Reversible Modulation of the Electronic and Spatial Environment around Ni(0) Centers Bearing Multifunctional Carbene Ligands with Triarylaluminum.

Designing and modulating the electronic and spatial environments surrounding metal centers is a crucial issue in a wide range of chemistry fields that use organometallic compounds. Herein, we demonstrate a Lewis-acid-mediated reversible expansion, contraction, and transformation of the spatial environment surrounding nickel(0) centers that bear N-phosphine oxide-substituted N-heterocyclic carbenes (henceforth referred to as (S)PoxIms). Reaction between tetrahedral (syn-κ-C,O-(S)PoxIm)Ni(CO)2 and Al(C6F5)3 smoothly afforded heterobimetallic Ni/Al species such as trigonal-planar {κ-C-Ni(CO)2}(µ-anti-(S)PoxIm){κ-O-Al(C6F5)3} via a complexation-induced rotation of the N-phosphine oxide moieties, while the addition of 4-dimethylaminopyridine resulted in the quantitative regeneration of the former Ni complexes. The corresponding interconversion also occurred between (SPoxIm)Ni(η2:η2-diphenyldivinylsilane) and {κ-C-Ni(η2:η2-diene)}(µ-anti-SPoxIm){κ-O-Al(C6F5)3} via the coordination and dissociation of Al(C6F5)3. The shape and size of the space around the Ni(0) center was drastically changed through this Lewis-acid-mediated interconversion. Moreover, the multinuclear NMR, IR, and XAS analyses of the aforementioned carbonyl complexes clarified the details of the changes in the electronic states on the Ni centers; i.e., the electron delocalization was effectively enhanced among the Ni atom and CO ligands in the heterobimetallic Ni/Al species. The results presented in this work thus provide a strategy for reversibly modulating both the electronic and spatial environment of organometallic complexes, in addition to the well-accepted Lewis-base-mediated ligand-substitution methods.

Acceleration Effect of Bowl-Shaped Structure in Aerobic Oxidation Reaction: Synthesis of Homosumanene ortho-Quinone and Azaacene-Fused Homosumanenes.

An oxidation reaction of hydroxyhomosumanene on silica gel providing homosumanene ortho-quinone and its synthetic application for azaacene-fused homosumanenes is described. Hydroxyhomosumanene is photochemically oxidized by air, when it is coated on silica gel; this aerobic oxidation proceeds faster than that of planar analogues. The difference of such reactivity was attributed to the unusual keto-enol tautomerization due to structural difference between planar and curved π-system. The homosumanene ortho-quinone was used in the synthesis of several azaacene-fused homosumanenes, azaacenohomosumanenes. X-ray diffraction analysis of the single crystals revealed their columnar stacking structures due to the interactions between each bowl. Azaacenohomosumanenes exhibited high electron affinity due to the combination of buckybowl and electron-deficient azaacene moieties.

Room-Temperature Reversible Chemisorption of Carbon Monoxide on Nickel(0) Complexes.

Chemisorption on organometallic-based adsorbents is crucial for the controlled separation and long-term storage of gaseous molecules. The formation of covalent bonds between the metal centers in the adsorbents and the targeted gases affects the desorption efficiency, especially when the oxidation state of the metal is low. Herein, we report a pressure-responsive nickel(0)-based system that is able to reversibly chemisorb carbon monoxide (CO) at room temperature. The use of N-heterocyclic carbene ligands with hemi-labile N-phosphine oxide substituents facilitates both the adsorption and desorption of CO on nickel(0) via ligand substitution. Ionic liquids were used as the reaction medium to enhance the desorption rate and establish a reusable system. These results showcase a way for the sustainable chemisorption of CO using a zero-valent transition-metal complex.

Synthesis of the C70 Fragment Buckybowl, Homosumanene, and Heterahomosumanenes via Ring-Expansion Reactions from Sumanenone.

