Dimerization Pattern Research Articles

Geleganidines A-C, Unusual Monoterpenoid Indole Alkaloids from Gelsemium elegans.

The first rotameric monoterpenoid indole alkaloids (MIAs), 1a and 1b, and two unusual dimeric MIAs, 2 and 3, with new dimerization patterns, together with their putative biosynthetic intermediates 4-7, were isolated from the roots of Gelsemium elegans. Compounds 2 and 3 represent the first natural aromatic azo- and the first urea-linked dimeric MIAs, respectively. Their structures and absolute configurations were elucidated by means of NMR spectroscopy, single-crystal X-ray diffraction, and electronic circular dichroism data analyses. The interconverting mechanism of rotamers 1a and 1b was studied by density functional theory computation. Compounds 2 and 3 showed moderate cytotoxic activity against MCF-7 and PC-12 cells, respectively. In addition, a plausible biosynthesis pathway for the new alkaloids was proposed on the basis of the coexistence of their biosynthetic precursors.

A cytosolic juxtamembrane interface modulates plexin A3 oligomerization and signal transduction.

Plexins (plxns) are transmembrane (TM) receptors involved in the guidance of vascular, lymphatic vessel, and neuron growth as well as cancer metastasis. Plxn signaling results in cytosolic GTPase-activating protein activity, and previous research implicates dimerization as important for activation of plxn signaling. Purified, soluble plxn extracellular and cytosolic domains exhibit only weak homomeric interactions, suggesting a role for the plxn TM and juxtamembrane regions in homooligomerization. In this study, we consider a heptad repeat in the Danio rerio PlxnA3 cytosolic juxtamembrane domain (JM) for its ability to influence PlxnA3 homooligomerization in TM-domain containing constructs. Site-directed mutagenesis in conjunction with the AraTM assay and bioluminescent energy transfer (BRET²) suggest an interface involving a JM heptad repeat, in particular residue M1281, regulates PlxnA3 homomeric interactions when examined in constructs containing an ectodomain, TM and JM domain. In the presence of a neuropilin-2a co-receptor and semaphorin 3F ligand, disruption to PlxnA3 homodimerization caused by an M1281F mutation is eliminated, suggesting destabilization of the PlxnA3 homodimer in the JM is not sufficient to disrupt co-receptor complex formation. In contrast, enhanced homodimerization of PlxnA3 caused by mutation M1281L remains even in the presence of ligand semaphorin 3F and co-receptor neuropilin-2a. Consistent with this pattern of PlxnA3 dimerization in the presence of ligand and co-receptor, destabilizing mutations to PlxnA3 homodimerization (M1281F) are able to rescue motor patterning defects in sidetracked zebrafish embryos, whereas mutations that enhance PlxnA3 homodimerization (M1281L) are not. Collectively, our results indicate the JM heptad repeat, in particular residue M1281, forms a switchable interface that modulates both PlxnA3 homomeric interactions and signal transduction.

Crystal structure of PhoU from Pseudomonas aeruginosa, a negative regulator of the Pho regulon.

In Escherichia coli, seven genes (pstS, pstC, pstA, pstB, phoU, phoR, and phoB) are involved in sensing environmental phosphate (Pi) and controlling the expression of the Pho regulon. PhoU is a negative regulator of the Pi-signaling pathway and modulates Pi transport through Pi transporter proteins (PstS, PstC, PstA, and PstB) through the two-component system PhoR and PhoB. Inactivation of PhoY2, one of the two PhoU homologs in Mycobacterium tuberculosis, causes defects in persistence phenotypes and increased susceptibility to antibiotics and stresses. Despite the important biological role, the mechanism of PhoU function is still unknown. Here we have determined the crystal structure of PhoU from Pseudomonas aeruginosa. It exists as a dimer in the crystal, with each monomer consisting of two structurally similar three-helix bundles. Our equilibrium sedimentation measurements support the reversible monomer-dimer equilibrium model in which P. aeruginosa PhoU exists in solution predominantly as dimers, with monomers in a minor fraction, at low protein concentrations. The dissociation constant for PhoU dimerization is 3.2×10(-6)M. The overall structure of P. aeruginosa PhoU dimer resembles those of Aquifex aeolicus PhoU and Thermotoga maritima PhoU2. However, it shows distinct structural features in some loops and the dimerization pattern.

