Aromatic Inhibitor Research Articles

Comparative Assessment of Aromatic Iron Corrosion Inhibitors with Electrochemical Methods

Molecular aromatic corrosion inhibitors are frequently applied to slow down the corrosion of iron, its alloys and numerous other metallic materials. This case study with three representative aromatic inhibitors and a pure iron electrode aims at the verification of the reported conclusions regarding these inhibitors and at the verification and comparison of electrochemical corrosion assessment methods with attention to differences between iron alloys (steels) and pure iron possibly related to the presence/absence of alloying elements and non-iron impurities.

Aromatic Metal Corrosion Inhibitors

Molecular inhibitors added to the corrosive medium attacking metallic materials are a well-established way of combating corrosion. The inhibitive action proceeds via adsorption of the inhibitor on the surface to be protected. Aromatic building blocks in the inhibitor play a major role in its protective action, and further details like substituents, heteroatoms, and molecular geometry contribute. An overview focused on aromatic inhibitors is provided, aiming at the identification of particularly promising inhibitors and their mode of action. Directions for further research and development are pointed out in the conclusion.

A comparative experimental and theoretical calculation study of CaAl-LDH modified with various aromatic inhibitors for corrosion protection study in epoxy coatings

The in-depth influence mechanism of the functional groups and conjugated structure of aromatic inhibitor on the corrosion protection ability of CaAl layered double hydroxide (CaAl-LDH) in epoxy coatings was investigated by performing the inhibitor modification using three typical aromatic inhibitors. The electrochemistry impedance spectroscopy (EIS) measurement demonstrated that CaAl-LDH-MBT showed superior protection for carbon steel in epoxy coatings. Density functional theory (DFT) calculation and molecular dynamic (MD) simulation indicated that the aromatic conjugated structure with larger π electron clouds and heteroatoms with lone pair electrons would contribute to the enhanced corrosion protection.

A comparison of methods for corrosion inhibitor assessment: Mild steel protected by disubstituted aromatics

AbstractBoth thermodynamic and kinetic corrosion process parameters are determined with electrochemical methods. Results are used for a deeper understanding of the established interfacial structures and ongoing processes and of the effects of experimental parameters. Frequently data are used for the evaluation of corrosion inhibitor efficiencies. In case data from just one electrochemical method are used, the validity of the method and data should be verified and critical points must be identified. In this study, we have compared results from three standard electrochemical methods obtained with a common steel sample in an acidic environment and in the presence of three representative aromatic inhibitors. We have noticed significant differences between the results; therefore we suggest rationalization and practical consequences.

Technical solution for supplying a wax (deposition) inhibitor to a tubing string of oil wells

For prevention and combating paraffin deposites different chemical regents are widely used (wax inhibitors). In field conditions many ways of chemical regents dosing are applied. Injection of chemical reagents in oil well tubing is the most effective for wax inhibitors; in this case consumption of reagents is largely decreasing by comparison with chemical reagents dosing through the well-casing annulus. The article describes design and operating processes of technology of wax inhibitor dosing in electric centrifugal well pumps installation. This process opens fluid access to oil well tubing at higher pressure at the wellhead. Reagent RT-1-3 is used as aromatic wax inhibitor. In RT-1-3 there is butylbenzene fraction of Kazanorgsintez PJSC containing a mixture of butylbenzene, isopropylbenzene and polyalkylbenzene.

Regulation of Artemisinin and Its Derivatives on the Assembly Behavior and Cytotoxicity of Amyloid Polypeptides hIAPP and Aβ.

