Photoresponsive molecular tools have become powerful platforms for manipulating biological functions with high spatiotemporal precision. In this review, we highlight recent advances in the development of light-activated compounds that interact with key signaling molecules and microenvironments. Inspired by various chemical reactions triggered by light-matter interactions, this review covers three representative systems: photoactivatable peroxynitrite (ONOO⁻) generators, visible-light-driven nitric oxide (NO) releasers, and optochemical oxygen (O₂) scavengers. ONOO⁻, a reactive nitrogen species formed from NO and superoxide (O₂⁻), plays a critical role in protein nitration and cellular oxidative stress. By designing molecules that generate both NO and O₂⁻ upon light exposure, efficient ONOO⁻ release was achieved and used to induce nitration reactions. For NO manipulation, the authors developed a class of photoresponsive releasers that utilize photoinduced electron transfer (PeT) to enable blue-to-red light-triggered NO release. These photoresponsive releasers allowed optical control of vasodilation both ex vivo and in vivo, which forms the basis of a minimally invasive approach to modulate blood flow. In addition, a light-responsive O₂ scavenger was developed to induce localized hypoxia in cell cultures. The light-responsive O₂ scavenger enabled optical regulation of the hypoxia-responsive pathway and activation of the transient receptor potential ankyrin 1 (TRPA1) calcium channel, which underscores the utility of this approach. Together, these studies illustrate how rational molecular design, combined with precise photochemical control, can create innovative systems for probing and directing biological events. These technologies are valuable as both a basic research tool and for potential future therapeutic applications.

A concise gram-scale total synthesis of (±)-makaluvamine F was accomplished. The left segment, 2-aminodihydrobenzothiophene possessing an N,S-acetal moiety, was prepared using commercially available 2-fluoro-4-methoxybenzaldehyde in 6 steps via Curtius rearrangement. Subsequent condensation of the 2-aminodihydrobenzothiophene segment with a pyrroloiminoquinone segment completed the total synthesis of makaluvamine F, which was achieved in a 23% overall yield via a longest linear sequence of 7 steps. The versatility of the synthetic route involving the Curtius rearrangement was demonstrated by applying it to synthesize several unnatural makaluvamine F derivatives.

Herein, we demonstrated a site-selective diazenylation of fluorinated alkyl iodides via 1,5-hydrogen atom transfer using diazonium salts, in combination with iron metal and ferrocene as an inexpensive catalytic system. The reactions proceeded under mild conditions with high regioselectivity, thereby enabling the efficient synthesis of a diverse range of azo compounds that have been difficult to access by traditional synthetic methods.

Guanine quadruplexes (G4s) are non-canonical nucleic acid structures that have emerged as attractive therapeutic targets owing to their involvement in diverse biological processes. Additionally, peptides derived from G4-binding proteins provide promising platforms for selective G4 recognition. In this study, we explored the G4-binding capacity of arginine–glycine–glycine (RGG)-rich sequences derived from the RGG3 domain translocated in liposarcoma/fused in sarcoma (TLS/FUS), a known G4 RNA binding protein. In this study, we synthesized a library of overlapping 15-mer peptides and evaluated their G4-binding affinities. Among the 10 evaluated native sequences, several peptides demonstrated measurable affinities toward G4 RNA structures, with STK5-1 exhibiting the highest G4-binding affinity. Furthermore, to investigate the impact of conformational constraints on G4 recognition, we introduced (E)-methylalkene dipeptide isosteres (MADIs) into selected Gly–Gly motifs, generating a series of RGG peptidomimetics. Subsequent binding assays revealed that some of these MADI peptidomimetics exhibited enhanced affinity and selectivity compared with their unmodified counterparts. Our findings offer new insights into the sequence and structural features governing G4-binding, establishing a foundation for the further development of peptide-based G4 ligands.

We report the development of triarylphenol-based photocatalysts that promote C–I bond borylation via halogen bonding (XB) interactions under visible-light irradiation. Traditional phenol system reactions often suffer from phenoxyl radical instability, limiting their catalytic utility. To overcome this issue, we designed sterically and electronically tuned triarylphenols that stabilize radical intermediates while maintaining high photoreactivity. Systematic evaluation revealed that 2,4,6-triphenylphenol efficiently facilitates photoinduced electron transfer (PET) and suppresses undesired side reactions such as phenol decomposition. The optimized reaction conditions enabled a broad substrate scope, showing efficient arylboronic ester formation. Density functional theory calculations confirmed the formation of XB complexes with charge-transfer character, providing mechanistic support for the PET pathway. This work shows the potential of rationally designed phenols as XB acceptors and offers a sustainable approach for C–I bond functionalization.