176P - Her-3 Targeting Affects the Dimerization Pattern of Egfr Family Members in Breast Carcinomas (Bc)

ABSTRACT Aim: Many BC patients present intrinsic or acquired resistance to anti-HER-2 directed therapies, mainly attributed to HER-3. Our goal was to evaluate the dimerization pattern of EGFR, HER2/3/4 with or without the addition of heregulin (Hg) and HER-3 targeting agents. Methods: MCF7 and SKBR3 cell lines were used. Dimerization patterns were studied using proximity ligation assay and immunofluorescence, where proteins in proximity can be visualized by combining classical immunocytochemistry with rolling circle amplification. Concentrations of used reagents were: HRG1-b1 10mM (R&D Systems), Pertuzumab (P) 30mM (Genetech), U3 (U) inhibitor 30mM (U3 Pharma). After blocking, cells were incubated with combination of primary antibodies (antiHER2/HER3, antiHER2/HER4, antiEGFR/HER3, anti-EGFR/HER4) in a preheated humidity chamber for 1 h at 37°C. Cells were then incubated with the PLA probes diluted 1:5 in antibody diluent (Olink Bioscience, Uppsala, Sweden) in a humidified chamber for 1 h at 37°C. Subsequent hybridization, ligation, amplification, and detection were performed as per manufacturer's instruction. Fluorescence images were acquired using a Zeiss Axiovert microscope (Carl Zeiss Microscopy, Thornwood, NY). Data analysis was done using Duolink ImageTool Software that has been developed for quantification of PLA signals. Results: In MCF7 cells (PLA signals scale 0-12), Hg addition increased dimmers EGFR/HER4 (9,7 vs 5,13), EGFR/HER3 (8,07 vs 3,36) and less HER2/HER3 (4,12 vs 3,35). The addition of Hg and P resulted in EGFR/HER4 4,67, EGFR/HER3 2,46, HER2/HER3 3,0 and Hg and U resulted in EGFR/HER4 0,6, EGFR/HER3 0,6, HER2/HER3 0,6. In SKBR3 cells (PLA signals scale 0-60), Hg addition increased dimmers EGFR/HER4 (60 vs 40), HER2/HER3 (26,93 vs 15,92) and less EGFR/HER3 (16 vs 10,6). The addition of Hg and P resulted in EGFR/HER4 17,0, HER2/HER3 19,9, EGFR/HER3 12,5 and Hg and U resulted in EGFR/HER4 0,7, HER2/HER3 0,7, EGFR/HER3 0,7. All images and data analysis will be presented in full detail. Conclusions: The addition of Hg enhances HER3-based dimmer formation, while HER-3 targeting agents lower HER3-containing dimmer formation. The technique can be used in paraffin-embedded BC specimens and may identify patient sub-groups who benefit by HER-3 targeting agents. Disclosure: All authors have declared no conflicts of interest.

Unconventional pairing and electronic dimerization instabilities in the doped Kitaev-Heisenberg model

We study the quantum many-body instabilities of the t−JK−JH Kitaev-Heisenberg Hamiltonian on the honeycomb lattice as a minimal model for a doped spin-orbit Mott insulator. This spin-1/2 model is believed to describe the magnetic properties of the layered transition-metal oxide Na2IrO3. We determine the ground state of the system with finite charge-carrier density from the functional renormalization group (fRG) for correlated fermionic systems. To this end, we derive fRG flow equations adapted to the lack of full spin-rotational invariance in the fermionic interactions, here represented by the highly frustrated and anisotropic Kitaev exchange term. Additionally employing a set of the Ward identities for the Kitaev-Heisenberg model, the numerical solution of the flow equations suggests a rich phase diagram emerging upon doping charge carriers into the ground-state manifold (Z2 quantum spin liquids and magnetically ordered phases). We corroborate superconducting triplet p-wave instabilities driven by ferromagnetic exchange and various singlet pairing phases. For filling δ>1/4, the p-wave pairing gives rise to a topological state with protected Majorana edge modes. For antiferromagnetic Kitaev and ferromagnetic Heisenberg exchanges, we obtain bond-order instabilities at van Hove filling supported by nesting and density-of-states enhancement, yielding dimerization patterns of the electronic degrees of freedom on the honeycomb lattice. Further, our flow equations are applicable to a wider class of model Hamiltonians.11 MoreReceived 1 May 2014Revised 30 June 2014DOI:https://doi.org/10.1103/PhysRevB.90.045135©2014 American Physical Society

