Order-order transitions in poly(N-octadecyl acrylamide-co-hydroxyethyl acrylamide) statistical copolymer films.

This study demonstrates that a simple statistical copolymer can form self-assembled lamellae, whose structures depend on both the comonomer composition and the annealing temperature. Statistical copolymers of octadecyl acrylamide and hydroxyethyl acrylamide [p(ODA/HEAm)] were prepared via free-radical copolymerization, and their thermal properties were studied by differential scanning calorimetry. Thin films of p(ODA/HEAm) were prepared via spin-coating, and their structures were analyzed using X-ray diffraction. It was found that copolymers with HEAm contents between 28 and 50% formed self-assembled lamellae upon annealing at a temperature ∼10 °C above the glass-transition temperature. The self-assembled form was found to possess a "side-chain-mixed" lamellar structure, in which the ODA and HEAm side chains are oriented perpendicular to the lamellar plane composed of the polymer main chain. Interestingly, a copolymer with a HEAm content between 36 and 50% transformed from the side-chain-mixed lamellar structure to generate a "side-chain-segregated" lamellar structure upon annealing at a significantly higher temperature (∼50 °C above Tg). In this structure, the ODA and HEAm side chains were found to be oriented in opposite directions but perpendicular to the lamellar plane. The packing of the side chains in the lamellar structures was studied using Fourier-transform infrared spectroscopy. It was concluded that the structures of the self-assembled lamellae are determined by the strain forces generated during self-assembly, and by the segregation forces existing between the comonomers.

Prolonged infective SARS-CoV-2 omicron variant shedding in a patient with diffuse large B cell lymphoma successfully cleared after three courses of remdesivir.

We report a case of prolonged shedding of the infective SARS-CoV-2 omicron variant BA.1.1.2 in a 79-year-old male patient with diffuse large B-cell lymphoma, after receiving chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). The patient was admitted to our hospital in late March 2022 for the sixth course of R-CHOP chemotherapy. Initially, the patient tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using an in-hospital loop-mediated amplification assay with a nasopharyngeal swab, both on the day of admission and three days later. However, the patient developed fever and was diagnosed with coronavirus disease (COVID-19) six days after admission and was suspected to have contracted the infection in the ward. Viral shedding continued for more than three months, with confirmed viral infectivity. As compared to the original Wuhan-Hu-1/2019 strain, amino acid substitutions including S36 N in non-structural protein (NSP)2, S148P, S1265del and L1266I in NSP3, G105D in NSP4, G496S, A831V, or V987F in spike protein, and I45T in open-reading frame (ORF)9b were randomly detected in isolated viruses. Although the patient had received two doses of the BNT162b2 vaccine approximately six months earlier and the third dose on day 127 after the infection, both serum anti-spike and anti-nuclear protein IgG and IgM tests were negative at day 92, 114, and 149 after the infection. The patient finally cleared the virus after the third course of remdesivir and did not have further recurrence.

A Photoredox/Sulfide Dual Catalysis System That Uses Sulfide Radical Cations to Promote Alkene Chlorotrifluoromethylation.

Sulfides and their derivatives are among the most important class of reagent in synthetic chemistry. Despite the importance of such compounds, the use of sulfide radical cations in synthetic chemistry is underdeveloped. To address this issue, herein, we describe alkene chlorotrifluoromethylation reactions promoted by photoredox/sulfide dual catalysis systems, which involves sulfide radical cations generated through the oxidation of sulfides by a photoredox catalyst. The high functional group tolerance of this chemistry was demonstrated using natural products and drug molecules as substrate alkenes.

Lineage-specific gene acquisition or loss is involved in interspecific hybrid sterility in rice.

