Indocyanine green (ICG) derivatives having nucleophilic substituents were synthesized as pH-responsive near-infrared dyes. pH-responsive dyes 1-C with closed-ring structures smoothly internalized and converted to emissive open-ring structures 1-O in response to relatively low pHs in acidic intracellular compartments of HeLa cells.

Polymers containing pyrrolopyrrole aza-BODIPY (PPAB) and thiophene-bridged BODIPY dimers (TBD) having poly(ethylene glycol) (PEG) or PEGylated hyaluronic acid (HA) were prepared by facile conjugation approaches. Self-assemblies consisting of TBD-conjugated polymers more efficiently generated photoacoustic (PA) signals than PPAB–PEG conjugate upon irradiation with near-infrared pulsed laser light. Among dye-conjugated polymers examined, TBD-HA-PEG conjugates efficiently generated photoacoustic signals, 1.49–1.83 times stronger than that of commercially available indocyanine green (ICG). We found that the following two factors are essential to enhance PA signals from self-assemblies: (1) the formation of strongly interacting TBD aggregates and (2) enhancement of the elastic modulus of self-assemblies by conjugating TBDs with HA. TBD-conjugated HA derivatives circulated in blood vessels for a longer time (15.6 ± 4.9% injected dose (ID) in blood 24 h after injection) and more specifically accumulated in tumor tissues (17.8 ± 3.5% ID/g in tumor 24 h after injection) than ICG-conjugated HA derivatives, visualizing a tumor site more clearly. The cell uptake experiment of dye–HA conjugates indicates that ICG-conjugated polymers internalized into cells or merged with cell walls to emit strong fluorescence, while TBD-conjugated polymers were not internalized into cells. Because the disassembly of the TBD-conjugated HA derivatives is suppressed, aggregated TBDs emit weak fluorescence but efficiently generate strong PA signals in tumor tissues.

The reaction of oxime esters with a rhodium(I) precursor to form five-membered rhodacycles via N–O bond cleavage followed by C–H bond activation has been investigated by isolating these complexes. Kinetic studies on the formation of rhodacycles show that the reversible oxidative addition of the N–O bond in the oxime ester to RhCl(PPh3)3 occurs at room temperature. The E-isomer of the oxime ester was found to undergo rhodacycle formation faster than the Z-isomer, which suggests that the geometry of the oxime esters reflects the geometry of intermediates during C–H activation. The rhodacycle reacted with an alkyne to construct an isoquinoline ring in both stoichiometric and catalytic conditions, despite its basic stability in air, in moisture, and even during heating, which demonstrates the potential of the rhodacycle as an intermediate for further catalytic transformation of oxime esters.

Direct catalytic cyanation of organoboronic acids with cyanogen iodide has been achieved by using a copper–bipyridine catalyst system. The cyanation reaction is likely to occur through two catalytic cycles: copper(II)-catalyzed iodination of organoboronic acids and the following cyanidocopper(I)-mediated cyanation of organic iodides.

We have developed an indium-catalyzed [2 + 2] cycloaddition of allylsilanes to alkynones leading to selective cyclobutenone formation. The resulting cyclobutenones were readily converted to the oxidized products by Tamao–Fleming oxidation or the ring-opened products by an electrocyclic reaction.

Amphiphilic hyaluronic acid (HA) derivatives bearing hydrophobic indocyanine green dye derivatives and hydrophilic poly(ethylene glycol) were synthesized through the use of condensation and copper-catalyzed click cyclization reactions. The amphiphilic HA derivatives dissolved in water and formed self-assemblies in which the near-infrared dyes were tightly packed and arranged to form dimers or H-aggregates. By irradiating an aqueous solution of HA derivatives with near-infrared light, photoacoustic signals were detected along with fluorescence emission. Self-assemblies consisting of HA derivatives could smoothly accumulate in tumor tissues by passive tumor targeting. By utilizing HA derivatives as a contrast agent, tumor sites were clearly visualized by optical imaging as well as by photoacoustic tomography.

Three-component coupling reactions of 2-(cyanomethyl)phenol, aryl halides, and carbon monoxide (CO) in orthogonal–tandem catalysis were investigated. In the reactions, 2-(cyanomethyl)phenyl esters, which are produced through Pd(PPh3)4-catalyzed alkoxycarbonylation of aryl halides with 2-(cyanomethyl)phenol, undergo cycloisomerization in situ catalyzed by Pd(PCy3)2 as a co-catalyst to give 3-acyl-2-aminobenzofurans. Palladium species with homoleptic tertiary phosphines, such as Pd(PPh3)4 and Pd(PCy3)2, can catalyze the mechanistically distinct reactions in an orthogonal–tandem manner without interference. By switching the base used in this reaction, 3-acyl-2-(N-acylamino)benzofurans were obtained as major products instead of 3-acyl-2-aminobenzofurans. Given that 2-(cyanomethyl)phenols can be synthesized from commercially available salicylic acid derivatives in two steps, the present method thus provides facile access to synthetically useful 3-acyl-2-aminobenzofurans.

Electron-rich cycloparaphenyleneacetylenes as well as their twin “glasses-like” conjugates form stable complexes with fullerenes.

