NanoUPLC-QTOF-MS/MS Determination of Major Rosuvastatin Degradation Products Generated by Gamma Radiation in Aqueous Solution.

Rosuvastatin, a member of the statin family of drugs, is used to regulate high cholesterol levels in the human body. Moreover, rosuvastatin and other statins demonstrate a protective role against free radical-induced oxidative stress. Our research aimed to investigate the end-products of free radical-induced degradation of rosuvastatin. To induce the radical degradation, an aqueous solution of rosuvastatin was irradiated using different doses of gamma radiation (50-1000 Gy) under oxidative conditions. Rosuvastatin and related degradation products were separated on nanoC18 column under gradient elution, and identification was carried out on hyphenated nanoUPLC and nanoESI-QTOF mass spectrometer system. Elemental composition analysis using highly accurate mass measurements together with isotope fitting algorithm identified nine major degradation products. This is the first study of gamma radiation-induced degradation of rosuvastatin, where chemical structures, MS/MS fragmentation pathways and formation mechanisms of the resulting degradation products are detailly described. The presented results contribute to the understanding of the degradation pathway of rosuvastatin and possibly other statins under gamma radiation conditions.

Transparent and Colorless Dye-Sensitized Solar Cells Exceeding 75% Average Visible Transmittance.

Most photovoltaic (PV) technologies are opaque to maximize visible light absorption. However, see-through solar cells open additional perspectives for PV integration. Looking beyond maximizing visible light harvesting, this work considers the human eye photopic response to optimize a selective near-infrared sensitizer based on a polymethine cyanine structure (VG20-C x ) to render dye-sensitized solar cells (DSSCs) fully transparent and colorless. This peculiarity was achieved by conferring to the dye the ability to strongly and sharply absorb beyond 800 nm (S0-S1 transition) while rejecting the upper S0-S n contributions far in the blue where the human retina is poorly sensitive. When associated with an aggregation-free anatase TiO2 photoanode, the selective NIR-DSSC can display 3.1% power conversion efficiency, up to 76% average visible transmittance (AVT), a value approaching the 78% AVT value of a standard double glazing window while reaching a color rendering index (CRI) of 92.1%. The ultrafast and fast charge transfer processes are herein discussed, clarifying the different relaxation channels from the dye monomer excited states and highlighting the limiting steps to provide future directions to enhance the performances of this nonintrusive NIR-DSSC technology.

Kinetics of chain reaction driven by proton-coupled electron transfer: α-hydroxyethyl radical and bromoacetate in buffered aqueous solutions.

We measured and computed the rate constants of the reaction between the α-hydroxyethyl radical (˙CH(CH3)OH) and bromoacetate (BrCH2CO2-) in the non-buffered (NB), as well as in the bicarbonate (HCO3-) and hydrogen phosphate (HPO42-) buffered aqueous solutions in the presence of ethanol. These complex multistep reactions are initiated by the proton-coupled electron transfer (PCET) which reduces BrCH2CO2- and incites its debromination. The PCET is followed by the step in which the resulting carboxymethyl radical propagates a radical chain reaction thus recovering ˙CH(CH3)OH and enhancing the debromination yields. It is found that the rate constants for the initial PCET step (k1) are raised by ca. an order of magnitude in the presence of the buffers (k1(NB) = 1.4 × 105 dm3 mol-1 s-1; k1(HCO3-) = 1.4 × 106 dm3 mol-1 s-1; k1(HPO42-) = 1.1 × 106 dm3 mol-1 s-1). To rationalize this, we used density functional theory at the M06-2X-D3/6-311+G(2d,p) level in conjunction with the polarizable continuum model (PCM) for an implicit description of the aqueous environment. To acceptably reproduce the measured rate constants, the minimal solute, consisting of ˙CH(CH3)OH, BrCH2CO2- and the buffer anion, has to be expanded by at least 2-3 explicit molecules of the water solvent. The used kinetic model consisting of a set of coupled differential equations indicates the sigmoid dependence of yields vs. k1 thereby confirming the autocatalytic trait of these reactions. The computations unravel the profound influence of the presence of buffers on these reaction systems. On the one hand, the buffer anions promote the PCET by accelerating the proton transfer; on the other hand, they slow down the propagation step by forming the strong hydrogen bonds with the carboxymethyl radical. The two opposing effects cancel out and cause the Br- yields to remain approximately comparable in the non-buffered and buffered media.

Proton-coupled electron transfer is the dominant mechanism of reduction of haloacetates by the α-hydroxyethyl radical in aqueous media.

The reaction systems of α-hydroxyalkyl radicals with halogenated organics in aqueous solutions are uniquely suited for studying the fundamentally important proton-coupled electron transfer (PCET) mechanism in competition with alternatives such as substitution, hydrogen abstraction, halogen atom abstraction etc. We report experimental (steady state γ-radiolysis) and theoretical (density functional theory) studies of reactions of the α-hydroxyethyl radical (˙EtOH) with the four monohaloacetate anions (XAc-): fluoroacetate (FAc-), chloroacetate (ClAc-), bromoacetate (BrAc-) and iodoacetate (IAc-). The reactions are conducted in non-buffered and buffered (bicarbonate or phosphate) aqueous solutions of ethanol. In these conditions, only IAc- and BrAc- are reduced by ˙EtOH, and the PCET is predicted to be the most feasible reaction mechanism. In contrast to analogous reaction systems with alkyl halides, halophenols and 5-bromouracil, the radical-mediated one-electron reduction and subsequent dehalogenation of IAc- and BrAc- proceed regardless of the presence of buffers as the external proton acceptors. This implies that the proton can be efficiently transferred to the carboxyl group. The proton transfer is predicted to take place directly as interposition of one water molecule raises the barriers to the PCET. The addition of HCO3- or HPO42- accelerates the PCET owing to their larger proton affinities compared to that of the carboxyl group. The reduction of IAc- and BrAc- generates daughter carboxymethyl radicals thus initiating a radical chain reaction which considerably enhances the Br- and I- yields. In contrast, ClAc- and FAc- are not degraded by ˙EtOH even at elevated temperatures. These comparatively simple reaction systems enable general insights into PCET processes in which the carboxyl group may assume the role of proton acceptor.