Number Of H-bonds Research Articles

Cubic mesophases of self-assembled amphiphiles separate miscible solvents

Sodium lauroyl lactylate (SLL) is soluble in water and insoluble in organic solvents, while glycerol monooleated (GMO) is soluble in organic solvents and insoluble in water. These amphiphiles separate miscible solvents (e.g., water and either dimethylsulfoxide, DMSO, dimethylformamide, DMF, acetonitrile, AN, or tehtrahydrofuran, THF). Separation segregates water and the organic solvents into either microdomains (emulsified droplets) or free phases. With mixtures containing 3:7–7:3 DMF:water ratios (v/v), SLL kinetically stabilizes DMF-water emulsions for over a week (longer times were not investigated). Emulsions are DMF in water with DMF:water ratios ≤ 2:3, and water in DMF for DMF:water ratios ≥ 1:1. Optical microscopy and SEM illustrate emulsification, and confocal microscopy qualitatively shows segregation between DMF (dyed with fluorescein) and water (which appears dark in confocal images). Water droplets in DMF are kinetically stable because they are surrounded by self-assembled SLL cubic mesophases, either gyroid or primitive, depending on the SLL and DMF concentrations (as demonstrated by x-ray diffraction, XRD). SLL also stabilizes DMSO-water emulsions (for over a week), thereby segregating the two solvents with similar mechanisms. DMSO-water separation is quantitatively demonstrated by mid-infrared (mid-IR) spectromicroscopy. Separation between AN and water occurs for AN-water mixtures in which SLL has intermediate solubility, i.e., with 3:2 and 4:1 AN:water ratios (v/v). In this range, SLL yields emulsions which destabilize overnight, separating into AN-rich and water-rich phases, as demonstrated using nuclear magnetic resonance (NMR). In water, SLL self-assembles into primitive cubic liquid mesophases and it affects hydrogen bonding (H-bonding) of water, as shown by deconvolving the H-bond peak into peaks representative of different water clusters, comprised of water molecules donating and accepting a different number of H-bonds. In water, SLL induces a blue shift of the hydrogen bonding (H-bonding) of absorbance peaks for double (DD) and single (SD) H-bond donors, indicating that it strengthens H-bonding. Importantly, it increases the ratio between the amplitude A of SD relative to DD, and SD are most effective at structuring water. As a result, SLL would inhibit interactions between organic solvents and water, initiating separation. Similar to SLL, GMO is known for its ability to form cubic mesophases. GMO stabilizes emulsions of water miscible solvents (THF, DMSO and DMF) and water. This result indicates that selected amphiphiles self-assembled into cubic mesophases can emulsify miscible solvents.

Molecular Mechanism of Autodissociation in Liquid Water: Ab Initio Molecular Dynamics Simulations.

Autodissociation in liquid water is one of the most important processes in various topics of physical chemistry, such as acid-base chemistry. Molecular simulations have elucidated most of the molecular mechanisms at the atomic level, yet quantitative analysis to compare with experiments using the potential of mean force (PMF) remains a hurdle, including the definition of reaction coordinates and the accuracy of liquid structures by ab initio molecular dynamics (AIMD) simulations with density functional theory (DFT) methods. Here, we perform AIMD simulations with the revPBE-D3 exchange-correlation functional to compute the PMF profiles of autoionization, or proton transfer (PT), in liquid water. For the quantitative analysis with physically meaningful reaction coordinates, we employ a PT coordinate, donor-acceptor (OH--H3O+) distance, and hydrogen (H)-bond number. The one-dimensional (1D) PMF profile along the PT coordinate shows no local minimum in the product state of PT (OH- and H3O+), which is necessary to accurately compute the acid dissociation constant (or pKa). On the other hand, the 2D PMF profiles along the PT coordinate and donor-acceptor distance show local minima in the product state and reaction barriers, and the computed pKw is comparable to the experiment. In addition, the 2D PMF profiles along the PT coordinate and the H-bond number reveal the molecular mechanism of the H-bond rearrangement concomitant with PT, in which the H-bond breaking before PT is slightly preferable. These findings indicate that an accurate evaluation of pKa by MD simulations requires the donor-acceptor distance in addition to the conventional PT coordinate.

