Green-Light-Driven Reductive Elimination of Chlorine from a Carbene-Xanthylium Gold(III) Complex.

With the discovery of late transition metal platforms that support clean photoreductive halogen eliminations, we now describe an indazol-3-ylidene gold trichloride complex ([7]+ ) decorated at the 4-position by a xanthylium unit. This orange complex features a low energy band in the visible part of the spectrum, assigned to the charge transfer excitation of the indazol-3-ylidene/xanthylium donor/acceptor dyad. Green-light irradiation of this complex in the presence of a chlorine trap elicits the clean photoelimination of chlorine radicals, producing the corresponding gold(I) complex. This visible-light-induced photoreduction is very efficient, reaching quantum yields close to 10 %. A neutral analog of [7]+ featuring an anthryl group rather than a xanthylium unit proved to be perfectly photostable, supporting the importance of the xanthylium-based photoredox unit present in [7]+ .

Conformational Switching through the One-Electron Reduction of an Acridinium-based, γ-Cationic Phosphine Gold Complex.

Our efforts in the chemistry of gold complexes featuring ambiphilic phosphine-carbenium L/Z-type ligand have led us to consider the reduction of the carbenium moiety as a means to modulate the gold-carbenium interaction present in these complexes. Here, it was shown that the one-electron reduction of [(o-Ph2 P(C6 H4 )Acr)AuCl]+ (Acr=9-N-methylacridinium) produces a neutral stable radical, the structure of which showed a marked increase in the Au-Acr distance. Related structural changes were observed for the phosphine oxide analogue [(o-Ph2 P(O)(C6 H4 )Acr]+ , the reduction of which interfered with the P=O→carbenium interaction. These structural effects, driven by a reduction-induced change in the electronic and electrostatic characteristics of the compounds, showed that the charge and accepting properties of the carbenium unit can be modulated. These results highlight the redox-noninnocence of carbenium Z-type ligand, a feature that can be exploited to induce specific conformational changes.

1,2-Migration of N-Diarylboryl Imidazol-2-ylidene through Intermolecular Radical Process.

1,2-Boryl migration of N-boryl N-heterocyclic carbene to 2-boryl imidazole is proposed to proceed through generation and recombination of two radical intermediates, namely, a neutral diarylboron radical and a N-heterocyclic carbene radical. Crossover experiments suggest that these two radical species are stable enough to escape solvent cages and recombine intermolecularly. The presence of radical intermediates is further supported by spin trapping experiments. Besides, the coordination of Li+ cation is found to be critical for the stability of the NHC radical.

Tocilizumab Exerts Anti-Tumor Effects on Colorectal Carcinoma Cell Xenografts Corresponding to Expression Levels of Interleukin-6 Receptor.

The use of tocilizumab against the interleukin-6 receptor (IL-6R) has been demonstrated as inhibiting the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels remains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as human CRC xenograft models with anti-IL-6R antibody (tocilizumab) therapy. The IL-6R expression levels, histology of CRC growth/invasiveness, and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels showed better responsiveness in tocilizumab therapy than in the treated HT-29 group. Likewise, therapeutic effects of tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, invasiveness with MMP-9 proteinase expressions, and ERK 1/2 and STAT3 signaling transduction in the SW480 treatment group were superior to the HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, tocilizumab may serve as a targeted and promising anti-CRC therapy.

Placing gold on a π+-surface: ligand design and impact on reactivity.

We describe a novel gold chloride complex supported by an ambiphilic phosphine/xanthylium ligand in which the AuCl moiety interacts with the π+ surface of the xanthylium unit as indicated by structural studies. Energy decomposition analyses carried out on a model system indicates the prevalence of non-covalent interactions in which the electrostatic and dispersion terms cumulatively dominate. The presence of these AuCl-π+ interactions correlates with the high catalytic activity of this complex in the cyclisation of 2-(phenylethynyl)phenylboronic acid, N-propargyl-t-butylamide, and 2-allyl-2-(2-propynyl)malonate. Comparison with the significantly less active acridinium and the 9-oxa-10-boraanthracene analogues reinforces this conclusion.

Synthesis of an Indazole/Indazolium Phosphine Ligand Scaffold and Its Application in Gold(I) Catalysis.

Advances in ligand development have allowed for the fine-tuning of gold catalysis. To contribute to this field, we designed an indazole phosphine ligand scaffold that allows facile introduction of cationic charge through methylation. With minimal changes to the structure upon methylation, we could assess the importance of the electronic effects of the insertion of a positive charge on the catalytic activity of the resulting gold(I) complex. Using the benchmark reactions of propargyl amide cyclization and enyne cyclization with and without hexafluoroisopropanol (HFIP), we observed marked differences in the catalytic activities of the neutral and cationic gold species.

A linear Di-coordinate boron radical cation.

The pursuit of di-coordinate boron radical has been continued for more than a half century, and their stabilization and structural characterization remains a challenge. Here we report the isolation and structural characterization of a linear di-coordinate boron radical cation, achieved by stabilizing the two reactive atomic orbitals of the central boron atom by two orthogonal π-donating and π-accepting functionalities. The electron deficient radical cation undergoes facile one-electron reduction to borylene and binds Lewis base to give heteroleptic tri-coordinate boron radical cation. The co-existence of half-filled and empty p orbitals at boron also allows the CO-regulated electron transfer to be explored. As the introduction of CO promotes the electron transfer from a tri-coordinate neutral boron radical to a boron radical cation, the removal of CO under vacuum furnishes the reverse electron transfer from borylene to yield a solution consisting of two boron radicals.

Antibody to Interleukin-6 Receptor Inhibits In Vivo Growth of Human Colorectal Carcinoma Cell Xenografts.