The misfolding and aggregation of human islet amyloid polypeptide (hIAPP) and amyloid-β (Aβ) protein are closely associated with type 2 diabetes mellitus (T2DM) and Alzheimer's disease, respectively. Inhibitors of amyloid peptides include short peptides, aromatic organic molecules, nanoparticles, and even metal compounds. Sesquiterpenoid artemisinins are widely used in anti-malaria treatments, and they may modulate glucose homeostasis against diabetes. However, the antidiabetic mechanism of these compounds remains unclear. In this work, four compounds, namely, artemisinin (1), dihydroartemisinin (2), artesunate (3), and artemether (4), were exploited to inhibit the assembly behavior of hIAPP and compared with that of Aβ. Although structurally distinct from other aromatic inhibitors of amyloid peptides, these sesquiterpenoids effectively altered the two peptides' fibril morphologies and disaggregated the mature fibrils mostly to the monomers. The interaction of artemisinins with the two peptides demonstrated a spontaneous, exothermic, and entropy-driven binding process predominantly through hydrophobic and hydrogen bonding interactions. Moreover, they reversed cytotoxicity and membrane leakage by reducing peptides' oligomerization. The results suggested that these compounds had better inhibition and disaggregation capability against hIAPP than against Aβ. Furthermore, the effects of these compounds' structural modification on the amyloid fibril formation of the two peptides were observed. The molecular screening offered a new perspective for artemisinins as promising inhibitors against amyloidosis related diseases.

Removal of aromatic inhibitors produced from lignocellulosic hydrolysates by Acinetobacter baylyi ADP1 with formation of ethanol by Kluyveromyces marxianus

BackgroundLignocellulosic biomass is an attractive, inexpensive source of potentially fermentable sugars. However, hydrolysis of lignocellulose results in a complex mixture containing microbial inhibitors at variable composition. A single microbial species is unable to detoxify or even tolerate these non-sugar components while converting the sugar mixtures effectively to a product of interest. Often multiple substrates are metabolized sequentially because of microbial regulatory mechanisms. To overcome these problems, we engineered strains of Acinetobacter baylyi ADP1 to comprise a consortium able to degrade benzoate and 4-hydroxybenzoate simultaneously under batch and continuous conditions in the presence of sugars. We furthermore used a thermotolerant yeast, Kluyveromyces marxianus, to convert the glucose remaining after detoxification to ethanol.ResultsThe two engineered strains, one unable to metabolize benzoate and another unable to metabolize 4-hydroxybenzoate, when grown together removed these two inhibitors simultaneously under batch conditions. Under continuous conditions, a single strain with a deletion in the gcd gene metabolized both inhibitors in the presence of sugars. After this batch detoxification using ADP1-derived mutants, K. marxianus generated 36.6 g/L ethanol.ConclusionsWe demonstrated approaches for the simultaneous removal of two aromatic inhibitors from a simulated lignocellulosic hydrolysate. A two-stage batch process converted the residual sugar into a non-growth-associated product, ethanol. Such a two-stage process with bacteria (A. baylyi) and yeast (K. marxianus) is advantageous, because the yeast fermentation occurs at a higher temperature which prevents growth and ethanol consumption of A. baylyi. Conceptually, the process can be extended to other inhibitors or sugars found in real hydrolysates. That is, additional strains which degrade components of lignocellulosic hydrolysates could be made substrate-selective and targeted for use with specific complex mixtures found in a hydrolysate.

Metabolic engineering of Acinetobacter baylyi ADP1 for removal of Clostridium butyricum growth inhibitors produced from lignocellulosic hydrolysates

