Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells via its spike (S) protein, which binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Glycans are thought to influence this interaction by modulating the binding affinity between the S protein and its receptor. In this study, we screened 300 carbohydrate species using a glycan array to identify potential ligands that interact with the S proteins of the Delta and Omicron variants. Among the identified candidates, two aminoglycoside antibiotics, tobramycin and sisomicin, exhibited notable binding to the S protein. Surface plasmon resonance (SPR), circular dichroism (CD), and in silico docking analyses confirmed direct interactions between these aminoglycosides and the S protein, revealing distinct binding characteristics. Nuclear magnetic resonance (NMR) analysis further localized the tobramycin-binding site within the receptor-binding domain (RBD) of the S protein. Tobramycin and sisomicin showed a tendency to inhibit SARS-CoV-2 replication in human induced pluripotent stem cell (hiPSC)-derived lung organoids, though the effect did not reach statistical significance. Docking simulations using the trimeric S model suggested that aminoglycosides bind at an inter-subunit interface. These findings demonstrate that aminoglycosides can directly interact with the SARS-CoV-2 S protein and may serve as scaffolds for developing host-independent antiviral agents against SARS-CoV-2 and its variants.

N-Methylation strongly influences the cis-trans (Z-E) preference of amides, especially in benzanilide. While the trans (E) conformation is preferred in NH-benzanilide, N-methylation shifts the balance to favor the cis (Z) form. This switch, often attributed to steric hindrance, is frequently utilized in molecular design. However, our findings suggest an alternative mechanism. Through bond model analysis (BMA), we explored the structural preferences driven by bond orbital interactions and assessed the stability of cis-trans (Z-E) preferences in response to electronic perturbations via electron-donating or -withdrawing groups on the benzene rings. Our results reveal that N-methylation rebalances conjugation: NH-benzanilides prefer the trans (E) form due to phenyl-amine conjugation, while N-Me benzanilides favor the cis form due to phenyl-carbonyl conjugation.

Two adamantane-containing macrocycles having halobenzene and tetrazine parts were employed as porous host materials in the crystalline sponge method for the structural elucidation of liquid pharmaceutical compounds. The macrocycles were arranged into molecular networks composed of tubular assemblies having onedimensional pores. Soaking of the porous crystals in methyl salicylate or eugenol afforded the adsorbed crystals in a single-crystal to single-crystal fashion. X-ray analysis revealed that the conformation and packing of the macrocycles in the porous crystals were changed compared with those in the original crystals. Similarly, 4-methylpyrazole (also known as fomepizole) or 3-methylpyrazole were captured within the macrocycle-based organic frameworks, and their molecular structures were confirmed. Remarkably, dimeric structures of the pyrazole derivatives were formed within the macrocycles through hydrogen bonds.

A key intermediate in the enantioselective synthesis of (+)-neovibsanins A and B was synthesized from (E)geranic acid in only six steps. Strategic asymmetric 1,4-addition and asymmetric aldol reactions were used to construct successive chiral centers adjacent to a chiral tetraalkylated (all-carbon) quaternary center and ring closing metathesis using Grubbs catalyst, forming the A-ring moiety was effective in reducing the number of steps leading to the key intermediate.

Macrocage molecules bearing a bridged π-electron system represent a unique platform for molecular gyrotops, in which the π-electron system acts as an internal rotor confined within a cage. Here, we report the design and synthesis of a novel molecular gyrotop 1a, incorporating a bridged catechol-3,6-diyl unit, together with its dimethoxy 1b and diethoxy 1c derivatives. Structural characterization and variable-temperature nuclear magnetic resonance (VT-NMR) spectroscopy clearly revealed the active rotational dynamics of the phenylene rotor. Remarkably, systematic tuning of the alkoxy substituents enabled modulation of the rotational energy barriers, highlighting a strategy for engineering controllable internal motion in macrocage frameworks. These findings not only display a new class of molecular gyrotops but also provide design principles for developing functional molecular machines.

