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Three-dimensional (3D) representation of a tumor with respect to its size, shape, location, and boundaries is still a challenge in photoacoustic (PA) imaging using artificial contrast agents as probes. We carried out PA imaging of tumors in mice using 800RS-PMPC, which was obtained by coupling of 800RS, a near-infrared cyanine dye, with PMPC, a highly selective tumor-targeting methacrylate polymer having phosphorylcholine side chains, as a probe. The conjugate 800RS-PMPC forms compact nanoparticles (dDLS = 14.3 nm), retains the biocompatibility of the parent polymer (PMPC) and exhibits unprecedented PA performance. When applied to mice bearing a 6 × 3 × 3 mm3 tumor buried 6 mm beneath the skin, the probe 800RS-PMPC selectively accumulates in the tumor and emits PA signals that are strong enough to be unambiguously distinguished from noise signals of endogenous blood/hemoglobin. The PA image thus obtained under high-threshold conditions allows 3D characterization of the tumor in terms of its size, shape, location, and boundaries.

Exogenous nucleic acids showed low efficiency regarding cellular uptake and low stability in biological conditions; therefore, a number of techniques have been developed to improve their basic properties. One of the best solutions is the application of nanosized particles consisting of oligonucleotides that penetrate the cell membrane without any additives and exhibit high stability in cells. In this report, we employed a simple approach to address the basic properties of nanoparticles of oligonucleotides in biological systems. We prepared BODIPY-labeled oligonucleotides that carried an exclusive modification at the strand end. BODIPY shows high hydrophobicity and fluorescent emission; therefore, the oligonucleotides formed nanosized aggregates in aqueous solution and their behaviors in cells or tissues were easily tracked. Detailed experiments revealed that aggregate formation was indispensable for the high cellular uptake of the oligonucleotides via scavenger-receptor-mediated endocytosis. In addition, the aggregates provided an efficient gene regulation in living cells and tumor tissues transplanted into mice.

Molecular oxygen plays an important role in living organisms. Its concentration and fluctuation in cells or tissues are related to many diseases. Therefore, there is a need for molecular systems that can be used to detect and quantify oxygen levels in vitro and in vivo. In this study, we synthesized phosphonated mesoporous silica nanoparticles bearing ruthenium complexes in their pores (pM-Rus) and evaluated their photophysical and biological properties. The pM-Rus were highly soluble in water and showed robust phosphorescence under hypoxic conditions, while the addition of oxygen suppressed this emission. Cellular experiments revealed that pM-Rus with a size of 100 nm showed efficient cellular uptake to emit phosphorescence in hypoxic cells. In addition, pM-Rus have negligible toxicity to cells due to the blockage of direct contact between ruthenium complexes and intracellular biomolecules and the deactivation of singlet oxygen (1O2) generated by photoexcitation of ruthenium complexes before leaking out of the pores. Animal experiments confirmed that pM-Rus showed robust emission at hypoxic regions in mice. Thus, pM-Rus are promising oxygen probes for living systems.

Tumor-selective accumulation of gold nanorods (GNR) has been demonstrated for visualization of tumor hypoxia by photoacoustic imaging. We prepared GNRs with hypoxia-targeting nitroimidazole units (G-NI) on their surface. Biological experiments revealed that G-NI produced a strong photoacoustic signal in hypoxic tumor cells and tissues.

We synthesized mesoporous silica nanoparticles bearing ruthenium complexes in their pores (MSN-Ru) and characterized their photochemical properties. The ruthenium complexes that were immobilized in the pores showed oxygen-dependent phosphorescence, similar to the complexes that were not tethered to nanoparticles. Cellular imaging and in vivo experiments revealed that hypoxic cells and tissues could be visualized by monitoring the phosphorescence of MSN-Ru. Our most important finding was that the toxic effect of singlet oxygen (1O2), which was generated by excitation of the complexes, was effectively suppressed by the deactivation before leaking out from the pores. In addition, we observed a negligible toxic effect of the ruthenium complexes themselves due to the blockage of their direct interaction with intracellular biomolecules. Thus, MSN-Ru is a promising molecular probe of oxygen levels in living cells and tissues.

