Water-soluble N-carboxymethylchitosan derivatives: Preparation,characteristics and its application

In this work, only N-substituted chitosan derivatives (water-soluble N-carboxymethylchitosan derivatives: N-CMC) with different degrees of substitution were obtained by reaction of a fully deacetylated chitosan (derived from deacetylation of chitosan using decrystallized method) with monochloroacetic acid at pH 8 and temperature of 90 °C. The structure of N-carboxymethylchitosan and chitosan was characterized by IR, ¹H, ¹³C and ¹H–¹³C NMR-HSQC spectra. In the IR spectrum of the N-carboxymethylchitosan, the appearance of peak at 1742 cm^?1 was assigned for CO group of NHCH₂COOH of substituted chitosan. In the ¹H NMR spectra, the peaks at about 3.81÷4.06 ppm, assigned for CH₂ groups of NHCH₂ and N(CH₂)₂, were the major feature, while in the ¹H–¹³C NMR-HSQC spectra, signals of CH₂ confirmed the presence of these two different substituted CH₂ groups. The degree of substitution (DS) of N-monosubstitution (DS_N-mono) decreased from 0.47 to 0.03 meanwhile that of N,N-disubstitution (DS_N,N-di) increased from 0.52 to 0.96 since the mass ratio of chitosan/monochloroacetic acid changing from 1/1 to 1/4. The N-carboxymethylchitosan derivatives have been used for adsorption Cu(II) ion from aqueous solution. The results shown that the optimum conditions for adsorption Cu(II) ion in nitrate solution were pH 6.5, temperature of 30 °C, for 60–90 min and the substituted chitosan derivative having DS_N-mono of 0.16 and DS_N,N-di of 0.81 had maximum adsorption capacity of 192 mg Cu(II) per gram of N-CMC.     

Adsorption characteristics of sulfur solution by acticarbon against drinking-water toxicosis

Sulfur and ammonia nitrogen are rich nutrient pollutants, after entering water can cause algal blooms, cause eutrophication of water body, the spread of them will not only pollute the environment, destroy the ecological balance, but also harm human health through food chain channels, especially drinking-water toxicosis. Acticarbon can adsorb harmful substances, it was beneficial for people’s health. In order to figure out the optimal adsorption condition and the intrinsic change of acticarbon, five chemicals were adsorbed by acticarbon and analyzed by FT-IR. The optimal adsorption condition of Fe₂(SO₄)₃, Na₂SO₄, Na₂S₂O₈, S and Na₂SO₃ was 9 g/1000 g at 80 min, 21 g/1000 g at 20 min, 15g/1000 g at 20 min, 21 g/1000 g at 60 min and 21 g/1000 g at 100 min, respectively. FT-IR spectra showed that acticarbon had eight characteristic peaks, such as S-S stretch, H₂O stretch, OH stretch, CH stretch, CO or CC stretch, CH₂ bend, CH were at 3850 cm⁻¹, 3740 cm⁻¹, 3435 cm⁻¹, 2925 cm⁻¹, 1630 cm⁻¹, 1390 cm⁻¹, 1115 cm⁻¹, 600 cm⁻¹, respectively. For FT-IR spectra of Fe₂(SO₄)₃, the peaks at 3850 cm⁻¹, 3740 cm⁻¹, 2925 cm⁻¹ achieved the maximum with 9 g/1000 g at 20 min. For Na₂SO₄, the peaks at 2925 cm⁻¹, 1630 cm⁻¹, 1390 cm⁻¹, 1115 cm⁻¹, 600 cm⁻¹ achieved the maximum with 21 g/1000 g at 120 min. For ones of Na₂S₂O₈, the peaks at 3850 cm⁻¹, 3740 cm⁻¹, 1390 cm⁻¹, 1115 cm⁻¹, 600 cm⁻¹, achieved the maximum with 2 g/1000 g at 80 min. For ones of S, the peaks at 3850 cm⁻¹, 3740 cm⁻¹, 2925 cm⁻¹ achieved the maximum with 19 g/1000 g at 100 min, the peaks at 1390 cm⁻¹, 1115 cm⁻¹, 600 cm⁻¹ achieved the maximum with 19 g/1000 g at 20 min. For FT-IR spectra of Na₂SO₃, the peaks at 1630 cm⁻¹, 1390 cm⁻¹, 1115 cm⁻¹, 600 cm⁻¹ achieved the maximum with 2 g/1000 g at 100 min. It provided that acticarbon could adsorb and desulphurize from sulfur solution against drinking-water toxicosis.     

Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors,in silico studies and DFT based stereochemical predictions

2-Indolcarbohydrazones 1–28 were synthesized and evaluated for their α-glucosidase inhibitory potential. A varying degree of inhibitory potential with IC₅₀ values in the range of 2.3 ± 0.11–226.4 ± 6.8 μM was observed while comparing these outcomes with the standard acarbose (IC₅₀ = 906.0 ± 6.3 μM). The stereochemistry of ten (10) randomly selected compounds (1, 3, 6, 8, 12, 18, 19, 23, 25 and 28) was predicted by Density Functional Theory (DFT). The stability of E isomer was deduced by comparing the calculated and experimental vibration modes of ν_CO, ν_NC and ν_CH (CH in NCH-R). It was observed that except compound 18, all other compounds were deduced to have E configuration while molecular modeling studies revealed the key interactions between enzyme and synthesized compounds.     

Adsorption characteristics of sulfur powder by bamboo charcoal to restrain sulfur allergies

Exposures to particulate matter with a diameter of 2.5 μm or less (PM2.5) may influence the risk of birth defects and make you allergic, which causes serious harm to human health. Bamboo charcoal can adsorb harmful substances,that was of benefitto people’s health. In order to figure out the optimal adsorbtion condition and the intrinsic change of bamboo charcoal, five chemicals were adsorbed by bamboo charcoal and were analyzed by FT-IR. The optimal blast time was 80 min of Na₂SO₃, 100 min of Na₂S₂O₈, 20 min of Na₂SO₄, 120 min of Fe₂(SO₄)₃ and 60 min or 100 min of S. FT-IR spectra showed that bamboo charcoal had five characteristic peaks of SS stretch, H₂O stretch, OH stretch, CO stretch or CC stretch, and NO₂ stretch at 3850 cm⁻¹, 3740 cm⁻¹, 3430 cm⁻¹, 1630 cm⁻¹ and 1530 cm⁻¹, respectively. For Na₂SO₃, the peaks at 3850 cm⁻¹, 3740 cm⁻¹, 3430 cm⁻¹, 1630 cm⁻¹ and 1530 cm⁻¹ achieved the maximum at 20 min. For Na₂S₂O₈, the peaks at 3850 cm⁻¹, 3740 cm⁻¹, 3430 cm⁻¹ and 1530 cm⁻¹ achieved the maximum at 40 min. For Na₂SO₄, the peaks at 3850 cm⁻¹, 3740 cm⁻¹ and 1530 cm⁻¹ achieved the maximum at 40 min. For Fe₂(SO₄)₃, the peaks at 3850 cm⁻¹, 3740 cm⁻¹, 1630 cm⁻¹ and 1530 cm⁻¹ achieved the maximum at 120 min. For S, the peaks at 3850 cm⁻¹ and 3740 cm⁻¹ achieved the maximum at 40 min, the peaks at 1630 cm⁻¹ and 1530 cm⁻¹ achieved the maximum at 40 min. It proved that bamboo charcoal could remove sulfur powder from air to restrain sulfur allergies.     

Effect of Pb2+ on the production of hydroxyl radical during solid-state fermentation of straw with Phanerochaete chrysosporium

Hydroxyl radical (OH) is a radical species highly destructive for lignin during solid-state fermentation (SSF) of straw with Phanerochaete chrysosporium (Pc). The production of OH at different initial Pb²⁺ concentrations during SSF of straw with Pc was investigated. The results showed that a modest amount (under 200 mg kg⁻¹) of Pb²⁺ could enhance the production of OH, while a higher Pb²⁺ concentration resulted in inhibition. The content of OH reached the peak value at day 12 in the whole tested samples, and the maximal content of OH was obtained at initial Pb²⁺ concentration of 100 mg kg⁻¹. It was also found that the production of OH was connected to enzymatic activity and oxalate content in some degree, in particular, a significant positive correlation was found between oxalate concentration and production of OH.We found that low concentration of Pb²⁺ can promote the degradation of lignin, and the higher initial Pb²⁺ concentration (400 mg kg⁻¹) resulted in inhibition. In addition, it appeared that there was no significant correlation between lignin degradation rate and the production of OH when Pb²⁺ concentration was taken into account.     

