In situ electro-organic synthesis of hydroquinone using anisole on MWCNT/Nafion modified electrode surface and its heterogeneous electrocatalytic reduction of toxic Cr(vi) species.

Owing to its electro-inactive character, anisole (phenylmethyl ether, PhOCH3) and its related derivatives have been used as electrolytes in electrochemistry. Herein, we report a simple one-step electro-organic conversion of PhOCH3 to hydroquinone (HQ) on a pristine-MWCNT-Nafion modified electrode glassy carbon electrode surface, GCE/Nf-MWCNT@HQ, in pH 2 KCl-HCl solution within 15 min of working time. The chemically modified electrode showed a highly redox-active and well-defined signal at an apparent standard electrode potential, E o' = 0.45 V vs. Ag/AgCl (A2/C2) with a surface excess value, Γ HQ = 2.1 × 10-9 mol cm-2. The formation of surface-confined HQ is confirmed by collective physicochemical and spectroscopic characterizations using TEM, UV-Vis, Raman, FTIR, NMR and GC-MS techniques and with several control experiments. Consent about the mechanism, the 2.1% of intrinsic iron present in the pristine-MWCNT is involved for specific complexation with oxygen donor organic molecule (PhOCH3) and hydroxylation in presence of H2O2 (nucleophilic attack) for HQ-product formation. The GCE/Nf-MWCNT@HQ showed an excellent heterogeneous-electrocatalytic reduction of Cr(vi) species in acidic solution with a linear calibration plot in a range, 5-500 ppm at an applied potential, 0.4 V vs. Ag/AgCl with a detection limit, 230 ppb (S/N = 3; amperometric i-t). As a proof of concept, selective detection of toxic Cr(vi) content in the tannery-waste water has been demonstrated with a recovery value ∼100%.

Facile Electrochemical Demethylation of 2-Methoxyphenol to Surface-Confined Catechol on the MWCNT and Its Efficient Electrocatalytic Hydrazine Oxidation and Sensing Applications.

Owing to its biological significance, preparation of stable surface-confined catechol (CA) is a long-standing interest in electrochemistry and surface chemistry. In this connection, various chemical approaches such as covalent immobilization (using amine- and carboxylate-functionalized CA, diazotization-based coupling, and Michael addition reaction), self-assembled monolayer on gold (thiol-functionalized CA is assembled on the gold surface), CA adsorption on the ad-layer of a defect-free single-crystal Pt surface, π-π bonding, CA pendant metal complexes, and CA-functionalized polymer-modified electrodes have been reported in the literature. In general, these conventional methods are involved with a series of time-consuming synthetic procedures. Indeed, the preparation of a surface-fouling-free surface-confined system is a challenging task. Herein, we introduce a new and facile approach based on electrochemical demethylation of 2-methoxyphenol as a precursor on the graphitic surface (MWCNT) at a bias potential, 0.5 V vs Ag/AgCl in neutral pH solution. Such an electrochemical performance resulted in the development of a stable and well-defined redox peak at E o' = 0.15 (A2/C2) V vs Ag/AgCl within 10 min of preparation time in pH 7 phosphate buffer solution. Calculated surface excess (16.65 × 10-9 mol cm-2) is about 10-1000 times higher than the values reported with other preparation methods. The product (catechol) formed on the modified electrode was confirmed by collective electrochemical and physicochemical characterizations such as potential segment analysis, TEM, Raman, IR, UV-vis, GC-MS, and NMR spectroscopic techniques, and thin-layer chromatographic studies. The electrocatalytic efficiency of the surface-confined CA system was demonstrated by studying hydrazine oxidation and sensing reactions in a neutral pH solution. This new system is found to be tolerant to various interfering biochemicals such as uric acid, xanthine, hypoxanthine, glucose, nitrate, hydrogen peroxide, ascorbic acid, Cu2+, and Fe2+. Since the approach is simple, rapid, and reproducible, a variety of surface-confined CA systems can be prepared.

Synthetic Guaiacol Derivatives as Promising Myeloperoxidase Inhibitors Targeting Atherosclerotic Cardiovascular Disease.

Myeloperoxidase (MPO) is known to cause oxidative stress and inflammation leading to cardiovascular disease (CVD) complications. MPO-mediated oxidation of lipoproteins leads to dysfunctional entities altering the landscape of lipoprotein functionality. The specificity of guaiacol derivatives toward preventing MPO-mediated oxidation to limit MPO's harmful effects is unknown. Diligent in silico studies were accomplished for a portfolio of compounds with guaiacol as a building block. The compounds' activity toward MPO inhibition was also validated. The role of these chemical entities in controlling MPO-mediated oxidation of lipoproteins (LDL and HDL) was shown to agree with our approach of developing powerful MPO inhibitors. The mechanism of MPO inhibition was demonstrated to be reversible in nature. This study reveals that there is great potential for guaiacol derivatives as therapeutics for CVD by modulating lipid profiles, reducing atherosclerotic plaque burden, and subsequently optimizing cardiovascular functions.

