3,932 research outputs found
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Photochemical delivery of nitric oxide.
There remains considerable interest in developing methods for the targeted delivery of nitric oxide and other small molecule bioregulators such as carbon monoxide to physiological targets. One such strategy is to use a "caged" NO that is "uncaged" by excitation with light. Such photochemical methods convey certain key advantages such as the ability to control the timing, location and dosage of delivery, but also have some important disadvantages, such as the relatively poor penetration of the ultraviolet and visible wavelengths often necessary for the uncaging process. Presented here is an overview of ongoing studies in the author's laboratory exploring new photochemical NO precursors including those with nanomaterial antennas designed to enhance the effectiveness of these precursors with longer excitation wavelengths
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Thiyl radicals are co-products of dinitrosyl iron complex (DNIC) formation.
Thiyl radicals are detected by EPR as co-products of dinitrosyl iron complex (DNIC) formation. In demonstrating that DNIC formation generates RSË™ in a NO rich environment, these results provide a novel route for S-nitroso thiol formation
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Dynamics of Dinitrosyl Iron Complex (DNIC) Formation with Low Molecular Weight Thiols.
Dinitrosyl iron complexes (DNICs) are ubiquitous in mammalian cells and tissues producing nitric oxide (NO) and have been argued to play key physiological and pathological roles. Nonetheless, the mechanism and dynamics of DNIC formation in aqueous media remain only partially understood. Here, we report a stopped-flow kinetics and density functional theory (DFT) investigation of the reaction of NO with ferrous ions and the low molecular weight thiols glutathione (GSH) and cysteine (CysSH) as well as the peptides WCGPC and WCGPY to produce DNICs in pH 7.4 aqueous media. With each thiol, a two-stage reaction pattern is observed. The first stage involves several rapidly established pre-equilibria leading to a ferrous intermediate concluded to have the composition FeII(NO)(RS)2(H2O)x (C). In the second stage, C undergoes rate-limiting, unimolecular autoreduction to give thiyl radical (RS•) plus the mononitrosyl Fe(I) complex FeI(NO)(RS)(H2O)x following the reactivity order of CysSH > WCGPC > WCGPY > GSH. Time course simulations using the experimentally determined kinetics parameters demonstrate that, at a NO flux characteristic of inflammation, DNICs will be rapidly formed from intracellular levels of ferrous iron and thiols. Furthermore, the proposed mechanism offers a novel pathway for S-nitroso thiol (RSNO) formation in a biological environment
High dose atorvastatin associated with increased risk of significant hepatotoxicity in comparison to simvastatin in UK GPRD cohort
Background and Aims:
Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment.
Methods:
The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions.
Results:
Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4–2.6]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS.
Conclusions:
The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small
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Near-Infrared and Visible Photoactivation to Uncage Carbon Monoxide from an Aqueous-Soluble PhotoCORM.
Multiphoton excitation allows one to access high energy excited states and perform valuable tasks in biological systems using tissue penetrating near-infrared (NIR) light. Here, we describe new photoactive manganese tricarbonyl complexes incorporating the ligand 4'-p-N,N-bis(2-hydroxyethyl)amino-benzyl-2,2':6',2″-terpyridine (TPYOH), which can serve as an antenna for two photon NIR excitation. Solutions of Mn(CO)3(TPYOH)X (X = Br- or CF3SO3-) complexes are very photoactive toward CO release under visible light excitation (405 nm, 451 nm). The same responses were also triggered by multiphoton excitation at 750 and 800 nm. In this context, we discuss the potential applications of these complexes as visible/NIR light photoactivated carbon monoxide releasing moieties (photoCORMs). We also report the isolation and crystal structures of the TPYOH complexes Mn(TPYOH)Cl2 and [Mn(TPYOH)2](CF3SO3)2, to illustrate a possible photolysis product(s)
New emissive mononuclear copper (I) complex: Structural and photophysical characterization focusing on solvatochromism, rigidochromism and oxygen sensing in mesoporous solid matrix
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Synthesis, structural characterization, and luminescence properties of mono- and di-nuclear platinum(II) complexes containing 2-(2-pyridyl)benzimidazole
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Chelating and Bridging Roles of 2-(2-Pyridyl)benzimidazole and Bis(diphenylphosphino)acetylene in Stabilizing a Cyclic Tetranuclear Platinum(II) Complex.
The reaction of complex [Pt(Me)(DMSO)(pbz)], 1, (pbz = 2-(2-pyridyl)benzimidazolate) with [PtMe(Cl)(DMSO)2], B, followed by addition of bis(diphenylphosphino)acetylene (dppac), gave the novel tetranuclear platinum complex [Pt4Me4(μ-dppac)2(pbz)2Cl2], 2, bearing both the pbz and dppac ligands. In this structure, the pbz ligands are both chelating and bridging to stabilize the tetraplatinum framework. The tetranuclear Pt(II) complex was fully characterized by NMR spectroscopy, X-ray crystallography, and mass spectrometry, and its electronic structure was investigated and supported by DFT calculations
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