Cyclic Sesquiterpene-Flavanone [4+2] Hybrids, Syzygioblanes A-C, Found in an Indonesian Traditional Medicine, "Jampu Salo" (Syzygium oblanceolatum).

A plant used in an Indonesian traditional herbal medicine as a diabetes treatment and known locally as "Jampu Salo" was collected on Sulawesi Island, Indonesia. It was identified as Syzygium oblanceolatum (C. B. Rob.) Merr. (Myrtaceae) and found for the first time in Sulawesi; it was previously reported only in the eastern Philippines and Borneo. A phytochemical study of S. oblanceolatum led to the isolation of three unprecedented meroterpenoids, syzygioblanes A-C (1-3, respectively). These compounds might be biosynthesized through [4+2] cycloaddition of various germacrane-based cyclic sesquiterpenoids with the flavone desmethoxymatteucinol to form a spiro skeleton. The unique and complex structures were elucidated by microcrystal electron diffraction analysis in addition to general analytical techniques such as high-resolution mass spectrometry, various nuclear magnetic resonance methods, and infrared spectroscopy. Synchrotron X-ray diffraction and calculations of electronic circular dichroism spectra helped to determine the absolute configurations. The newly isolated compounds exhibited collateral sensitivity to more strongly inhibit the growth of a multidrug resistant tumor cell line compared to a chemosensitive tumor cell line.

Conformational Analysis of (+)-Germacrene D-4-ol Using the Crystalline Sponge Method to Elucidate the Origin of its Instability.

Unsaturated cyclic terpenes often exhibit instability due to the proximation of C=C bonds in the cyclic skeleton, leading to nonenzymatic degradation. In this study, the crystalline sponge (CS) method was employed for the X-ray conformational analysis of a minute amount of oily and cyclic terpene compound, (+)-germacrene D-4-ol, which was produced by a terpene synthase OILTS under in vitro conditions. The CS method revealed a reactive conformation of the cyclic terpene with proximal double bonds. Under weakly acidic in vivo conditions, OILTS gave four pseudo-natural products or artifacts. The CS method also elucidated the structures of these degraded compounds, proposing a degradation mechanism triggered by the transannular reactions.

Rapid Synthesis of Chiral Figure-Eight Macrocycles Using a Preorganized Natural Product-Based Scaffold.

Chiral D2 -symmetric figure-eight shaped macrocycles are promising scaffolds for amplifying the chiroptical properties of π-conjugated systems. By harnessing the inherent and adaptable conformational dynamics of a chiral C2 -symmetric bispyrrolidinoindoline (BPI) manifold, we developed an enantio-divergent modular synthetic platform to rapidly generate a diverse range of chiral macrocycles, spanning from 14- to 66-membered rings, eliminating the need for optical resolution. Notably, a 32-membered figure-eight macrocycle showed excellent circularly polarized luminescence (CPL: |glum |=1.1×10-2 ) complemented by a robust emission quantum yield (Φfl =0.74), to achieve outstanding CPL brightness (BCPL : ϵ×Φfl ×|glum |/2=480). Using quadruple Sonogashira couplings, this versatile synthetic platform enables precise adjustments of the angle, distance, and length among intersecting π-conjugated chromophores. Our synthetic strategy offers a streamlined and systematic approach to significantly enhance BCPL values for a variety of chiral D2 -symmetric figure-eight macrocycles.

Enantioselective synthesis of 3-(N-indolyl)quinolines containing axial and central chiralities.

Quinoline and indole are important core structures in biologically active compounds and materials. Atropisomeric biaryls consisting of quinoline and indole are a unique class of axially chiral molecules. We report herein enantioselective synthesis of 3-(N-indolyl)quinolines having both C-N axial chirality and carbon central chirality by a photoredox Minisci-type addition reaction catalyzed by a chiral lithium phosphate/Ir-photoredox complex. The catalytic system enabled access to a unique class of 3-(N-indolyl)quinolines with high chemo-, regio-, and stereoselectivities in good yields through the appropriate choice of an acid catalyst and a photocatalyst. This is the first example of the synthesis of 3-(N-indolyl)quinoline atropisomers in a highly enantioselective manner.

Function and Structure of a Terpene Synthase Encoded in a Giant Virus Genome.