Allosteric Binding Sites of Aβ Peptides on the Acetylcholine Synthesizing Enzyme ChAT as Deduced by In Silico Molecular Modeling.

The native function of amyloid-β (Aβ) peptides is still unexplored. However, several recent reports suggest a prominent role of Aβ peptides in acetylcholine homeostasis. To clarify this role of Aβ, we have reported that Aβ peptides at physiological concentrations can directly enhance the catalytic efficiency of the key cholinergic enzyme, choline acetyltransferase (ChAT), via an allosteric interaction. In the current study, we further aimed to elucidate the underlying ChAT-Aβ interaction mechanism using in silico molecular docking and dynamics analysis. Docking analysis suggested two most probable binding clusters on ChAT for Aβ40 and three for Aβ42. Most importantly, the docking results were challenged with molecular dynamic studies of 100 ns long simulation in triplicates (100 ns × 3 = 300 ns) and were analyzed for RMSD, RMSF, RoG, H-bond number and distance, SASA, and secondary structure assessment performed together with principal component analysis and the free-energy landscape diagram, which indicated that the ChAT-Aβ complex system was stable throughout the simulation time period with no abrupt motion during the evolution of the simulation across the triplicates, which also validated the robustness of the simulation study. Finally, the free-energy landscape analysis confirmed the docking results and demonstrated that the ChAT-Aβ complexes were energetically stable despite the unstructured nature of C- and N-terminals in Aβ peptides. Overall, this study supports the reported in vitro findings that Aβ peptides, particularly Aβ42, act as endogenous ChAT-Potentiating-Ligand (CPL), and thereby supports the hypothesis that one of the native biological functions of Aβ peptides is the regulation of acetylcholine homeostasis.

Virtual screening of potential inhibitor against breast cancer-causing estrogen receptor alpha (ERα): molecular docking and dynamic simulations

ABSTRACT Breast cancer (Bca) causes the highest rate of mortality in females owing to the out-of-control cell division in breast cells. In this work, we perform an in-silico screening based on molecular docking and molecular dynamic of curcumin derivatives against ERα. In this study, we carry out, molecular docking of fifty (50) curcumin derivatives having anticancer potential by using virtual screening tools. Ten (10) ligands were selected based on binding energy ranged from (-7.4 kcal/mol to -9 kcal/mol), lower values of inhibition constant (0.23µmol to 3.59µmol), and visualisation of intermolecular interactions. Additionally, we also assess ADMET properties of selected ligands for prediction of their toxicity and drug-likeness. The molecular dynamic simulations (MD) including RMSD, RMSF, Rg, SASA, number of H-bonds and MM-PBSA binding free energy results showed that ligand L2 and L8 bind to estrogen protein ERα more proficiently with good stability over 120 ns. These results suggest lead anticancer compounds L2 (Salicylidenecurcumin) and L8 (Curcumin difluorinated) are the most promising inhibitor against ERα of Bca with ∆G bind values of (-2.939 and -4.369) kcal/mol. we expect that our findings will evoke the scientific community to further do in-vitro and in-vivo investigations for screened curcumin derivatives against ERα of Bca.

Experimental and simulative study of bonding properties on fiber/epoxy interfaces by digital image correlation (DIC) technique and molecular dynamics

Fiber/epoxy interfacial bonding properties play a vital role in the utilization of fiber reinforced polymer (FRP) bars in concrete because almost all durability deficiencies of FRP-reinforced concrete are attributed to the failure of the fiber/epoxy/concrete interface. This study aims to study the evolution of fiber/epoxy debonding under a simulated concrete pore solution environment, combining a self-developed debonding device and the digital image correlation (DIC) technique. The bonding degradation mechanism of the fiber/epoxy interface was revealed by molecular dynamics (MD) simulation. The results show that the interfacial bonding property between glass fiber (GF) and epoxy was superior to that of basalt fiber (BF), and a more significant bonding degradation was observed in BF after the corrosion of water and chloride ions due to the reduction in the number of H-bonds caused by partial replacement of Si by Al, as concluded from MD simulation. Moreover, the bond stresses of GF and BF were reduced to approximately 15% and 12% after 28 days of corrosion in the simulated concrete pore solutions, respectively. Meanwhile, the reduction in bond strength was more significant in the simulated concrete pore solution of seawater and sea sand concrete (SWSSC).

