Kinetics and mechanism of the oxidation of alkenes and silanes by hydrogen peroxide catalyzed by methylrhenium trioxide (MTO) and a novel application of electrospray mass spectrometry to study the hydrolysis of MTO

Conjugated dienes were oxidized by hydrogen peroxide with methylrhenium trioxide as catalyst. As is true for other MTO-catalyzed reactions, methylrhenium bis-peroxide (CH3Re(O)(eta2-O2)2(H 2O)) was the major reactive catalyst present. The rate constants between it and the dienes, increase or decrease as substituents add or remove electron density from the double bond, suggesting a concerted mechanism in which the peroxide oxygen attacks the double bond electrophilically. The H2O 2/MTO oxidation system was also used in the regioselective cyclization of hydroxyalkenes to tetrahydrofurans and unsaturated carboxylic acids to lactones. In these reactions MTO acts as a bifunctional catalyst for both epoxidation and cyclization reactions. The reactions of trisubstituted silane with hydrogen peroxide catalyzed by MTO result in its quantitative convertion to silanol. An oxene mechanism is proposed for this reaction based on the kinetics and isotope ratio study;The full kinetics pH profile for the base-promoted decomposition of MTO to CH4 and ReO4-- was examined with the inclusion of new data at pH 7--10. Spectroscopic and kinetics data gave evidence for mono-and dihydroxo complexes: MTO(OH--) and MTO(OH--)2. Some kinetic data were acquired with electrospray mass spectrometry to monitor the build up in the concentration of perrhenate ions

Experimental and Theoretical Study of Oxygen Insertion into Trialkylsilanes by Methyltrioxorhenium Catalyst

Among the reactions of hydrogen peroxide that are catalyzed by methyltrioxorhenium, the oxidation of alkylsilanes is unique. It is not a reaction in which an oxygen atom is added to a substrate, but one featuring a net insertion, R3Si−H + H2O2 → R3Si−OH + H2O. Kinetics studies were carried out on 10 compounds. Rate constant were determined for the bimolecular reaction of the silane with the peroxo compound CH3Re(O)(η2-O2)2(H2O). The variation of rate constant with the alkyl groups R follows two trends:  the values of log(k) are linear functions of (a) the stretching frequency of the Si−H group and (b) the total Taft constant for these substituents. The reactions of (n-Bu)3Si−H and (n-Bu)3Si−D exhibit a kinetic isotope effect of 2.1 at 0 °C. From these data, a model for the transition state was formulated in which O−H and Si−O bond making accompany Si−H bond breaking. Quantum mechanical calculations have been carried out on the gas-phase reaction between Et3SiH and CH3Re(O)2(η2-O2). These results support this structure, calculating a structure and energy that are in agreement. The theoretical activation energy is 28.5 kcal mol-1, twice the experimental value in aqueous acetonitrile, 12.4 kcal mol-1. The difference can be attributed to the solvation of the polar transition state in this medium

The Natural Compound Myricetin Effectively Represses the Malignant Progression of Prostate Cancer by Inhibiting PIM1 and Disrupting the PIM1/CXCR4 Interaction

Background/Aims: Natural compounds are a promising resource for anti-tumor drugs. Myricetin, an abundant flavonoid found in the bark and leaves of bayberry, shows multiple promising anti-tumor functions in various cancers. Methods: The cytotoxic, pro-apoptotic, and anti-metastatic effects of myricetin on prostate cancer cells were investigated in both in vitro and in vivo studies. Short-hairpin RNA knockdown of the proviral integration site for Moloney murine leukemia virus-1 (PIM1), pull-down and co-immunoprecipitation assays, and an intracellular Ca2+ flux assay were used to investigate the potential underlying mechanism of myricetin. ONCOMINE database data mining and immunohistochemical analysis of prostate cancer tissues were used to evaluate the expression of PIM1 and CXCR4, as well as the correlation between PIM1 and CXCR4 expression and the clinicopathologic characteristics and prognoses of prostate cancer patients. Results: Myricetin exerted selective cytotoxic, pro-apoptotic, and anti-metastatic effects on prostate cancer cells by inhibiting PIM1 and disrupting the PIM1/CXCR4 interaction. Moreover, PIM1 and CXCR4 were coexpressed and associated with aggressive clinicopathologic traits and poor prognosis in prostate cancer patients. Conclusion: These results offer preclinical evidence for myricetin as a potential chemopreventive and therapeutic agent for precision medicine tailored to prostate cancer patients characterized by concomitant elevated expression of PIM1 and CXCR4

Kinetics and mechanism of the oxidation of alkenes and silanes by hydrogen peroxide catalyzed by methylrhenium trioxide (MTO) and a novel application of electrospray mass spectrometry to study the hydrolysis of MTO

