Peptide nucleic acid (PNA) is a DNA analog, in which the sugar-phosphate backbone in DNA is replaced by poly[N-(2-aminoethyl)glycine]. Since its discovery in the early 1990s, PNA has been widely employed in chemistry, biochemistry, medicine, nanotechnology, and many other fields. This account surveys recent developments on the design of PNA derivatives and their applications. In the first part, PNAs for sequence-specific recognition of DNA and RNA (single-strands, double-strands, G-quadruplexes, i-motifs, and others) are comprehensively covered. Modifications of nucleobases and of the main chain effectively promote both the strength of binding and the selectivity of recognition. In the second half of this account, practical applications of PNA are presented. Structural restraints, induced by complex formation of PNA with DNA and RNA substrates, lead to selective transformation of target sites to desired structures. Applications to regulation of gene expression, gene editing, construction of sophisticated nanostructures, and others are also described. Advantages and disadvantages of PNAs, compared with other sequence-recognizing molecules hitherto reported, are discussed in terms of various physicochemical and biological features.

COVID-19 is currently spreading all over the world, and causing enormous damage to health, economies, and daily lives. In order to overcome this pandemic, huge amounts of work have been accomplished, and many papers published. However, most of these works are from medical institutes and/or hospitals, and the attempts to solve this tragedy by chemical approaches have been rather scarce. This account surveys chemical information on COVID-19 with special emphasis on molecular-level understanding. In the first part, the fundamentals of causative pathogen SARS-CoV-2 (structures of genome and proteins of this virus) are briefly described. Next, the molecular structure of the spike on the viral surface, the key component for the infection of human beings, is shown. Then, the binding mode of these spikes to the receptors on human cells (ACE2) is presented in detail, based on the structural data. The conformational change of spike proteins is critically important for the virus to enter human cells. Furthermore, the roles of mutation of SARS-CoV-2 in the promotion of pathogenicity are discussed primarily in terms of the spike/ACE2 interactions. Finally, the origins of unprecedentedly high pathogenicity of this virus are proposed. This account should help the readers to understand the current status of our chemical knowledge on COVID-19, promoting the research to attack the worst pandemic of the last 100 years.

Genetic code manipulation enables the ribosomal synthesis of peptide libraries bearing diverse nonproteinogenic amino acids, which can be applied to the discovery of bioactive peptides in combination with screening methodologies, such as mRNA display. Despite a tremendous number of successes in incorporation of l-α-amino acids with non-proteinogenic sidechains and N-methyl-l-α-amino acids into nascent peptide chains, d-, β-, and γ-amino acids have suffered from low translation efficiency. This obstacle has been hindering their integration into such peptide libraries. However, the use of engineered tRNAs, which can effectively recruit EF-Tu or/and EF-P, has recently made possible significant improvement of their incorporation efficiency into nascent peptides. This article comprehensively summarizes advances in such methodology and applications to the discovery of peptide ligands against target proteins of interest.

Ring-structured DNA and RNA exhibit a variety of unique features in chemistry, biology, medicine, material science, and so on, which cannot be accomplished by their non-cyclic counterparts. In this review, both naturally occurring DNA/RNA rings and artificially synthesized ones have been comprehensively covered, mainly to bridge these two growing fields. In the first part, the structures and functions of naturally occurring DNA/RNA rings (extrachromosomal circular DNA, circulating cell-free DNAs, cyclic RNAs, and others) are described. Their roles as biomarkers for disease diagnosis are especially noteworthy. The second part mainly presents recent methods to synthesize DNA/RNA rings selectively and efficiently from oligonucleotide fragments. DNA/RNA rings of desired sequences and sizes are successfully prepared in large amounts for versatile applications. Production of RNA rings in cells using autocatalytic transcripts is also described. Lastly, practical applications of DNA/RNA rings are briefly reviewed. Critical significance of the cooperation of these two areas for further developments, as well as strong potential for interdisciplinary studies, have been emphasized.

We here describe our various concepts and achievements for material science, which have been introduced through liquid-crystalline (LC) and polymer chemistry. They have resulted in the development of new classes of functional organic, polymer, and hybrid materials. Supramolecular LC complexes and polymers with well-defined structures were found to be built through complimentary hydrogen bonding between carboxylic acid and pyridine. Since then, a variety of intermolecular interactions such as hydrogen bonding, ionic interactions, ion-dipolar interactions, and halogen bonding were used for the formation of supramolecular liquid crystal organic materials and polymers. The nanosegregation in molecular assemblies in liquid crystals leads to the various 1D, 2D and 3D self-assembled nanostructures. These strategy and material designs lead to the development of new dynamically functional materials, which exhibit stimuli-responsive properties, photoluminescence, transport of charge, ions, and molecules, electro-optic properties, and templates. We also show new hybrid liquid crystals, biomineral-inspired nanorod and nanodisk liquid crystals. These nanomaterials form colloidal LC solutions, which exhibit stimuli-responsive properties.