Diameter Dependent Melting and Softening of dsDNA Under Cylindrical Confinement

Carbon nanotubes (CNTs) are considered promising candidates for biomolecular confinement, including DNA encapsulation for gene delivery. Threshold values of diameters have been reported for double-stranded DNA (dsDNA) encapsulation inside CNTs. We have performed all-atom molecular dynamics (MD) simulations of dsDNAs confined inside single-walled CNTs (SWCNTs) at the physiologically relevant temperature of 300 K. We found that the dsDNA can be confined without being denatured only when the diameter of the SWCNT exceeds a threshold value. Below this threshold diameter, the dsDNA gets denatured and melts even at the temperature of 300 K. Our simulations using SWCNTs with chirality indices (20,20) to (30,30) at 300 K found the critical diameter to be 3.25 nm (corresponding to (24,24) chirality). Analyses of the hydrogen bonds (H-bonds), Van der Walls (VdW) energy, and other inter-base interactions show drastic reduction in the number of H-bonds, VdW energy, and electrostatic energies between the bases of dsDNA when it is confined in narrower SWCNTs (up to diameter of 3.12 nm). On the other hand, the higher interaction energy between the dsDNA and the SWCNT surface in narrower SWCNTs assists in the melting of the dsDNA. Electrostatic mapping and hydration status analyses show that the dsDNA is not adequately hydrated and the counter ion distribution is not uniform below the critical diameter of the SWCNT. As properly hydrated counter ions provide stability to the dsDNA, we infer that the inappropriate hydration of counter ions and their non-uniform distribution around the dsDNA cause the melting of the dsDNA inside SWCNTs of diameter below the critical value of 3.25 nm. For confined dsDNAs that do not get denatured, we computed their elastic properties. The persistence length of dsDNA was found to increase by a factor of about two and the torsional stiffness by a factor of 1.5 for confinement inside SWCNTs of diameters up to 3.79 nm, the stretch modulus also following nearly the same trend. Interestingly, for higher diameters of SWCNT, 3.79 nm and above, the dsDNA becomes more flexible, demonstrating that the mechanical properties of the dsDNA under cylindrical confinement depend non-monotonically on the confinement diameter.

In Silico Identification of Novel Quinoline-3-carboxamide Derivatives Targeting Platelet-Derived Growth Factor Receptor

Background: Several computer-aided drug design (CADD) methods enable the design and development of novel chemical entities. Structure-based drug design (SBDD) and the knowledge of in silico methods enable the visualization of the binding process of ligands to targets and to predict the key binding pocket sites and affinity of ligands to their target macromolecules. Objective: The present study was carried out to identify novel N-2-amino-N-phenyl quinoline-3- carboxamide (AQCMs) derivatives targeting Platelet-derived growth factor receptor (PDGFR) to cure cancer using in silico approach. Materials and Methods: AQCMs were designed using ChemAxon Marvin Sketch 5.11.5 software. SwissADME and admetSAR online webserver were used to predict physicochemical properties as well as the toxicity of compounds. Ligand-receptor interactions between quinoline-3-carboxamide derivatives with the target receptor (PDB: 5GRN) were carried out using molecular docking technique by employing various software like AutoDock 1.1.2, MGL Tools 1.5.6, Discovery Studio Visualizer v 20.1.0.19295, Procheck, ProtParam tool, and PyMOL. Results: In silico results reveal that all designed compounds had acceptable pharmacokinetic properties, were found to be orally bioavailable, and less harmful. Molecules from 36 to 39 showed better docking scores as compared to standard drugs sunitinib and tasquinimod. Conclusion: Increase in binding energy and the number of H-bonds established by AQCMs with below 3.40 Å distance interactions allows a valuable starting point in order to optimize compounds for further investigation. Pharmacokinetics and toxicological profile build up the applicability of quinoline-3-carboxamide moiety as a potential new candidate for the cure of cancer that could help the medicinal chemists for additional extensive in vitro, in vivo chemical, and pharmacological investigations.