Enhancements of enantio and diastereoselectivities in reduction of (Z)-3-halo-4-phenyl-3-buten-2-one mediated by microorganisms in ionic liquid/water biphasic system

Reductions of (Z)-C₆H₅CHCXC(O)CH₃ (X = Cl, Br) mediated by Saccharomyces cerevisiae, Candida albicans, Rhodotorula glutinis, Geotrichum candidum and Micrococcus luteus gave the corresponding halohydrins through consecutive reduction reactions of CC and CO bonds. In general, the reactions performed in the biphasic system water/[(bmim)PF₆] gave better diastereoselectivity and enantioselectivity than in pure water.     

Calibration of nitric oxide flux generation from diazeniumdiolate NO donors

The 1-(secondary amino) diazen-1-ium-1,2-diolates (NONOates) are the most commonly utilized nitric oxide (NO, nitrogen monoxide) donor because of the ability of different NONOates to spontaneously break down liberating NO at different rates, which can be utilized to control NO fluxes. However, the parameters that determine these fluxes of NO generation, half-lives and stoichiometry of NO per donor, can vary significantly with specific experimental conditions in addition to the donor chosen. Here we report straightforward methods that can be used to determine these parameters. For donors of intermediate half-life (10–80 min) a real-time oxymyoglobin (oxyMb) assay can be analyzed to simultaneously determine both the half-life and the total amount of NO liberated, from which the NO flux can be obtained for any given donor concentration. The half-lives obtained by oxyMb assay are very similar to those obtained by following NONOate decomposition kinetics spectrophotometrically, and a survey of several NONOates from different commercial sources show consistent results. These data provide validation for the methodologies employed. In addition, procedures are described for calibration of donors with shorter (<10 min) and longer (>80 min) half-lives. These procedures can be used to reproducibly and routinely calibrate NO fluxes for a variety of donors under any specific condition.     

Differential roles of nitric oxide synthases in regulation of ultraviolet B light-induced apoptosis

Ultraviolet B light (UVB) activates nitric oxide synthase(s) (NOSs) and nitric oxide (NO) production, which plays a role in regulation of apoptosis. However, the role of NO in UVB-induced apoptosis remains controversial. In this study, we analyzed expression and activation of constitutive NOSs (cNOSs) and their roles in UV-induced apoptosis of HaCaT keratinocytes. Our data showed that the expression of neuronal NOS (nNOS) was increased while endothelial NOS (eNOS) was uncoupled in the early phase (0–6 h) post-UVB. The expression of both cNOSs peaked at 12 h post-UVB and NO was transiently elevated with 30 min and then steadily rose from 6 to 18 h post-UVB. The expression of iNOS was detected at 6 h post-UVB and then sturdily increased. Inhibition of cNOSs with l-NAME reduced the inducibility of NO in the early and late phases of irradiation. Along with the eNOS uncoupling, an increased level of peroxynitrite (ONOO^?) was detected in the early phase, but not in the late phase post-UVB. Inhibition of cNOSs reduced the production of ONOO^? in the early time, but led to an increase of ONOO^? in the late time after UVB-irradiation. The results indicate that cNOSs regulate NO/ONOO^? imbalance after UVB-irradiation. Our data suggested that the activation of cNOSs in the early phase post-UVB leads to NO/ONOO^? imbalance and promotes apoptosis via a caspase 3-independent pathway. The elevation of NO in the late phase of UVB-irradiation is mainly produced by inducible NOS (iNOS). However, cNOSs also contribute to the NO production and to maintain a higher NO/ONOO^? ratio, which reduces caspase 3 activity and protects cells from UVB-induced apoptosis.     

