Antiscaling Evaluation and Quantum Chemical Studies of Nitrogen-Free Organophosphorus Compounds for Oilfield Scale Management

Nonpolymeric aminomethylenephosphonates are widely used as powerful scale inhibitors in the petroleum industry. However, most of these inhibitors have certain drawbacks, such as low biodegradability and incompatibilities with high calcium brines. Therefore, there is a great need to explore more biodegradable phosphonated oilfield scale inhibitors affording high calcium-ion tolerance. In this project, known and new nitrogen-free phosphonates have been tested as scale inhibitors against carbonate and sulfate scales according to the Heidrun oilfield, Norway. The considered nitrogen-free scale inhibitors are 1,2,4-phosphonobutanetricarboxylic acid (PBTCA), hydroxyphosphonoacetic acid (HPAA), phosphonoacetic acid (PAA), and 3-phosphonopropanoic acid (PPA). A high-pressure dynamic tube-blocking test, calcium tolerance, thermal aging, and seawater biodegradation were used to assess the antiscaling performance of these inhibitors. A very good to excellent performance of all nitrogen-free phosphonate scale inhibitors has been observed against the calcite scaling. A biodegradable naturally occurring PAA displayed a very good calcite inhibition efficiency and afforded excellent thermal stability at 130 °C for 7 days under anaerobic conditions. PAA also gave outstanding tolerance activity with all concentrations up to 10 000 ppm calcium ions. Density functional theory (DFT) simulations predicted higher affinities of the commercial SIs compared to the nitrogen-free molecules, which is in line with their calcium compatibilities. The high calcium tolerance of nitrogen-free molecules makes them more efficient than commercial inhibitors. Further, DFT solid-state simulations reveal that the affinities of the nitrogen-free molecules for the calcite surface are higher than the barite surface, which agrees well with the experimental fail inhibitor concentration (FIC) data. The sluggish and complicated kinetics of the barite scale formation compared to the calcite scale explain well the high concentrations of the nitrogen-free molecules required for barite inhibition. In summary, our results showed that the nitrogen-free molecules show good potential as scale inhibitors for both calcite and barite. However, for the latter scale, further optimization is needed for optimal performance.publishedVersio

Investigation of the Antiscaling Performance of Phosphonated Chitosan for Upstream Petroleum Industry Application

Scale deposition is one of the main water-based production problems in the upstream oil and gas industry. Few environmentally friendly scale inhibitors show good thermal stability as well as calcium compatibility. We report the synthesis of phosphonated chitosan (PCH) in a two-step route via a phosphonate ester. Chitosan is made from chitin, a natural polysaccharide. In dynamic tube blocking tests, PCH showed good performance as a calcium carbonate scale inhibitor, similar to some commercial nonpolymeric aminophosphonates. Performance was not lost even after thermal aging as a 5 wt % aqueous anaerobic solution for 1 week at 130 °C. The performance as a barite inhibitor was shown to be significantly worse. PCH showed excellent calcium compatibility from 100 to 10 000 ppm Ca2+ and 100 to 50 000 ppm PCH for 24 h at 80 °C. Density functional theory (DFT) and molecular dynamics (MD) simulations are employed to gain atomic insights into the interaction of PCH with the mineral surface as well as the polymer morphology. DFT predicts that PCH interacts as strongly as commercial scale inhibitors. MD simulations reveal a conformational contraction of PCH due to its internal hydrogen bonding network, which makes the inhibition mechanism complicated. Our simulation results bring new insights into the inhibition mechanism of polymeric inhibitors compared to small molecules. For example, a polymer with a well-defined structure such as carboxymethyl inulin (CMI) performs better than random folded polymers (PCH). The structural regularity maximizes the interaction sites of the mineral particles on the polymer surface. The compact morphology of PCH and the slow barite kinetics could be the main reason for the bad performance of PCH for barite scale inhibition.publishedVersio

Structural Basis for the Recognition in an Idiotype-Anti-Idiotype Antibody Complex Related to Celiac Disease

Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2

Phosphonated Lower-Molecular-Weight Polyethyleneimines as Oilfield Scale Inhibitors: An Experimental and Theoretical Study