Molecular and Clinical Characterization of 7 Iranian Patients with Severe Congenital Factor V Deficiency: Identification of 4 Novel Mutations

Background and Aims: Congenital factor V (FV) deficiency is a rare bleeding disorder with 1 in 1000000 persons in the general population. Individuals with FV activity <1% and very low FV antigen levels are characterized as severe FV deficient patients. Little data is available about the molecular basis of this bleeding disorder in Iran.
 Materials and Methods: We analyzed 7 unrelated Iranian FV deficient patients regarding clinical manifestation and genotype. The molecular dynamic simulation was carried out to analyze the effect of novel mutations on the FV structure. 
 Results: All cases had recurrence epistaxis, oral cavity bleeding, and hematoma were frequent in our patients. The molecular analysis led to the identification of three already reported mutations (IVS 19+3 A>T, 4014-4017 del TCAG and p.P419R) and four novel mutations (IVS9-1 G>C, Y478D, L1844P, I1556T) in the FV gene of our patients. According to the molecular modeling results, it seems that in the two mutations Y478D and I1556T, an increased number of H-bonds in mutant proteins compared to natural ones reduces the flexibility and increases the stability of the mutant proteins. The results also show that in L1844P and I1556T mutations, the total solvent accessible surface area (both hydrophilic and hydrophobic) significantly decreases compared to the natural variants. 
 Conclusion: Identifying the causative mutation in patients with FV deficiency helps to determine the molecular basis of this bleeding disorder and gain more insight into explaining the variable clinical manifestations of patients with FV deficiency.

Design, synthesis and in vivo evaluation of 1,4-dioxo-2-butenyl aryl amine derivatives as a promising anti-inflammatory drug prototype

Inflammation is a natural response of the organism to an infection, trauma, or cellular stress. Pain is the first symptom of acute and chronic inflammation. The standard class of medication to treat inflammatory pain is the nonsteroidal anti-inflammatory drug (NSAID). These drugs are associated with severe side effects such as gastric ulcers, gastritis, or internal bleeding. One of NSAIDs, Dipyrone® (metamizole) is largely used in many European and South American countries despite its dubious effectivity and its withdrawal from the market of several countries. Here, aiming to identify a new anti-inflammatory drug prototype based on Dipyrone® structure, a set of 27 molecules were virtually screened, and 4 compounds containing the active metabolite 4-aminoantipyrine and 1,4-dioxo-2-butenyl fragment were selected for docking, synthesis, and biological evaluation. The selection was based on the number of H-bonds and π- π stacking interactions between the inhibitor and the amino acids within the binding site of the enzyme. Carrageenan-induced paw edema, acetic acid-induced writhing, and formalin assays were used to evaluate inflammation and pain response. The selected compounds 1–4 inhibited the involvement of biogenic amines in the formation of paw edema. Compounds 1–4 also reduced pain in the inflammatory response phase. It has to be noted that 4-AA may cause agranulocytosis, which should be borne in mind when developing drug candidates of similar structure. Our new drug prototypes based on 4-aminoantipyrine and 1,4-dioxo-2-butenyl moieties open a gate for developing a prototype of nonsteroidal anti-inflammatory drugs.

