J.Y. Park

Metal-organic cooperative catalysis in C-H and C-C bond activation and its concurrent recovery.

The development of an efficient catalytic activation (cleavage) system for C-H and C-C bonds is an important challenge in organic synthesis, because these bonds comprise a variety of organic molecules such as natural products, petroleum oils, and polymers on the earth. Among many elegant approaches utilizing transition metals to activate C-H and C-C bonds facilely, chelation-assisted protocols based on the coordinating ability of an organic moiety have attracted great attention, though they have often suffered from the need for an intact coordinating group in a substrate. In this Account, we describe our entire efforts to activate C-H or C-C bonds adjacent to carbonyl groups by employing a new concept of metal-organic cooperative catalysis (MOCC), which enables the temporal installation of a 2-aminopyridyl group into common aldehydes or ketones in a catalytic way. Consequently, a series of new catalytic reactions such as alcohol hydroacylation, oxo-ester synthesis, C-C triple bond cleavage, hydrative dimerization of alkynes, and skeletal rearrangements of cyclic ketones was realized through MOCC. In particular, in the quest for an optimized MOCC system composed of a Wilkinsons catalyst (Ph 3P) 3RhCl and an organic catalyst (2-amino-3-picoline), surprising efficiency enhancements could be achieved when benzoic acid and aniline were introduced as promoters for the aldimine formation process. Furthermore, a notable accomplishment of C-C bond activation has been made using 2-amino-3-picoline as a temporary chelating auxiliary in the reactions of unstrained ketones with various terminal olefins and Wilkinsons catalyst. In the case of seven-membered cyclic ketones, an interesting ring contraction to five- or six-membered ones takes place through skeletal rearrangements initiated by the C-C bond activation of MOCC. On the other hand, the fundamental advances of these catalytic systems into recyclable processes could be achieved by immobilizing both metal and organic components using a hydrogen-bonded self-assembled system as a catalyst support. This catalyst-recovery system provides a homogeneous phase at high temperature during the reaction and a heterogeneous phase at room temperature after the reaction. The product could be separated conveniently from the self-assembly support system by decanting the upper layer. The immobilized catalysts of both 2-aminopyridine and rhodium metal species sustained high catalytic activity for up to the eight catalytic reactions. In conclusion, the successful incorporation of an organocatalytic cycle into a transition metal catalyzed reaction led us to find MOCC for C-H and C-C bond activation. In addition, the hydrogen-bonded self-assembled support has been developed for an efficient and effective recovery system of homogeneous catalysts and could be successful in immobilizing both metal and organic catalysts.

Radiological response predicts survival following transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma

It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular carcinoma (HCC).

Post-grafting of silica surfaces with pre-functionalized organosilanes: new synthetic equivalents of conventional trialkoxysilanes

This article describes recent advances that have been made in the development of methods for post-grafting of silica surfaces using functionalized organosilanes. While procedures employing conventional trialkoxysilane precursors have been utilized to immobilize organic and biological molecules onto inorganic supports, such as silica and glass, they have intrinsic limitations including sensitivity to hydrolysis and slow reaction rates. In this context, new synthetic equivalents to conventional trialkoxysilanes and new grafting methods have been devised to overcome these drawbacks and improve post-grafting processes. A key feature of the new strategies is the stability of the immobilizing groups that enables the silane precursors to be functionalized and purified without decomposition before immobilization. Recent developments made in the design of immobilization methods, which employ non-catalytic and catalytic approaches, are described.

High prevalence of significant histology in asymptomatic chronic hepatitis B patients with genotype C and high serum HBV DNA levels

Summary.u2002 Current treatment guidelines suggest that antiviral therapy be considered for chronic hepatitis B (CHB) patients with high viral load if a biopsy shows significant liver disease despite alanine aminotransferase (ALT) levels two times or less than the upper limit of normal (ULN). We evaluated the histological findings in CHB patients with high viral load and persistently normal or slightly elevated serum ALT levels. Between January 2003 and June 2006, 105 consecutive treatment‐naive patients with CHB who underwent ultrasonography‐guided percutaneous liver biopsy, had detectable serum HBV DNA (>105 copies/mL) in a direct hybridization assay and normal or slightly elevated serum ALT levels (≤2u2003×u2003ULN) for at least 12u2003months were included in a prospective study. Histological assessment was based on the METAVIR scoring system. Significant histology was defined as fibrosis stage ≥F2 or necroinflammation grade ≥A2. Among the 105 CHB patients with high viral load and persistently normal or slightly elevated serum ALT levels for at least 12u2003months, significant fibrosis (F2–F4 fibrosis) was observed in 63 patients (60.0%) and the actual significant histology was found in 65 patients (61.9%). On multivariate analysis, serum ALT levels and age at which they entered the study were independent factors associated with significant histology. Odds ratios for significant histology increased progressively according to serum ALT levels and age. In conclusion, a large proportion of CHB patients with genotype C, high viral load and ALT ≤2u2003×u2003ULN had significant liver disease on liver biopsy and should be considered for antiviral therapy.