Structural Basis for Dimerization and Catalysis of a Novel Esterase from the GTSAG Motif Subfamily of the Bacterial Hormone-sensitive Lipase Family

Hormone-sensitive lipases (HSLs) are widely distributed in microorganisms, plants, and animals. Microbial HSLs are classified into two subfamilies, an unnamed new subfamily and the GDSAG motif subfamily. Due to the lack of structural information, the detailed catalytic mechanism of the new subfamily is not yet clarified. Based on sequence analysis, we propose to name the new subfamily as the GTSAG motif subfamily. We identified a novel HSL esterase E25, a member of the GTSAG motif subfamily, by functional metagenomic screening, and resolved its structure at 2.05 Å. E25 is mesophilic (optimum temperature at 50 °C), salt-tolerant, slightly alkaline (optimum pH at 8.5) for its activity, and capable of hydrolyzing short chain monoesters (C2-C10). E25 tends to form dimers both in the crystal and in solution. An E25 monomer contains an N-terminal CAP domain, and a classical α/β hydrolase-fold domain. Residues Ser(186), Asp(282), and His(312) comprise the catalytic triad. Structural and mutational analyses indicated that E25 adopts a dimerization pattern distinct from other HSLs. E25 dimer is mainly stabilized by an N-terminal loop intersection from the CAP domains and hydrogen bonds and salt bridges involving seven highly conserved hydrophilic residues from the catalytic domains. Further analysis indicated that E25 also has some catalytic profiles different from other HSLs. Dimerization is essential for E25 to exert its catalytic activity by keeping the accurate orientation of the catalytic Asp(282) within the catalytic triad. Our results reveal the structural basis for dimerization and catalysis of an esterase from the GTSAG motif subfamily of the HSL family.

EGFR, HER2 and HER3 dimerization patterns guide targeted inhibition in two histotypes of esophageal cancer

Receptor tyrosine kinases (RTKs) are in the focus of targeted therapy for epithelial tumors. Our study addressed the role of EGFR, HER2 and HER3 expression and dimerization in esophageal cancers in situ and in vitro in the context of therapeutic EGFR and HER2 inhibitors. In archival pretreatment biopsies of esophageal carcinomas (n = 110), EGFR was preferentially expressed in esophageal squamous cell carcinomas (ESCCs) (22.4%; p = 0.088) and HER2 (34.4%; p < 0.001) with HER3 (91.5%; p < 0.001) in esophageal (Barrett's) adenocarcinomas (EACs). In situ proximity ligation assays revealed mainly EGFR and HER2 homodimers in ESCC and EAC cases, respectively. However, EAC cases also exhibited HER2/HER3 heterodimers. In vitro ESCC (OE21) cells displayed a significant response to erlotinib, gefitinib and lapatinib, with loss of AKT phosphorylation, G0/G1 cell cycle arrest and induction of apoptosis. In EAC cells (OE19, OE33 and SK-GT-4), lapatinib was similarly effective in strongly HER2-positive (mainly HER2 homodimers and some HER2/EGFR heterodimers) OE19 and OE33 cells. The HER2-targeting antibodies (trastuzumab and pertuzumab) given alone were largely ineffective in ESCC and EAC cells. However, both antibodies significantly induced antibody-dependent cellular cytotoxicity in EAC (OE19 and OE33) cells upon co-culture with peripheral blood mononuclear cells. The study reveals that overexpression of EGFR and HER2 predominantly results in homodimers in ESCCs and EACs, respectively. Still, some EACs also show HER2 dimerization plasticity, e.g., with HER3. Such RTK dimerization patterns affect responses to EGFR and HER2 targeting inhibitors in ESCC and EAC cells in vitro and hence may influence future prediction for particularly HER2-targeting inhibitors in EACs.

