The scope, chemoselectivity, and utility of the click-like tyrosine labeling reaction with 4-phenyl-3H-1,2,4-triazoline-3,5(4H)-diones (PTADs) is reported. To study the utility and chemoselectivity of PTAD derivatives in peptide and protein chemistry, we synthesized PTAD derivatives possessing azide, alkyne, and ketone groups and studied their reactions with amino acid derivatives and peptides of increasing complexity. With proteins we studied the compatibility of the tyrosine click reaction with cysteine and lysine-targeted labeling approaches and demonstrate that chemoselective tri-functionalization of proteins is readily achieved. In particular cases, we noted PTAD decomposition resulted in formation of a putative isocyanate by-product that was promiscuous in labeling. This side reaction product, however, was readily scavenged by the addition of a small amount of 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris) to the reaction medium. To study the potential of the tyrosine click reaction to introduce poly(ethylene) glycol chains onto proteins (PEGylation), we demonstrate that this novel reagent provides for the selective PEGylation of chymotrypsinogen whereas traditional succinimide-based PEGylation targeting lysine residues provided a more diverse range of PEGylated products. Finally, we applied the tyrosine click reaction to create a novel antibody drug conjugate. For this purpose, we synthesized a PTAD derivative linked to the HIV entry inhibitor aplaviroc. Labeling of the antibody trastuzumab with this reagent provided a labeled antibody conjugate that demonstrated potent HIV-1 neutralization activity demonstrating the potential of this reaction in creating protein conjugates with small molecules. The tyrosine click linkage demonstrated stability to extremes of pH, temperature and exposure to human blood plasma indicating that this linkage is significantly more robust than maleimide-type linkages that are commonly employed in bioconjugations. These studies support the broad utility of this reaction in the chemoselective modification of small molecules, peptides, and proteins under mild aqueous conditions over a broad pH range using a wide variety of biologically acceptable buffers such as phosphate buffered saline (PBS) and 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris) buffers as well as others and mixed buffered compositions.

Structure, optical absorption and photoluminescence (PL) properties of SiOx films subjected to thermal annealing at 750–1100 °C are investigated. Si crystallites with a few nanometers in size are observed in the SiO1.3 and SiO1.65 films annealed at 1100 °C. Threshold energies in optical absorption of the Si nanocrystallites are higher than that for bulk Si, suggesting a contribution from quantum confinement effects. The PL spectrum shows a remarkable increase in intensity after annealing at temperatures above 1000 °C. This PL behavior is closely related to the formation of Si nanocrystallites by the annealing. The PL peak energy of the annealed films shifts to higher energy with decreasing crystallite size but does not follow the blueshift for the absorption threshold energy. These results suggest that a localized state contributes to the PL mechanism. The SiO1.8 film annealed at 1100 °C, which contains no Si crystallites, exhibits an intense PL similar to the annealed SiO1.3 and SiO1.65 films. It is implied that noncrystalline Si nanoparticles are formed in the SiO1.8 film under high-temperature annealing.

A thiourea-catalyzed asymmetric Michael addition of activated methylene compounds to alpha,beta-unsaturated imides derived from 2-pyrrolidinone and 2-methoxybenzamide has been developed. In the case of 2-pyrrolidinone derivatives, the reaction with malononitrile proceeded in toluene with high enantioselectivity, providing the Michael adducts in good yields. However, the nucleophiles that could be used for this reaction were limited to malononitrile due to poor reactivity of the substrate. Further examination revealed that N-alkenoyl-2-methoxybenzamide was the best substrate among the corresponding benzamide derivatives bearing different substituents on the aromatic ring. Indeed, several activated methylene compounds such as malononitrile, methyl alpha-cyanoacetate, and nitromethane could be employed as a nucleophile to give the Michael adducts in good to excellent yields with up to 93% ee. The results of spectroscopic experiments clarified that this enhanced reactivity can be attributed to the intramolecular hydrogen-bonding interaction between the N-H of the imide and the methoxy group of the benzamide moiety. Thus, the key to the success of the catalytic enantioselective Michael addition is dual activation of the substrate by both intramolecular hydrogen bonding in the imide and intermolecular hydrogen bonding with thiourea 1a, as well as the activation of a nucleophile by the tertiary amine of the bifunctional thiourea.

We fabricated inversion channel diamond metal-oxide-semiconductor field-effect transistors (MOSFETs) with normally off characteristics. At present, Si MOSFETs and insulated gate bipolar transistors (IGBTs) with inversion channels are widely used because of their high controllability of electric power and high tolerance. Although a diamond semiconductor is considered to be a material with a strong potential for application in next-generation power devices, diamond MOSFETs with an inversion channel have not yet been reported. We precisely controlled the MOS interface for diamond by wet annealing and fabricated p-channel and planar-type MOSFETs with phosphorus-doped n-type body on diamond (111) substrate. The gate oxide of Al2O3 was deposited onto the n-type diamond body by atomic layer deposition at 300 °C. The drain current was controlled by the negative gate voltage, indicating that an inversion channel with a p-type character was formed at a high-quality n-type diamond body/Al2O3 interface. The maximum drain current density and the field-effect mobility of a diamond MOSFET with a gate electrode length of 5 μm were 1.6 mA/mm and 8.0 cm2/Vs, respectively, at room temperature.

Hydrogen-bond (HB)-donor catalysts that bear a 2-aminoquinazolin-4-(1H)-one or a 3-aminobenzothiadiazine-1,1-dioxide skeleton have been developed, and it has been shown that these catalyst motifs act similarly to other HB-donor catalysts such as thioureas. The highly enantioselective hydrazination of 1,3-dicarbonyl compounds was realized even at room temperature with up to 96% ee for 2-aminoquinazolin-4-(1H)-one-type catalysts, which were more effective than the corresponding urea and thiourea catalysts. In addition, benzothiadiazine-1,1-dioxide-type catalysts were shown to promote the isomerization of alkynoates to allenoates with high enantioselectivity. To overcome the problem that the products were obtained as mixtures with the starting alkynoates, we developed the tandem isomerization and cycloaddition of alkynoates for the synthesis of advanced chiral compounds such as bicyclo[2.2.1]heptenes and 3-alkylidene pyrrolidine without a significant loss of enantioselectivity.