BACKGROUND: Interleukin-6 receptor antibody (IL6R) inhibits colony formation and invasion by colorectal carcinoma (CRC) in vitro. We examined the effect of IL6R antibody on tumor growth of CRC xenografts in vivo. MATERIALS AND METHODS: SW480 cells inoculated subcutaneously into NU/NU mice were treated with anti-IL6R and tumor histology and growth-related signaling were subsequently estimated by hematoxylin and eosin and immunohistochemical staining. RESULTS: Tumor growth was inhibited by anti-IL6R treatment at dosages of both 0.1 and 1.0 mg/kg. Tumor cells had invaded into surrounding tissues in untreated mice, while there was no invasion of tumors in the IL6R antibody-treated mice. The expression of Ki-67, signal transducer and activator of transcription protein 3 (STAT3) and phosphor-extracellular signal-regulated kinase 1 and 2 (ERK1/2) were suppressed in anti-IL6R-treated tumors. CONCLUSION: IL6R antibody inhibited tumor growth and invasiveness in vivo by suppressing the expression of Ki-67, STAT3 and phosphor-ERK1/2. The results imply that the anti-IL6R may be a promising targeted drug for CRC.

Guillain-Barré syndrome in a heart transplantation recipient.

ABSTRACT: A rare case of a heart transplantation recipient with Guillain-Barré syndrome occurred, which was associated with peripheral nervous system damage. Based on a review of epidemiological research, the symptom development process, and diagnostic tools, the authors highlight the extreme rarity of this postinfectious immune disease. After diagnosis, plasma exchange and immunoregulatory therapy should be performed because they result in rapid recovery. If there is delayed diagnosis and treatment, there is a high risk of disability or death. When patients experience acute limb paralysis as the main symptom, nurse practitioners (NPs) should focus on the patient's history, particularly with regard to infectious agents. Closely monitoring the patient to detect respiratory failure and the need for early respiratory intervention can help the patient to avoid the severe complication of permanent brain injury. For NPs, performance of early differential diagnosis is important, especially among patients who have immunosuppressive dependence after transplantation.

[Electrostatic protection of oxygen pressure cabins].

This paper describes electrostatic harms to oxygen pressure cabins and protection measures which should be taken.

Structural and functional roles of glycosylation in fungal laccase from Lentinus sp.

Laccases are multi-copper oxidases that catalyze the oxidation of various organic and inorganic compounds by reducing O2 to water. Here we report the crystal structure at 1.8 Å resolution of a native laccase (designated nLcc4) isolated from a white-rot fungus Lentinus sp. nLcc4 is composed of three cupredoxin-like domains D1-D3 each folded into a Greek key ß-barrel topology. T1 and T2/T3 copper binding sites and three N-glycosylated sites at Asn75, Asn238, and Asn458 were elucidated. Initial rate kinetic analysis revealed that the kcat, Km, and kcat/Km of nLcc4 with substrate ABTS were 3,382 s-1, 65.0 ± 6.5 µM, and 52 s-1µM-1, respectively; and the values with lignosulfonic acid determined using isothermal titration calorimetry were 0.234 s-1, 56.7 ± 3.2 µM, and 0.004 s-1µM-1, respectively. Endo H-deglycosylated nLcc4 (dLcc4), with only one GlcNAc residue remaining at each of the three N-glycosylation sites in the enzyme, exhibited similar kinetic efficiency and thermal stability to that of nLcc4. The isolated Lcc4 gene contains an open reading frame of 1563 bp with a deduced polypeptide of 521 amino acid residues including a predicted signaling peptide of 21 residues at the N-terminus. Recombinant wild-type Lcc4 and mutant enzymes N75D, N238D and N458D were expressed in Pichia pastoris cells to evaluate the effect on enzyme activity by single glycosylation site deficiency. The mutant enzymes secreted in the cultural media of P. pastoris cells were observed to maintain only 4-50% of the activity of the wild-type laccase. Molecular dynamics simulations analyses of various states of (de-)glycosylation in nLcc support the kinetic results and suggest that the local H-bond networks between the domain connecting loop D2-D3 and the glycan moieties play a crucial role in the laccase activity. This study provides new insights into the role of glycosylation in the structure and function of a Basidiomycete fungal laccase.

Engineering of dual-functional hybrid glucanases.

1,3-1,4-ß-D-Glucanase (lichenase) and 1,3-ß-D-glucanase (laminarinase) are fibrolytic enzymes which play an important role in the hydrolysis of polysaccharide components. Both of these glucanases have been employed in a number of industrial applications. This study aims to improve or combine the novel properties of both glucanases in an attempt to create desirable hybrid enzymes with economic benefits for industrial applications. A truncated and mutated 1,3-1,4-ß-D-glucanase gene (TFs(W203F)) from Fibrobacter succinogenes, and a 1,3-ß-D-glucanase gene (TmLam) from hyperthermophilic Thermotoga maritima were used as target enzymes. The substrate-binding domains (TmB1 and TmB2) and the catalytic domain (TmLam(CD)) of TmLam were ligated to the N- or C-terminus of TFsW203F to create four hybrid enzymes, TmB1-TFs(W203F), TFs(W203F)-TmB2, TmB1-TFs(W203F)-TmB2 and TFs(W203F)-TmLam(CD). The results obtained from kinetic studies show that increased specific activities and turnover rate for lichenan and laminarin were observed in TmB1-TFs(W203F)-TmB2 and TFs(W203F)-TmLam(CD), respectively. Furthermore, fluorescence and circular dichroism spectrometric analyses indicated that the hybrid TFs(W203F)-TmLam(CD) was structurally more stable than the parental TFs(W203F), which was attributed to an improved thermal tolerance of the hybrid enzyme. This study has been successful in creating bifunctional hybrid glucanases with dual substrate catalytic functions which warrant further evaluation of their possible use in industrial applications.