Functional and evolutionary analysis of the AP1/SEP/AGL6 superclade of MADS-box genes in the basal eudicot Epimedium sagittatum

MADS-box transcriptional regulators play important roles during plant development. Based on phylogenetic reconstruction, the AP1/SEP/AGL6 superclade of floral MADS-box genes underwent one or two duplication events in the common ancestor of the core eudicots. However, the functional evolution of the AP1/SEP/AGL6 superclade in basal eudicots remains uncharacterized. Epimedium sagittatum is a basal eudicot species valued for its medicinal properties and showing unique floral morphology. In this study, structural and functional variation of FUL-like (AP1 subfamily), SEP-like and AGL6-like genes in this species was investigated to further our understanding of flower evolution in angiosperms. Detailed investigations into the microsynteny and evolutionary history of the floral A and E class MADS-box genes in eudicots were undertaken and used to trace their genomic rearrangements. One AP1-like gene, two SEP-like genes and one AGL6-like gene were cloned from E. sagittatum. Their expression patterns were examined using quantitative RT-PCR in different vegetative and reproductive organs at two developmental stages. Yeast two-hybrid assays were carried out among AP1/SEP/AGL6 superclade, AP3/PI and AGAMOUS subfamily members for elucidation of dimerization patterns. In addition, possible formation of a ternary complex involving B class proteins with the A class protein EsFUL-like, the E class SEP-like protein EsAGL2-1 or the AGL6-class protein EsAGL6 were detected using yeast three-hybrid assays. Transgenic Arabidopsis or tobacco plants expressing EsFUL-like, EsAGL2-1 and EsAGL6-like under the cauliflower mosaic virus (CaMV) 35S promoter were generated and analysed. Genomic studies of AP1 syntenic regions in arabidopsis, columbine, strawberry, papaya, peach, grapevine and tomato were conducted for microsyntenic analyses. Sequence and phylogenetic analyses showed that EsFUL-like is a member of the AP1 (A class) subfamily, EsAGL2-1 and EsAGL2-2 belong to the SEP-like (E class) subfamily, and EsAGL6-like belongs to the AGL6 (AGL6 class) subfamily. Quantitative RT-PCR analyses revealed that the transcripts of the four genes are absent, or minimal, in vegetative tissues and are most highly expressed in floral organs. Yeast two-hybrid results revealed that of the eight MADS-box proteins tested, only EsAGL6-like, EsAGL2-1 and EsAGL2 were able to form strong homo- and heterodimers, with EsAGL6-like and EsAGL2-1 showing similar interaction patterns. Yeast three-hybrid analysis revealed that EsFUL1-like, EsAGL6-like and EsAGL2-1 (representing the three major lineages of the Epimedium AGL/SEP/ALG6 superclade) could act as bridging proteins in ternary complexes with both EsAP3-2 (B class) and EsPI (B class), which do not heterodimerize themselves. Syntenic analyses of sequenced basal eudicots, rosids and asterids showed that most AP1-like and SEP-like genes have been tightly associated as neighbours since the origin of basal eudicots. Ectopic expression of EsFUL-like in arabidopsis caused early flowering through endogenous high-level expression of AP1 and formation of secondary flowers between the first and second whorls. Tobacco plants with ectopic expression of EsAGL2-1 showed shortened pistils and styles, as well as axillary and extra petals in the initial flower. This study provides a description of EsFUL-like, EsAGL2-1, EsAGL2-2 and EsAGL6-like function divergence and conservation in comparison with a selection of model core eudicots. The study also highlights how organization in genomic segments containing A and E class genes in sequenced model species has resulted in similar topologies of AP1 and SEP-like gene trees.

0- and 2/3-magnetization plateaus in three-leg antiferromagnetic Heisenberg spin-1/2 ladders with leg-dimerization

Abstract Magnetic properties of three-leg antiferromagnetic Heisenberg spin-1/2 ladders with different dimerization patterns have been studied using the bond mean-field theory. Our results show that rung-columnar ladders are thermodynamically stable states for large rung-to-leg coupling ratios. Magnetization curves of leg-columnar and leg-staggered ladders always exhibit 0- and 2/3-magnetization plateaus, which do not appear in rung-columnar and rung-staggered ladders. In leg-dimerized ladders, the formation of spin dimers in the three legs results in the appearance of the 0- and 2/3-magnetization plateaus. Spin configuration in the 2/3-magnetization plateau can be understood from the mean-field bond parameters.