Mechanisms and kinetic profiles of superoxide-stimulated nitrosative processes in cells using a diaminofluorescein probe

In this study, we examined the mechanisms and kinetic profiles of intracellular nitrosative processes using diaminofluorescein (DAF-2) as a target in RAW 264.7 cells. The intracellular formation of the fluorescent, nitrosated product diaminofluorescein triazol (DAFT) from both endogenous and exogenous nitric oxide (NO) was prevented by deoxygenation and by cell membrane-permeable superoxide (O₂⁻) scavengers but not by extracellular bovine Cu,Zn-SOD. In addition, the DAFT formation rate decreased in the presence of cell membrane-permeable Mn porphyrins that are known to scavenge peroxynitrite (ONOO⁻) but was enhanced by HCO₃⁻/CO₂. Together, these results indicate that nitrosative processes in RAW 264.7 cells depend on endogenous intracellular O₂⁻ and are stimulated by ONOO⁻/CO₂-derived radical oxidants. The N₂O₃ scavenger sodium azide (NaN₃) only partially attenuated the DAFT formation rate and only with high NO (>120 nM), suggesting that DAFT formation occurs by nitrosation (azide-susceptible DAFT formation) and predominantly by oxidative nitrosylation (azide-resistant DAFT formation). Interestingly, the DAFT formation rate increased linearly with NO concentrations of up to 120–140 nM but thereafter underwent a sharp transition and became insensitive to NO. This behavior indicates the sudden exhaustion of an endogenous cell substrate that reacts rapidly with NO and induces nitrosative processes, consistent with the involvement of intracellular O₂⁻. On the other hand, intracellular DAFT formation stimulated by a fixed flux of xanthine oxidase-derived extracellular O₂⁻ that also occurs by nitrosation and oxidative nitrosylation increased, peaked, and then decreased with increasing NO, as previously observed. Thus, our findings complementarily show that intra- and extracellular O₂⁻-dependent nitrosative processes occurring by the same chemical mechanisms do not necessarily depend on NO concentration and exhibit different unusual kinetic profiles with NO dynamics, depending on the biological compartment in which NO and O₂⁻ interact.     

Rational derivation of CETP self-binding helical peptides by π-π stacking and halogen bonding: Therapeutic implication for atherosclerosis

The human cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from high-density lipoprotein (HDL) to other lipoproteins and has been established as an attractive target for reducing the risk of atherosclerosis. Here, an amphipathic α-helix peptide, namely SBH-peptide (⁴⁶⁵EHLLVDFLQSLS⁴⁷⁶), was derived from the C-terminal tail of CETP. The peptide exhibits self-binding capability towards the CETP. Crystal structure analysis, molecular dynamics (MD) simulations and ab initio electron correlation characterizations of CETP–SBH-peptide complex system revealed that the Phe471 residue plays a key role in SBH-peptide binding, which can form a π-π stacking with the Phe197 residue of CETP. In addition, substitution of the hydrogen atom H4 of Phe471 with halogen atoms, in particular the bromine atom Br4, can constitute a geometrically satisfactory halogen bonding with the oxygen atom O of CETP Ile193 residue. Fluorescence polarization assays substantiated that (i) mutation of the aromatic Phe471 to small Ala residue would impair the SBH-peptide affinity with K_d change from 10.5 to 26.4 μM, indicating that the π-π stacking should exist in Phe471⋯Phe197 adduct, and (ii) substitution with Br4 can considerably improve SBH-peptide affinity by ∼3-fold, but the SBH-peptide binding does not change essentially upon substitution with Br3 (a negative control that is theoretically unable to form the halogen bonding), indicating that the rationally designed halogen bonding should form between the Phe471(Br4) residue of SBH-peptide and the Ile193 residue of CETP protein.     