Homogeneous Sc(OTf)3 used in nitromethane showed excellent catalytic activity for the direct allylation reactions of general alcohols including benzylic, propargylic, allylic, and some aliphatic alcohols with allyltrimethylsilane under mild and neutral reaction conditions. Metal-free β-silyl-substituted carbocations are intermediates generated by the highly oxophilic Sc(OTf)3-assisted rapid removal of a hydroxyl group in alcohols, which is supported by the result that allylation of (R)-1-(naphthalen-2-yl)ethan-1-ol with allytrimethylsilanes using the Sc(OTf)3 catalyst combined with (R)- or (S)-[1,1′-binaphthalene]-2,2′-diol ligands gave only racemic 2-(pent-4-en-2-yl)naphthalene in quantitative yield. The present study resolves the argument about the uncertain catalytic activity of Sc(OTf)3.

Molecular oxygen in living cells is distributed and consumed inhomogeneously, depending on the activity of each organelle. Therefore, tractable methods that can be used to monitor the oxygen status in each organelle are needed to understand cellular function. Here we report the design of a new oxygen-sensing probe for use in the cell nucleus. We prepared "Ru-Hoechsts", each consisting of a phosphorescent ruthenium complex linked to a Hoechst 33258 moiety, and characterized their properties as oxygen sensors. The Hoechst unit shows strong DNA-binding properties in the nucleus, and the ruthenium complex shows oxygen-dependent phosphorescence. Thus, Ru-Hoechsts accumulated in the cell nucleus and showed oxygen-dependent signals that could be monitored. Of the Ru-Hoechsts prepared in this study, Ru-Hoechst b, in which the ruthenium complex and the Hoechst unit were linked through a hexyl chain, showed the most suitable properties for monitoring the oxygen status. Ru-Hoechsts are probes with high potential for visualizing oxygen fluctuations in the nucleus.

Ru3(CO)12-catalyzed divergent ring-opening coupling reactions of a cyclopropenone with methyl acrylate (an electron-deficient alkene) are developed. Under an argon atmosphere, a decarbonylative linear codimer is obtained, while cyclopentenones are obtained under carbon monoxide (20 atm) without decarbonylation. While ruthenium complexes show no catalytic activity for the ring-opening cocyclization of cyclopropenones with ethylene (20 atm) or bicyclo[2.2.1]hept-2-ene (2-norbornene), rhodium complexes, especially [RhCl(η4-1,5-cod)]2, show high catalytic activity for the desired cocyclization reactions to give the corresponding cyclopentenones in high yields and selectivities. In addition, [RhCl(η4-1,5-cod)]2 realizes the catalytic ring-opening co­cyclization of cyclopropenones with internal alkynes to give the corresponding cyclopentadienones. In all these reactions, ruthena- or rhodacyclobutenones are considered to be key intermediates, generated by strain-driven oxidative addition of a cyclopropenone C–C bond to an ­active ruthenium or rhodium species.

Magnetic resonance imaging (MRI) has become a prominent non- or low-invasive imaging technique, providing high-resolution, three-dimensional images as well as physiological information about tissues. Low-molecular-weight Gd-MRI contrast agents (CAs), such as Gd-DTPA (DTPA: diethylenetriaminepentaacetic acid), are commonly used in the clinical diagnosis, while macromolecular Gd-MRI CAs have several advantages over low-molecular-weight Gd-MRI CAs, which help minimize the dose of CAs and the risk of side effects. Accordingly, we developed chiral dendrimer Gd-MRI CAs, which showed high r1 values. The association constant values (Ka ) of S-isomeric dendrimer CAs to bovine serum albumin (BSA) were higher than those of R-isomeric dendrimer CAs. Besides, based on a totally new concept, we developed 13 C/15 N-enriched multiple-resonance NMR/MRI probes, which realized highly selective observation of the probes and analysis of metabolic reactions of interest. This account summarizes our recent study on developing both chiral dendrimer Gd-MRI CAs, and self-traceable 13 C/15 N-enriched phosphorylcholine polymer probes for early detection of tumors.

We designed a chemiluminescent system using nanoparticles. We prepared mesoporous nanoparticles bearing naphthalene endoperoxide as a singlet oxygen generator in the pore and vinyl phenol derivative as an emission unit. The combination of these functional molecules gave highly efficient and bright chemiluminescence through the formation of a 1,2-dioxetane intermediate.