Bowl-shaped aromatic molecules, buckybowls, are attractive molecules because of the unique properties derived from their curved-π scaffolds. Doping heteroatoms into buckybowl frameworks is a powerful method to change their structural and electronical properties. Herein, we report the synthesis of C70 fragment buckybowl, homosumanene, and heterahomosumanenes having a lactone moiety and a lactam moiety via three ring-expansion reactions using sumanenone as a common intermediate. X-ray diffraction analysis of the single crystals reveals their columnar packing structure with a shallow bowl-depth. The lactam moiety is readily derivatized to give azahomosumanene derivatives, nitrogen-doped analogues of homosumanene possessing a pyridine ring at the peripheral carbon. The synthetic application of the α-phenyl azahomosumanene as a cyclometalating ligand with platinum also revealed its utility for preparing a metal complex bearing a buckybowl ligand.

Synthesis of Benzoisoselenazolones via Rh(III)-Catalyzed Direct Annulative Selenation by Using Elemental Selenium.

Isoselenazolone derivatives have attracted significant research interest because of their potent therapeutic activities and indispensable applications in organic synthesis. Efficient construction of functionalized isoselenazolone scaffolds is still challenging, and thus new synthetic approaches with improved operational simplicity have been of particular interest. In this manuscript, we introduce a rhodium-catalyzed direct selenium annulation by using stable and tractable elemental selenium. A series of benzamides as well as acrylamides were successfully coupled with selenium under mild reaction conditions, and the obtained isoselenazolones could be pivotal synthetic precursors for several organoselenium compounds. Based on the designed control experiments and X-ray absorption spectroscopy measurements, we propose an unprecedented selenation mechanism involving a highly electrophilic Se(IV) species as the reactive selenium donor. The reaction mechanism was further verified by a computational study.

Convergent Synthesis of Fluoroalkenes Using a Dual-Reactive Unit.

Fluoroalkenes have shown importance as a metabolically stable isostere of amide compounds. To expedite the synthesis of diverse fluoroalkenes, we have developed a dual-reactive C2-unit, (Z)-1-boryl-1-fluoro-2-tosyloxyethene, containing nucleophilic and electrophilic moieties. Consecutive palladium-catalyzed cross-coupling reactions of this unit with aryl bromides and aryl boronic acids allow for the convergent synthesis of diverse trans-1,2-diaryl-substituted fluoroethenes in a chemoselective and stereoretentive manner.

Practical Synthesis of [18F]Pitavastatin and Evaluation of Hepatobiliary Transport Activity in Rats by Positron Emission Tomography.

We developed a practical synthetic method for fluorine-18 (18F)-labeled pitavastatin ([18F]PTV) as a positron emission tomography (PET) tracer to assess hepatobiliary transporter activity and conducted a PET scan as a preclinical study for proof-of-concept in rats. This method is a one-pot synthesis involving aromatic 18F-fluorination of an arylboronic acid ester followed by deprotection under acidic conditions, which can be reproduced in general clinical sites equipped with a standard radiolabeling system due to the simplified procedure. PET imaging confirmed that intravenously administered [18F]PTV was rapidly accumulated in the liver and gradually transferred into the intestinal lumen through the bile duct. Radiometabolite analysis showed that [18F]PTV was metabolically stable, and 80% of the injected dose was detected as the unchanged form in both blood and bile. We applied integration plot analysis to assess tissue uptake clearance (CLuptake, liver and CLuptake, kidney) and canalicular efflux clearance (CLint, bile), and examined the effects of inhibitors on membrane transport. Treatment with rifampicin, an organic anion transporting polypeptide inhibitor, significantly reduced CLuptake, liver and CLuptake, kidney to 44% and 64% of control, respectively. In contrast, Ko143, a breast cancer resistance protein inhibitor, did not affect CLuptake, liver but significantly reduced CLint, bile to 39% of control without change in [18F]PTV blood concentration. In addition, we found decreased CLuptake, liver and increased CLint, bile in Eisai hyperbilirubinemic rats in response to altered expression levels of transporters. We expect that [18F]PTV can be translated into clinical application, as our synthetic method does not need special apparatus in the radiolabeling system and PET scan with [18F]PTV can quantitatively evaluate transporter activity in vivo.