For many years, amino methylenephosphonate (-CH2-N-PO3H2)-based scale inhibitors (SIs) have been deployed for preventing various scales in the oil and gas industry, particularly for squeeze treatment applications. However, this class of phosphonate inhibitors showed several limitations related to environmental concerns and compatibility with brine solutions. The low toxicity of low-molecular-weight polyethyleneimine (LMW-PEI) encouraged us to phosphonate a series of branched and linear PEIs via the Moedritzer–Irani reaction. The phosphonated polyethyleneimine PPEIs are branched PPEI-600, branched PPEI-1200, branched PPEI-2000, and linear PPEI-5000. The newly synthesized PPEIs (branched and linear) were screened for calcium carbonate and barium sulfate utilizing a high-pressure dynamic tube-blocking rig at 100 °C and 80 bar. Moreover, we report the compatibility activity of all PPEIs with various concentrations of calcium ions (up to 10000 ppm). The morphology of the calcium carbonate and barium sulfate scale crystals in the absence and presence of linear PPEI-5000 was also investigated under static conditions using scanning electron microscopy (SEM). The obtained results showed that all branched and linear PPEIs gave moderate calcite and barite inhibition activities. It was also found that all branched PPEIs gave moderate to poor calcium compatibility at high dosages of calcium ions (1000–10 000 ppm). Interestingly, linear PPEI-5000 displayed superior compatibility properties at high dosages of SI (up to 50 000 ppm) and high concentrations of Ca2+ ions (up to 10 000 ppm). Furthermore, field emission scanning electron microscopy analysis confirmed that the crystal shapes of CaCO3 and BaSO4 mineral scales are greatly changed in the presence of linear PPEI-5000. At high dosages of linear PPEI-5000 SI (100 ppm), the CaCO3 crystals are completely converted from cubic-shaped blocks (blank calcite) into long cluster shapes. Density functional theory (DFT) simulations reveal favorable interactions of PPEI polymers with the two mineral facets (calcite and barite) with more affinity toward the calcite surface. PPEI with more phosphonate groups exhibits affinities comparable to the commercial-scale inhibitors. The high density of the phosphonate groups on the branched PPEI and its strong affinity toward calcium ions explain its poor calcium compatibility. The polymer flocculation and sluggish barite kinetics are the potential reasons for its low performance against thepublishedVersio

In Silico

Most antiretroviral medical treatments were developed and tested principally on HIV-1 B nonrecombinant strain, which represents less than 10% of the worldwide HIV-1-infected population. HIV-1 circulating recombinant form CRF02_AG is prevalent in West Africa and is becoming more frequent in other countries. Previous studies suggested that the HIV-1 polymorphisms might be associated to variable susceptibility to antiretrovirals. This study is pointed to compare the susceptibility to integrase (IN) inhibitors of HIV-1 subtype CRF02_AG IN respectively to HIV-1 B. Structural models of B and CRF02_AG HIV-1 INs as unbound enzymes and in complex with the DNA substrate were built by homology modeling. IN inhibitors—raltegravir (RAL), elvitegravir (ELV) and L731,988—were docked onto the models, and their binding affinity for both HIV-1 B and CRF02_AG INs was compared. CRF02_AG INs were cloned and expressed from plasma of integrase strand transfer inhibitor (INSTI)-naïve infected patients. Our in silico and in vitro studies showed that the sequence variations between the INs of CRF02_AG and B strains did not lead to any notable difference in the structural features of the enzyme and did not impact the susceptibility to the IN inhibitors. The binding modes and affinities of INSTI inhibitors to B and CRF02_AG INs were found to be similar. Although previous studies suggested that several naturally occurring variations of CRF02_AG IN might alter either IN/vDNA interactions or INSTIs binding, our study demonstrate that these variations do affect neither IN activity nor its susceptibility to INSTIs

Limits for Recombination in a Low Energy Loss Organic Heterojunction

Donor–acceptor organic solar cells often show high quantum yields for charge collection, but relatively low open-circuit voltages (V$_{OC}$) limit power conversion efficiencies to around 12%. We report here the behavior of a system, PIPCP:PC$_{61}$BM, that exhibits very low electronic disorder (Urbach energy less than 27 meV), very high carrier mobilities in the blend (field-effect mobility for holes >10$^{-2}$ cm$^{2}$ V$^{-1}$ s$^{-1}$), and a very low driving energy for initial charge separation (50 meV). These characteristics should give excellent performance, and indeed, the V$_{OC}$ is high relative to the donor energy gap. However, we find the overall performance is limited by recombination, with formation of lower-lying triplet excitons on the donor accounting for 90% of the recombination. We find this is a bimolecular process that happens on time scales as short as 100 ps. Thus, although the absence of disorder and the associated high carrier mobility speeds up charge diffusion and extraction at the electrodes, which we measure as early as 1 ns, this also speeds up the recombination channel, giving overall a modest quantum yield of around 60%. We discuss strategies to remove the triplet exciton recombination channel.SMM, RHF, MKR, SAA, and JLB acknowledge support from the KAUST Competitive Research Grant Program. MKR, SAA, and JLB also acknowledge generous support of their work by KAUST and the Office of Naval Research Global (Award N62909­15­1­2003); they thank the KAUST IT Research Computing Team and Supercomputing Laboratory for providing computational and storage resources. NAR, MW, TQN, and GCB acknowledge support from the Department of the Navy, Office of Naval Research (Award Nos. N00014-14-1-0580 and N00014-16-1-25200. AS would like to acknowledge the funding and support from the India-UK APEX project. HLS acknowledges support from the Winton Programme for the Physics of Sustainability. MN and HS gratefully acknowledge financial support from the Engineering and Physical Sciences Research Council though a Programme Grant (EP/M005141/1)