Pristine π-extended aromatic compounds are attractive as organic functional materials including organic semiconductors, but are difficult to synthesize in pure form because of their low solubility in common organic solvents. The precursor approach is a very useful method to synthesize pure π-extended aromatic compounds that cannot be prepared via traditional organic synthesis in flasks. In this approach, pure precursors are first prepared; these precursors are then converted quantitatively to the target molecules via a retro-Diels–Alder reaction or Strating–Zwanenburg photodecarbonylation reaction. This approach has also been used for the on-surface synthesis of the large acenes, heptacene and nonacene, under ultra-high vacuum in order to investigate their electronic properties, and is useful for the control of the packing structure of organic semiconductors in solution–processed films. The charge carrier mobilities of organic photovoltaics and organic field effect transistors have been improved using the precursor approach in combination with substituent effects. This account focuses on the synthesis and morphological control of aromatic compounds using the precursor approach in our group in the last decade.

Microcystins are a class of toxins that are mainly produced by cyanobacteria and among them, microcystin-leucine arginine (microcystin-LR) is one of the most toxic and harmful of the fresh water toxins causing many accidents and threats to human health. The detection of microcystin-LR in drinking water and environmental water samples is therefore crucial. To date, methods such as high performance liquid chromatography, protein phosphatase inhibition assay, enzyme-linked immunosorbent assay, and Raman spectroscopy have been employed to monitor microcystin-LR levels. Although these techniques are precise and sensitive, they require expensive instrumentation, well-trained personnel and involve time-consuming processes meaning that their application is generally limited to well-resourced and centralized laboratory facilities. Among the emerging microcystin-LR detection methods, biosensors have received great attention because of their remarkable sensitivity, selectivity, and simplicity. In this review, we will discuss the current state-of-the-art microcystin-LR biosensing platforms, and evaluate the advantages and limitations of typical transduction technologies to identify the most efficient detection system for the potentially harmful cyanobacteria.

The advancements in the field of imaging and diagnostics have been benefitted by the concurrent expansion of molecular probes space to monitor the diverse biological targets and events. The misfolding and aggregation of amyloid β peptide as well as Tau protein generate toxic polymorphic species (referred to as alloforms in this article) which are formally designated as core AD biomarkers by National Institute on Aging and Alzheimer’s Association Research Framework (NIA-AA 2018). Positron emission tomography and magnetic resonance imaging, which are currently the efficient and sophisticated techniques in the clinical diagnosis, are incapable of detection and differentiation of various alloforms besides being not easily operable and affordable by the common people. As a consequence, fluorescence optical imaging has gained great impetus besides many recent technological advancements that have positioned its sensitivity at par with PET and MRI in addition to offering the possibility of alloform detection, rapid analyses and economic benefits to cater to a larger population. In addition, there exists an array of biomarkers or pathophysiological conditions that are known to aggravate the disease progression. This emphasises the importance of molecular tools and methods for the detection of various known as well as yet to be identified AD biomarkers. The molecular and hybrid tools intended for detection and imaging of biomarkers inside the AD brain must cross the blood brain barrier which is one of the persistent challenges for synthetic organic chemists and in this context various strategies are discussed. In this review, we have proposed multiplexed and multimodal analytical approach for the in vitro and in vivo detection and imaging of the core and indirect biomarkers in brain and bio-fluids such as cerebrospinal fluid (CSF) and blood among others to generate characteristic fingerprints to distinguish between healthy and AD patients with precision. Overall, this review offers critical discussions on design, properties, functions, advantages and limitations of the existing molecular probes besides providing current and future prospects for the development of novel diagnostic and theranostic tools for AD.