BackgroundPretreatment of lignocellulosic biomass can produce inhibitory compounds that are harmful for microorganisms used in the production of biofuels and other chemicals from lignocellulosic sugars. Selective inhibitor removal can be achieved with biodetoxification where microorganisms catabolize the inhibitors without consuming the sugars. We engineered the strictly aerobic Acinetobacter baylyi ADP1 for detoxification of lignocellulosic hydrolysates by removing the gene for glucose dehydrogenase, gcd, which catalyzes the first step in its glucose catabolism.ResultsThe engineered A. baylyi ADP1 strain was shown to be incapable of consuming the main sugar components of lignocellulosic hydrolysates, i.e., glucose, xylose, and arabinose, but rapidly utilized acetate and formate. Formate was consumed during growth on acetate and by stationary phase cells, and this was enhanced in the presence of a common aromatic inhibitor of lignocellulosic hydrolysates, 4-hydroxybenzoate. The engineered strain tolerated glucose well up to 70 g/l, and the consumption of glucose, xylose, or arabinose was not observed in prolonged cultivations. The engineered strain was applied in removal of oxygen, a gaseous inhibitor of anaerobic fermentations. Co-cultivation with the A. baylyi ADP1 gcd knockout strain under initially aerobic conditions allowed the strictly anaerobic Clostridium butyricum to grow and produce hydrogen (H2) from sugars of the enzymatic rice straw hydrolysate.ConclusionsWe demonstrated that the model organism of bacterial genetics and metabolism, A. baylyi ADP1, could be engineered to be an efficient biodetoxification strain of lignocellulosic hydrolysates. Only one gene knockout was required to completely eliminate sugar consumption and the strain could be used in production of anaerobic conditions for the strictly anaerobic hydrogen producer, C. butyricum. Because of these encouraging results, we believe that A. baylyi ADP1 is a promising candidate for the detoxification of lignocellulosic hydrolysates for bioprocesses.

Identification of inhibitors that target dual-specificity phosphatase 5 provide new insights into the binding requirements for the two phosphate pockets.

BackgroundDual-specificity phosphatase-5 (DUSP5) plays a central role in vascular development and disease. We present a p-nitrophenol phosphate (pNPP) based enzymatic assay to screen for inhibitors of the phosphatase domain of DUSP5.MethodspNPP is a mimic of the phosphorylated tyrosine on the ERK2 substrate (pERK2) and binds the DUSP5 phosphatase domain with a Km of 7.6 ± 0.4 mM. Docking followed by inhibitor verification using the pNPP assay identified a series of polysulfonated aromatic inhibitors that occupy the DUSP5 active site in the region that is likely occupied by the dual-phosphorylated ERK2 substrate tripeptide (pThr-Glu-pTyr). Secondary assays were performed with full length DUSP5 with ERK2 as substrate.ResultsThe most potent inhibitor has a naphthalene trisulfonate (NTS) core. A search for similar compounds in a drug database identified suramin, a dimerized form of NTS. While suramin appears to be a potent and competitive inhibitor (25 ± 5 μM), binding to the DUSP5 phosphatase domain more tightly than the monomeric ligands of which it is comprised, it also aggregates. Further ligand-based screening, based on a pharmacophore derived from the 7 Å separation of sulfonates on inhibitors and on sulfates present in the DUSP5 crystal structure, identified a disulfonated and phenolic naphthalene inhibitor (CSD3_2320) with IC50 of 33 μM that is similar to NTS and does not aggregate.ConclusionsThe new DUSP5 inhibitors we identify in this study typically have sulfonates 7 Å apart, likely positioning them where the two phosphates of the substrate peptide (pThr-Glu-pTyr) bind, with one inhibitor also positioning a phenolic hydroxyl where the water nucleophile may reside. Polysulfonated aromatic compounds do not commonly appear in drugs and have a tendency to aggregate. One FDA-approved polysulfonated drug, suramin, inhibits DUSP5 and also aggregates. Docking and modeling studies presented herein identify polysulfonated aromatic inhibitors that do not aggregate, and provide insights to guide future design of mimics of the dual-phosphate loops of the ERK substrates for DUSPs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12858-015-0048-3) contains supplementary material, which is available to authorized users.