In Situ Immobilized Sesamol-Quinone/Carbon Nanoblack-Based Electrochemical Redox Platform for Efficient Bioelectrocatalytic and Immunosensor Applications.

Most of the common redox mediators such as organic dyes and cyanide ligand-associated metal complex systems that have been used for various electrochemical applications are hazardous nature. Sesamol, a vital nutrient that exists in natural products like sesame seeds and oil, shows several therapeutic benefits including anticancer, antidiabetic, cardiovascular protective properties, etc. Herein, we introduce a new electrochemical redox platform based on a sesamol derivative, sesamol-quinone (Ses-Qn; oxidized sesamol), prepared by the in situ electrochemical oxidation method on a carbon nanoblack chemically modified glassy carbon electrode surface (GCE/CB@Ses-Qn) in pH 7 phosphate buffer solution, for nontoxic and sustainable electrochemical, electroanalytical, and bioelectroanalytical applications. The new Ses-Qn-modified electrode showed a well-defined redox peak at E o = 0.1 V vs Ag/AgCl without any surface-fouling behavior. Following three representative applications were demonstrated with this new redox system: (i) simple and quick estimation of sesamol content in the natural herbal products by electrochemical oxidation on GCE/CB followed by analyzing the oxidation current signal. (ii) Utilization of the GCE/CB@Ses-Qn as a transducer, bioelectrocatalytic reduction, and sensing of H2O2 after absorbing the horseradish peroxidase (HRP)-based enzymatic system on the underlying surface. The biosensor showed a highly selective H2O2 signal with current sensitivity and detection limit values 0.1303 µA µM-1 and 990 nM, respectively, with tolerable interference from the common biochemicals like dissolved oxygen, cysteine, ascorbic acid, glucose, xanthine, hypoxanthine, uric acid, and hydrazine. (iii) Electrochemical immunosensing of white spot syndrome virus by sequentially modifying primary antibody, antigen, secondary antibody (HRP-linked), and bovine serum albumin on the redox electrode, followed by selective bioelectrochemical detection of H2O2.

UPEI-400, a conjugate of lipoic acid and scopoletin, mediates neuroprotection in a rat model of ischemia/reperfusion.

Previously, our laboratory provided evidence that lipoic acid (LA) covalently bonded to various antioxidants, resulted in enhanced neuroprotection compared to LA on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. The present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of LA and scopoletin covalently bonded together, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy. Using a rat stroke model, male rats were anesthetized (Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 h (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 h of reperfusion (ischemia/reperfusion; I/R). Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p < 0.05), but not in the pMCAO model of stroke. UPEI-400 was ∼1000 times more potent compared to scopoletin alone. Since UPEI-400 was only effective in a model of I/R, it is possible that it may act to enhance neuronal antioxidant capacity and/or upregulate anti-inflammatory pathways to prevent the neuronal cell death.

Co-administration of resveratrol and lipoic acid, or their synthetic combination, enhances neuroprotection in a rat model of ischemia/reperfusion.

The present study demonstrates the benefits of combinatorial antioxidant therapy in the treatment of ischemic stroke. Male Sprague-Dawley rats were anaesthetised and the middle cerebral artery (MCA) was occluded for 30 minutes followed by 5.5 hours of reperfusion. Pretreatment with resveratrol 30 minutes prior to MCA occlusion resulted in a significant, dose-dependent decrease in infarct volume (p<0.05) compared to vehicle-treated animals. Neuroprotection was also observed when resveratrol (2 × 10(-3) mg/kg; iv) was administered within 60 minutes following the return of blood flow (reperfusion). Pretreatment with non-neuroprotective doses of resveratrol (2 × 10(-6) mg/kg) and lipoic acid (LA; 0.005 mg/kg) in combination produced significant neuroprotection as well. This neuroprotection was also observed when resveratrol and LA were administered 15 minutes following the onset of MCA occlusion. Subsequently, we synthetically combined resveratrol and LA in both a 1 ∶ 3 (UPEI-200) and 1 ∶ 1 (UPEI-201) ratio, and screened these new chemical entities in both permanent and transient ischemia models. UPEI-200 was ineffective, while UPEI-201 demonstrated significant, dose-dependent neuroprotection. These results demonstrate that combining subthreshold doses of resveratrol and LA prior to ischemia-reperfusion can provide significant neuroprotection likely resulting from concurrent effects on multiple pathways. The additional protection observed in the novel compound UPEI 201 may present opportunities for addressing ischemia-induced damage in patients presenting with transient ischemic episodes.

Novel Neurovascular Protective Agents: Effects of INV-155, INV-157, INV-159, and INV-161 versus Lipoic Acid and Captopril in a Rat Stroke Model.