In contrast to zero-bandgap graphene, nanostructures of graphene, such as graphene quantum dots (GQDs) and graphene nanoribbons (GNRs) have open bandgaps due to the quantum confinement effect, and are thus highly interesting for semiconductor applications, for example in nanoelectronics and optoelectronics. While conventional methods cannot provide GQDs and GNRs with chemically precise structures, large polycyclic aromatic hydrocarbon (PAH) molecules can be regarded as atomically precise GQDs. Moreover, extension of the PAH synthesis can lead to GNRs with well-defined chemical structures. In this account, we summarize our recent achievements in our synthetic exploration of PAHs and GNRs with novel structures and properties. For example, we have developed new PAHs having zigzag edges, such as dibenzo[hi,st]ovalene derivatives with strong red luminescence and stimulated emission, which are promising for light-emitting devices and bioimaging applications. We have also accomplished a synthesis of magnetic GNRs through edge functionalization with organic radicals, which can be interesting for spintronic as well as quantum computing applications. Moreover, incorporation of zigzag edges in GNR structures, through on-surface syntheses under ultrahigh (UHV) vacuum conditions, allowed for significant modulations of the electronic structures of GNRs, leading to the emergence of topological quantum phases. On the other hand, we have also explored on-surface synthesis of GNRs without UHV, namely using a setup for chemical vapor deposition (CVD). Scalable fabrication of GNR films could thus be achieved on gold on mica substrates, which could be integrated into field-effect transistor devices. These results highlight the importance of developing novel PAHs and GNRs and their potentials for various applications, including quantum technologies, energy and optoelectronic devices, and bioimaging.

In the recent decades, separation technologies have been significantly furthered by the development of a variety of new separation media. Especially, carbon-based nanomaterials (CNMs), including graphene, carbon nanotubes, and fullerenes, have been applied for effective separations and sensitive detections in recent years. Here, the fundamental preparation protocols of new separation media consisting of CNMs and a great number of their applications summarize the fundamental preparation protocols of new separation media consisting of CNMs and a great number of their applications are summarized.

We have developed two novel approaches for the construction of artificial metalloenzymes showing either unique catalytic activities or substrate specificity. The first example is the use of a hollow cage of apo-ferritin as a reaction vessel for hydrogenation of olefins, Suzuki-Miyaura C-C coupling and phenylacetylene polymerization by employing Pd⁰ nano-clusters, Pd²⁺(η³-C₃H₅) complexes and Rh¹⁺(nbd) (nbd = norbornadiene) complexes introduced in the hollow cage, respectively. The second approach is the use of “decoy molecules” to change substrate specificity of P450s, allowing epoxidation and hydroxylation activities toward nonnative organic substrates in P450_SPα, P450_BSβ and P450BM3 without the mutation of any amino acid. Finally, the decoy strategy has been applied to an in vivo system of P450, i.e., the use of P450BM3 expressed in the whole cell of E. coli to oxidize benzene to phenol.

Carbon-carbon coupling reactions are one of the most important systems to be studied and the design of palladium based phosphine free catalysts is crucial. In this account, we present a summary of the work carried out by our research group on the design and synthesis of efficient palladium based phosphine free catalysts for the Heck and Suzuki coupling reactions of deactivated and sterically hindered substrates.

With the increasing knowledge about the diverse roles of RNAs within cells, much attention has been paid to the development of RNA-binding fluorescent probes for the study of RNA functions. Especially, the probes for double-stranded RNA (dsRNA) structures are highly useful given the importance of the secondary and tertiary RNA structures on their biological functions. This account describes our recent efforts to develop synthetic fluorescent probes based on peptide nucleic acids (PNAs) carrying fluorogenic cyanine dyes for targeting the overhang structures of dsRNAs with a view toward the analysis of the intracellular delivery process of small interfering RNAs. We also describe the design of triplex-forming PNA probes carrying cyanine dye base surrogates for the sequence-selective detection of dsRNAs.

Molecular probes are useful chemical tools that are widely applied in life science research, including in molecular biology and drug discovery. However, the preparation of molecular probes often requires considerable time and effort even if the synthesis is conducted by well-trained organic chemists. This is mostly due to the complex structure of the target molecules or their precursors, which typically contain sensitive functional moieties. Furthermore, the synthetic route to probes must frequently be modified from that of the original compounds because the functional moiety of the probe should be preferably introduced into the molecule at a late stage of the synthesis. To address these issues, we propose a new concept that we named a “molecular renovation strategy” that can expedite the synthesis of molecular probes. This approach involves direct transformation of the original bioactive compounds to the probe precursors, followed by the introduction of a functional moiety. This account describes our recent efforts to realize this concept, particularly made for expeditious preparation of imaging probes for positron emission tomography (PET) via transition metal-catalyzed borylation reactions via cleavage of stable chemical bonds and transition metal-mediated deborylative radiolabeling reactions with PET nuclides.

As part of our research over the past 20 years, we have designed sequence-specific DNA-binding ligands that are based on the chemical molecular recognition of bases in nucleic acids. The DNA minor groove-binding molecules, N-methylpyrrole (P), and N-methylimidazole (I) polyamides, have been developed to regulate the specific gene expression or high-order DNA structures and visualize specific DNA sequences in cells. The binding properties of PI polyamides were designed to target specific sequences for various chemical applications. The development of PI polyamides may be useful when applying the vast base sequence information obtained from recent genomic-level research.