Targeting STAT1 by myricetin and delphinidin provides efficient protection of the heart from ischemia/reperfusion-induced injury

AbstractFlavonoids exhibit a variety of beneficial effects in cardiovascular diseases. Although their therapeutic properties have been attributed mainly to their antioxidant action, they have additional protective mechanisms such as inhibition of signal transducer and activator of transcription 1 (STAT1) activation. Here, we have investigated the cardioprotective mechanisms of strong antioxidant flavonoids such as quercetin, myricetin and delphinidin. Although all of them protect the heart from ischemia/reperfusion-injury, myricetin and delphinidin exert a more pronounced protective action than quercetin by their capacity to inhibit STAT1 activation. Biochemical and computer modeling analysis indicated the direct interaction between STAT1 and flavonoids with anti-STAT1 activity

Unprocessed Viral DNA Could Be the Primary Target of the HIV-1 Integrase Inhibitor Raltegravir

Integration of HIV DNA into host chromosome requires a 3′-processing (3′-P) and a strand transfer (ST) reactions catalyzed by virus integrase (IN). Raltegravir (RAL), commonly used in AIDS therapy, belongs to the family of IN ST inhibitors (INSTIs) acting on IN-viral DNA complexes (intasomes). However, studies show that RAL fails to bind IN alone, but nothing has been reported on the behaviour of RAL toward free viral DNA. Here, we assessed whether free viral DNA could be a primary target for RAL, assuming that the DNA molecule is a receptor for a huge number of pharmacological agents. Optical spectroscopy, molecular dynamics and free energy calculations, showed that RAL is a tight binder of both processed and unprocessed LTR (long terminal repeat) ends. Complex formation involved mainly van der Waals forces and was enthalpy driven. Dissociation constants (Kds) revealed that RAL affinity for unbound LTRs was stronger than for bound LTRs. Moreover, Kd value for binding of RAL to LTRs and IC50 value (half concentration for inhibition) were in same range, suggesting that RAL binding to DNA and ST inhibition are correlated events. Accommodation of RAL into terminal base-pairs of unprocessed LTR is facilitated by an extensive end fraying that lowers the RAL binding energy barrier. The RAL binding entails a weak damping of fraying and correlatively of 3′-P inhibition. Noteworthy, present calculated RAL structures bound to free viral DNA resemble those found in RAL-intasome crystals, especially concerning the contacts between the fluorobenzyl group and the conserved 5′C4pA33′ step. We propose that RAL inhibits IN, in binding first unprocessed DNA. Similarly to anticancer drug poisons acting on topoisomerases, its interaction with DNA does not alter the cut, but blocks the subsequent joining reaction. We also speculate that INSTIs having viral DNA rather IN as main target could induce less resistance

Study of protein-ligand interactions by quantum and molecular mechanical approaches

ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Dynamics, Aggregation, and Interfacial Properties of the Partially Hydrolyzed Polyacrylamide Polymer for Enhanced Oil Recovery Applications: Insights from Molecular Dynamics Simulations

We hereby employ molecular dynamics (MD) simulations (∼6 μs in total) to investigate the chain dynamics, aggregation, and interfacial properties of the partially hydrolyzed polyacrylamide (HPAM) polymer. HPAM is widely used in chemical enhanced oil recovery (cEOR) applications. The conformational changes and aggregation properties are examined in different conditions simulating cEOR activities. Also, we examined the degree of polymerization (20-, 50-, and 100 -mers) effect on the polymer chain dynamics and aggregation. MD simulations showed that HPAM has a high conformational diversity ranging from coiled to compact conformations. The former is abundantly found in fresh water. In brine solutions, HPAM is found to be very sensitive to ions and adopts a more compact conformation. HPAM-ion interactions drive the conformational thermodynamic equilibrium between the compact and coiled conformations toward the compact conformation. Furthermore, ion interactions are largely impcating its aggregation. HPAM has a high propensity to form large-size aggregates in brine solution. An interesting ionic effect has been observed; Ca²⁺ ions showed a high affinity toward HAPM compared to Mg²⁺ and Na⁺ ions. The electrostatic forces and ionic dehydration free energy penalty are the two main factors that determine the HPAM ionic affinity. Short oligomers are noted to overestimate the tendency of the polymer to have compact conformations and underestimate its aggregation capacity in brine solutions. Simulations of oil–water systems show that HPAM has a spectator role on the interfacial tension in the absence of surfactants