Mechanisms of solvent separation using sugars and sugar alcohols

This study uses sugars (dextrose, sucrose, ribose, fructose and mannose) and sugar alcohols (maltitol, erythritol, sorbitol, xylitol) to separate water from tetrahydrofuran (THF) and acetonitrile (AN). Bottle tests and nuclear magnetic resonance (NMR) show that above 0.25 M all sugars and sugar alcohols effectively separate water from either THF or AN. At 0.5 M concentrations, maltitol and sucrose yield a non-negligible interfacial tension between AN and water, while the interfacial tension is negligible with all other compounds. This indicates that while all compounds have similar separation effectiveness above a benchmark concentration, maltitol and sucrose (which are dimers) have a stronger effect on water structure compared to the other compounds tested (which are monomers). Attenuated Total Reflectance – Fourier Transform Infrared spectroscopy (ATR-FTIR) was used to explain solvent separation, based on the effect of sugars on hydrogen bonding (H-bonding) and on the nitrile band. The H-bonding peak was deconvolved into peaks representative of different water clusters, comprised of water molecules donating and accepting a different number of H-bonds. Principal component analysis (PCA) shows that single H-bond donors (SD) (at approximately 3200 cm−1) and double H-bond donor (DD) (at approximately 3400 cm−1) are most affected by maltitol and sucrose. All sugars tested induce a blue shift of the H-bonding of absorbance peaks for DD and SD, in either water or in mixtures of water-AN and water-THF. This indicates that they strengthen H-bonding in these clusters. The effect of all sugars is comparable when concentrations are expressed as OH equivalents. Sugars increase the ratio between the amplitude A of SD relative to DD, and SD are most effective at structuring water. The difference between the ratio A(SD)/A(DD) after and before sugar addition is lowest in water (≈0.9), followed by THF-water mixtures (≈1.1) and AN-water mixtures (≈1.2). This indicates that solvents enhance the effect of sugars on H bonding. This is likely because sugars are not soluble in either THF or AN, which therefore excludes them and promotes their interactions with water. In turn, water-sugar H-bonding weakens interactions between AN-water or THF-water, leading to solvent separation. The analysis of the nitrile band shows that sugars and sugar alcohols increase the relative amount of free nitrile, which is correlated to weaker interactions between AN and water. Maltitol and sucrose display approximately two times the relative amount of free nitrile compared to dextrose and erythritol. Our study confirms that sugars and sugar alcohols weaken solvent-water interactions, and reveals that they separate solvents by increasing the proportion of SD relative to DD.

In silico detection of potential inhibitors from vitamins and their derivatives compounds against SARS-CoV-2 main protease by using molecular docking, molecular dynamic simulation and ADMET profiling

COVID-19 is a new infectious disease caused by SARS-COV-2 virus of the coronavirus Family. The identification of drugs against this serious infection is a significant requirement due to the rapid rise in the positive cases and deaths around the world. With this concept, a molecular docking analysis for vitamins and their derivatives (28 molecules) with the active site of SARS-CoV-2 main protease was carried out.The results of molecular docking indicate that the structures with best binding energy in the binding site of the studied enzyme (lowest energy level) are observed for the compounds; Folacin, Riboflavin, and Phylloquinone oxide (Vitamin K1 oxide). A Molecular Dynamic simulation was carried out to study the binding stability for the selected vitamins with the active site of SARS-CoV-2 main protease enzyme. Molecular Dynamic shows that Phylloquinone oxide and Folacin are quite unstable in binding to SARS-CoV-2 main protease, while the Riboflavin is comparatively rigid. The higher fluctuations in Phylloquinone oxide and Folacin indicate that they may not fit very well into the binding site. As expected, the Phylloquinone oxide exhibits small number of H-bonds with protein and Folacin does not form a good interaction with protein. Riboflavin exhibits the highest number of Hydrogen bonds and forms consistent interactions with protein. Additionally, this molecule respect the conditions mentioned in Lipinski's rule and have acceptable ADMET proprieties which indicates that Riboflavin (Vitamin B2) could be interesting for the antiviral treatment of COVID-19.

Identification of Halogen-Based Derivatives as Potent Inhibitors of Estrogen Receptor Alpha of Breast Cancer: An In-Silico Investigation