The synthesis of new functional organic molecules that cannot be obtained by a simple combination of conventional synthetic methods is a challenging subject in organic, organometallic, and industrial chemistry as well as in atom-efficient and environmental organic synthesis. Among the various possibilities that have been considered, the catalytic cleavage and reconstruction of the C–C bond has opened the door to a new branch of synthetic organic chemistry. This microreview summarizes progress on the ruthenium- and rhodium-catalyzed strain-driven cleavage of the C–C bond, the methods of which were mostly developed by the author. The direct oxidative addition of 2,5-norbornadienes, cyclopropenones, cyclobutenones, and cyclobutenediones, and to catalytically active metal species followed by the construction of the C–C bond has been used for the preparation of new organic molecules.

In an attempt to monitor μm-level trace constituents, we applied here (1)H-{(13)C-(15)N} triple-resonance nuclear magnetic resonance (NMR) to (13)C/(15)N-enriched l-Dopa as the inevitable precursor of the neurotransmitter dopamine in the brain. The perfect selectivity (to render endogenous components silent) and μm-level sensitivity (700 MHz spectrometer equipped with a cryogenic probe) of triple-resonance allowed the unambiguous and quantitative metabolic and pharmacokinetic analyses of administered l-Dopa/dopamine in the brain and liver of mice. The level of dopamine generated in the brain (within the range 7-76 μm, which covers the typical stimulated level of ∼30 μm) could be clearly monitored ex vivo, but was slightly short of the detection limit of a 7 T MR machine for small animals. This work suggests that μm-level trace constituents are potential targets of ex vivo monitoring as long as they contain N atom(s) and their appropriate (13)C/(15)N-enrichment is synthetically accessible.

Novel chiral dendrimer-triamine-coordinated Gd complexes with polyaminoalcohol end groups were synthesized and shown to have longitudinal relaxivity (r1) values 5 times higher than that of clinically used Gd-DTPA. The affinities of Gd-4a and Gd-4b for bovine serum albumin (BSA), respectively, were estimated by a quartz crystal microbalance (QCM) measurement. The amino groups of the dendrimer were then conjugated with PEG. This conjugation with PEG strongly affected its ability to attenuate signals in T1-weighted MRI.

Magnetic resonance imaging (MRI) has become a prominent non- or low-invasive imaging technique, providing high-resolution, three-dimensional images as well as physiological information about tissues. Low-molecular-weight Gd-MRI contrast agents (CAs), such as Gd-DTPA (DTPA: diethylenetriaminepentaacetic acid), are commonly used in the clinical diagnosis, while macromolecular Gd-MRI CAs have several advantages over low-molecular-weight Gd-MRI CAs, which help minimize the dose of CAs and the risk of side effects. Accordingly, we developed chiral dendrimer Gd-MRI CAs, which showed high r

The synthesis of new functional organic molecules that cannot be obtained by a simple combination of conventional synthetic methods is a challenging subject in organic, organometallic, and industrial chemistry as well as in atom-efficient and environmental organic synthesis. Among the various possibilities that have been considered, the catalytic cleavage and reconstruction of the C–C bond has opened the door to a new branch of synthetic organic chemistry. This microreview summarizes progress on the ruthenium- and rhodium-catalyzed strain-driven cleavage of the C–C bond, the methods of which were mostly developed by the author. The direct oxidative addition of 2,5-norbornadienes, cyclopropenones, cyclobutenones, and cyclobutenediones, and to catalytically active metal species followed by the construction of the C–C bond has been used for the preparation of new organic molecules.

A (13)C-enriched phosphorylcholine polymer ((13)C-PMPC) as a self-traceable MR (magnetic resonance) tag was conjugated with a fragment (scFv) of Herceptin, a clinical antibody against antigen Her2. When injected in model mice bearing Her2(+) (gastric) and Her2(-) (pancreatic) tumors, the antibody-tag conjugate (13)C-PMPC-scFv selectively accumulated in the Her2(+) tumor with a rapid build-up/decay (accumulation/clearance) profile and, with the use of the (1)H-(13)C double-resonance (heteronuclear correlation) technique, the Her2(+) gastric tumor was clearly MR imaged.