Background. Lipoic acid (LA), which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO) in rats. Methods. Male Sprague-Dawley rats were injected intravenously with captopril (1-50 mg/kg) 30 minutes prior to MCAO. Blood pressure, heart rate, baroreceptor reflex sensitivity, and infarct size were measured. In addition, dose response effect on infarct size and cardiovascular parameters was determined using INV-155, INV-157, INV-159, and INV-161 and compared to captopril and LA. Results. Pretreatment with captopril and LA at all doses tested was neuroprotective. The compounds INV-159 (0.5-10 mg/kg) and INV-161 (1-10 mg/kg) produced a significant,dose-dependent decrease in infarct size. In contrast, INV-155 and INV-157 had no effect on infarct size. Conclusions. Combined pretreatment with captopril potentiated the neuroprotective benefit observed following LA alone. Both INV-159 and INV-161 were also neuroprotective. These results suggest that patients taking combinations of captopril and LA, either as combination therapy or in the form of INV-159 or INV-161, may also benefit from significant protection against cerebral infarction.

UPEI-100, a conjugate of lipoic acid and apocynin, mediates neuroprotection in a rat model of ischemia/reperfusion.

Previous work in our laboratory has provided evidence that preadministration of apocynin and lipoic acid at subthreshold levels for neuroprotection enhanced the neuroprotective capacity when injected in combination. Therefore, the present investigation was designed to determine whether a co-drug consisting of lipoic acid and apocynin functional groups bound by a covalent bond, named UPEI-100, is capable of similar efficacy using a rodent model of stroke. Male rats were anesthetized with Inactin (100 mg/kg iv), and the middle cerebral artery was occluded for 6 h or allowed to reperfuse for 5.5 h following a 30-min occlusion (ischemia/reperfusion, I/R). Preadministration of UPEI-100 dose-dependently decreased infarct volume in the I/R model (P < 0.05), but not in the middle cerebral artery occlusion model of stroke. Using the optimal dose, we then injected UPEI-100 during the stroke or at several time points during reperfusion, and significant neuroprotection was observed when UPEI-100 was administered up to 90 min following the start of reperfusion (P < 0.05). A time course for this neuroprotective effect showed that UPEI-100 resulted in a decrease in infarct volume following 2 h of reperfusion compared with vehicle. The time course of this neuroprotective effect was also used to study several mediators along the antioxidant pathway and showed that UPEI-100 increased the level of mitochondrial superoxide dismutase and oxidized glutathione and decreased a marker of lipid peroxidation due to oxidative stress (HNE-His adduct formation). Taken together, the data suggest that UPEI-100 may utilize similar pathways to those observed for the two parent compounds; however, it may also act through a different mechanism of action.

Unimolecular rectification of monolayers of CH3C(O)S-C14H28Q(+)-3CNQ(-) and CH3C(O)S-C16H32Q(+)-3CNQ(-) organized by self-assembly, Langmuir-Blodgett, and Langmuir-Schaefer techniques.

The advantage of "self-assembly" (strong covalent binding to substrates) was combined with the advantage of Langmuir-Blodgett (LB) or Langmuir-Schaefer (LS) transfer to a solid substrate (quantitative transfer of monolayers to the substrate). The electrical rectification (asymmetric conduction) by a monolayer of thioacetylalkylquinolinium tricyanoquinodimethanide was critically compared when these molecules had been transferred, by such competing techniques, onto gold electrodes, and then covered by a "cold gold" pad electrode. Unimolecular rectification was observed in the expected directions in the LB and LS monolayers. The Self-Assembled Monolayers (SAMs) were disordered; macroscopic measurements of rectification were unsuccessful for the SAMs, but successful for the down-stroke LB and LS monolayers, whose orientation and potential bonding to the Au surface should be identical to that of an ideal SAM.

Thiophene isosteres of 9,10-dithioanthraquinone.

[reaction: see text] The preparation of 1,3,5,7-tetramethyl-4,8-dihydrobenzo[1,2-c:4,5-c']dithiophene-4,8-dione and its conversion to the corresponding mono- and dithione are described.

Synthesis of the first 1,3-ditellurole-containing radialene-type TTF derivatives.

[reaction: see text] The first synthesis of dendralene-type TTF derivatives bearing a 1,3-ditellurole ring has been achieved. Preliminary electrochemical results are presented.

Generation of the first tellurium-containing diheteropentalene.

[reaction: see text] The known diester dibromomethylthiophene was converted to the tellurolo[3,4-c]thiphene, the first example of a diheteropentalene containing a tellurophene annelated across the 3,4-c position to thiophene. It is stable in solution and adds to DMAD across the 2,5-positions in tellurophene. The intermediate loses tellurium and collapses to a tetracarbomethoxy benzo[c]thiophene derivative.