Breast cancer is the most common cancer among women worldwide. Breast cancer is caused by the overexpression of genes that facilitate breast cell proliferation. Estrogen receptor alpha (ER[Formula: see text]) mediation is mostly responsible for the development of malignant tumors by regulating the transcription of various genes as a transcription factor. ER[Formula: see text] is regarded as an important receptor for the proliferation of this disease and its inhibition is necessary for the treatment of breast cancer. In our study, the aim is to find out potential inhibitors for ER[Formula: see text] by docking 100 anticancer constituents of different halogen-based derivatives against ER[Formula: see text]. Among the 100 [Formula: see text]-based derivatives, 20 ligands were selected based on the interaction energy ranging from [Formula: see text]6.7[Formula: see text]kcal/mol to [Formula: see text]8.2[Formula: see text]kcal/mol and lower values of inhibition constant (0.92–11.77[Formula: see text][Formula: see text]). We have performed a comprehensive analysis of five most popular ligands (L17, L57, L61, L67, and L70) among these 20 selected derivatives. The interaction analysis is mainly stabilized by making different interactions including hydrogen bonding, hydrophobic, electrostatic, and halogen bonding with the active site of ER[Formula: see text]. A quantum study based on frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), and global chemical reactivity descriptor (GCRD) is carried out to explore the structural chemistry of our most popular ligands which indicates that they are quite reactive and kinetically stable. Additionally, we also assess the ADMET profiles to predict the toxicity and drug-likeness of our lead compounds. Our selected ligands have the highest absorption and good clearance rate and have no AMES toxicity, skin sensitization, and hepatotoxicity. Molecular dynamics simulations were run to check the conformational stability of apo form of ER[Formula: see text] and complex state, at 60-ns time scale. The molecular dynamics simulations are based on the plots of RMSD, RMSF, [Formula: see text], SASA, and the number of H-bonds. The results of RMSD and RMSF showed that the lead compounds L17, L57, L61, L67, and L70 are most stable and have no significant residual fluctuations and deviation. The analysis of the plots of [Formula: see text], SASA, and the number of H-bonds revealed that the complexes L17, L57, and L70 are most stable. So, the lead anticancer compounds L17, L57, L61, L67, and L70 are the most promising inhibitors against ER[Formula: see text] of breast cancer. The comprehensive analysis of all studied parameters highlighted that our selected ligands have great potential to inhibit ER[Formula: see text]. So, it can be concluded that the selected halogen-based derivatives can promote rational drug design for the target therapies of ER[Formula: see text] of breast cancer.

Inhibitory efficacy of 2, 4-diacetylphloroglucinol against SARS-COV-2 proteins: in silico study.

The pandemic of Severe Acute Respiratory Syndrome Coronavirus-2 has affected millions of people worldwide with common symptoms of fever, cough, and respiratory complications. The pandemic has posed a huge challenge to emergency health services due to unavailability of potent therapeutic drugs. The proteins associated with the viral pathogenesis has been identified as suitable targets for drug design and warrants effective drug discovery to abate COVID-19. The papain-like protease (PLpro), nucleocapsid (N), main protease (Mpro) and non-structural protein (nsp12) of SARS-CoV-2, key component of processing of viral polyproteins, transcription, assembly and replication. On this streak, present study evaluated the interaction of ligand 2,4-diacetylphloroglucinol (DAPG) with viral proteins using molecular docking with (i) AutoDock 4.2.6 and (ii) AutoDock Vina followed by molecular dynamic simulation studies of protein-ligand complex configuration. The analysis revealed that PLpro (3E9S) and N (4J3K) protein corresponds to the highest docking score and therefore, selected for molecular dynamics simulation study (100 ns). The study comprised analysis of parameters: (i) RMSD and RMSF, (ii) radius of gyration- which indicated interaction of protein entities with ligand supported steadiness of the complex, (iii) Coulombic and Lennard–Jones interactions, which played a significant role in complex stability. DAPG showed a good number of H-bonds with PLpro and MM-PBSA binding energy when compared to the N protein. This study showed DAPG as a potential bioactive molecule to act as an inhibitor for the PLpro thereby, DAPG can be used as potential inhibitor against SARS-CoV-2 and is potential drug candidate against COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11756-021-00979-4.

Insights on choline chloride-based deep eutectic solvent (reline) + primary alcohol mixtures: a molecular dynamics simulation study.

Deep eutectic solvents (DESs) emerged as green solvents for new generation technologies owing to their high chemical and thermal stability. Addition of restricted amount of organic solvents into the DESs plays a significant role in the improvement of thermodynamic and the transport properties to work as a potential solvent in process industries. In this paper, molecular dynamics (MD) simulations were performed to understand the thermophysical and transport properties of choline chloride-based DES (reline) and primary alcohol (methanol and ethanol) mixture in relation to microscopic structure. Density, radial distribution function, coordination number, average number of H-bond, diffusion coefficient and spatial distribution function was calculated in order to understand the structure and involvement of H-bond network at an atomic level. H-bond and spatial distribution function analyses revealed that the chloride ion prefers to be spatially distributed around hydroxyl group of alcohol and found to be more pronounced upon increase in alcohol concentration. As a consequence, it was observed that the H-bonds between Cl- and urea decreases overall with the loading of alcohol and effect is more pronounced beyond a concentration of 0.4. Self-diffusion values for choline, Cl- and urea were found to be increased significantly upon increase in concentration of alcohol from 0.6 to 0.8. Overall, our simulation points to the interplay and interactions between the chloride ions and the solvents in determining the structural and transport properties of choline chloride-based DES.