Zinc protects Ceratophyllum demersum L. (free-floating hydrophyte) against reactive oxygen species induced by cadmium

Evidence for Zn protection against Cd-induced reactive oxygen species in the free-floating hydrophyte Ceratophyllum demersum L. is presented in this paper. Metal treatments of 10 μmol/L Cd, 10 Cd μmol/L supplemented with Zn (10, 50, 100 and 200 μmol/L) and Zn-alone treatments of the same concentrations were used. Using 5,5 dimethyl pyrroline-N-oxide as the spin-probe, electron spin resonance spectra indicated a drastic increase in hydroxyl radicals (OH) in Cd-10 μmol/L treatments, which was closely correlating with the enhanced formation of hydrogen peroxide (H₂O₂) and generation of superoxide radical (O₂^?) triggered by the oxidation of NADPH. The supplementation of adding Zn (10–200 μmol/L) to the Cd-10 μmol/L treatments significantly decreased the production of free radicals especially by eliminating the precursors of OH through inhibition of NADPH oxidation. Cd-enhanced ROS production which substantially increased the oxidative products of proteins measured as carbonyls was effectively inhibited by Zn supplementation.     

Free radical scavenging activity from different extracts of leaves of Bauhinia vahlii Wight & Arn.

The objectives of this study were to determine phenolic content and antioxidant activities of chloroform, acetone, methanol and hot water extracts of Bauhinia vahlii leaves. The hot water extract afforded the highest yield (6.3%) while the lowest yield was obtained from the chloroform extract (2.1%). The methanol extract contains higher levels of total phenolics (48.7 ± 0.7 g GAE/100 g extract), tannins (21.7 ± 0.7 g GAE/100 g extract) and flavonoids (10.3 ± 0.2 RE/100 g extract). The extracts were subjected to assess their antioxidant potential using various in vitro systems such as DPPH, ABTS⁺, FRAP, OH, β-carotene linoleic acid bleaching system, phosphomolybdenum reduction and Fe²⁺ chelation. It is concluded that the methanolic extract of B. vahlii leaves have strong antioxidant potential. Further study is necessary for isolation and characterization of the active antioxidants, which may serve as a potential source of natural antioxidants.     

Synthesis of new mer,trans-rhodium(III) hydrido-bis(acetylide) complexes: Structure of mer,trans-[(PMe3)3Rh(CC–C6H4-4-NMe2)2H]

Terminal alkynes (R–CC–H, R = 1-naphthyl, 9-anthryl, 4-Me₂N–C₆H₄–, or the longer analogue, 4-(4-Me₂N–C₆H₄–CC–)–C₆H₄–) react with [Rh(PMe₃)₄Me] at ambient temperature, with loss of methane and one PMe₃ ligand, to form the corresponding mer,trans-[(PMe₃)₃Rh(CCR)₂H] compounds in excellent yield. In this preliminary study, the synthesis and spectroscopic characterization of the four new compounds are reported, along with the single-crystal structure of the R = 4-Me₂N–C₆H₄ derivative.     

Synthesis,antioxidant, and antimicrobial evaluation of some 2-arylbenzimidazole derivatives

A series of 2-arylbenzimidazole derivatives (3a–3p and 4a–4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO) scavenging, superoxide radical anion (O₂^?) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO scavenging activity (EC₅₀ = 46 μM) in vitro had a significant reduction of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H₂O₂-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations.     

Kinetics and mechanism of auto- and copper-catalyzed oxidation of 1,4-naphthohydroquinone

Although quinones represent a class of organic compounds that may exert toxic effects both in vitro and in vivo, the molecular mechanisms involved in quinone species toxicity are still largely unknown, especially in the presence of transition metals, which may both induce the transformation of the various quinone species and result in generation of harmful reactive oxygen species. In this study, the oxidation of 1,4-naphthohydroquinone (NH₂Q) in the absence and presence of nanomolar concentrations of Cu(II) in 10 mM NaCl solution over a pH range of 6.5–7.5 has been investigated, with detailed kinetic models developed to describe the predominant mechanisms operative in these systems. In the absence of copper, the apparent oxidation rate of NH₂Q increased with increasing pH and initial NH₂Q concentration, with concomitant oxygen consumption and peroxide generation. The doubly dissociated species, NQ²⁻, has been shown to be the reactive species with regard to the one-electron oxidation by O₂ and comproportionation with the quinone species, both generating the semiquinone radical (NSQ⁻). The oxidation of NSQ⁻ by O₂ is shown to be the most important pathway for superoxide (O₂⁻) generation with a high intrinsic rate constant of 1.0×10⁸ M⁻¹ s⁻¹. Both NSQ⁻ and O₂⁻ served as chain-propagating species in the autoxidation of NH₂Q. Cu(II) is capable of catalyzing the oxidation of NH₂Q in the presence of O₂ with the oxidation also accelerated by increasing the pH. Both the uncharged (NH₂Q⁰) and the mono-anionic (NHQ⁻) species were found to be the kinetically active forms, reducing Cu(II) with an intrinsic rate constant of 4.0×10⁴ and 1.2×10⁷ M⁻¹ s⁻¹, respectively. The presence of O₂ facilitated the catalytic role of Cu(II) by rapidly regenerating Cu(II) via continuous oxidation of Cu(I) and also by efficient removal of NSQ⁻ resulting in the generation of O₂⁻. The half-cell reduction potentials of various redox couples at neutral pH indicated good agreement between thermodynamic and kinetic considerations for various key reactions involved, further validating the proposed mechanisms involved in both the autoxidation and the copper-catalyzed oxidation of NH₂Q in circumneutral pH solutions.     