Model-Based Analysis of HER Activation in Cells Co-Expressing EGFR, HER2 and HER3

The HER/ErbB family of receptor tyrosine kinases drives critical responses in normal physiology and cancer, and the expression levels of the various HER receptors are critical determinants of clinical outcomes. HER activation is driven by the formation of various dimer complexes between members of this receptor family. The HER dimer types can have differential effects on downstream signaling and phenotypic outcomes. We constructed an integrated mathematical model of HER activation, and trafficking to quantitatively link receptor expression levels to dimerization and activation. We parameterized the model with a comprehensive set of HER phosphorylation and abundance data collected in a panel of human mammary epithelial cells expressing varying levels of EGFR/HER1, HER2 and HER3. Although parameter estimation yielded multiple solutions, predictions for dimer phosphorylation were in agreement with each other. We validated the model using experiments where pertuzumab was used to block HER2 dimerization. We used the model to predict HER dimerization and activation patterns in a panel of human mammary epithelial cells lines with known HER expression levels in response to stimulations with ligands EGF and HRG. Simulations over the range of expression levels seen in various cell lines indicate that: i) EGFR phosphorylation is driven by HER1-HER1 and HER1-HER2 dimers, and not HER1-HER3 dimers, ii) HER1-HER2 and HER2-HER3 dimers both contribute significantly to HER2 activation with the EGFR expression level determining the relative importance of these species, and iii) the HER2-HER3 dimer is largely responsible for HER3 activation. The model can be used to predict phosphorylated dimer levels for any given HER expression profile. This information in turn can be used to quantify the potencies of the various HER dimers, and can potentially inform personalized therapeutic approaches.

The molecular structure, geometry, stability, thermal and fundamental modes of vibration of glycine dimer by DFT methods

Glycine is an important amino acid for building up protein synthesis. Single crystal of glycine dimer was grown from aqueous solution by slow evaporation method. Powder X-ray diffraction analysis confirms the crystalline nature of grown crystal. It is interesting to study the molecular structure of a dimer, having well-defined channels formed through amphoterism bonding between CO⋯H bonds with split-valence basis sets, and the conformer is mirror symmetrical, in which the protonated organic cation plays a significant role to have a dimer pattern. Amphiprotic molecules, like dimeric glycine which can either donate or accept a proton (H+) from each other. Optical absorption study reveals that the transparency of the crystal in the entire visible region and the cutoff wavelength was found to be 235nm. Powder SHG test and thermogravimetric analysis shows glycine dimer crystal is optically active and thermally stable. The molecular structure, geometry, stability and theoretical vibrational spectra were calculated for glycine as a monomer and as a dimer linked by the amphoterism hydrogen bonding. The theoretical studies were performed using the B3LYP density functional method with the 6-311G (d,p) basis set. The detailed interpretation of the vibrational spectra has been made on the basis of normal coordinate analysis.

Targeting low-expressing ERBB-2 and acquired resistant high-expressing ERBB-2 breast carcinomas.

e11513 Background: Human epidermal growth factor receptors and their ligands are involved in carcinogenesis. Four ERBB receptors have been identified; ERBB1 (EB1), ERBB2 (EB2), ERBB3 (EB3) and ERBB4 (EB4). EB2 is over-expressed/amplified in 20-30% of BCa. Molecularly targeting agents, such as pertuzumab (P), in combination with standard therapy have shown important clinical results in EB2 (+) BCa patients. The aim of the project is to evaluate the expression/localization and dimerization pattern of EB1, EB2, EB3, EB4 in breast cancer cell lines (BCCLs) with or without heregulin-1 (He) and various EB2, EB3 and He inhibitors. The identification of a molecular phenotype of low-expressing and acquired resistant high-expressing EB2 BCa will enhance the targeted use of EB2 inhibitors in certain BCa patients Methods: Using confocal microscopy, localization/expression patterns were studied for EB1, EB2, EB3, EB4 in various human BCCs; here presented in MCF7 and SKBR3. Additionally, the dimerization pattern of EB2, EB3 and/or EB4 was studied with and without stimulation with He plus or minus P (kindly provided by Genentech, US). The dimers formation was studied using proximity ligation assay and immunofluorescence (DUOLINK; OLINK Biosciences, Sweden). Results: In MCF7-He stimulated cells EB2/EB3, EB2/EB4 and EB1/EB3 dimmers showed a 3-fold decrease formation compared to untreated cells. The EB1/EB4 dimmers were not significantly affected. After P addition in MCF7 cells a 3-fold decrease of dimmer formation was noticed compared to untreated cells for EB2/EB3, EB2/EB4 and EB1/EB3. The EB1/EB4 formation seemed only slightly affected by P. SKBR3-He stimulated cells resulted in a similar decrease of EB2/EB3, EB2/EB4 and EB1/EB3 dimmer formation compared to untreated cells. In the same BCLL, EB1/EB4 dimmer did not show any decrease after He treatment compared to untreated control cells. Further results quantified and analyzed for statistical significance will be shown Conclusions: The addition of P seems to block ligand-dependent heterodimerization of EB2 with other ERBB family members, such as EB3 and EB4.