A molecular insight into the effect of key ions on the detachment of crude oil from calcite surface: Implication for low salinity water flooding in carbonate reservoirs

The detachment of crude oil from calcite surface plays an important role in oil recovery and wettability alteration during low salinity water flooding in carbonate reservoirs. The effects of brine salinities and key ions on the dynamic detachment process have been much of debate in the past decades in theories and experiments due to complex mechanisms behind the crude oil-calcite interactions. Herein, molecular dynamic simulation was used to study the influence of brine salinities and ion concentrations on the detachment mechanism of crude oil from calcite surface by establishing 20 brine-crude oil-calcite molecular models varying salinities and key ion concentrations in brine. Molecular configurations, concentration distribution profiles, interaction energies, H-bond numbers and center of mass (COM) distances were carefully analyzed to characterize the dynamic crude oil detachment performance. The results reveal that reducing the brine salinities and ion concentrations can significantly weaken the interaction intensity between oil and calcite and accelerate the detachment process. Therefore, the oil detachment is induced and the effect of low salinity on oil detachment process is significantly time-dependent. The concentration distribution profiles shows that the strong polar oil molecules, for example acetic acid molecules, can't be detached from calcite surface by tuning the brine salinity and key ions. The present of Mg2+ and Na+ is able to delay the detachment process of oil molecules and as a consequence, result in the impeded oil detachment process according to time-dependent dynamic molecular configurations, interaction energies and COM distances analysis. Furthermore, the present of Ca2+ is able to strengthen the interaction between oil and calcite and in consequence, hinder the detachment of oil molecules from the calcite surface according to the interaction energy, the molecular configuration and COM distances. This study should provide the molecular-scale insights into wettability alteration and enhanced oil recovery by low salinity water flooding in carbonate reservoirs.

Destabilization of Aβ fibrils by omega-3 polyunsaturated fatty acids: a molecular dynamics study

The senile plaques of neurotoxic aggregates of Aβ protein, deposited extraneuronally, mark the pathological hallmark of Alzheimer’s disease (AD). The natural compounds such as omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), which can access blood–brain barrier, are believed to be potential disruptors of preformed Aβ fibrils to cure AD with unknown mechanism. Herein, we present the destabilization potential of three ω-3 PUFAs, viz. Eicosapentaenoic acid (EPA), Docosahexaenoic acid (HXA), and α-linolenic acid (LNL) by molecular dynamics simulation. After an initial testing of 300 ns, EPA and HXA have been considered further for extended production run time, 500 ns. The increased value of root mean square deviation (RMSD), radius of gyration, and solvent-accessible surface area (SASA), the reduced number of H-bonds and β-sheet content, and disruption of salt bridges and hydrophobic contacts establish the binding of these ligands to Aβ fibril leading to destabilization. The polar head was found to interact with positively charged lysine (K28) residue in the fibril. However, the hydrophobicity of the long aliphatic tail competes with the intrinsic hydrophobic interactions of Aβ fibril. This amphiphilic nature of EPA and HXA led to the breaking of inherent hydrophobic contacts and formation of new bonds between the tail of PUFA and hydrophobic residues of Aβ fibril, leading to the destabilization of fibril. The Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) results explain the binding of EPA and HXA to Aβ fibril by interacting with different residues. The destabilization potential of EPA and HXA establishes them as promising drug leads to cure AD, and encourages prospecting of other fatty acids for therapeutic intervention in AD. Communicated by Ramaswamy H. Sarma

Synthesis and Fungicidal Activity of Hydrated Geranylated Phenols against Botrytis cinerea.

