Local Electrostatic Potential Research Articles

Modulation of heteromeric glycine receptor function through high concentration clustering.

Ion channels are targeted by many drugs for treating neurological, musculoskeletal, renal and other diseases. These drugs bind to and alter the function of individual channels to achieve desired therapeutic effects. However, many ion channels function in high concentration clusters in their native environment. It is unclear if and how clustering modulates ion channel function. Human heteromeric glycine receptors (GlyRs) are the major inhibitory neurotransmitter receptors in the spinal cord and are active targets for developing chronic pain medications. We show that the α2β heteromeric GlyR assembles with the master postsynaptic scaffolding gephyrin (GPHN) into micron-sized clustered at the plasma membrane after heterologous expression. The inhibitory trans- synaptic adhesion protein neuroligin-2 (NL2) further increases both the cluster sizes and GlyR concentration. The apparent glycine affinity increases monotonically as a function of GlyR concentration but not with cluster size. We also show that ligand re-binding to adjacent GlyRs alters kinetics but not chemical equilibrium. A positively charged N- terminus sequence of the GlyR β subunit was further identified essential for glycine affinity modulation through clustering. Taken together, we propose a mechanism where clustering enhances local electrostatic potential, which in turn concentrates ions and ligands, modulating the function of GlyR. This mechanism is likely universal across ion channel clusters found ubiquitously in biology and provides new perspectives in possible pharmaceutical development.

Synthesis, Crystal Structure and Antifungal Activity of (E)-1-(4-Methylbenzylidene)-4-(3-Isopropylphenyl) Thiosemicarbazone: Quantum Chemical and Experimental Studies.

A novel (E)-1-(4-methylbenzylidene)-4-(3-isopropylphenyl) thiosemicarbazone was synthesized in a one-pot four-step synthetic route. Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic resonances (NMR), single-crystal X-ray diffraction, and UV-visible absorption spectroscopy were utilized to confirm the successful preparation of the title compound. Single-crystal data indicated that the intramolecular hydrogen bond N(3)-H(3)···N(1) and intermolecular hydrogen bond N(2)-H(2)···S(1) (1 - x, 1 - y, 1 - z) existed in the crystal structure and packing of the title compound. Besides the covalent interaction, the non-covalent weak intramolecular hydrogen bond N(3)-H(3)···N(1) discussed by atoms in molecules (AIM) theory also functioned in maintaining the title compound's crystal structure. The strong intermolecular hydrogen bond N(2)-H(2)···S(1) (1 - x, 1 - y, 1 - z) discussed by Hirshfeld surface analysis played a major role in maintaining the title compound's crystal packing. The local maximum and minimum electrostatic potential of the title compound was predicted by electrostatic potential (ESP) analysis. The UV-visible spectra and HOMO-LUMO analysis revealed that the title compound has a low ΔEHOMO-LUMO energy gap (3.86 eV), which implied its high chemical reactivity due to the easy occurrence of charge transfer interactions within the molecule. Molecular docking and in vitro antifungal assays evidenced that its antifungal activity is comparable to the reported pyrimethanil, indicating its usage as a potential candidate for future antifungal drugs.

Effect of nitrogen- and oxygen-containing functional groups on adsorption of styrene by activated carbon: A theoretical study by density functional theory

Activated carbon adsorption is one of the mainstream technologies for controlling VOCs emissions such as styrene, with surface functional groups significantly influencing its adsorption capacity. The adsorption mechanism of styrene on functionalized AC was studied using DFT calculations. Results show that nitrogen and oxygen doping altered the local electrostatic potential of AC, reduced the average LOLIPOP index of the internal ring, and enhanced styrene adsorption to varying degrees. AC with hydroxyl and pyrrolic groups significantly improved styrene adsorption (Ead = -13.76, -12.86 kcal/mol). Styrene adsorption on AC is a physisorption process, primarily dominated by π-π stacking, with dispersion interactions as the main contributor (61–70 %). In addition to π-π stacking, weak hydrogen bonds between styrene and AC functionalized with hydroxyl, amino, and pyrrolic N groups further enhance the adsorption capacity. Enhancing the synergistic effect of hydrogen bonding and π-π stacking is key to significantly improving adsorption capacity.

