Combined Photoredox/Enzymatic C−H Benzylic Hydroxylations

Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value‐added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single‐flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.     

The structural and spectroscopic characterisation of three actinyl complexes with coordinated and uncoordinated perrhenate: [UO2(ReO4)2(TPPO)3], [[(UO2)(TPPO)3]2(mu2-O2)][ReO4]2 and [NpO2(TPPO)4][ReO4

The first structural characterization of an actinide complex with coordinated perrhenate is reported, [UO2(ReO4)2(TPPO)3] (1). In this [UO2]2+ complex two [ReO4]- anions and three TPPO (triphenylphosphine oxide) P=O donor ligands are coordinated in the equatorial plane in a cisoid arrangement. This bonding arrangement, and apparent strain observed in the equatorially bonded ligands, is attributed to the solid state packing in adjacent molecules in which hydrophobic TPPO ligands form an effective "shell" around a hydrophilic core of two UO2(ReO4)2 moieties. Solid state vibrational spectroscopy (infrared and Raman), 31P CP MAS NMR and elemental analysis are also consistent with the formula of 1. Solution state vibrational spectroscopy and 31P NMR measurements in EtOH indicate the lability of the TPPO and [ReO4]- groups. The photolytic generation of peroxide in EtOH solutions of 1 leads to the formation of trace quantities of [[(UO2)(TPPO)3]2(mu2-O2)][ReO4]2, 2, in which the coordinated [ReO4]- groups of 1 have been displaced by bridging O2(2-), derived from atmospheric O2. Finally, attempts to synthesise a [NpO2]+ analogue of have resulted only in the formation of [NpO2(TPPO)4][ReO4], 3, in which [ReO4]- acts solely as a counter anion. From these results it can be concluded that [ReO4]- will bond to [UO2]2+, but will be readily displaced by a more strongly coordinating ligand (e.g. peroxide) and will not coordinate to an actinyl cation with a lower charge, [NpO2]+, under the same reaction conditions.     

Covalently functionalized hexagonal boron nitride nanosheets by nitrene addition

The covalent functionalization of exfoliated hexagonal boron nitride (h-BN) nanosheets by nitrene addition is described. Integration of functionalized h-BN nanosheets within a polycarbonate matrix is demonstrated and was found to afford significant increases in mechanical properties. This integration methodology was further extended by the covalent modification of the h-BN nanosheets with polymer chains of a polycarbonate analogue, and the integration of the polymer modified h-BN within the polymer matrix.     

Detection and Quantitation of Afucosylated N-Linked Oligosaccharides in Recombinant Monoclonal Antibodies Using Enzymatic Digestion and LC-MS

The presence of N-linked oligosaccharides in the CH2 domain has a significant impact on the structure, stability, and biological functions of recombinant monoclonal antibodies. The impact is also highly dependent on the specific oligosaccharide structures. The absence of core-fucose has been demonstrated to result in increased binding affinity to Fcγ receptors and, thus, enhanced antibody-dependent cellular cytotoxicity (ADCC). Therefore, a method that can specifically determine the level of oligosaccharides without the core-fucose (afucosylation) is highly desired. In the current study, recombinant monoclonal antibodies and tryptic peptides from the antibodies were digested using endoglycosidases F2 and H, which cleaves the glycosidic bond between the two primary GlcNAc residues. As a result, various oligosaccharides of either complex type or high mannose type that are commonly observed for recombinant monoclonal antibodies are converted to either GlcNAc residue only or GlcNAc with the core-fucose. The level of GlcNAc represents the sum of all afucosylated oligosaccharides, whereas the level of GlcNAc with the core-fucose represents the sum of all fucosylated oligosaccharides. LC-MS analysis of the enzymatically digested antibodies after reduction provided a quick estimate of the levels of afucosylation. An accurate determination of the level of afucosylation was obtained by LC-MS analysis of glycopeptides after trypsin digestion.     

Purified oxygen- and nitrogen-modified multi-walled carbon nanotubes as metal-free catalysts for selective olefin hydrogenation

Oxygen- and nitrogen-functionalized carbon nanotubes (OCNTs and NCNTs) were applied as metal-free catalysts in selective olefin hydrogenation. A series of NCNTs was synthesized by NH₃ post-treatment of OCNTs. Temperature-programmed desorption, N₂ physisorption, Raman spectroscopy, high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy were employed to characterize the surface properties of OCNTs and NCNTs, aiming at a detailed analysis of the type and amount of oxygen- and nitrogen-containing groups as well as surface defects. The gas-phase treatments applied for oxygen and nitrogen functionalization at elevated temperatures up to 600 °C led to the increase of surface defects, but did not cause structural damages in the bulk. NCNTs showed a clearly higher activity than the pristine CNTs and OCNTs in the hydrogenation of 1,5-cyclooctadiene, and also the selectivity to cyclooctene was higher. The favorable catalytic properties are ascribed to the nitrogen-containing surface functional groups as well as surface defects related to nitrogen species. In contrast, oxygen-containing surface groups and the surface defects caused by oxygen species did not show clear contribution to the hydrogenation catalysis.     