Identification of Polysulfonated Inhibitors that Target Dual Specificity Phosphatase 5 and Provide New Insights into the Binding Requirements for Dual‐Phosphate Substrate Pockets

Dual specific phosphatase‐5 (DUSP5) plays a central role in vascular development and disease. We present a p‐nitrophenol phosphate (pNPP) based enzymatic assay to screen for inhibitors of the phosphatase domain of DUSP5. pNPP is a mimic of the phosphorylated tyrosine on the ERK2 substrate (pERK2) and binds with a Km of 7.6 + 0.5 mM. Docking followed by inhibitor verification using the pNPP assay identified a series of polysulfonated aromatic inhibitors that occupy the DUSP5 active site in the region that is likely occupied by the dual‐phosphorylated ERK2 substrate (pThr‐Glu‐pTyr). A first lead molecule has a naphthalene trisulfonate (NTS) core. A search for similar compounds in a drug database identified an analog that is FDA approved (making it a candidate for repurposing), and is a potent and competitive inhibitor (25 + 5 µM). Further screening and ligand optimization identified additional analogs, including two new scaffolds – one based on a diphenyl‐ether core, and another based on a fused tricyclic core; the latter formerly FDA approved as a drug for topical use. Modeling suggests these inhibitors may have broader relevance for mimicking the dual‐phosphate loops recognized by DUSPs, as they position sulfonates or other negatively charged groups where the two phosphates on the substrate peptide (pThr‐Glu‐pTyr) bind.

Aromatic inhibitors derived from ammonia-pretreated lignocellulose hinder bacterial ethanologenesis by activating regulatory circuits controlling inhibitor efflux and detoxification.

Efficient microbial conversion of lignocellulosic hydrolysates to biofuels is a key barrier to the economically viable deployment of lignocellulosic biofuels. A chief contributor to this barrier is the impact on microbial processes and energy metabolism of lignocellulose-derived inhibitors, including phenolic carboxylates, phenolic amides (for ammonia-pretreated biomass), phenolic aldehydes, and furfurals. To understand the bacterial pathways induced by inhibitors present in ammonia-pretreated biomass hydrolysates, which are less well studied than acid-pretreated biomass hydrolysates, we developed and exploited synthetic mimics of ammonia-pretreated corn stover hydrolysate (ACSH). To determine regulatory responses to the inhibitors normally present in ACSH, we measured transcript and protein levels in an Escherichia coli ethanologen using RNA-seq and quantitative proteomics during fermentation to ethanol of synthetic hydrolysates containing or lacking the inhibitors. Our study identified four major regulators mediating these responses, the MarA/SoxS/Rob network, AaeR, FrmR, and YqhC. Induction of these regulons was correlated with a reduced rate of ethanol production, buildup of pyruvate, depletion of ATP and NAD(P)H, and an inhibition of xylose conversion. The aromatic aldehyde inhibitor 5-hydroxymethylfurfural appeared to be reduced to its alcohol form by the ethanologen during fermentation, whereas phenolic acid and amide inhibitors were not metabolized. Together, our findings establish that the major regulatory responses to lignocellulose-derived inhibitors are mediated by transcriptional rather than translational regulators, suggest that energy consumed for inhibitor efflux and detoxification may limit biofuel production, and identify a network of regulators for future synthetic biology efforts.

Mutagenic Activation Reduces Carcinogenic Activity of Ortho-Aminoazotoluene for Mouse Liver

Pentachlorophenol (aromatic amine and azo stain metabolic stimulation inhibitor) reduced the hepatocarcinogenic activity of 4-aminoazobenzene and reduced that of ortho-aminoazotoluene in suckling mice. Both 4-aminoazobenzene and ortho-aminoazotoluene exhibited mutagenic activity in Ames' test in vitro on S. typhimurium TA 98 strain with activation with liver enzymes; this mutagenic activity was similarly suppressed by adding pentachlorophenol into activation medium. Induction of xenobiotic metabolism enzymes, stimulating the mutagenic activity of ortho-aminoazotoluene, suppressed its carcinogenic effect on mouse liver. Hence, ortho-aminotoluene (the initial compound), but not its mutagenic metabolites, was the direct active hepatocarcinogen for mice.