Free light chain monomer–dimer patterns in the diagnosis of multiple sclerosis

In our search of new biomarkers for multiple sclerosis (MS), we aimed to characterize the immunoglobulin (Ig) free light chains (FLC) in patients' cerebrospinal fluid (CSF) and serum, and to evaluate the diagnostic utility of FLC monomer–dimer patterns for MS. FLC were analyzed by Western blotting and mass spectroscopy. CSF and serum samples were examined for the presence of oligoclonal Ig bands by a conventional laboratory test for MS. Three distinct pathological FLC monomer–dimer patterns, typical of MS but not of other neurological diseases, were revealed. In 31 out 56 MS patients the highly increased CSF levels of κ monomers and dimers were demonstrated. In 18 MS patients, the increased κ-FLC levels were accompanied by highly elevated λ dimers. Five MS cases showed no significant elevation in κ-FLC, but they displayed abnormally high λ dimer levels. The intensity of the immunoreactive FLC bands was measured to account for κ and λ monomer and dimer levels and their ratios in the CSF and serum. Combined usage of different FLC parameters allowed the determination of the appropriate FLC threshold values to diagnose MS. The developed method showed higher sensitivity and specificity (96% and 90%, respectively), as compared to those of the conventional OCB test (82% and 70%, respectively). Our study highlights the role of the differential analysis of monomeric and dimeric κ- and λ-FLC for the precise diagnosis of MS.

Electronic band structure and magnetic states of zigzag graphene nanoribbons: quantum chemical calculations

Quantum-chemical semi-empirical molecular-orbital calculations of zigzag graphene nanoribbons (nzGNRs) were done for the number of zigzag carbon chains n=4 and 10. The antiferromagnetic (AFM) nature of zGNRs' ground state was confirmed. The energy difference between AFM and ferromagnetic (FM) states was calculated, and dimerization patterns of their chemical bond lengths were elucidated. The electron energy band structure calculations show that narrow nanoribbon (4 zGNR) is semiconducting in both AFM and FM states. For wider nanoribbon (10 zGNR), the AFM state is semiconducting (≈0.1 eV band gap), whereas the FM state is half-metallic (electrical conduction with only one spin orientation).

Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules.

Sorting nexins (SNXs) are regulators of endosomal sorting. For the SNX-BAR subgroup, a Bin/Amphiphysin/Rvs (BAR) domain is vital for formation/stabilization of tubular subdomains that mediate cargo recycling. Here, by analysing the in vitro membrane remodelling properties of all 12 human SNX-BARs, we report that some, but not all, can elicit the formation of tubules with diameters that resemble sorting tubules observed in cells. We reveal that SNX-BARs display a restricted pattern of BAR domain-mediated dimerization, and by resolving a 2.8 Å structure of a SNX1-BAR domain homodimer, establish that dimerization is achieved in part through neutralization of charged residues in the hydrophobic BAR-dimerization interface. Membrane remodelling also requires functional amphipathic helices, predicted to be present in all SNX-BARs, and the formation of high order SNX-BAR oligomers through selective 'tip-loop' interactions. Overall, the restricted and selective nature of these interactions provide a molecular explanation for how distinct SNX-BAR-decorated tubules are nucleated from the same endosomal vacuole, as observed in living cells. Our data provide insight into the molecular mechanism that generates and organizes the tubular endosomal network.