Atomic-Scale View of Water Chemistry on Nanostructured Iron Oxide Films.

The interaction of water with solid surfaces is crucial for a wide range of disciplines, including catalysis, environmental science, corrosion, geology, and biology. In this study, we present a combined experimental and theoretical investigation that elucidates the interaction of water with a model iron oxide surface under near ambient conditions (i.e., room temperature and water vapor in the mbar range). Our findings reveal that surface hydroxylation can be controlled at the nanoscale by the local properties of the oxide film, such as local rumpling and electrostatic potential. The iron oxide surface presents alternating hydrophilic and hydrophobic domains, creating after water exposure a hexagonal pattern with a pitch of approximately 3 nm, where the highly hydroxylated regions act as nucleation centers for nanoconfined water molecule clusters.

Dynamic density functional theory of polymers with salt in electric fields.

We present a dynamic density functional theory for modeling the effects of applied electric fields on the local structure of polymers with added salt (polymer electrolytes). Time-dependent equations for the local electrostatic potential and volume fractions of polymer, cation, and anion of added salt are developed using the principles of linear irreversible thermodynamics. For such a development, a field theoretic description of the free energy of polymer melts doped with salts is used, which captures the effects of local variations in the dielectric function. Connections of the dynamic density functional theory with experiments are established by relating the three phenomenological Onsager's transport coefficients of the theory to the mutual diffusion of electrolyte, ionic conductivity, and transference number of one of the ions. The theory is connected with a statistical mechanical model developed by Bearman and Kirkwood [J. Chem. Phys. 28, 136 (1958)] after relating the three transport coefficients to friction coefficients. The steady-state limit of the dynamic density functional theory is used to understand the effects of dielectric inhomogeneity on the phase separation in polymer electrolytes. The theory developed here provides not only a way to connect with experiments but also to develop multi-scale models for studying connections between local structure and ion transport in polymer electrolytes.

Influence of local cation order on the electronic structure and optical properties of cation-disordered semiconductor AgBiS2

Abstract Site disorder exists in some practical semiconductors and can significantly impact their intrinsic properties both beneficially and detrimentally. However, the uncertain local order and structure poses a challenge for both experimental and theoretical research. Especially, it hinders the investigation of the effects of the diverse local atomic environments resulting from the site disorder. In this study, we employ the special quasi-random structure method to perform first-principles research on the connection between local site disorder and electronic/optical properties, using the cation-disordered AgBiS2 (rock salt phase) as an example. We predict that cation-disordered AgBiS2 has a bandgap ranging from 0.6 to 0.8 eV without spin-orbit coupling and that spin-orbit coupling reduces this by approximately 0.3 eV. We observe the effects of local structural features in the disordered lattice, such as the one-dimensional chain-like aggregation of cations that results in the formation of doping energy bands near the band edges, the formation and broadening of band-tail states, and the disturbance in the local electrostatic potential, which significantly reduces the bandgap and stability. The influence of these ordered features on the optical properties is confined to alterations in the bandgap and does not markedly affect the joint density of states or optical absorption. Our study provides a research roadmap for exploring the electronic structure of site-disordered semiconductor materials, suggests that the ordered chain-like aggregation of cations is an effective way to regulate the bandgap of AgBiS2, and provides insight into how variations in local order associated with processing can affect properties.

Theoretical analysis of naproxen reaction with sulfate and hydroxyl radicals in the aqueous phase: Investigating reactive sites and reaction kinetics

In this study, we have utilized theoretical calculations to predict the reaction active sites of naproxen when reacting with radicals and to further study the thermodynamics and kinetics of the reactions with ·OH and SO4−·. The evidence, derived from the average local ionization energy and electrostatic potential, points to the naphthalene ring as the preferred site of attack, especially for the C2, C6, C9, and C10 sites. The changes in Gibbs free energy and enthalpy of the reactions initiated by ·OH and SO4−· ranged between −19.6 kcal/mol - 26.3 kcal/mol and −22.3 kcal/mol −18.5 kcal/mol, respectively. More in-depth investigation revealed that RA2 pathway for ·OH exhibited the lowest free energy of activation, suggesting this reaction is more inclined to proceed. The second-order rate constant results indicate the ·OH attacking reaction is faster than reactions initiated by SO4·-, yet controlled by diffusion. The consistency between theoretical findings and experimental data underscores the validity of this computational method for our study.