Bent-shaped compounds are attractive building blocks because they self-assemble into unique two- or three-dimensional structures. We used bent-shaped host molecule (1), which is composed of two nitrophenols linked to adamantane. Vapor diffusion of hexane into a tetrahydrofuran solution of 1 afforded inclusion crystals. The host molecules were assembled into tetrameric H-shaped structures as a motif through the quadruple pi-stacking of nitrophenol moieties within a unit cell, in which eight hydroxy groups interacted with eight guests through hydrogen bonds. These assemblies were fabricated to form network structures with channels. In inclusion crystals with 1,4-dioxane, 1 was arranged into layer architectures that were packed into the channel structures. In inclusion crystals with gamma-butyrolactone, 1 was aligned into network structures with channels, where cyclic dimeric structures without cavities were formed. These results demonstrate the crucial role of solvent molecules in the creation of tetrameric and dimeric motifs in the crystalline state.

Co-crystallization of a macrocycle and 1,5-dihydroxynaphthalene afforded co-crystals with solvents, which, when soaked in diethyl ether, formed crystals of the macrocycle through solvent exchange and the release of 1,5-dihydroxynaphthalene.

Ten oligostilbenoids namely piceid (1), (- )-epsilon-viniferin (2), viniferifuran (3), hemsleyanol A (4), (-)-ampelopsin F (5), vaticanol A (6), vaticanol E (7), pauciflorol B (8), vaticanol G (9) and vaticanol B (10) were isolated from the wood and the stem bark of Vatica lowii. The elucidation of the isolated compounds was executed using 1D and 2D NMR, UV, IR, MS, optical rotation and comparison with the literature data. The chemotaxonomic significance of these compounds was also discussed.

Stable hypervalent bromine(III) compounds were synthesized via aryl bromine oxidation with sp-hybridized nitrogen cations generated by oxime N-O bond cleavage in trifluoroacetic acid. The resulting intramolecular N-Br hypervalent bond is effectively stabilized by the planar xanthone structure. The structures and physicochemical properties of these lambda 3-bromanes were characterized by X-ray crystallography, cyclic voltammetry, UV-vis spectroscopy, and computational analysis.

Here we show that the sp-hybridized nitrogen cation is strongly stabilized by a peri-iodine substituent in the tetralone system. The cation is captured by anionic species such as CF3 CO2 - , affording hypervalent iodine(III) compounds with a short nitrogen-iodine (N-I) bond, in which the cation serves as a Lewis acid. Notably, the O-I bond of the O-trifluoroacetate or O-acetate is intrinsically weaker than the N-I bond due to its more ionic character and is further weakened by protonation in trifluoroacetic acid. As a result, the oxygen ligand can dissociate in the presence of a Brønsted acid, affording a I+ cation intermediate that retains the N-I bond. We isolated the cation as the tetrafluoroborate, and characterized it experimentally by 1 H NMR spectroscopy and X-ray structure analysis, and theoretically by means of DFT calculation. The results suggest that the N-I bonded cation is intrinsically stable, and is weakly coordinated with water and the BF4 counter anion or trifluoroacetate anion. This cation can be employed as a reagent for α-oxidation of ketones.

Ion mobility-mass spectrometry (IM-MS) has recently contributed to the structural analysis of molecules, including supramolecules and proteins, by determining the ion arrival time distributions correlated with the collision cross sections (CCSs), as well as the mass-to-charge ratios. However, its application range is still limited owing to the lack of general CCSs simulation methods based on possible molecular conformations. Here, a molecular dynamics-based conformational search method for simulating CCS distributions using projection approximation is reported. As a case study, the gas-phase conformations of the sodium adducts of conformationally flexible polyketones with 3,3-dimethylpentane-2,4-dione as the monomer are analyzed. The sodium adduct of the hexamer (m/z 781.4 for [1 + Na]+) showed a monomodal arrival time distribution, but that of the octamer sodium adduct (m/z 1033.5 for [2 + Na]+) is multimodal. The conformational analysis indicated an unimodal CCS distribution of simulated [1 + Na]+ conformations in which the sodium cation is mainly bound at the chain terminal. Conversely, four clusters of conformations are obtained for [2 + Na]+ based on the Na+-coordination sites, which qualitatively reproduced the observed CCS distribution. This approach will extend the utility of IM-MS for the conformational analysis of flexible molecules in the gas phase. A conformation search method based on molecular dynamics is developed to analyze the arrival time distributions correlated with the collision cross sections (CCSs) obtained by ion mobility mass spectrometry. This method is applied to the gas-phase conformational analysis of structurally flexible polyketones, and it qualitatively reproduced the CCS distributions observed for the Na+-adducts of dodeca- and hexadecaketones. image

