• Bulletin of the Korean Chemical Society
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• v.23 no.8
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• pp.1089-1096
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• 2002

Solvolyses rate constants of trimethylacetyl chloride (2), isobutyryl chloride (3), diphenylacetyl chloride (4) and p-methoxyphenylacetyl chloride (5) in 2,2,2-trifluoroethanol (TFE)-water, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)-water and TFE-et hanol solvent systems at $10^{\circ}C$ are determined by a conductimetric method. Kinetic solvent isotope effects (KSIE) are reported from additional kinetic data for methanolyses of various substituted acetylchlorides in methanol According to the results of those reactions analyzed in terms of rate-rate profiles,extended Grunwald-Winstein type correlations, application of a third order reaction model based a general base catalyzed (GBC) and KSIE values. Regardless of the kind of neighboring groups (CH3- or Ph-groups) of reaction center, for aqueous fluorinated alcohol systems, solvolyses of 2, 3, 4, and 5 were exposed to the reaction with the same mechanism (a loose SN2 type mechanism by electrophilic solvation) controlled by a similarity of solvation of the transition sate (TS). Whereas, for TFE-ethanol solvent systems, the reactivity depended on whether substituted acetyl chloride have aromatic rings (Ph-) or alkyl groups (CH3-); the solvations by the predominant stoichiometric effect (third order reaction mechanism by GBC and/or by push-pull type) for Ph- groups (4 and 5) and the same solvation effects as those shown in TFE-water solvent systems for CH3- groups (2 and 3) were exhibited Such phenomena can be interpreted as having relevance to the inductive effect ( $\sigmaI)$ of substituted groups; the plot of log (KSIE) vs. ${\sigma}I$ parameter give an acceptable the linear correlation with r = 0.970 (slope = 0.44 $\pm$ 0.06, n = 5).

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2325-2329
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• 2013

Second-order rate constants $k_N$ have been measured for reactions of benzyl 2-pyridyl thionocarbonate (4b) and t-butyl 2-pyridyl thionocarbonate (5b) with a series of cyclic secondary amines in MeCN at $25.0{\pm}0.1^{\circ}C$. The $k_N$ values for the reactions of 4b and 5b have been compared with those reported previously for the corresponding reactions of benzyl 2-pyridyl carbonate (4a) and t-butyl 2-pyridyl carbonate (5a) to investigate the effect of changing the electrophilic center from C=O to C=S on reactivity and reaction mechanism. The thiono compound 4b is more reactive than its oxygen analogue 4a. The Br${\o}$nsted-type plots for the reactions of 4a and 4b are linear with ${\beta}_{nuc}=0.57$ and 0.37, respectively. The reactions of 4a were previously reported to proceed through a concerted mechanism, while those of 4b in this study have been concluded to proceed through a stepwise mechanism with formation of an intermediate being the rate-determining step on the basis of the ${\beta}_{nuc}$ value of 0.37. Enhanced polarizability upon changing the C=O in 4a by C=S has been suggested to be responsible for the reactivity order and the contrasting reaction mechanisms. In contrast, the reactivity of 5a and 5b is similar, but they are much less reactive than 4a and 4b. Furthermore, the reactions of 5a and 5b have been concluded to proceed through the same mechanism (i.e., a concerted mechanism) on the basis of linear Bronsted-type plots with ${\beta}_{nuc}=0.45$ or 0.47. It has been concluded that the strong steric hindrance exerted by the t-Bu in 5a and 5b causes a decrease in their reactivity and forces the reactions to proceed through a concerted mechanism.

• Molecules and Cells
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• v.38 no.4
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• pp.327-335
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• 2015

Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic ${\alpha},{\beta}$-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.391-395
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• 2014

Background: We aimed to evaluate the role of genetic polymorphisms in tobacco carcinogen-metabolizing genes and their interactions with smoking in a hospital-based case-control study of Japanese subjects. Materials and Methods: We examine the associations of pancreatic cancer risk with genetic polymorphisms in GSTM1, GSTT1 and GSTP1, phase II enzymes that catalyze the conjugation of toxic and carcinogenic electrophilic molecules. The study population consisted of 360 patients and 400 control subjects, who were recruited from several medical facilities in Japan. Unconditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and pancreatic cancer risk. Results: Among the control subjects, the prevalence of the GSTM1-null genotype and the GSTT1-null genotype was approximately 56% and 48%, respectively. Cases and controls were comparable in terms of GSTM1 and GSTT1 genotype distributions. Neither of the deleted polymorphisms in GSTM1 and GSTT1 was associated with the risk of pancreatic cancer, with an age- and sex-adjusted OR of 0.99 (95%CI: 0.74-1.32) for the GSTM1-null genotype, and 0.98 (95%CI: 0.73-1.31) for the GSTT1-null genotype. The OR was 0.97 (95%CI: 0.64-1.47) for individuals with the GSTM1 and GSTT1-null genotypes compared with those with the GSTM1 and GSTT1- present genotypes. No synergistic effects of smoking or GST genotypes were observed. Conclusions: Our results indicate no overall association between the GSTM1 and GSTT1 deletion polymorphisms and pancreatic cancer risk in the Japanese subjects in our study.

• Nuclear Engineering and Technology
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• v.13 no.3
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• pp.145-152
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• 1981

Even though a lately reported method of high temperature exchange labelling of o-iodo-hippuric acid (Hippuran) in the absence of oxidizing agent was considered to be an attractive one, the exchange mechanism was somewhat unclear. In this study iodine isotope exchanges between o-iodohippuric acid (OIH) and radioiodide ($^{125}$ $I^{ }$) or between OIH and molecular radioiodine ($^{125}$ $I_2$) were carried out at two different temperatures. Rate constants and activation parameters were measured by applying a radio-paper chromatography technique. Since o-iodobenzoic acid is known as a by-product in the exchange labelling of OIH, data were also obtained for the OIB-iodide systems for comparison. The rate constant was increased in the order of OIB...$^{125}$ $I^{[-10]}$ >OIB...$^{125}$ $I_2$>OIH..$^{125}$ $I^{[-10]}$ >OIH...$^{125}$ $I_2$ and the activation parameters for OIH were generally larger than those for OIB :$\Delta$H$\neq$$_{OIH}$>$\Delta$H$\neq$$_{OIB}$, $\Delta$S$\neq$$_{OIH}$>$\Delta$S$\neq$$_{OIB}$. These results suggest that the mechanism of the high temperature exchange is predominantly nucleophilic even though some electrophilic character can also be involved depending upon reaction conditions. Such a fact may well be caused by a feasible formation of hydrogen bonding type transition state due probably to the ortho substituent effect of-CONHC $H_2$COOH. Thus, the high temperature exchange method is estimated to be quite effective for labelling Hippuran especially at a small research center where reducing agent-free $^{131}$ I is unavailable.ailable..