Influence of an Intrinsically Disordered Region on Protein Domains Revealed by NMR-Based Electrostatic Potential Measurements.

Many human proteins possess intrinsically disordered regions containing consecutive aspartate or glutamate residues ("D/E repeats"). Approximately half of them are DNA/RNA-binding proteins. In this study, using nuclear magnetic resonance (NMR) spectroscopy, we investigated the electrostatic properties of D/E repeats and their influence on folded domains within the same protein. Local electrostatic potentials were directly measured for the HMGB1 protein, its isolated D/E repeats, and DNA-binding domains by NMR. The data provide quantitative information about the electrostatic interactions between distinct segments of HMGB1. Due to the interactions between the D/E repeats and the DNA-binding domains, local electrostatic potentials of the DNA-binding domains within the full-length HMGB1 protein were largely negative despite the presence of many positively charged residues. Our NMR data on counterions and electrostatic potentials show that the D/E repeats and DNA have similar electrostatic properties and compete for the DNA-binding domains. The competition promotes dissociation of the protein-DNA complex and influences the molecular behavior of the HMGB1 protein. These effects may be general among the DNA/RNA-binding proteins with D/E repeats.

Three-Dimensional Structural Stability and Local Electrostatic Potential at Point Mutations in Spike Protein of SARS-CoV-2 Coronavirus.

The contagiousness of SARS-CoV-2 β-coronavirus is determined by the virus-receptor electrostatic association of its positively charged spike (S) protein with the negatively charged angiotensin converting enzyme-2 (ACE2 receptor) of the epithelial cells. If some mutations occur, the electrostatic potential on the surface of the receptor-binding domain (RBD) could be altered, and the S-ACE2 association could become stronger or weaker. The aim of the current research is to investigate whether point mutations can noticeably alter the electrostatic potential on the RBD and the 3D stability of the S1-subunit of the S-protein. For this purpose, 15 mutants with different hydrophilicity and electric charge (positive, negative, or uncharged) of the substituted and substituting amino acid residues, located on the RBD at the S1-ACE2 interface, are selected, and the 3D structure of the S1-subunit is reconstructed on the base of the crystallographic structure of the S-protein of the wild-type strain and the amino acid sequence of the unfolded polypeptide chain of the mutants. Then, the Gibbs free energy of folding, isoelectric point, and pH-dependent surface electrostatic potential of the S1-subunit are computed using programs for protein electrostatics. The results show alterations in the local electrostatic potential in the vicinity of the mutant amino acid residue, which can influence the S-ACE2 association. This approach allows prediction of the relative infectivity, transmissibility, and contagiousness (at equal social immune status) of new SARS-CoV-2 mutants by reconstruction of the 3D structure of the S1-subunit and calculation of the surface electrostatic potential.

Comprehensive solubility study and inter-molecular interactions on fenbendazole dissolved in some aqueous aprotic and protic co-solvent solutions