A copper-catalyzed reaction of terminal alkynes with cyanogen iodide (ICN) that produces alkynyl cyanides has been developed. The use of tetramethylpiperidine as a sterically congested base was successful in this reaction. Some control experiments revealed that the reaction involves the noncatalyzed formation of alkynyl iodides followed by copper-catalyzed cyanation of the iodides without the formation of copper(I) acetylide. This observation contrasts with what is normally observed in various copper-mediated reactions using terminal alkynes.

Gold(I)-catalysed tandem oxygen-transfer/cycloisomerisation reaction of 2-(2-propynyl)pyridine N-oxides provides an atom-economical route to indolizinone frameworks.

A gallium-catalysed, direct cyanation reaction of aromatic and heteroaromatic C–H bonds with cyanogen bromide was developed as a practical synthetic method for the preparation of aromatic nitriles.

An unprecedented nickel-catalysed disproportional reaction of 2,3-diaryl-2H-azirines forming azabutadienes and aromatic nitriles was discovered. This reaction involves the cleavage of two bonds of the 2H-azirine framework, which provides a novel type of transformation of 2H-azirines.

A novel palladium- and copper-catalyzed one-pot multicomponent synthesis of hetero α,α′-dimers of heterocycles via Sonogashira coupling and double cyclization cascade involving imine formation has been developed. This reaction cascade proceeded under mild conditions, providing a powerful synthetic tool for the assembly of π-conjugated systems with a combination of palladium-catalyzed post-direct C–H bond arylations.

Complexes of novel alkyne-chelating tridentate ligands bound to a rhodium atom were isolated and characterised. The present alkyne–rhodium complex underwent dimerisation simply by heating to afford the unprecedented cyclobutadiene dirhodium complex. It is also found that the ligands at the trans positions influence the π-coordination of alkynes.

Treatment of arylacetylenes and cyanogen bromide in ClCH2CH2Cl with a catalytic amount of GaCl3 afforded (Z)-β-bromoacrylonitriles with high regio- and stereoselectivity.

The reaction of carbonyl-ene-nitrile compounds with propargyl carboxylates in the presence of a catalytic amount of PtCl2 afforded the α-alkylidene-N-furylimines with high stereoselectivities.

A new type of structurally rigid BODIPY dye having spirofluorene moieties has been synthesized. These structurally constrained BODIPY dyes with spirofluorene moieties exhibit an intense bathochromic fluorescence. The solvent dependence of fluorescence ON/OFF switching of a BODIPY dye having an amino moiety was observed.

Treatment of 2-(cyanomethyl)phenyl esters with a catalytic amount of Pd(OAc)2, PCy3, and Zn afforded 3-acyl-2-aminobenzofuran derivatives in good to excellent yields, which can be used as building blocks for the synthesis of benzofuran fused heterocycles.

Water-soluble triblock copolymers consisting of hydrophobic−hydrophilic−dye segments were synthesized by ring-opening metathesis polymerization (ROMP) of norbornadiene monomers, copper-catalyzed click reaction, osmium-catalyzed dihydroxylation, and the following transformations. These polymers in aqueous conditions could form spherical assemblies, whose diameters were 50−60 nm by TEM measurement. From in vivo optical imaging experiments, the spherical assemblies of these copolymers could be efficiently accumulated in tumor cells. In addition, the spherical assemblies of water-soluble polymers accumulated in a tumor cell over two weeks.

An unprecedented nickel-catalysed disproportional reaction of 2,3-diaryl-2H-azirines forming azabutadienes and aromatic nitriles was discovered. This reaction involves the cleavage of two bonds of the 2H-azirine framework, which provides a novel type of transformation of 2H-azirines.

Gold(I)-catalysed tandem oxygen-transfer/cycloisomerisation reaction of 2-(2-propynyl)pyridine N-oxides provides an atom-economical route to indolizinone frameworks.

Electron-rich cycloparaphenyleneacetylenes as well as their twin “glasses-like” conjugates form stable complexes with fullerenes.

The reaction of carbonyl-ene-nitrile compounds with propargyl carboxylates in the presence of a catalytic amount of PtCl2 afforded the α-alkylidene-N-furylimines with high stereoselectivities.

Indocyanine green (ICG) derivatives having nucleophilic substituents were synthesized as pH-responsive near-infrared dyes. pH-responsive dyes 1-C with closed-ring structures smoothly internalized and converted to emissive open-ring structures 1-O in response to relatively low pHs in acidic intracellular compartments of HeLa cells.

Complexes of novel alkyne-chelating tridentate ligands bound to a rhodium atom were isolated and characterised. The present alkyne–rhodium complex underwent dimerisation simply by heating to afford the unprecedented cyclobutadiene dirhodium complex. It is also found that the ligands at the trans positions influence the π-coordination of alkynes.

Treatment of 2-(cyanomethyl)phenyl esters with a catalytic amount of Pd(OAc)2, PCy3, and Zn afforded 3-acyl-2-aminobenzofuran derivatives in good to excellent yields, which can be used as building blocks for the synthesis of benzofuran fused heterocycles.

Treatment of arylacetylenes and cyanogen bromide in ClCH2CH2Cl with a catalytic amount of GaCl3 afforded (Z)-β-bromoacrylonitriles with high regio- and stereoselectivity.

A gallium-catalysed, direct cyanation reaction of aromatic and heteroaromatic C–H bonds with cyanogen bromide was developed as a practical synthetic method for the preparation of aromatic nitriles.