Organotellurium chain transfer agents (CTAs) used for organotellurium-mediated radical polymerization (TERP) are highly photosensitive and generate radicals by carbon-tellurium bond homolysis upon absorbing UV-vis light at approximately 350–500 nm. The controlled radical polymerization of various vinyl monomers takes place in the presence of organotellurium CTAs under photoirradiation. The use of low-intensity light is important to attain structural control because of the need to maintain a low radical concentration. Photo-TERP not only preserves the synthetic advantages of TERP under thermal conditions, as exemplified by its high versatility in polymerizable monomer families, but also attains new benefits, including decreasing the amount of dead polymers, increasing the control of the macromolecular structure, lowering the polymerization temperature, and providing temporal control. In contrast, irradiation of a polymer prepared by TERP in the presence of dienes and styrenes with high-intensity light selectively gives the dimer via a polymer-end radical coupling reaction. Various symmetrical telechelic and mid-chain-functionalized polymers and ABA-triblock copolymers can be synthesized. Due to the mild conditions for both photo-TERP and the coupling reaction, unique macromolecular structures, and high structural control, these methods provide a new method in macromolecular engineering for fabricating functional polymer materials with improved and/or new functions.

Ultrasound has attracted much attention in recent years as an external stimulus capable of activating different types of nanomaterials for therapeutic application. One of the characteristics that makes ultrasound an especially appealing triggering stimulus for nanomedicine is its capacity to be non-invasively applied in a focused manner at deep regions of the body. Combining ultrasound with nanoparticles, different biological effects can be achieved. In this work, an overview of the four main types of inducible responses will be provided: inducing drug release, producing ultrasound-derived biological effects, modifying nanoparticle biodistribution and developing theranostic agents. Several examples of each one of these applications are presented here to illustrate the key concepts underlying recent developments in the discipline.

In the last several decades, 2-dimensional (2D) nanomaterials have been studied in various bio-fields such as drug delivery systems, diagnostic and imaging materials, etc. In particular, many investigations have been intensively conducted to explore 2D nanomaterials for drug delivery devices such as layered double salts (LDSs), layered rear-earth hydroxides (LRHs), and layered double hydroxides (LDHs) due to their low toxicity, high solubility in body fluid, high tumor targeting efficiency, large drug loading capacity, etc. However, only a few reports have been made to date on diagnostic and imaging effects on those 2D nanomaterials. In this review, therefore, an attempt is made to underline how important such 2D nanoparticles would be applicable for optical imaging, magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT), etc., and to discuss on their potential molecular imaging modalities for image-guided and precision therapy as well.

Rhodopsins, which are also called retinal proteins, are photoreceptive proteins. Their photoreactions have attracted many researchers in physics, chemistry and biology. In addition, they are now used as key tools in optogenetics. Although rhodopsin was originally named as a red-colored pigment for vision, the modern meaning of rhodopsin encompasses photoactive proteins containing a retinal chromophore in animals and microbes. Animal and microbial rhodopsins possess 11-cis and all-trans retinal, respectively, to capture light in seven transmembrane α-helices, and photoisomerizations into all-trans and 13-cis forms, respectively, initiate each function. Unlike animal rhodopsins, several kinds of microbial rhodopsins are able to transport ions in a passive or an active manner, and light-gated channels or light-driven pumps, respectively, are the main tools in optogenetics. In this article, historical aspects and recent advances of retinal protein research are reviewed. After general introduction of rhodopsins, the molecular mechanism of bacteriorodopsin, a light-driven H⁺ pump and the best studied microbial rhodopsin, is described. Then, molecular properties and several variants of channelrhodopsin, the light-gated ion channel, are introduced. As history has proven, understanding the molecular mechanism of microbial rhodopsins is a prerequisite for useful functional design of optogenetics tools in future.

The basic formula of Li-ion battery electrolytes (i.e., LiPF₆ and ethylene carbonate) has remained unchanged ever since commercialization in the early 1990s. However, toward advanced batteries with higher energy density and higher safety, a new electrolyte design that leads to better functions is required. Recently, various new functions have been discovered for highly concentrated electrolytes (over 3 mol dm⁻³ (M) vs. standard 1 M), which arises from their unique coordination states of ions and solvent molecules. Based on this achievement, the coordination states are increasingly recognized as key to further functionalizing battery electrolytes. This account introduces an electrolyte design based on the coordination states and provides future visions on rechargeable batteries that will be realized thereby.