The isothermal shake-flask saturation method was used to experimentally determine the mole-fraction solubility of fenbendazole in three aqueous co-solvent blends of 1,4-dioxane/acetone/NMP encompassing the range of 283.15 to 328.15 K. The solubility of fenbendazole in various blended solvents ranks NMP + water (4.852 × 10−2) > 1,4-dioxane + water (14.81 × 10−4) > acetone + water (2.285 × 10−4) with composition of 1,4-dioxane (acetone or NMP) of 1 at 298.15 K. The solubility data rises monotonically with 1,4-dioxane/acetone/NMP concentration at the same temperature. X-ray power diffraction images show that no solvate production or crystal transition appeared throughout the studies. The solubility to solvent composition and temperature was satisfactorily associated by the modified van't Hoff-Jouyban-Acree, quantitative structure–property relationship, and Jouyban-Acree models with relative average deviations of no higher than 7.05 % and root-mean-square deviation of no higher than 1.225 × 10−3. In addition, the 1,4-dioxane/acetone/NMP + water blends studied in this paper and the methanol/ethanol/EG/DMF + water blends previously reported both used the extended Hildebrand solubility approach to quantitatively describe the solubility behavior at 298.15 K. The average relative deviations were kept under 4.06 % on both cases. As stated by the examination of the linear solvation energy relationship, the solubility parameter and dipolarity-polarizability of solutions have a significant influence on the solubility variation. The effective method of inverse Kirkwood-Buff integrals was used to investigate the preferred solvation of fenbendazole at 298.15 K. In blends with intermediate and rich ethanol/DMF/1,4-dioxane/acetone/NMP composition areas, the preferred solvation parameters of ethanol/DMF/1,4-dioxane/acetone/NMP displayed positive values, indicating the preferential solvation of fenbendazole by the co-solvents. Thermodynamic examination of the entropy-enthalpy compensation and dissolution parameters for fenbendazole dissolving in blends led to the identification of an enthalpy and/or entropy-driven mechanism as well as an endothermic process. Moreover, the average local ionization energy and electrostatic potential of molecular surface were utilized as effective instruments to demonstrate the microscopic electrostatic properties of acidity and basicity, respectively. The fenbendazole molecule's groups of –N in the five-membered ring and –NH in the straight chain serve as the main targets for electrophilic and nucleophilic assault. The weak interactions between fenbendazole and several solvents were shown using an independent gradient model based on Hirshfeld partition analysis.

Statistical field theory of mechanical stresses in Coulomb fluids: general covariant approach vs Noether’s theorem

In this paper, we introduce a statistical field theory that describes the macroscopic mechanical forces in inhomogeneous Coulomb fluids. Our approach employs the generalization of Noether’s first theorem for the case of a fluctuating order parameter to calculate the stress tensor for Coulomb fluids. This tensor encompasses the mean-field stress tensor and fluctuation corrections derived through the one-loop approximation. The correction for fluctuations includes a term that accounts for the thermal fluctuations of the local electrostatic potential and field in the vicinity of the mean-field configuration. This correlation stress tensor determines how electrostatic correlation affects local stresses in a nonuniform Coulomb fluid. We also use a previously formulated general covariant methodology (Brandyshev and Budkov 2023 J. Chem. Phys. 158 174114) in conjunction with a functional Legendre transformation method and derive within it the same total stress tensor. We would like to emphasize that our general approaches are applicable not only to Coulomb fluids but also to nonionic simple or complex fluids, for which the field-theoretic Hamiltonian is known as a function of the relevant scalar order parameters.

PH-Dependent Structure and Dynamics of the Catalytic Domains of Human Carbonic Anhydrase II and IX.

Extensive computer simulation studies have been carried out to probe the pH-dependent structure and dynamics of the two most efficient isoenzymes II and IX of human carbonic anhydrase (HCA) that control the pH in the human body. The equilibrium structure and hydration of their catalytic domains are found to be largely unaffected by the variation of pH in the range studied, in close agreement with the known experimental results. In contrast, a significant effect of the change in pH is observed for the first time on the local electrostatic potential of the active site walls and the dynamics of active site water molecules. We also report for the first time the free energy and kinetics of coupled fluctuations of orientation and protonation states of the well-known His-mediated proton shuttle (His-64) in both isozymes at pH 7 and 8. The transitions between different tautomers of in or out conformations of His-64 side chain range between 109 and 106 s-1 depending on pH. Possible implications of these results on conformation-dependent pKa of His-64 side chain and its role in driving the catalysis toward hydration of CO2 or dehydration of HCO3- with varying pH are discussed.

The Use of Model-Predicted Internal States from Locally Linear, Gain-Scheduled, Reduced-Order Physics-Based Models in Model-Predictive Control Strategies