Understanding the genetic basis of reproductive barriers between species has been a central issue in evolutionary biology. The S1 locus in rice causes hybrid sterility and is a major reproductive barrier between two rice species, Oryza sativa and Oryza glaberrima The O. glaberrima-derived allele (denoted S1g) on the S1 locus causes preferential abortion of gametes with its allelic alternative (denoted S1s) in S1g/S1s heterozygotes. Here, we used mutagenesis and screening of fertile hybrid plants to isolate a mutant with an allele, S1mut, which does not confer sterility in the S1mut/S1g and S1mut/S1s hybrids. We found that the causal mutation of the S1mut allele was a deletion in the peptidase-coding gene (denoted "SSP") in the S1 locus of O. glaberrima No orthologous genes of SSP were found in the O. sativa genome. Transformation experiments indicated that the introduction of SSP in carriers of the S1s allele did not induce sterility. In S1mut/S1s heterozygotes, the insertion of SSP led to sterility, suggesting that SSP complemented the loss of the functional phenotype of the mutant and that multiple factors are involved in the phenomenon. The polymorphisms caused by the lineage-specific acquisition or loss of the SSP gene were implicated in the generation of hybrid sterility. Our results demonstrated that artificial disruption of a single gene for the reproductive barrier creates a "neutral" allele, which facilitates interspecific hybridization for breeding programs.

Does Selectivity of Molecular Catalysts Change with Time? Polymerization Imaged by Single-Molecule Spectroscopy.

The chemoselectivity of molecular catalysts underpins much of modern synthetic organic chemistry. However, little is known about the selectivity of individual catalysts because this single-catalyst-level behavior is hidden by the bulk catalytic behavior. Here, for the first time, the selectivity of individual molecular catalysts for two different reactions is imaged in real time at the single-catalyst level. This imaging is achieved through fluorescence microscopy paired with spectral probes that produce a snapshot of the instantaneous chemoselectivity of a single catalyst for either a single-chain-elongation or a single-chain-termination event during ruthenium-catalyzed polymerization. Superresolution imaging of multiple selectivity events, each at a different single-molecular ruthenium catalyst, indicates that catalyst selectivity may be unexpectedly spatially and time-variable.

Ferroelectric Alkylamide-Substituted Helicene Derivative with Two-Dimensional Hydrogen-Bonding Lamellar Phase.

Alkylamide (-CONHC nH2 n+1)-substituted benzene and its pyrene derivatives have shown a discotic hexagonal columnar liquid-crystalline phase through a one-dimensional (1D) intermolecular N-H···O═ hydrogen-bonding interaction, the direction of which is inverted through the application of an alternate current voltage. The polar hydrogen-bonding chains and dipole inversion reveal a ferroelectric polarization-electric field ( P- E) hysteresis curve. Non-π-planar helicene derivatives bearing two -CONHC14H29 chains also indicate a ferroelectric response. The racemic helicene derivative shows a bilayer lamellar liquid-crystal phase within a temperature range of 330-420 K, whereas there is no liquid crystallinity for the optically active derivative because of the different molecular assembly structure. The racemic phase is constructed through a two-dimensional (2D) N-H···O═ hydrogen-bonding network, which shows ferroelectric P- E hysteresis curves at above 340 K. The collective dipole inversion in the 2D layer contributes to the ferroelectricity in the lamellar phase. The remanent polarization ( Pr) of 11.1 µC cm-2 is about 6 times higher than those of the π-planar benzene- and pyrene-based 1D ferroelectrics. Both the density of the hydrogen-bonding site and the domain orientation in the 2D system are higher than those of the 1D columnar system.

Long-Range Anisotropic Structural Films and Fibers Formed from Lyotropic Liquid Crystal Gels Containing Hetero-Double-Helices with C16 Terminal Groups.

Long-range anisotropic structural materials exhibit notable optical and mechanical properties, and an efficient method for synthesizing such materials involving self-assembly of well-defined monodispersed organic molecules is described here. Hetero-double-helices are formed in toluene using a pseudoenantiomeric mixture of an ethynylhelicene ( M)-tetramer with C16 terminal groups and a ( P)-pentamer. When the concentration of the mixture was increased, the hetero-double-helices self-assembled to form lyotropic liquid crystal gels. On evaporating the solvent by drop casting, a long-range anisotropic structural film with a single domain and a size of up to centimeter order was spontaneously formed. Kinetics analysis of the film formation indicated the generation of perpendicularly aligned liquid crystal domains at the interface of the liquid and solid phases. When the lyotropic liquid crystal gel was extruded into methanol, a long-range anisotropic structural fiber with a single domain was formed. Different shapes of long-range anisotropic structural materials were obtained by different mechanical treatments of lyotropic liquid crystal gels.

Proximate stochastic chiral symmetry breaking is mechanically tunable: formation of enantiomeric hetero-double-helices and aggregates from racemic oxymethylenehelicene oligomers.