Conjugated dienes were oxidized by hydrogen peroxide with methylrhenium trioxide as catalyst. As is true for other MTO-catalyzed reactions, methylrhenium bis-peroxide (CH3Re(O)(eta2-O2)2(H 2O)) was the major reactive catalyst present. The rate constants between it and the dienes, increase or decrease as substituents add or remove electron density from the double bond, suggesting a concerted mechanism in which the peroxide oxygen attacks the double bond electrophilically. The H2O 2/MTO oxidation system was also used in the regioselective cyclization of hydroxyalkenes to tetrahydrofurans and unsaturated carboxylic acids to lactones. In these reactions MTO acts as a bifunctional catalyst for both epoxidation and cyclization reactions. The reactions of trisubstituted silane with hydrogen peroxide catalyzed by MTO result in its quantitative convertion to silanol. An oxene mechanism is proposed for this reaction based on the kinetics and isotope ratio study;The full kinetics pH profile for the base-promoted decomposition of MTO to CH4 and ReO4-- was examined with the inclusion of new data at pH 7--10. Spectroscopic and kinetics data gave evidence for mono-and dihydroxo complexes: MTO(OH--) and MTO(OH--)2. Some kinetic data were acquired with electrospray mass spectrometry to monitor the build up in the concentration of perrhenate ions.</p

Kinetics and mechanism of the oxidation of alkenes and silanes by hydrogen peroxide catalyzed by methylrhenium trioxide (MTO) and a novel application of electrospray mass spectrometry to study the hydrolysis of MTO

Conjugated dienes were oxidized by hydrogen peroxide with methylrhenium trioxide (MTO) as catalyst. Methylrhenium bis-peroxide was the major reactive catalyst present. Hydroxyalkenes and trisubstituted silane were also tested. Mechanisms for each of these reactions are presented

Experimental and Theoretical Study of Oxygen Insertion into Trialkylsilanes by Methyltrioxorhenium Catalyst

Among the reactions of hydrogen peroxide that are catalyzed by methyltrioxorhenium, the oxidation of alkylsilanes is unique. It is not a reaction in which an oxygen atom is added to a substrate, but one featuring a net insertion, R3Si−H + H2O2 → R3Si−OH + H2O. Kinetics studies were carried out on 10 compounds. Rate constant were determined for the bimolecular reaction of the silane with the peroxo compound CH3Re(O)(η2-O2)2(H2O). The variation of rate constant with the alkyl groups R follows two trends:  the values of log(k) are linear functions of (a) the stretching frequency of the Si−H group and (b) the total Taft constant for these substituents. The reactions of (n-Bu)3Si−H and (n-Bu)3Si−D exhibit a kinetic isotope effect of 2.1 at 0 °C. From these data, a model for the transition state was formulated in which O−H and Si−O bond making accompany Si−H bond breaking. Quantum mechanical calculations have been carried out on the gas-phase reaction between Et3SiH and CH3Re(O)2(η2-O2). These results support this structure, calculating a structure and energy that are in agreement. The theoretical activation energy is 28.5 kcal mol-1, twice the experimental value in aqueous acetonitrile, 12.4 kcal mol-1. The difference can be attributed to the solvation of the polar transition state in this medium.Reprinted (adapted) with permission from Organometallics 18 (1999): 4753, doi:10.1021/om990579d. Copyright 1999 American Chemical Society.</p

Molecular Mechanisms of Noncoding RNA in the Occurrence of Castration-Resistant Prostate Cancer

Although several therapeutic options have been shown to improve survival of most patients with prostate cancer, progression to castration-refractory state continues to present challenges in clinics and scientific research. As a highly heterogeneous disease entity, the mechanisms of castration-resistant prostate cancer (CRPC) are complicated and arise from multiple factors. Among them, noncoding RNAs (ncRNAs), the untranslated part of the human transcriptome, are closely related to almost all biological regulation, including tumor metabolisms, epigenetic modifications and immune escape, which has encouraged scientists to investigate their role in CRPC. In clinical practice, ncRNAs, especially miRNAs and lncRNAs, may function as potential biomarkers for diagnosis and prognosis of CRPC. Therefore, understanding the molecular biology of CRPC will help boost a shift in the treatment of CRPC patients. In this review, we summarize the recent findings of miRNAs and lncRNAs, discuss their potential functional mechanisms and highlight their clinical application prospects in CRPC

The Mechanism and Role of N6-Methyladenosine (m6A) Modification in Atherosclerosis and Atherosclerotic Diseases

N6-methyladenosine (m6A) modification is a newly discovered regulatory mechanism in eukaryotes. As one of the most common epigenetic mechanisms, m6A&rsquo;s role in the development of atherosclerosis (AS) and atherosclerotic diseases (AD) has also received increasing attention. Herein, we elucidate the effect of m6A on major risk factors for AS, including lipid metabolism disorders, hypertension, and hyperglycemia. We also describe how m6A methylation contributes to endothelial cell injury, macrophage response, inflammation, and smooth muscle cell response in AS and AD. Subsequently, we illustrate the m6A-mediated aberrant biological role in the pathogenesis of AS and AD, and analyze the levels of m6A methylation in peripheral blood or local tissues of AS and AD, which helps to further discuss the diagnostic and therapeutic potential of m6A regulation for AS and AD. In summary, studies on m6A methylation provide new insights into the pathophysiologic mechanisms of AS and AD, and m6A methylation could be a novel diagnostic biomarker and therapeutic target for AS and AD