Quantitative Structure-Activity Relationship Study of Aromatic Inhibitors Against Rat Lens Aldose Reductase Activity Using Variable Selections

A quantitative structure-activity relationship (QSAR) study of aromatic inhibitors against aldose reductase (AR) activity was performed using variable selection from stepwise multiple linear regression (MLR) and genetic algorithm (GA)-MLR. As a result of variable selection, stepwise MLR and GA-MLR gave the same results with one, two, three and five descriptors and different results with four and six descriptors. GA-MLR produced higher values and was better in explanatory and predictive power than stepwise MLR in four variables. AR activity (pIC50) of aromatic derivatives was expressed with acceptable explanatory (74.6-81.2%) and predictive power (68.8-74.4%) in models 3 and 4. The resulting models with the given descriptors illustrate that hydrophobic and electrostatic interactions play a significant role in inhibition of AR activity. This study suggests that the QSAR models can be used as guidelines to predict improved aldose reductase inhibitory activity and to obtain reliable predictions in structurally diverse compounds.

Kinetic profile of amyloid formation in the presence of an aromatic inhibitor by nuclear magnetic resonance.

The self-assembly of amyloid proteins into β-sheet rich assemblies is associated with human amyloidoses including Alzheimer's disease, Parkinson's disease, and type 2 diabetes. An attractive therapeutic strategy therefore is to develop small molecules that would inhibit protein self-assembly. Natural polyphenols are potential inhibitors of β-sheet formation. How these compounds affect the kinetics of self-assembly studied by thioflavin T (ThT) fluorescence is not understood primarily because their presence interferes with ThT fluorescence. Here, we show that by plotting peak intensities from nuclear magnetic resonance (NMR) against incubation time, kinetic profiles in the presence of the polyphenol can be obtained from which kinetic parameters of self-assembly can be easily determined. In applying this technique to the self-assembly of the islet amyloid polypeptide in the presence of curcumin, a biphenolic compound found in turmeric, we show that the kinetic profile is atypical in that it shows a prenucleation period during which there is no observable decrease in NMR peak intensities.

Implications of Binding Mode and Active Site Flexibility for Inhibitor Potency against the Salicylate Synthase from Mycobacterium tuberculosis

MbtI is the salicylate synthase that catalyzes the first committed step in the synthesis of the iron chelating compound mycobactin in Mycobacterium tuberculosis. We previously developed a series of aromatic inhibitors against MbtI based on the reaction intermediate for this enzyme, isochorismate. The most potent of these inhibitors had hydrophobic substituents, ranging in size from a methyl to a phenyl group, appended to the terminal alkene of the enolpyruvyl group. These compounds exhibited low micromolar inhibition constants against MbtI and were at least an order of magnitude more potent than the parental compound for the series, which carries a native enolpyruvyl group. In this study, we sought to understand how the substituted enolpyruvyl group confers greater potency, by determining cocrystal structures of MbtI with six inhibitors from the series. A switch in binding mode at the MbtI active site is observed for inhibitors carrying a substituted enolpyruvyl group, relative to the parental compound. Computational studies suggest that the change in binding mode, and higher potency, is due to the effect of the substituents on the conformational landscape of the core inhibitor structure. The crystal structures and fluorescence-based thermal shift assays indicate that substituents larger than a methyl group are accommodated in the MbtI active site through significant but localized flexibility in the peptide backbone. These findings have implications for the design of improved inhibitors of MbtI, as well as other chorismate-utilizing enzymes from this family.

Three new aromatic sulfonamide inhibitors of carbonic anhydrases I, II, IV and XII

4-Sulfamoyl-N-(3-morpholinopropyl)benzamide (I-1), N-(3-morpholinopropyl)benzene-1,4-disulfonamide (I-2) and N-(4-diethylaminoethoxybenzyl)benzene-1,4-bis(sulfonamide (I-3), were prepared and assayed as inhibitors of four carbonic anhydrase (CA) isoenzymes hCA I, hCA II, hCA IV and hCA XII. These compounds exhibited nanomolar half maximal inhibitory concentration (IC50) ranging from 58 to 740 nmol/L. All three aromatic sulfonamides show different activities for the isoenzymes studied with lowest affinity against isoenzyme hCA XII.