Protection against cardiac injury by small Ca2 +-sensitive K+ channels identified in guinea pig cardiac inner mitochondrial membrane

We tested if small conductance, Ca^2 +‐sensitive K⁺ channels (SK_Ca) precondition hearts against ischemia reperfusion (IR) injury by improving mitochondrial (m) bioenergetics, if O₂‐derived free radicals are required to initiate protection via SK_Ca channels, and, importantly, if SK_Ca channels are present in cardiac cell inner mitochondrial membrane (IMM). NADH and FAD, superoxide (O₂^?), and m[Ca^2 +] were measured in guinea pig isolated hearts by fluorescence spectrophotometry. SK_Ca and IK_Ca channel opener DCEBIO (DCEB) was given for 10 min and ended 20 min before IR. Either TBAP, a dismutator of O₂^?, NS8593, an antagonist of SK_Ca isoforms, or other K_Ca and K_ATP channel antagonists, were given before DCEB and before ischemia. DCEB treatment resulted in a 2-fold increase in LV pressure on reperfusion and a 2.5 fold decrease in infarct size vs. non-treated hearts associated with reduced O₂^? and m[Ca^2 +], and more normalized NADH and FAD during IR. Only NS8593 and TBAP antagonized protection by DCEB. Localization of SK_Ca channels to mitochondria and IMM was evidenced by a) identification of purified mSK_Ca protein by Western blotting, immuno-histochemical staining, confocal microscopy, and immuno-gold electron microscopy, b) 2-D gel electrophoresis and mass spectroscopy of IMM protein, c) [Ca^2 +]‐dependence of mSK_Ca channels in planar lipid bilayers, and d) matrix K⁺ influx induced by DCEB and blocked by SK_Ca antagonist UCL1684. This study shows that 1) SK_Ca channels are located and functional in IMM, 2) mSK_Ca channel opening by DCEB leads to protection that is O₂^? dependent, and 3) protection by DCEB is evident beginning during ischemia.     

The kinetics of the reaction of nitrogen dioxide with iron(II)- and iron(III) cytochrome c

The reactions of NO₂ with both oxidized and reduced cytochrome c at pH 7.2 and 7.4, respectively, and with N-acetyltyrosine amide and N-acetyltryptophan amide at pH 7.3 were studied by pulse radiolysis at 23 °C. NO₂ oxidizes N-acetyltyrosine amide and N-acetyltryptophan amide with rate constants of (3.1±0.3)×10⁵ and (1.1±0.1)×10⁶ M⁻¹ s⁻¹, respectively. With iron(III)cytochrome c, the reaction involves only its amino acids, because no changes in the visible spectrum of cytochrome c are observed. The second-order rate constant is (5.8±0.7)×10⁶ M⁻¹ s⁻¹ at pH 7.2. NO₂ oxidizes iron(II)cytochrome c with a second-order rate constant of (6.6±0.5)×10⁷ M⁻¹ s⁻¹ at pH 7.4; formation of iron(III)cytochrome c is quantitative. Based on these rate constants, we propose that the reaction with iron(II)cytochrome c proceeds via a mechanism in which 90% of NO₂ oxidizes the iron center directly—most probably via reaction at the solvent-accessible heme edge—whereas 10% oxidizes the amino acid residues to the corresponding radicals, which, in turn, oxidize iron(II). Iron(II)cytochrome c is also oxidized by peroxynitrite in the presence of CO₂ to iron(III)cytochrome c, with a yield of ~60% relative to peroxynitrite. Our results indicate that, in vivo, NO₂ will attack preferentially the reduced form of cytochrome c; protein damage is expected to be marginal, the consequence of formation of amino acid radicals on iron(III)cytochrome c.     