The objective of the research is to develop reduced-order state-space models that can predict internal states that are not directly observable with existing sensors. In doing so, battery management systems (BMS) can make real-time control decisions based upon sensor inferences. For example, estimating local electrode Li and electrolyte Li-ion concentrations or local electrostatic potential differences between electrode and electrolyte phases offer valuable knowledge in predicting behaviors such as Li plating, dendrite growth, or electrode fracture. Such indirect predictive capabilities, for example, can enable fast-charging protocols that avoid damage mechanisms.This talk explores the mathematical feasibility of estimating local Li concentrations and electrostatic potentials using observed current-voltage sequences. The approach for determining internal battery states begins with an estimator that uses observed input-output data from a physics-based reduced-order state-space model. If the model satisfies the property of observability, a sufficiently long window of input-output data can predict unique internal-state trajectories that are compatible with the observable data. The research considers understanding the effects of sampling time and state of charge on internal-state observability.Efficient estimation algorithms must incorporate battery physics and chemistry yet be sufficiently simple as to run in real-time on a battery management system (BMS). The present research first develops a physics-based pseudo-two-dimensional (P2D) model, which describes battery thermodynamics, transport, and kinetics, results in a system of nonlinear, coupled, differential-algebraic equations that can be solved computationally, but too slow for real-time implementation. The P2D model is then reduced to a gain-scheduled, locally linear, state-space model that can be run in real-time. Both models are implemented within the MATLAB/Simulink framework that facilitates development and evaluation of control strategies.

Omicron Coronavirus: pH-Dependent Electrostatic Potential and Energy of Association of Spike Protein to ACE2 Receptor.

The association of the S-protein of the SARS-CoV-2 beta coronavirus to ACE2 receptors of the human epithelial cells determines its contagiousness and pathogenicity. We computed the pH-dependent electric potential on the surface of the interacting globular proteins and pH-dependent Gibbs free energy at the association of the wild-type strain and the omicron variant. The calculated isoelectric points of the ACE2 receptor (pI 5.4) and the S-protein in trimeric form (pI 7.3, wild type), (pI 7.8, omicron variant), experimentally verified by isoelectric focusing, show that at pH 6-7, the S1-ACE2 association is conditioned by electrostatic attraction of the oppositely charged receptor and viral protein. The comparison of the local electrostatic potentials of the omicron variant and the wild-type strain shows that the point mutations alter the electrostatic potential in a relatively small area on the surface of the receptor-binding domain (RBD) of the S1 subunit. The appearance of seven charge-changing point mutations in RBD (equivalent to three additional positive charges) leads to a stronger S1-ACE2 association at pH 5.5 (typical for the respiratory tract) and a weaker one at pH 7.4 (characteristic of the blood plasma); this reveals the reason for the higher contagiousness but lower pathogenicity of the omicron variant in comparison to the wild-type strain.

Theoretical and experimental investigation of novel quinazoline derivatives: synthesis, photophysical, reactive properties, molecular docking and selective HSA biointeraction

Two new quinazoline derivatives (2a and 2b) were successfully synthesized in this work using the condensation technique in excellent yields. Using spectroscopic techniques and elemental analyses, the compounds were completely characterized. Density functional theory (DFT) computations have been used to examine the title compound’s reactive characteristics. Chemical reactivity was predicted using local reactive descriptors and molecule electrostatic potential. Additionally, Time dependent DFT (TD-DFT) simulations were used to examine the impact of solvents on the photophysical characteristics. The affinity of compounds 2a and 2b for human serum albumin (HSA) was further explored using several electronic spectroscopies. Through static mechanisms, both compounds reduce the intrinsic fluorescence of HSA. It is determined that the HSA-2b complex’s binding constant is significantly greater than the HSA-2a complex. The fluorescence spectrum measurements proved that the HSA underwent structural changes after interaction with these compounds. It was demonstrated by site marker competitive displacement studies that compounds 2a and 2b preferred to bind to site I in HSA subdomain IIA. Additionally, synchronised fluorescence spectra were utilized to analyze how HSA’s conformation changed after interacting with various substances. The molecular docking investigations of these compounds with the three critical HSA binding sites, comprising subdomains IIA, IIIA, and IB, further confirmed the experimental findings. The significant contact between the investigated compounds and HSA was supported by the docking simulations. Communicated by Ramaswamy H. Sarma

Study of the reaction mechanism based on the formation of the first carbocyclic ring from propargyl and diacetylene