The flowability of powders in pharmaceutical formulations is critical for manufacturing robustness and content uniformity. Shear cell measurements aid in assessing flowability under consolidation and provide useful parameters for predicting powder behavior in real manufacturing. However, some of the parameters vary with void fraction (indentation load), thereby necessitating specification of the consolidation conditions under which the value was obtained; moreover, the given single value still cannot be used to predict flowability under different conditions. If flowability could be expressed using a parameter that reflects an intrinsic property of the powder, it would be useful for quality control of raw materials and for efficient formulation design. Therefore, we investigated the relationship between various parameters obtained from constant-volume shear cell measurements and consolidation conditions using pharmaceutical powders with different particle sizes and shapes. We found that, when the substance of the sample is the same, the preshear points align on a single straight line passing through the origin, regardless of differences in indentation load, particle size, or shape. In other words, the slope of the critical state line (ϕ_CSL) connecting the preshear points was relatively insensitive to particle size and shape, indicating high robustness. These findings reveal that ϕ_CSL could serve as an intrinsic flowability parameter of the powder. The ϕ_CSL values of several fine powders with particle sizes <10 µm deviated from this trend, suggesting that interparticle cohesive forces may have influenced their flowability.

Aspergillus and Penicillium species produce a variety of quinazolinobenzodiazepine (QBD) alkaloids by using different biosynthetic gene clusters (BGCs). During the course of metabolome analysis of Aspergillus fumigatiaffinis IFM55214, we discovered an atropisomeric pair of QBD natural products, benzomalvin G (1) and H (2), that are produced by this fungus. The isomer 1 was favored in organic solvents, and 2 was favored in aqueous solutions. The stereochemistry and conformation of these 2 compounds were determined unambiguously by Marfey’s method and nuclear Overhauser effect (NOE) analysis, respectively. Furthermore, a putative BGC for 1 and 2 (Afben cluster), composed of 3 genes (AfbenX, AfbenY, and AfbenZ) shared between the ben cluster in Aspergillus terreus and 4 additional genes (methyltransferases and oxygenases), was identified in the genome of A. fumigatiaffinis IFM55214.

Owing to the recent detection of pharmaceutical residues in aquatic environments, the development of methods for their removal has attracted increasing research attention. Considering the rich host–guest chemistry of cucurbit[7]uril (CB[7]), which can form stable inclusion complexes with various compounds, we envisioned that CB[7] could be used for capturing pharmaceutical residues in aquatic environments. In this study, using ¹H-NMR spectroscopy, we examined the formation of inclusion complexes between CB[7] and new quinolone antibiotics that have been linked to the emergence of resistant bacteria, that is, ciprofloxacin hydrochloride monohydrate (CPFX), levofloxacin hydrochloride (LVFX), lomefloxacin hydrochloride (LFLX), and pazufloxacin mesylate (PZFX). The results showed that CPFX, LVFX, and LFLX formed inclusion complexes with CB[7] at a molar ratio of 1 : 1, with complex formation constants (K) of 0.529, 0.877, and 3.65 (×10⁴ M⁻¹), respectively, whereas PZFX did not. This difference was attributed to the presence or absence of a piperazine ring, indicating that it is a critical feature for the formation of inclusion complexes with CB[7]. In addition, the thermodynamic parameters calculated using van’t Hoff plots revealed that LVFX and LFLX with a methyl group on the piperazine ring expel high-energy water from the cavity of CB[7] more efficiently, resulting in larger K values. Because the piperazine ring structure is commonly found in many drugs, CB[7] can be expected to capture other drugs apart from those evaluated in this study. Therefore, CB[7] is a promising candidate as a host molecule for use in drug removal in aquatic environments through host–guest chemistry.

A new furan-type metabolite named marinofuran (1) was isolated along with echinomycin (2), echinoserine (3), and 5-prenyltryptophol (4) from a solid culture of the marine-derived actinomycete Streptomyces sp. KM14-19. The structure of 1 was elucidated by an analysis of spectroscopic data, including 1 dimensional (1D) and 2D-NMR and single-crystal X-ray diffraction.

The stratum corneum, the outermost layer of the skin, is composed of keratinized cells known as corneocytes and intercellular lipids (IC lipids) such as ceramides (Cers), cholesterol (Chol), and free fatty acids (FFAs). These lipids form highly ordered multilamellar membranes in the intercellular spaces, serving as a key regulator of the skin barrier function. To investigate the mechanistic relation between the membrane structure and the skin barrier function, model membranes composed of Cers/Chol/FFA mixtures have been widely employed. In most of those studies, highly toxic solvents such as chloroform (CHCl₃) and methanol (MeOH) were used to dissolve and mix the IC lipids. However, growing concerns regarding safety and environmental hygiene have driven the selection of safer alternative solvents. In this study, we developed a new protocol for preparing model membranes using less toxic ethanol (EtOH). In the EtOH-based protocol, IC lipids were dissolved in near-boiling EtOH, diluted by a fivefold large volume of buffer, and cooled to 30°C. After 18 h of equilibration at 30°C, the model intercellular lamellae were collected by centrifugation. In addition, we demonstrated that the lamellar sample exhibited thermodynamic and structural properties comparable to those of the lamellae prepared by the conventional CHCl₃/MeOH-based protocols. Moreover, the developed EtOH-based protocol enhanced the miscibility of IC lipids to some extent. Therefore, the EtOH-based protocol would be a useful methodology for preparing model intercellular membranes, being well-suited for environmental hygiene.