Inhibition of CYP2E1 attenuates chronic alcohol intake-induced myocardial contractile dysfunction and apoptosis

Alcohol intake is associated with myocardial contractile dysfunction and apoptosis although the precise mechanism is unclear. This study was designed to examine the effect of the cytochrome P450 enzyme CYP2E1 inhibition on ethanol-induced cardiac dysfunction. Adult male mice were fed a 4% ethanol liquid or pair-fed control diet for 6 weeks. Following 2 weeks of diet feeding, a cohort of mice started to receive the CYP2E1 inhibitor diallyl sulfide (100 mg/kg/d, i.p.) for the remaining feeding duration. Cardiac function was assessed using echocardiographic and IonOptix systems. Western blot analysis was used to evaluate CYP2E1, heme oxygenase-1 (HO-1), iNOS, the intracellular Ca^2 + regulatory proteins sarco(endo)plasmic reticulum Ca^2 +-ATPase, Na⁺Ca^2 + exchanger and phospholamban, pro-apoptotic protein cleaved caspase-3, Bax, c-Jun-NH₂-terminal kinase (JNK) and apoptosis signal-regulating kinase (ASK-1). Ethanol led to elevated levels of CYP2E1, iNOS and phospholamban, decreased levels of HO-1 and Na⁺Ca^2 + exchanger, cardiac contractile and intracellular Ca^2 + defects, cardiac fibrosis, overt O₂^? production, and apoptosis accompanied with increased phosphorylation of JNK and ASK-1, the effects were significantly attenuated or ablated by diallyl sulfide. Inhibitors of JNK and ASK-1 but not HO-1 inducer or iNOS inhibitor obliterated ethanol-induced cardiomyocyte contractile dysfunction, substantiating a role for JNK and ASK-1 signaling in ethanol-induced myocardial injury. Taken together, these findings suggest that ethanol metabolism through CYP2E1 may contribute to the pathogenesis of alcoholic cardiomyopathy including myocardial contractile dysfunction, oxidative stress and apoptosis, possibly through activation of JNK and ASK-1 signaling.     

An experimental and theoretical study of the electronic spectra of tetraethylammonium [bis(1,3-dithiole-2-thione-4,5-dithiolato)zincate(II)], [NEt4]2[Zn(dmit)2], and tetraethylammonium [bis(1,3-dithiole-2-one-4,5-dithiolato)zincate(II)], [NEt4]2[Zn(dmio)2]

Metal-dmit complexes and related compounds have been the object of intense study in the last decade. Despite such efforts on the study of its structural properties, very few attempts have been made to the spectroscopic study of these metal complexes. Experimental reports of its infrared, Raman and UV–Vis spectra present the main spectroscopic features, however, many details of the electronic structure have still to be fully investigated and inconsistent assignments are found in the literature. This work presents a detailed analysis of the UV–Vis spectra of the zinc-dmit, [Zn(dmit)₂]⁻², and the zinc-dmio complex, [Zn(dmio)₂]⁻². The experimental spectrum was deconvoluted and analysed with several theoretical methodologies including ab initio CI calculations, ab initio TD and zindo semi-empirical methods. The results confirm the multi-configuration nature of several excited states and the calculated results were concordant for several transitions. The results lead to a new assignment of the 457 nm band in the [Zn(dmit)₂]⁻² as π(pS_m) → π*CS band. In the metal-dmio, the sulfur substitution by oxygen results in a larger HOMO–LUMO gap and a change in the nature of the frontier orbitals. As the first transition we found, for the dmit compound, a high-intensity π → π*CS while for the zinc-dmio, a low-intensity π → σ*C–S transition.