occupy the activated LBD conformation (full efficacy) but homodimers of group III mGluRs do not. Strikingly, the reduced efficacy of Group III homodimers does not arise from differences in the glutamate binding pocket but, instead, from interactions within the extracellular dimerization interface that impede active state occupancy. By contrast, the functionally boosted mGluR II/III heterodimers lack these interface brakes to activation and heterodimer asymmetry in the flexibility of a disulfide loop connecting LBDs greatly favors occupancy of the activated conformation. Our results suggest that dimerization interface interactions generate substantial functional diversity by differentially stabilizing the activated conformation. This diversity may optimize mGluR responsiveness for the distinct spatio-temporal profiles of synaptic versus extrasynaptic glutamate.

In the title compound, bis[aqua(2,2′-bipyridine)fluoridotin(II)] hexafluoridotin(IV), [SnF(C10H8N2)(H2O)]2[SnF6], an ionic mixed-valent tin(II)–tin(IV) compound, the bivalent tin atom is the center atom of the cation and the tetravalent tin atom is the center atom of the anion. With respect to the first coordination sphere, the cation is monomeric, with the tin(II) atom having a fourfold seesaw coordination with a fluorine atom in an equatorial position, a water molecule in an axial position and the two nitrogen atoms of the chelating 2,2′-bipyridine ligand in the remaining axial and equatorial positions. The bond lengths and angles of this hypervalent first coordination sphere are described by 2c–2e and 3c–4e bonds, respectively, all of which are based on the orthogonal 5p orbitals of the tin atom. In the second coordination sphere, which is based on an additional, very long tin–fluorine bond that leads to dimerization of the cation, the tin atom is trapezoidal–pyramidally coordinated. The tetravalent tin atom of the centrosymmetric anion has an octahedral coordination. The differences in its tin–fluorine bond lengths are attributed to hydrogen bonding, as the two of the four fluorine atoms are each involved in two hydrogen bonds, linking anions and cations together to form strands.