Selective Synthesis and Structural Confirmation of 1,3-Oxazines and Schiff Bases with Controllable Substitution Patterns

Selective synthesis of 2,4-diaryl-2,3-dihydro-3H-naphtho[1,2-e]-1,3-oxazines and Schiff bases ((E)-[1-arylmethyl(benzylideneamino)]naphth-2-ols) that contain two identical or two different aryl substituents was achieved through one-pot synthesis with ammonium acetate. From the proposed mechanism the dual role of ammonium acetate was identified. The synthesized products were characterized by 1H and 13C NMR spectroscopy, as well as FTIR and mass spectrometry. Crystal structures of the 1,3-oxazines and Schiff base derivatives were examined. A notable feature is the conspicuous absence of strong donors (NH/OH) in any intermolecular hydrogen-bonding scheme. Instead, packing is characterized by weak intermolecular CH⋅⋅⋅O, CH⋅⋅⋅π and CCl⋅⋅⋅π interactions, which lead to dimeric and zig-zag one-dimensional molecular patterns. The oxazine moiety of the tricyclic ring system predominantly adopts a half-chair conformation. The present Mannich procedure is an environmentally benign and cost-effective method for the preparation of industrially and pharmaceutically useful heterocyclic scaffolds.

Serratustones A and B Representing a New Dimerization Pattern of Two Types of Sesquiterpenoids from Chloranthus serratus

Serratustones A (1) and B (2), featuring a new carbon skeleton and representing a novel dimerization pattern of two different types of sesquiterpenoids, were isolated from Chloranthus serratus. Their structures with absolute configuration were determined on the basis of a detailed explanation of spectroscopic data, X-ray crystallography, and CD analysis in combination with ECD calculation.

Universal Néel temperature in three-dimensional quantum antiferromagnets

We study three-dimensional dimerized $S=1/2$ Heisenberg antiferromagnets, using quantum Monte Carlo simulations of systems with three different dimerization patterns. We propose a way to relate the N\'eel temperature ${T}_{N}$ to the staggered moment ${m}_{s}$ of the ground state. Mean-field arguments suggest ${T}_{N}\ensuremath{\propto}{m}_{s}$ close to a quantum-critical point. We find an almost perfect universality (including the prefactor) if ${T}_{N}$ is normalized by a proper lattice-scale energy. We show that the temperature ${T}^{*}$ at which the magnetic susceptibility has a maximum is a good choice, i.e., ${T}_{N}/{T}^{*}$ versus ${m}_{s}$ is a universal function (also beyond the linear regime). These results are useful for analyzing experiments on systems where the spin couplings are not known precisely, e.g., ${\mathrm{TlCuCl}}_{3}$.

Quaternary association in β-prism I fold plant lectins: Insights from X-ray crystallography, modelling and molecular dynamics

Dimeric banana lectin and calsepa, tetrameric artocarpin and octameric heltuba are mannose-specific beta-prism I fold lectins of nearly the same tertiary structure. MD simulations on individual subunits and the oligomers provide insights into the changes in the structure brought about in the protomers on oligomerization, including swapping of the N-terminal stretch in one instance. The regions that undergo changes also tend to exhibit dynamic flexibility during MD simulations. The internal symmetries of individual oligomers are substantially retained during the calculations. Energy minimization and simulations were also carried out on models using all possible oligomers by employing the four different protomers. The unique dimerization pattern observed in calsepa could be traced to unique substitutions in a peptide stretch involved in dimerization. The impossibility of a specific mode of oligomerization involving a particular protomer is often expressed in terms of unacceptable steric contacts or dissociation of the oligomer during simulations. The calculations also led to a rationale for the observation of a heltuba tetramer in solution although the lectin exists as an octamer in the crystal, in addition to providing insights into relations among evolution, oligomerization and ligand binding.

First-principles study of elastic properties of high hydrogenated single-walled carbon nanotube

Using the first-principles calculations based on the density functional theory (DFT), we have investigated the mechanical properties of three typical patterns of the highly hydrogenated SWCNTs. For the stable parallel polyacetylene-like chains pattern (pattern III), Young's modulus of the type A configuration, which is one of the stable configurations of pattern III, has larger Young's modulus than that of the others with the same coverage on the same pristine tube, i.e. the vertical chain pattern (pattern I) and the dimer pattern (pattern II) ones. On the other hand, Young's modulus of type B configuration also belonged to pattern III changes slightly. We also verified that Young's modulus decreases enormously as the coverage increases above 50% and reduces to about one-third of that of the pristine carbon nanotubes at 100% coverage.