A typical naturally occurring disulfide structure in proteins is an 8-membered disulfide ring formed between two adjacent cysteine (Cys-Cys) residues. Based on this structure, we designed 7- to 9-membered disulfide ring molecules, embedded in the 7-azabicyclo[2.2.1]heptane skeleton, that switch their conformation from exclusively trans-amide to exclusively cis-amide upon redox transformation from dithiol to disulfide, and vice versa. Constrained shape of disulfide rings is rare in nature, and the present molecular structure is expected to be a useful fundamental component for the construction of new conformation-switching systems.

Ring-closing metathesis of dialkenyldisilacycloalkane using the Grubbs catalyst, followed by hydrogenation, afforded a mixture of two disilabicycloalkanes and tetrasilatricycloalkanes. This method can synthesize a diastereomer mixture of disilabicycloalkanes with one differing alkyl side chain. The observed symmetries of the NMR spectra of anti-bicycloalkanes depend significantly on the length of the side chain. The findings may contribute to the molecular design of functional bicycloalkanes based on structural transformations of the stable forms.

Applications of mass spectrometry to analyses of complexes are described. First, the ionization method is discussed as the basis of mass spectrometry. Then, the procedures of ion and mass spectral analysis are briefly explained. Next, mass spectrometers currently used for metal complexes are reviewed, and the measurement methods are discussed. Finally, examples of actual mass spectrometry targeting complex molecules are presented. Examples of rare earth complexes, capsule-type formulations, and supramolecular polymers are shown.

Water-mediated hydrogen-bonded structures were built from a disubstituted adamantane with dimethoxyphenol moieties, where halobenzenes were accommodated within the cavity of cyclic dimers composed of host compounds and waters.

Isoprenylation of the indole C3-position of tryptophan accompanied by cyclization (c-Trp) is one of the most attractive post-translational modifications because of C-C bond formation and drastic conformational alteration. As the modification generates two stereoisomers of the 6/5/5-fused ring system and consequently, a mixture of four possible conformations as considered in proline, it is expected to influence the biological activity in Bacillus quorum sensing pheromone ComX containing the c-Trp residue. In this study, the simultaneous control of the amide cis-trans equilibrium and pyrrolidine ring puckering was achieved by utilizing an N-carbamoylated and α-methylated 6/5/5-fused ring system. Furthermore, the conformationally defined tripeptides containing the c-Trp residue were utilized to examine the relationship between the biological activity and the conformation of the ComX pheromone. Several mimics showed high bioactivity, and more biologically active ComX mimics were created to reinforce the CH-π interaction of the c-Trp and the adjacent aromatic residue.

Ketones and esters were captured within porous crystals of an adamantane-containing macrocycle through single-crystal-to-single-crystal guest exchange with or without structural changes.

Tryptophan (Trp) is an essential amino acid that functions in various biological processes and human daily health. As the significant functions of Trp become more apparent, its measurement is becoming increasingly important in various situations. Herein, we improved the Trp color reaction based on the Hopkins-Cole reaction and established a simple colorimetric method for Trp determination using several different reagents, including sodium hypochlorite pentahydrate and monosodium glutamate. The detection method can be performed using safe materials, rather than conventional toxic substances, and induces a crimson color change with an absorption peak at 525 nm, enabling the quantification of Trp by simple spectrophotometry in just 10 min. This assay exhibited a linear detection range from 10 to 100 mg/L (R2 = 0.9996). The average recoveries in the spiked cerebrospinal fluid ranged from 90.5% to 104.3%, with a relative standard deviation of 0.27% (n = 3, 29.40 mg/L Trp) to 1.19% (n = 3, 72.90 mg/L Trp). This novel spectrophotometric method may enable many researchers and laboratory technicians to detect Trp in various sample solutions without expensive analytical instruments or complicated operations.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Solid-state fluorescence was quenched by libration of a fluorophore in a dimethylfluorene-diyl bridged macrocage.