Transition-Metal-Catalyzed Immobilization of Organic Functional Groups onto Solid Supports through Vinylsilane Coupling Reactions

A novel and efficient grafting method for covalent bonding of functional organic molecules to silica or glass surfaces has been developed. The protocol employs transition-metal-catalyzed reactions of vinylsilanes with surface hydroxyl groups. Dimethyldivinylsilane can be used in this procedure as a linker in which one vinyl group is used for direct C-C bond formation with a functional organic molecule and the other is employed to immobilize the alkylsilyl group onto the hydroxyl surface of the solid support.

Dual Functionalities of Hydrogen-Bonding Self-Assembled Catalysts in Chelation-Assisted Hydroacylation

A recyclable catalyst for chelation-assisted hydroacylation of an olefin with primary alcohol was developed using hydrogen-bonding self-assembled catalysts consisting of 2,6-diaminopyridine and barbiturate phosphine-rhodium(I) complex. Upon heating, these two catalysts act as homogeneous catalysts due to cleavage of the hydrogen bond, and these associate to form supramolecular assemblies via hydrogen bonding that can be separated from immiscible product phase upon cooling after the reaction.

Facile One-Step Catalytic Grafting of N-Hydroxysuccinimidyl-Ester-Functionalized Methallylsilane onto Silica for Enzyme Immobilization

A one-step grafting method of NHS-ester group is described for the immobilization of enzymes onto a silica surface at room temperature. Pure NHS-ester functionalized methallylsilane was prepared as a grafting reagent and showed remarkable grafting efficiency with acid catalysts at room temperature. As a result, mesoporous silica balls bearing a covalently immobilized enzyme could be obtained with a high loading rate compared to conventional multistep grafting methods. This one-step procedure offers the advantages of precise measurement of the high loading efficiency of the NHS-ester group, and the exclusive formation of only the NHS-ester group, which reduces the presence of unreacted functionalities.

Tenofovir versus tenofovir plus entecavir for chronic hepatitis B with lamivudine resistance and entecavir resistance

We compared the viral suppressive efficacy of tenofovir disoproxil fumarate (TDF) mono‐rescue therapy (TDF group) and TDF plus entecavir (ETV) combination‐rescue therapy (TDF + ETV group) in chronic hepatitis B (CHB) patients with lamivudine resistance and entecavir resistance. One hundred and thirty‐three CHB patients with lamivudine and entecavir resistance were investigated. Ninety‐six patients were treated with TDF and 37 with TDF + ETV for at least 6 months. We compared the virologic response rate (HBV DNA level <20 IU/mL) between the two groups and identified the predictive factors of treatment outcome. There were no significant differences between the two groups in demographic characteristics. Up to 24 months [median: 18 (range 6‐24) months], 85.4% and 89.2% of the TDF group and TDF + ETV group, respectively, achieved a virologic response (P=.068). Only the HBV DNA level at baseline was significantly associated with a virologic response in the multivariate analysis. In a subanalysis of patients with HBV DNA levels ≥4 log (IU/mL) at baseline, a higher proportion of patients in the TDF + ETV group than the TDF group achieved a virologic response (92.9% vs 68.3%; P<.001), while 90% of patients with HBV DNA (IU/mL) levels <4 log in all both TDF and TDF + ETV groups achieved a virologic response. TDF mono‐rescue therapy is a reasonable option in patients with lamivudine resistance and entecavir resistance. However, the combination strategy should be considered in patients with high baseline HBV DNA levels.

A method for highly efficient catalytic immobilisation of glucose oxidase on the surface of silica

A simple, mild and convenient method has been developed for catalytic immobilisation of glucose oxidase (GOx), chemically modified to contain pendant methallylsilyl groups, on an untreated silica surface.

Sarcopenia is associated with the risk of significant liver fibrosis in metabolically unhealthy subjects with chronic hepatitis B

Sarcopenia is significantly associated with the degree of liver fibrosis. This study investigated the influence of sarcopenia on liver fibrosis in individuals with chronic hepatitis B.