A mixture of oxymethylenehelicene (P)-hexamer and (M)-hexamer in solution exhibited chiral symmetry breaking, which was induced by mechanical stirring, during the formation of enantiomeric hetero-double-helices and their aggregates. A racemic 50 : 50 mixture was heated to 90 °C to form a dissociated state, and then cooled to 25 °C. Mechanical stirring with a magnetic stirrer at 2000 rpm for 100 h resulted in the exhibition of a strong negative Cotton effect at 322 nm. Repeated experiments provided negative Cotton effects, which is due to the deterministic chiral symmetry breaking. No change in the Cotton effect occurred in the absence of stirring. The (P)-hexamer to (M)-hexamer mixing molar fraction was varied, and a positive Cotton effect appeared at molar fractions between 40 : 60 and 46 : 54 and a negative Cotton effect at molar fractions between 48 : 52 and 60 : 40, which was reversed at 47 : 53. The slight deviation of symmetry from that at 50 : 50 was termed proximate stochastic chiral symmetry breaking. The process of chiral symmetry breaking could be tuned by varying the procedures of mechanical stirring and mixing procedures for solutions of (P)-hexamer and/or (M)-hexamer.

Synthesis and Self-Assembly of Chiral Cylindrical Molecular Complexes: Functional Heterogeneous Liquid-Solid Materials Formed by Helicene Oligomers.

Chiral cylindrical molecular complexes of homo- and hetero-double-helices derived from helicene oligomers self-assemble in solution, providing functional heterogeneous liquid-solid materials. Gels and liotropic liquid crystals are formed by fibril self-assembly in solution; molecular monolayers and fibril films are formed by self-assembly on solid surfaces; gels containing gold nanoparticles emit light; silica nanoparticles aggregate and adsorb double-helices. Notable dynamics appears during self-assembly, including multistep self-assembly, solid surface catalyzed double-helix formation, sigmoidal and stairwise kinetics, molecular recognition of nanoparticles, discontinuous self-assembly, materials clocking, chiral symmetry breaking and homogeneous-heterogeneous transitions. These phenomena are derived from strong intercomplex interactions of chiral cylindrical molecular complexes.

Deterministic and Stochastic Chiral Symmetry Breaking Exhibited by Racemic Aminomethylenehelicene Oligomers.

Racemic mixtures of aminomethylenehelicene (P)- and (M)-pentamers exhibited deterministic and stochastic chiral symmetry breaking during hetero-double-helix formation and self-assembly in solution. Heating a 50:50 mixture of (P)- and (M)-pentamers at 90 °C, and then cooling the mixture to 70 °C resulted in hetero-double-helix formation; a Cotton effect with negative Δε at λ=315 nm appeared. Chiral self-assembly occurred when the mixture was cooled to 25 °C. A strong tendency of deterministic chiral symmetry breaking appeared at the molecular and self-assembled levels, which was indicated by the negative Δε at λ=315 nm that appeared in most cases in repeated experiments. Mixtures containing 60:40 and 40:60 (P)-/(M)-pentamers also self-assembled with the same chirality. When a homo-double-helix (P)-/(M)-pentamer and a random coil (M)-/(P)-pentamer were mixed, the chiral self-assembly formed stochastically, and heating and cooling resulted in deterministic chiral symmetry breaking.

Direct C2-Functionalization of Indoles Triggered by the Generation of Iminium Species from Indole and Sulfonium Salt.

An indole core bearing a functional group on the C2 position is often found as a key structure in biologically active natural products and pharmaceuticals. Here, we report direct C2-functionalization of indoles triggered by the formation of an iminium species generated from indole and a sulfonium reagent. The reaction proceeded under very mild conditions to give the corresponding C2-substituted indole derivatives in good to high yields.

Pendant-Type Helicene Oligomers with p-Phenylene Ethynylene Main Chains: Synthesis, Reversible Formation of Ladderlike Bimolecular Aggregates, and Control of Intramolecular and Intermolecular Aggregation.