Copper-Catalyzed Regioselective Monodefluoroborylation of Polyfluoroalkenes en Route to Diverse Fluoroalkenes.

Monodefluoroborylation of polyfluoroalkenes has been achieved in a regioselective manner under mild conditions via copper catalysis. The method has shown an extremely broad scope of substrates, including (difluorovinyl)arenes, tetrafluoroethylene (TFE), (trifluorovinyl)arenes, and trifluoromethylated monofluoroalkenes. The choice of boron source was important for the efficient transformation of (difluorovinyl)arenes; (Bpin)2 was suitable for substrates with an electron-deficient aryl group and (Bnep)2 for those with an electron-rich aryl group. Derivatization of the (fluoroalkenyl)boronic acid esters to the corresponding potassium trifluoroborate salts has rendered the products easily isolable, which greatly improved the synthetic practicality of the monodefluoroborylation reaction. Stoichiometric experiments indicate that the fate of the regioselectivity depends on the mode of ß-fluorine elimination, which depends on the substrate. Further transformation of the boryl group has allowed facile preparation of fluoroalkene derivatives as exemplified by the synthesis of a fluoroalkene mimic of atorvastatin, which potently inhibited the enzyme activity of HMG-CoA reductase.

Rhodium-Catalyzed Decarbonylative Borylation of Aromatic Thioesters for Facile Diversification of Aromatic Carboxylic Acids.

Transformation of aromatic thioesters into arylboronic esters was achieved efficiently using a rhodium catalyst. The broad functional-group tolerance and mild conditions of the method have allowed for the two-step decarboxylative borylation of a wide range of aromatic carboxylic acids, including commercially available drugs.

Enantioselective approach to polycyclic polyprenylated acylphloroglucinols via catalytic asymmetric intramolecular cyclopropanation.

The formal enantioselective total synthesis of nemorosone, garsubellin A, clusianone, and hyperforin is described. The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of an α-diazo ketone, a common synthetic intermediate for the above four polycyclic polyprenylated acylphloroglucinols previously reported by us, exhibited low enantioselectivity. However, CAIMCP of the corresponding α-diazo ß-keto sulfone afforded the desired product in 79% yield with 84% ee. Investigation of the CAIMCP of the α-diazo ß-keto sulfone demonstrated the formation of a rearrangement product in the presence of molecular sieves 4 Å, whereas, in the presence of H2O, the byproduct derived from ring-opening of the desired cyclopropane was observed. X-ray crystallographic analysis suggested that the above two products are derived from the same chiral intermediate. The product derived from ring-opening of the cyclopropane was successfully transformed to the respective synthetic intermediates for the total syntheses of nemorosone, garsubellin A, clusianone, and hyperforin, which had previously been reported by us.

Strain-induced carbon-carbon bond cleavage of bowl-shaped sumanenone.

This study details a highly effective ring-opening reaction that involves acid-mediated carbon-carbon bond cleavage of the buckybowl, sumanenone. The reaction of the bowl-shaped sumanenone with AcOH and TfOH results in the formation of a planar carboxylic acid. The examination of reactivity in comparison to planar analogues, along with theoretical calculations, suggests that the release of curved strain is a crucial factor for the success of this reaction.

Dehydrogenative oxidation of hydrosilanes using gold nanoparticle deposited on citric acid-modified fibrillated cellulose: unveiling the role of molecular oxygen.