Giant viruses are nonstandard viruses with large particles and genomes. While previous studies have shown that their genomes contain various sequences of interest, their genes related specifically to natural product biosynthesis remain unexplored. Here we analyze the function and structure of a terpene synthase encoded by the gene of a giant virus. The enzyme is phylogenetically separated from the terpene synthases of cellular organisms; however, heterologous gene expression revealed that it still functions as a terpene synthase and produces a cyclic terpene from a farnesyl diphosphate precursor. Crystallographic analysis revealed its protein structure, which is relatively compact but retains essential motifs of the terpene synthases. We thus suggest that like cellular organisms, giant viruses produce and utilize natural products for their ecological strategies.

X-ray and Electron Diffraction Observations of Steric Zipper Interactions in Metal-Induced Peptide Cross-ß Nanostructures.

The steric zipper is a common hydrophobic packing structure of peptide side chains that forms between two adjacent ß-sheet layers in amyloid and related fibrils. Although previous studies have revealed that peptide fragments derived from native protein sequences exhibit steric zipper structures, their de novo designs have rarely been studied. Herein, steric zipper structures were artificially constructed in the crystalline state by metal-induced folding and assembly of tetrapeptide fragments Boc-3pa-X1-3pa-X2-OMe (3pa: ß-(3-pyridyl)-l-alanine; X1 and X2: hydrophobic amino acids). Crystallographic studies revealed two types of packing structures, interdigitation and hydrophobic contact, that result in a class 1 steric zipper geometry when the X1 and X2 residues contain alkyl side chains. Furthermore, a class 3 steric zipper geometry was also observed for the first time among any reported steric zippers when using tetrapeptide fragments with (X1, X2) = (Thr, Thr) and (Phe, Leu). The system could also be extended to a knob-hole-type zipper using a pentapeptide sequence.

Synthetic Modulation of an Unstable Dehydrosecodine-type Intermediate and Its Encapsulation into a Confined Cavity Enable Its X-ray Crystallographic Observation.

Numerous indole alkaloids such as the iboga- and aspidosperma-type are believed to be biosynthesized via a common hypothetical intermediate, dehydrosecodine. The highly reactive nature of dehydrosecodine-type compounds has hampered their isolation and structural elucidation. In this study, we achieved the first X-ray structural determination of a dehydrosecodine-type compound by integrating synthetic optimization of the reactivity and stabilizing the fragile molecule by encapsulation into a supramolecular host. Formation of a 1 : 1 complex of the dehydrosecodine-type labile guest bearing both vinyl indole and dihydropyridine units with the host was observed. This integrated approach not only provides insights into the biosynthetic conversions but also allows stabilization and storage of the reactive and otherwise short-lived intermediate within the confined hydrophobic cavity.

Imprinting Spatial Helicity Structure of Vector Vortex Beam on Spin Texture in Semiconductors.

We present the transfer of the spatially variant polarization of topologically structured light to the spatial spin texture in a semiconductor quantum well. The electron spin texture, which is a circular pattern with repeating spin-up and spin-down states whose repetition rate is determined by the topological charge, is directly excited by a vector vortex beam with a spatial helicity structure. The generated spin texture efficiently evolves into a helical spin wave pattern owing to the spin-orbit effective magnetic fields in the persistent spin helix state by controlling the spatial wave number of the excited spin mode. By tuning the repetition length and azimuthal angle, we simultaneously generate helical spin waves with opposite phases by a single beam.

Hysteresis behavior in the unfolding/refolding processes of a protein trapped in metallo-cages.

Confinement of molecules in a synthetic host can physically isolate even their unstable temporary structures, which has potential for application to protein transient structure analysis. Here we report the NMR snapshot observation of protein unfolding and refolding processes by confining a target protein in a self-assembled coordination cage. With increasing acetonitrile content in CD3CN/H2O media (50 to 90 vol%), the folding structure of a protein sharply denatured at 83 vol%, clearly revealing the regions of initial unfolding. Unfavorable aggregation of the protein leading to irreversible precipitation is completely prevented because of the spatial isolation of the single protein molecule in the cage. When the acetonitrile content reversed (84 to 70 vol%), the once-denatured protein started to regain its original folded structure at 80 vol%, showing that the protein folding/unfolding process can be referred to as a phase transition with hysteresis behavior.

Synthesis and structure elucidation of triarylmethyl radicals with anthryl substitution.

Two stable triarylmethyl radicals with one or two anthryl substitutions are synthesized in gram scale, and are isolated in the crystalline state. Detailed structural elucidation with X-ray crystallographic analysis and DFT calculations revealed that the twisted structure is more energetically favorable than the folded structure, and consequently, the spin density is mainly localized at the methyl carbon. The spin distribution leads to unique physical properties, making them promising open-shell organic materials.

Modular synthesis, host-guest complexation and solvation-controlled relaxation of nanohoops with donor-acceptor structures.