Pendant-type (P)-helicene oligomers with p-phenylene ethynylene main chains up to a tetramer were synthesized by a building block method. The (P)-tetramer reversibly formed a ladderlike bimolecular aggregate upon cooling and disaggregated upon heating in (trifluoromethyl)benzene. Two bis(tetramer)s, in which two (P)-tetramers were connected by hexadecamethylene linkers, were also synthesized. The head-to-tail bis(tetramer) formed an intramolecular aggregate, and the head-to-head bis(tetramer) formed an intermolecular aggregate in toluene. The results suggest the antiparallel aggregation structure of the pendant-type (P)-tetramers. The structure of the linker was proven to be effective in controlling intramolecular and intermolecular aggregations.

Spatially Heterogeneous Nature of Self-Catalytic Reaction in Hetero-Double Helix Formation of Helicene Oligomers.

A 1:1 mixture of pseudoenantiomeric aminomethylenehelicene oligomers, (P)-tetramer and (M)-pentamer, in fluorobenzene show a self-catalytic phenomenon in the formation of hetero-double helices from random coils. This study visualizes the spatially heterogeneous nature of the self-catalytic reaction in dilute solution. UV/Vis imaging analysis of the mixture at 70 °C, containing random coils, exhibits a homogeneous bright area. When the solution is cooled from 70 to 30 °C and held at that temperature, dark domains of approximately 1 mm in size appear, which move approximately at a rate of 1 mm min-1 . The dark domains indicate that weaker UV/Vis absorption results from the formation of hetero-double helices, which is supported by circular dichroism (CD) imaging experiments. Then a homogeneous mixture is regenerated upon heating to 55 °C, as shown by CD imaging. Under self-catalytic conditions, a homogeneous solution spontaneously changed to a heterogeneous solution in the process of hetero-double-helix formation.

Enantioselective synthesis of ß-amino acid derivatives via nickel-promoted regioselective carboxylation of ynamides and rhodium-catalyzed asymmetric hydrogenation.

We succeeded in the development of a new method for enantioselective synthesis of α-substituted-ß-amino acid derivatives. Thus, nickel(0)-promoted carboxylation of ynamide gave the α-substituted-ß-aminoacrylate derivative in a highly regioselective manner. Then, rhodium-catalyzed asymmetric hydrogenation of the α-substituted ß-aminoacrylate produced the corresponding α-substituted ß-amino acid derivative as an optically active form.

Dynamic and Reversible Polymorphism of Self-Assembled Lyotropic Liquid Crystalline Systems Derived from Cyclic Bis(ethynylhelicene) Oligomers.

A self-assembled lyotropic liquid crystal (LLC) system exhibiting dynamic and reversible polymorphism was developed using the synthetic cyclic ethynylhelicene oligomers cyclobis[(M)-D-n] (n = 4 and 6), in which two oligomer moieties are connected by two flexible linkers. The cyclic molecular structure was designed to control aggregation properties ranging from the molecular level to the macroscopic level. The cyclic oligomer changed its structure between random coils and an intramolecular homo-double helix induced by temperature and solvents. In the presence of pseudoenantiomeric acyclic oligomers, cyclobis[(M)-D-4] formed trimolecular complexes with a total molecular weight of over 10 000 Da containing two intermolecular hetero-double helices. The trimolecular complex formation predominated over bimolecular complex formation. The trimolecular complex self-assembled at high concentrations and formed LLCs composed of anisotropically aligned fibers. The result is in contrast to acyclic systems, which form gels composed of randomly oriented fibers. The LLCs changed into turbid gels composed of randomly oriented bundles upon cooling, and the LLCs were regenerated by heating. This is a notable example of a self-assembled LLC system exhibiting dynamic and reversible polymorphism between two ordered structures in a closed system consisting of fully synthetic molecules.

Development of Novel Bioluminescent Sensor to Detect and Discriminate between Vitamin D Receptor Agonists and Antagonists in Living Cells.