Botrytis cinerea is a ubiquitous fungus that affects hundreds of plants, resulting in economic losses to the horticulture and fruit industry. The search for new antifungal agents is a matter of current interest. Thus, in this work a series of geranylated phenols in which the side alkyl chain has been hydrated have been synthesized, and their activity against B. cinerea has been evaluated. The coupling of phenol and geraniol has been accomplished under microwave irradiation obtaining the highest reaction yields in the shortest reaction times. Hydration of the side chain was carried out in dioxane with p-toluenesulfonic acid polymer-bound as the catalyst. All synthesized compounds were tested against B. cinerea using the growth inhibition assay and EC50 values were determined. The results show that activity depends on the number and nature of functional groups in the phenol ring and hydration degree of the geranyl chain. The most active compound is 1,4-dihydroquinone with one hydroxyl group attached at the end of the alkyl chain. Results from a molecular docking study suggest that hydroxyl groups in the phenol ring and alkyl chain are important in the binding of compounds to the active site, and that the experimental antifungal activity correlates with the number of H-bond that can be formed in the binding site.

Affinity enhancement of CR3022 binding to RBD; in silico site directed mutagenesis using molecular dynamics simulation approaches

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a disease which caused by a novel beta coronavirus. Structural and non-structural proteins are expressed by the virus gene fragments. The RBD of the S1 protein of the virus has the ability to interact with potent antibodies including CR3022, which was characterized to target the S protein of the virus which can efficiently neutralize the SARS-CoV in vitro and in vivo. In current study, we aimed to design CR3022 based antibody with high affinity compared with wild-type CR3022 using MD simulation method. Two variants were designed based on the amino acid binding conformation and the free binding energy of the critical amino acids which involved in CR3022-RBD interactions were evaluated. In this study three complexes were evaluated; CR3022-RBD, V1-RBD and V2-RBD using molecular dynamics simulations carried out for 100 ns in each case. Then, all the complexes were simulated for 100 ns. In the next step, to calculate the free binding affinity of the wild CR3022 and mutant antibody (V1 and V2) with RBD, the PMF method was performed. The RMSD profile demonstrated that all three complexes were equilibrated after 85 ns. Furthermore, the free binding energy results indicated that the V2-RBD complex has the higher binding affinity than V1-RBD and CR3022-RBD complexes. It should be noted that in above variants, the electrostatic energy and the number of H-bonds between the antibody and RBD increased. Thus, it is suggested that both designed antibodies could be considered as appropriate candidates for covid-19 disease treatment. Communicated by Ramaswamy H. Sarma

Probing Water State during Lipidic Mesophases Phase Transitions.

We investigate the static and dynamic states of water network during the phase transitions from double gyroid (Ia3‾d ) to double diamond (Pn3‾m ) bicontinuous cubic phases and from the latter to the reverse hexagonal (H II) phase in monolinolein based lipidic mesophases by combining FTIR and broadband dielectric spectroscopy (BDS). In both cubic(s) and H II phase, two dynamically different fractions of water are detected and attributed to bound and interstitial free water. The dynamics of the two water fractions are all slower than bulk water due to the hydrogen‐bonds between water molecules and the lipid's polar headgroups and to nanoconfinement. Both FTIR and BDS results suggest that a larger fraction of water is hydrogen‐bonded to the headgroup of lipids in the H II phase at higher temperature than in the cubic phase at lower temperature via H‐bonds, which is different from the common expectation that the number of H‐bonds should decrease with increase of temperature. These findings are rationalized by considering the topological ratio of interface/volume of the two mesophases.

Structure, chain dynamics and mechanical properties of poly(vinyl alcohol)/phytic acid composites

The global micro- and nano-plastic issue has greatly triggered the development of advanced biodegradable polymeric materials. The creation of biodegradable polyvinyl alcohol (PVA)/phytic acid (PhyAc) composite represents a sustainable solution. However, it remains unclear how PhyAc molecules affect intermolecular hydrogen-bonding (H-bonding), structure, chain dynamics and mechanical properties of PVA so far. Herein, we explore structure, chain dynamics and mechanical properties of PVA/PhyAc composite by combining molecular dynamics simulation and experimental. The number of PVA-PhyAc H-bonds per PhyAc molecule and that of total H-bonds show different PhyAc content dependence. The PVA composite with 1.9 wt% of PhyAc shows a lower free volume and a smaller diffusion coefficient. Meanwhile, the glass transition temperature (Tg) of PVA reaches the maximum value at ca. 1.25 wt% of PhyAc. Interestingly, 10 wt% PhyAc endows PVA with the highest tensile strength in addition to a good antibacterial capability. This work reveals how small molecules affect structure and mechanical properties of polymers and contributes to expanding practical applications of PVA/PhyAc in industry.