Scale‐up and integration of alkaline hydrogen peroxide pretreatment, enzymatic hydrolysis, and ethanolic fermentation

Alkaline hydrogen peroxide (AHP) has several attractive features as a pretreatment in the lignocellulosic biomass-to-ethanol pipeline. Here, the feasibility of scaling-up the AHP process and integrating it with enzymatic hydrolysis and fermentation was studied. Corn stover (1 kg) was subjected to AHP pretreatment, hydrolyzed enzymatically, and the resulting sugars fermented to ethanol. The AHP pretreatment was performed at 0.125 g H(2) O(2) /g biomass, 22°C, and atmospheric pressure for 48 h with periodic pH readjustment. The enzymatic hydrolysis was performed in the same reactor following pH neutralization of the biomass slurry and without washing. After 48 h, glucose and xylose yields were 75% and 71% of the theoretical maximum. Sterility was maintained during pretreatment and enzymatic hydrolysis without the use of antibiotics. During fermentation using a glucose- and xylose-utilizing strain of Saccharomyces cerevisiae, all of the Glc and 67% of the Xyl were consumed in 120 h. The final ethanol titer was 13.7 g/L. Treatment of the enzymatic hydrolysate with activated carbon prior to fermentation had little effect on Glc fermentation but markedly improved utilization of Xyl, presumably due to the removal of soluble aromatic inhibitors. The results indicate that AHP is readily scalable and can be integrated with enzyme hydrolysis and fermentation. Compared to other leading pretreatments for lignocellulosic biomass, AHP has potential advantages with regard to capital costs, process simplicity, feedstock handling, and compatibility with enzymatic deconstruction and fermentation. Biotechnol. Bioeng. 2012; 109:922-931. © 2011 Wiley Periodicals, Inc.

Abstract B222: Anticancer effects of S4, a new carbonic anhydrase inhibitor, on MDA-MB-231 and HCT116 tumors.

Abstract Carbonic anhydrase IX (CA IX) is strongly overexpressed in multiple human solid tumours in response to oxygen deprivation (hypoxia). In tumours high CA-IX expression is closely associated with higher incidence of metastasis and poor prognosis. Hypoxic tumours are also less sensitive to classical chemo- and radiotherapy. The potential of CA-IX in cancer therapy has encouraged the search for potent and selective CA-IX inhibitors over recent years. We have evaluated a panel of novel aromatic sulphonamide inhibitors of CA-IX for their anti-metastatic potential and ability to enhance response to standard therapies. From an initial screen of 10 agents, the compound S4 (whose complete chemical structure will be disclosed at the time of the presentation) showed potent inhibition of cell migration and cell spreading under hypoxic conditions in MDA231 breast cancer cells. In MTT assays, the cytotoxicity to MDA231 cells exposure to S4 for 24 or 96 hours revealed an IC50 of 48 μM and 27 μM, subsequently. Under complete hypoxia for 24 hours (anoxia), S4 in the 33–100 μM range inhibited the migration of MDA231 cells and cell spreading on collagen and fibronectin coated coverslips. In vivo S4 was evaluated in mice bearing xenografts of breast or colon carcinoma tumours i.e. MDA-MB-231 or HCT116 tumours, respectively. MDA231 tumours were established within the mammary fat pad and HCT116 within the liver following intrasplenic injection. We investigated the effect of i.p. administration of S4 on primary tumour growth and on metastases formation in the lung. S4 was given at the maintenance dosage of 10 mg/kg on 5 days on 2 days off regiment for two whole cycles for the duration of the experiment. Ex vivo clonogenicity assays or counting of tumours in haematoxylin & eosin stained sections of lung indicated that S4 treatment reduced the number of viable cells that metastasised to the lung in both models. The primary tumour growth of MDA231 and HCT116 were not affected by the S4. T2-weighted MR imaging (Rare) was successfully used to identify and monitor the HCT116 tumour growth within livers. In preliminary in vitro studies using 3D-spheroid cultures, S4 appears also capable of enhancing chemo- and radiotherapy response. Clonogenicity assays showed that S4 was able to enhance the cytotoxic effect of the anticancer drug doxorubicin hydrochloride (10 μM) against FaDu spheroids by reducing the number of recovered colonies. S4 also enhanced cell death induced by a single dose of 10 Gy of radiation to FaDu spheroids. The precise mechanisms by which CA IX inhibition via S4 impacts on chemotherapy, radiation response and migratory phenotype is as yet unclear, but changes in pH environment, effects on proliferation, apoptosis and interplay with migratory machinery have all been associated with CA IX activity. We conclude that CA IX inhibition is an attractive therapeutic approach with multiple applications in the clinical setting. We acknowledge the financial support from the European Commission for the METOXIA program. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B222.