Carbon nanohoops with donor-acceptor (D-A) structures are attractive electronic materials and biological fluorophores, but their synthesis is usually challenging. Moreover, the preparation of D-A nanohoop fluorophores exhibiting high fluorescence quantum yields beyond 500 nm remains a key challenge. This study presents a modular synthetic approach based on an efficient metal-free cyclocondensation reaction that readily produced nine congeners with D-A or donor-acceptor-donor' (D-A-D') structures, one of which is water-soluble. The tailored molecular design of nanohoops enabled a systematic and detailed study of their host-guest complexation with fullerene, optical properties, and charge transfer (CT) dynamics using X-ray crystallography, fluorescence titration, steady and ultrafast transient absorption spectroscopy, and theoretical calculations. The findings revealed intriguing physical properties associated with D-A motifs, such as tight binding with fullerene, moderate fluorescence quantum yields (37-67%) beyond 540 nm, and unique solvation-controlled CT relaxation of D-A-D' nanohoops, where two CT states (D-A and A-D') can be effectively tuned by solvation, resulting in dramatically changed relaxation pathways in different solvents.

Photo-conversion of self-assembled structures into continuous covalent structures via [2 + 2]-cycloaddition reactions.

In this study, the conversion of self-assembled structures into continuous polymeric structures by linking the self-assembled molecules using the [2 + 2]-cycloaddition reaction was investigated. Synthesized bio-inspired thymine-based bolaamphiphilic molecules were designed to force the interactions between two molecules to engage two thymines in their self-assembled structure to undergo a cycloaddition reaction. Thymine-based bolaamphiphilic molecules were designed and synthesized using different phenylene spacers based on aromatic substituents (ortho-) (meta-) (para-). The formed self-assembled structures from these molecules were characterized and compared using molecular mechanical simulations. Simulations were performed to discuss the relationship between the inter- and intramolecular cycloaddition sensitivity to different substituents. This study provides a strategy for creating higher molecular weight linear polymers by controlling the photocyclization sites within the self-assembly by spacers between thymines. An intermolecular [2 + 2] cycloaddition reaction of thymine-based bolaamphiphilic molecules proceeded within the self-assembled nano-ribbon-like structure to form the continuous covalent structure.

Synthesis of a Negatively Curved Nanocarbon Molecule with an Octagonal Omphalos via Design-of-Experiments Optimizations Supplemented by Machine Learning.

A saddle-shaped nanocarbon molecule was synthesized, which revealed the existence of negative Gauss curvatures on a >3-nm molecular structure possessing 192 π-electrons. The synthesis was facilitated by a protocol developed with Design-of-Experiments optimizations and machine-learning predictions, and spectroscopy and crystallography were used to reveal the saddle-shaped structure of the molecule. Solution-phase analyses showed the presence of dimeric assembly, and crystallographic analyses revealed the stacked dimeric structures. The stacked crystal structure was scrutinized by various methods, including Gauss curvatures derived from the discrete surface theory of geometry, to reveal the important role of the molecular Gauss curvature in dimeric assembly.

Single-crystal structure analysis of non-deuterated triglycine sulfate by neutron diffraction at 20 and 298†K: a new disorder model for the 298†K structure.

Precise single-crystal structure analyses of the title compound, bis-(glycinium) sulfate-glycine (1/1), 2C2H6NO2 +·SO4 2-·C2H5NO2 (or C6H17N3O10S), non-deuterated triglycine sulfate (HTGS) at 20 K and 298 K were undertaken using time-of-flight neutron diffraction data. At 20 K for the O-H⋯O hydrogen bond between the glycinium cation and the zwitterionic, unprotonated glycine mol-ecule that is associated with the ferroelectric behaviour of HTGS, O-H = 1.070 (3), H⋯O = 1.408 (3) [δ = 0.338 (4)], O⋯O = 2.4777 (15) Šand O-H⋯O = 179.0 (4)°, which is in good agreement with previous studies. Two reasonable structures for the same three atoms were refined for the 298 K dataset. One is a single-minimum potential-energy model, with O-H = 1.090 (12), H⋯O = 1.361 (12) [δ = 0.271 (17)], O⋯O = 2.450 (7) Šand O-H⋯O = 179.2 (10)°, having the H atom with a large ellipticity along the bond path between the O atoms. The other is a double-minimum potential-energy model having two H atom sites with occupancies of 0.876 (8) and 0.124 (8): for the major occupancy component, O-H = 1.065 (12), H⋯O = 1.387 (12), O⋯O = 2.451 (7) Šand O-H⋯O = 178.2 (11)° and for the minor component, O-H = 1.06 (4), H⋯O = 1.41 (4), O⋯O = 2.451 (7) Šand O-H⋯O = 166 (2)°. These models did not show any significant differences in R factors. In addition, the unit-cell parameters and other structural parameters of HTGS did not show any major differences compared to those of partially deuterated TGS and fully deuterated TGS for both 20 K and 298 K.