We previously discovered metabolites that are either enhanced or specifically produced by actinomycetes in high-temperature cultures, which were designated as heat-shock metabolites (HSMs). In this study, we investigated HSMs produced by thermotolerant Streptomyces sp. HR41. HPLC-UV analysis revealed the presence of a peak, designated HSM (1), with maximum UV absorptions at 204, 246, and 282 nm, in ethyl acetate extract of Streptomyces sp. HR41. NMR and MS analyses indicated that the planar structure of 1 was 3,4-dihydro-4-methyl-2(1H)-quinazolinone. The chiral-phase HPLC analysis and comparison of the optical rotation value with that of related compounds were performed to examine the stereochemistry of 1 at C4. Thus, 1 was estimated to be an enantiomeric mixture of (S)- and (R)-3,4-dihydro-4-methyl-2(1H)-quinazolinone (1a and 1b), with an approximate enantiomer ratio of S/R = 18 : 82. This is the first discovery of 1 as a natural product, and it was therefore designated (S)- and (R)-heasquinazolinone. The biological activity of 1a and 1b was evaluated using several bioassay systems. The compounds selectively suppressed the growth of HT29 cells in 3-dimensional (3D) culture, with 50% inhibitory concentrations of 19 and 30 µM, respectively, indicating no apparent cytotoxicity in 2D culture.

Pharmaceutical solid dosage forms necessitate long-term stability, which can be effectively achieved by removing excess residual water from the final products. To enhance the drying process in pharmaceutical manufacturing, we propose a new method: vacuum rotary kiln drying. This method allows for drying at low temperatures and imposes minimal mechanical restrictions on dosage forms. This report examines the drying of aspirin tablets and acetaminophen granules, aiming to improve the stability of moisture-sensitive drugs and apply the method to wet granulation processes. Aspirin tablets dried in a vacuum rotary kiln within a few hours showed no degradation, even after 3 months of storage. The physical properties of acetaminophen granules dried using this method and the tablets produced from them were comparable to those obtained using fluidized bed drying or tray drying. We conclude that vacuum rotary kiln drying is applicable to pharmaceutical manufacturing, with potential benefits including improved drug stability and reduced drying time.

Polyunsaturated fatty acids (PUFAs) are signaling molecules exhibiting diverse bioactivities. Due to their flexible nature, PUFAs can theoretically adopt an enormous number of conformations, and it is not easy to identify the biologically active conformation(s), so rational drug design targeting the corresponding receptors is difficult. Here, we established a method to characterize conformational similarity by combining the replica exchange molecular dynamics simulation with the 3-dimensional WHIM (Weighted Holistic Invariant Molecular) descriptor. Using this method, we explored the total conformational space of 6 PUFAs and identified their conformational preferences for binding to known proteins. We found that upon binding, a specific cluster of conformers from the solution state is populated, which can be termed as bioactive conformations. By comparing the dynamics of synthetic modulators with those of PUFAs, we found that these compounds can be regarded as rigid mimics of the bioactive conformations of PUFAs, though this perspective has not been previously described. This approach is expected to be helpful in designing new bioactive molecules.

Bone-seeking radiopharmaceuticals are essential for the early detection of bone metastases. In this study, we developed three Technetium-99m (^99mTc)-labeled oligopeptides composed of acidic amino acids and evaluated their bone-targeting ability. Hydrazinonicotinamide (HYNIC)-conjugated oligopeptides with five residues of aspartic acid (Asp), glutamic acid (Glu), or γ-carboxyglutamic acid (Gla) were synthesized and radiolabeled with ^99mTc using tricine and 3-acetylpyridine as co-ligands. Their hydroxyapatite binding, in vitro stability, biodistribution, and single-photon emission computed tomography (SPECT)/CT imaging in normal mice were evaluated. Among the three tracers, [^99mTc]Tc-HYNIC-(tricine)(AcP)-(dl-Gla)₅ ([^99mTc]3) showed the highest hydroxyapatite binding and bone uptake, with clear visualization in SPECT/CT. All compounds exhibited high radiochemical purity and in vivo stability. Oligopeptides containing Gla residues exhibited superior bone affinity and imaging performance, suggesting that Gla-based oligopeptides are promising scaffolds for the development of ^99mTc-labeled bone imaging agents.