Efficient and environmentally friendly synthesis of silanols is a crucial issue across the broad fields of academic and industrial chemistry. Herein, we describe the dehydrogenative oxidation of hydrosilane using a gold nanoparticle catalyst supported by fibrillated citric acid-modified cellulose (F-CAC). Au:F-CAC catalysts with various particle sizes (1.7 nm, 4.9 nm, and 7.7 nm) were prepared using the trans-deposition method, a technique previously reported by our group. These catalysts exhibited significant catalytic activity to produce silanols with high turnover frequency (TOF) of up to 7028 h-1. Recycling experiments and transmission electron microscopy (TEM) observation represented the high durability of Au:F-CAC under the reaction conditions, allowing kinetic studies on size dependency. Mechanistic studies were conducted, including isotope labelling experiments, kinetics, and various spectroscopies. Notably, the near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) of the model catalyst (Au:PVP) revealed the formation of catalytically active cationic Au sites on the surface through the adsorption of molecular oxygen, providing a new insight into the reaction mechanism.

Thermodynamic Differentiation of the Two Sides of Azabuckybowl through Complexation with Square Planar Platinum(II).

The precise control of the two faces, concave/convex faces, is an attractive challenge to realizing novel dynamic molecular systems. Herein, we report the synthesis, X-ray crystal structure, and bowl-to-bowl inversion behavior of a platinum complex with azabuckybowl as a monodentate ligand. X-ray crystallography revealed that the azabuckybowl is orthogonally coordinated to the plane containing the Pt center and other ligands. One and two-dimensional NMR studies have also confirmed that this complex was observed as mixtures of two isomers, although the isomeric ratio was highly biased. Theoretical calculations indicate that the difference in thermodynamic stability of these isomers is due to the direction of the concave/convex face of an azabuckybowl ligand.

Derivatization of sumanenetrione through Lewis acid-mediated Suzuki-Miyaura coupling and an unprecedented ring opening.

A series of sumanenetrione derivatives were synthesized through Lewis acid-mediated Suzuki-Miyaura cross-coupling. Their optical properties reflected the significantly strong electron-accepting ability of sumanenetrione. The bowl strain of the 2-hydroxyphenyl derivative brought the ring-opening response adjacent to the substituent even at room temperature without any activation, which generally requires harsh conditions.

Dihydroxyacetone production by glycerol oxidation under moderate condition using Pt loaded on La1-xBixOF solids.

Pt/La1-xBixOF/SBA-16 (SBA-16: Santa Barbara Amorphous no. 16) catalysts were prepared to produce dihydroxyacetone (DHA) from glycerol under moderate conditions. By using 7 wt% Pt/16 wt% La0.95Bi0.05OF/SBA-16, the DHA yield reached up to 78.4% (glycerol conversion: 100%) after reacting for 6 h at 30 °C in an atmospheric open-air system.

Ultra-Rapid and Specific Gelation of Collagen Molecules for Transparent and Tough Gels by Transition Metal Complexation.

Collagen is the most abundant protein in the human body and one of the main components of stromal tissues in tumors which have a high elastic modulus of over 50 kPa. Although collagen has been widely used as a cell culture scaffold for cancer cells, there have been limitations when attempting to fabricate a tough collagen gel with cells like a cancer stroma. Here, rapid gelation of a collagen solution within a few minutes by transition metal complexation is demonstrated. Type I collagen solution at neutral pH shows rapid gelation with a transparency of 81% and a high modulus of 1,781 kPa by mixing with K2 PtCl4 solution within 3 min. Other transition metal ions also show the same rapid gelation, but not basic metal ions. Interestingly, although type I to IV collagen molecules show rapid gelation, other extracellular matrices  do not exhibit this phenomenon. Live imaging of colon cancer organoids in 3D culture indicates a collective migration property with modulating high elastic modulus, suggesting activation for metastasis progress. This technology will be useful as a new class of 3D culture for cells and organoids due to its facility for deep-live observation and mechanical stiffness adjustment.

Intramolecular hydroamination catalysed by gold nanoparticles deposited on fibrillated cellulose.