Improved procedure for the synthesis of thiazolium-type peptide coupling reagents: BMTB as a new efficient reagent

An efficient scalable synthesis of 2-halothiazolium-type peptide coupling reagents has been developed. The key step is the formation of the 2-bromothiazole scaffold through cyclization of α-thiocyanato ketones with hydrogen bromide. Using this method, the new coupling reagent 2-bromo-N-methylthiazolium bromide (BMTB) was synthesized. BMTB was tested in a difficult model coupling reaction of two sterically hindered N-methylated amino acids and showed higher activity than the well-established peptide coupling reagent HATU.     

Insertion Reactions of Carbon Disulfide into Mg‐C and Mg‐N Bonds: Syntheses and Structural Determinations of Mg(S2CY)2(THF)n(Y=NEt2, NiPr2, iPr,Ph) and BrMg(S2CZ)(THF)3(Z=Ph,iPr)

The insertion reaction of CS₂ with Mg(NR₂)₂ (R= Et, ⁱPr), MgR′₂ (R′= Et, Ph) and R″MgBr (R″= ⁱPr, Ph) respectively lead solid products, Mg(S₂CNR₂)₂(THF)_n ( 1 : R= Et, n=2; 2 : R= ⁱPr, n=1), Mg(S₂C′R)₂(THF)₂ ( 3 : ′R= Et, 4 : ′R= Ph), BrMg(S₂C″R) (THF)₃ ( 5 : ″R= ⁱPr, 6 : ″R= Ph) in which the inserted carbon disulfides act as terminal chelating ligands. These compounds were characterized with ¹H, ¹³C NMR, IR spectroscopy, mass spectrometry, elemental analyses, and X‐ray crystallography.     

Formation of Metallo-6(A)-((2-(bis(2-aminoethyl)amino)ethyl)amino)-6(A)-deoxy-beta-cyclodextrins and Their Complexation of Tryptophan in Aqueous Solution

A pH titration study shows that 6(A)-((2-(bis(2-aminoethyl)amino)ethyl)amino)-6(A)-deoxy-beta-cyclodextrin (betaCDtren) forms binary metallocyclodextrins, [M(betaCDtren)](2+), for which log(K/dm(3) mol(-)(1)) = 11.65 +/- 0.06, 17.29 +/- 0.05, and 12.25 +/- 0.03, respectively, when M(2+) = Ni(2+), Cu(2+), and Zn(2+), where K is the stability constant in aqueous solution at 298.2 K and I = 0.10 mol dm(-)(3) (NaClO(4)). The ternary metallocyclodextrins [M(betaCDtren)Trp](+), where Trp(-) is the tryptophan anion, are characterized by log(K/dm(3) mol(-)(1)) = 8.2 +/- 0.2 and 8.1 +/- 0.2, 9.5 +/- 0.3 and 9.4 +/- 0.2, and 8.1 +/- 0.1 and 8.3 +/- 0.1, respectively, where the first and second values represent the stepwise stability constants for the complexation of (R)- and (S)-Trp(-), respectively, when M(2+) = Ni(2+), Cu(2+), and Zn(2+). From comparisons of stabilities and UV-visible spectra, the binary and ternary metallocyclodextrins appear to be six-coordinate when M(2+) = Ni(2+) and Zn(2+) and five-coordinate when M(2+) = Cu(2+). The factors affecting the stoichiometries and stabilities of the metallocyclodextrins, are discussed and comparisons are made with related systems.     

Synthesis of certain 5-substituted thieno[2,3-b]thiophene-2-sulfonamides and thieno[2,3-b]thiophene-2-sulfonamide 6,6-dioxides

A series of the title compounds were prepared for evaluation as inhibitors of carbonic anhydrase II. Oxidation of 5-substituted thieno[2,3-b]thiophene-2-sulfonamides provided the first examples of thiophene[2,3-b]thiophene-2-sulfonarnide 6,6-dioxides. These cyclic vinyl sulfones readily underwent addi tion to give predominately that 4,5-cis addition product.