Disordered binding of small molecules to Aβ(12-28).

In recent years, an increasing number of small molecules and short peptides have been identified that interfere with aggregation and/or oligomerization of the Alzheimer β-amyloid peptide (Aβ). Many of them possess aromatic moieties, suggesting a dominant role for those in interacting with Aβ along various stages of the aggregation process. In this study, we attempt to elucidate whether interactions of such aromatic inhibitors with monomeric Aβ(12-28) point to a common mechanism of action by performing atomistic molecular dynamics simulations at equilibrium. Our results suggest that, independently of the presence of inhibitors, monomeric Aβ(12-28) populates a partially collapsed ensemble that is largely devoid of canonical secondary structure at 300 K and neutral pH. The small molecules have different affinities for Aβ(12-28) that can be partially rationalized by the balance of aromatic and charged moieties constituting the molecules. There are no predominant binding modes, although aggregation inhibitors preferentially interact with the N-terminal portion of the fragment (residues 13-20). Analysis of the free energy landscape of Aβ(12-28) reveals differences highlighted by altered populations of a looplike conformer in the presence of inhibitors. We conclude that intrinsic disorder of Aβ persists at the level of binding small molecules and that inhibitors can significantly alter properties of monomeric Aβ via multiple routes of differing specificity.

Distillate Hydrotreating to Ultra-low-sulfur Diesel – the Impact of Aromatics

Distillate hydrotreating has become a key concern in the refining industry owing to ultra-low-sulfur diesel legislation. Rate-limiting parameters that had previously been overlooked, such as aromatic inhibition, may need to be considered for the production of ultra-low-sulfur diesel (<10 weight parts per million wppm sulfur). As hydrodesulfurization (HDS) and aromatic saturation (HDA) reactions occur in parallel in a shared environment, they compete for the necessary resources, namely, hydrogen and catalyst sites. A series of pilot plant and numerical simulation experiments were completed in order to explore how the competition for hydrogen and catalyst sites impacts the rate of HDS in the presence of poly-cyclic aromatics. A diagnostic pilot plant test showed that external mass transfer was not rate-limiting. Intra-particle mass and energy transport were investigated by calculating the concentration and temperature gradients in a catalyst pellet. The effectiveness factors for HDS and HDA decreased in the presence of increased aromatics concentrations. However, the magnitude of the changes was insufficient to conclude that the competition for hydrogen was the sole mechanism needed to explain the suppression of HDS activity. Furthermore, the pilot plant data indicated that the presence of poly-aromatics has a more significant impact on the slower HDS reactions (sterically hindered dibenzothiophenes). As a result, it was concluded that aromatics inhibition (competitive adsorption on catalyst sites) impacted the rate of HDS most significantly. Although the consequences were significant, the impact of aromatic inhibition was minor relative to the analogous nitrogen inhibition.