Active forms of vitamin D regulate the expression of multiple genes that play essential roles in calcium and phosphate homeostasis, cell differentiation, and the immune system via the vitamin D receptor (VDR). Many vitamin D analogs have been synthesized for clinical use in the treatment of type I rickets, osteoporosis, renal osteodystrophy, psoriasis, leukemia, and breast cancer. We have constructed two fusion proteins containing split-luciferase and the ligand binding domain (LBD) of the VDR designated as LucN-LBD-LucC and LucC-LBD-LucN. Remarkably, the LucC-LBD-LucN, which has the C-terminal domain of luciferase at the N-terminus of the fusion protein, was a significantly better biosensor than LucN-LBD-LucC. Addition of the VDR agonists to COS-7 cells expressing LucC-LBD-LucN dramatically reduced luciferase activity. In contrast, the VDR antagonist significantly increased the chimeric luciferase activity in a dose- and time-dependent manner. Our results on chimeric luciferases containing the LBDs of mutant VDRs derived from patients with vitamin D-dependent type II rickets indicated that our system could detect a conformational change of the LBD of the VDR likely based on a positional change of the helix 12, which occurs upon ligand binding. This novel system to detect and discriminate between VDR agonists and antagonists could be useful for the screening and identification of chemical compounds that bind to normal or mutant VDRs with high affinity.

Synthesis, π-face-selective aggregation, and π-face chiral recognition of configurationally stable C(3)-symmetric propeller-chiral molecules with a π-core.

The C3 -symmetric propeller-chiral compounds (P,P,P)-1 and (M,M,M)-1 with planar π-cores perpendicular to the C3 -axis were synthesized in optically pure states. (P,P,P)-1 possesses two distinguishable propeller-chiral π-faces with rims of different heights named the (P/L)-face and (P/H)-face. Each face is configurationally stable because of the rigid structure of the helicenes contained in the π-core. (P,P,P)-1 formed dimeric aggregates in organic solutions as indicated by the results of (1) H NMR, CD, and UV/Vis spectroscopy and vapor pressure osmometry analyses. The (P/L)/(P/L) interactions were observed in the solid state by single-crystal X-ray analysis, and they were also predominant over the (P/H)/(P/H) and (P/L)/(P/H) interactions in solution, as indicated by the results of (1) H and 2D NMR spectroscopy analyses. The dimerization constant was obtained for a racemic mixture, which showed that the heterochiral (P,P,P)-1/(M,M,M)-1 interactions were much weaker than the homochiral (P,P,P)-1/(P,P,P)-1 interactions. The results indicated that the propeller-chiral (P/L)-face interacts with the (P/L)-face more strongly than with the (P/H)-face, (M/L)-face, and (M/H)-face. The study showed the π-face-selective aggregation and π-face chiral recognition of the configurationally stable propeller-chiral molecules.

Synthesis, double-helix formation, and higher-assembly formation of chiral polycyclic aromatic compounds: conceptual development of polyketide aldol synthesis.

Polycyclic aromatic compounds are an important group of substances in chemistry, and the study of their properties is a subject of interest in the development of drugs and materials. We have been conducting studies to develop chiral polycyclic aromatic compounds, i.e., helicenes and equatorenes. These helical molecules showed notable aggregate-forming properties and the capability for chiral recognition exerted by noncovalent bond interactions, which were not observed in compounds with central chirality. Homo- and hetero-double-helix-forming helicene oligomers were developed, and the latter self-assembled to form gels and vesicles. In this article, we describe such hierarchical studies of polycyclic aromatic compounds, which were started from polyketide aldol synthesis.

Fluorescent gold nanoparticles: synthesis of composite materials of two-component disulfide gels and gold nanoparticles.

Pseudoenantiomeric ethynylhelicene oligomers containing a disulfide group formed two-component gels, which showed different solvent properties from gels without the disulfide group. The disulfide gels reacted with gold nanoparticles, and the resulting organic-inorganic composite materials exhibited fluorescence emission between 600-800 nm, along with emission from the oligomers at 450 nm. The disulfide gels and isolated gold nanoparticles loaded with the oligomers did not show the former emission. The 600-800 nm emission reversibly disappeared upon sol formation with heating, which was accompanied by an enhancement of the emission at 450 nm. The novel emission was also observed in the solid state.

Synthesis of N-(acyloxy)-N-alkynylamides via generation of "C2" from hypervalent alkynyliodane and a weak base.

The first synthesis of N-(acyloxy)ynamides was realized through the coupling of N-(acyloxy)amides and hypervalent alkynyliodane under mild conditions. This reaction probably involves biradical species ("C2") generation and radical processes. Furthermore, we also demonstrated that N-(acyloxy)ynamide could be transformed into a N-sulfonylimidate derivative by a copper catalyst. This study provides new building blocks for synthetic organic chemistry reactions and improves understanding of the chemical reactivity of "C2".