Gold nanoparticles stabilised by fibrillated citric acid-modified cellulose (Au:F-CAC) catalyse the intramolecular cycloamination of amines to unactivated alkenes under an aerobic atmosphere to afford pyrrolidine derivatives. Only 0.2 mol% of Au loading is required to complete the reaction. The high sensitivity of the Au:F-CAC catalyst to the substitution pattern of alkenes allows a unique chemoselective cycloamination, affording new compounds.

Clinical evaluation of [18F]pitavastatin for quantitative analysis of hepatobiliary transporter activity.

It is widely accepted that uptake and efflux transporters on clearance organs play crucial roles in drug disposition. Although in vitro transporter assay system can identify the intrinsic properties of the target transporters, it is not so easy to precisely predict in vivo pharmacokinetic parameters from in vitro data. Positron emission tomography (PET) imaging is a useful tool to directly assess the activity of drug transporters in humans. We recently developed a practical synthetic method for fluorine-18-labeled pitavastatin ([18F]PTV) as a PET probe for quantitative evaluation of hepatobiliary transport. In the present study, we conducted clinical PET imaging with [18F]PTV and compared the pharmacokinetic properties of the probe for healthy subjects with or without rifampicin pretreatment. Rifampicin pretreatment significantly suppressed the hepatic maximum concentration and biliary excretion of the probe to 52% and 34% of the control values, respectively. Rifampicin treatment markedly decreased hepatic uptake clearance (21% of the control), and moderately canalicular efflux clearance with regard to hepatic concentration (52% of the control). These results demonstrate that [18F]PTV is a useful probe for clinical investigation of the activities of hepatobiliary uptake/efflux transporters in humans.

Volcano-type correlation between particle size and catalytic activity on hydrodechlorination catalyzed by AuPd nanoalloy.

Although changing the size of metal nanoparticles (NPs) is a reasonable way to tune and/or enhance their catalytic activity, size-selective preparation of NPs possessing random-alloy morphology has been challenging because of the differences in the ionization potential of each metal ion. This study demonstrates a time-controlled aggregation-stabilization method for the size-selective preparation of random alloy NPs composed of Au and Pd, which are stabilized by poly(N-vinyl-2-pyrrolidone) (PVP). By adjusting the mixing time in the presence of a small amount of PVP, aggregation was induced to produce AuPd:PVP with sizes ranging between 1.2 and 8.2 nm at approximately 1 nm intervals. Transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and extended X-ray absorption fine structure (EXAFS) analyses indicated the formation of various sizes of AuPd nanoalloys, and size-dependent catalytic activity was observed when hydrodechlorination of 4-chloroanisole was performed using 2-propanol as a reducing agent. AuPd:PVP with a size of 3.1 nm exhibited the highest catalytic activity. A comparison of the absorption edges of X-ray absorption near edge structure (XANES) spectra suggested that the electronic state of the Au and Pd species correlated with their catalytic activity, presumably affecting the rate-determining step.

Synthesis and Pyrolysis of Fullerenol-stabilized Pt Nanocolloids as a unique Approach to Pt-doped Carbon.

An aqueous colloidal dispersion of Pt nanoparticles (NPs) stabilized by fullerenol C60 (OH)12 (Pt:C60 (OH)12 ) was successfully synthesized via liquid-phase chemical reduction. The subsequent pyrolysis of Pt:C60 (OH)12 at different temperatures was conducted to afford Pt-doped carbon with different chemical compositions (Pt:C60n ). X-ray absorption spectroscopy (XAS) and Infrared (IR) absorption spectroscopy and thermogravimetric measurements revealed that the thus-prepared nanocomposite consists of Pt NPs and high valent Pt-C60 (OH)12 complex. One distinct feature of C60 (OH)12 matrix as catalyst support is the suppression of size growth of Pt NPs during the pyrolysis up to 300 °C. Electrochemical experiments using cyclic voltammetry (CV) and linear sweep voltammetry (LSV) were performed to find that Pt:C60300 (pyrolyzed at 300 °C) exhibited higher activity than others, that was attributed to the π-extended feature of the as-obtained carbon.