π-Extended Doublet Open-Shell Graphene Fragments Exhibiting One-Dimensional Chain Stacking.

The hitherto elusive benzo[c]anthanthrenyl radical derivatives composed of seven fused six-membered rings are synthesized and isolated in the crystalline form, representing a laterally π-extended doublet open-shell graphene fragment compared to the phenalenyl and olympicenyl radical structures. X-ray crystallographic analysis revealed one-dimensional chain stacking with relatively close intermolecular contacts, which is an important precondition for achieving single-component conductors. The magnetic, optical, and redox properties are investigated in the solution phase. In combination with the good stability, such open-shell molecular systems have potentials as functional electronic materials.

Comprehensive Structural Analysis of the Bitter Components in Beer by the HPLC-Assisted Crystalline Sponge Method.

Trans-iso-α-acid is one of the main contributors to the bitter taste of fresh beer and is known to transform into various derivatives during beer aging. However, structural characterization of the derivatives has been a challenging task because of the formation of too many components. Herein, we report that most of the transformation products of trans-iso-α-acid, isolated in this study in only small quantities by HPLC, can be structurally analyzed with the crystalline sponge method. Thirteen compounds, including eight that were previously unreported, have been successfully isolated and analyzed with complete assignment of their absolute configuration. This provides an improved understanding of the chemical transformations that occur during beer aging.

Overcrowded Ethylene-Bridged Nanohoop Dimers: Regioselective Synthesis, Multiconfigurational Electronic States, and Global Hückel/Möbius Aromaticity.

The design and preparation of molecular systems with multiple geometric and electronic configurations are the cornerstones for multifunctional materials with stimuli-responsive behaviors. We describe here the regioselective and facile synthesis of two types of overcrowded ethylene-bridged nanohoop dimers, with folded and twisted geometric structures as well as closed-shell, diradical and dication electronic structures. The strained nanohoop structures have a profound effect on the overall molecular and electronic configurations, which resulted in the destabilized diradical state. X-ray crystallographic analysis revealed the folded molecular geometry for the neutral species and twisted geometry for the dication species. The unique molecular dynamics, optical properties, and dynamic redox properties were disclosed in the solution phase by spectroscopic and electrochemical methods. Furthermore, the global Hückel and Möbius aromaticity were revealed by a combination of experimental and theoretical approaches. Our studies shed light on the design of nanohoop-incorporated multiconfigurational materials with unique topologies and functions.

Cycloparaphenylene Double Nanohoop: Structure, Lamellar Packing, and Encapsulation of C60 in the Solid State.

A new member of the cycloparaphenylene double-nanohoop family was synthesized. Its π-framework features two oval cavities that display different shapes depending on the crystallization conditions. Incorporation of the peropyrene bridge within the nanoring cycles via bay-regions alleviates steric effects and thus allows 1:1 complexation with C60 in the solid state. This nanocarbon adopts a lamellar packing motif, and our results suggest that the structural adjustment of this double nanohoop could enable its use in supramolecular and semiconductive materials.

Pilot Demonstration of a Strengthening Method for Steel-Bolted Connections Using Pre-Formable Carbon Fiber Cloth with VaRTM.

In recent years, many seismic retrofitting methods have been performed to improve the structural performance and prevent the brittle failure of structural members. In the case of steel structures, slender seismic braces have been widely used for buildings, towers, and bridges. The brace connections should resist the full plastic axial tension load to ensure adequate plastic deformation performance for vibration energy absorption. However, certain connections do not satisfy these requirements. Recently, carbon fiber reinforced plastic (CFRP) has been used extensively to strengthen existing structures because of its high-strength, high elastic modulus, and light-weight characteristics. In this paper, we investigate the applicability of CFRP strengthening for brace connections and gusset plates with stepped surfaces using the vacuum-assisted resin transfer molding technique as a pilot demonstration. Stepped surfaces can be eliminated by using alternative CFRP layers to straighten the structural CFRP layers in order to effectively transfer the axial stress. Eventually, it is shown that CFRP strengthening can improve the connection strength and plastic deformation with 3% elongation, even if the CFRP is molded on the stepped surface.