The formation of the first carbon ring is a crucial rate-controlling step in developing polycyclic aromatic hydrocarbons (PAHs). It is vital to investigate the mechanism of the creation of the first carbon ring to inhibit the formation of PAHs. To explore the growth process of the first carbocyclic ring, this work used the average localized ionization energy (ALIE) and electrostatic potential (ESP) to predict the reaction sites. Moreover, the reaction paths and chemical kinetic parameters for the generation of the first carbocyclic ring from propargyl (C3H3) + diacetylene (C4H2) are calculated based on the density functional theory (DFT) method and transition state theory (TST). The results showed that the addition reaction of C3H3 +C4H2 can form five-, six- and seven-membered ring molecules, in which the five-membered ring formation is fastest and the six-membered ring formation is slowest. During the formation of the first carbon ring, the activation energy required for the H transfer and cyclization reactions is large, and the reaction rate is slow, which determines the formation rate of the first carbon ring. The rate of H-transfer reaction on each carbon ring depends on the number of C atoms of the carbon ring, with the five-membered ring being the fastest and the six-membered ring the slowest. This paper improves the reaction kinetics and thermodynamic data of the first carbon ring formation during the combustion of hydrocarbon fuels, which offers a powerful theoretical basis for predicting the generation of PAHs.

Disorder to order: how halide mixing in MAPbI3-xBrx perovskites restricts MA dynamics.

Mixed-halide lead perovskites are of particular interest for the design of tandem solar cells currently reaching record efficiencies. While halide phase segregation upon illumination of mixed perovskites is extensively studied, the effect of halide disorder on A cation dynamics is not well understood, despite its importance for charge carrier diffusion and lifetime. Here, we study the methylammonium (MA) reorientational dynamics in mixed halide MAPbI3-xBrx perovskites by a combined approach of experimental solid-state NMR spectroscopy and molecular dynamics (MD) simulations based on machine-learning force-fields (MLFF). 207Pb NMR spectra indicate the halides are randomly distributed over their lattice positions, whereas PXRD measurements show that all mixed MAPbI3-xBrx samples are cubic. The experimental 14N spectra and 1H double-quantum (DQ) NMR data reveal anisotropic MA reorientations depending on the halide composition and thus associated disorder in the inorganic sublattice. MD calculations allow us to correlate these experimental results to restrictions of MA dynamics due to preferred MA orientations in their local Pb8I12-nBrn "cages". Based on the experimental and simulated results, we develop a phenomenological model that correlates the 1H dipolar coupling and thus the MA dynamics with the local composition and reproduces the experimental data over the whole composition range. We show that the dominant interaction between the MA cations and the Pb-X lattice that influences the cation dynamics is the local electrostatic potential being inhomogeneous in mixed halide systems. As such, we generate a fundamental understanding of the predominant interaction between the MA cations and the inorganic sublattice, as well as MA dynamics in asymmetric halide coordinations.

Measuring Local Electrostatic Potentials Around Nucleic Acids by Paramagnetic NMR Spectroscopy.

Electrostatic potentials around macromolecules in the presence of mobile charges are difficult to assess especially for highly charged systems. Here, we report measurements of local electrostatic potentials around DNA by paramagnetic NMR. Through quantitative analysis of NMR paramagnetic relaxation enhancement arising from positively charged or neutral paramagnetic cosolutes, we were able to determine local electrostatic potentials around 1H nuclei at >100 sites in major and minor grooves of 13C,15N-labeled 15-bp DNA at 100 mM NaCl. Our experimental electrostatic potential data directly confirmed the Coulombic end effects of DNA. The effective near-surface electrostatic potentials from the NMR data were in good agreement with the theoretical predictions with the Poisson-Boltzmann equation. This NMR method allows for unprecedented experimental investigations into the electrostatic properties of nucleic acids.

Quantum computational, spectroscopic, topological investigations and molecular docking studies on piperazine derivatives: A comparative study on Ethyl, Benzene and Furan sulfonyl Piperazine

The hetero-cyclic aromatic compounds are largely acclimated for pharmaceutical and agrochemicals. Piperazine is a heterocyclic aromatic compound in affiliation with sulfonyl has pharmacological and therapeutic implementation. The title compound Ethyl sulfonyl piperazine (ESP), Benzene sulfonyl piperaine (BSP) and Furan sulfonyl pipierazine (FSP) are compared for their spectroscopic and topological behavior. DFT/B3LYP with the basis set 6–311++G(d,p) is used to optimize the structures and obtain their geometrical parameters. These compounds were characterized for assigning the vibrational modes and to augur their functional groups by FTIR and FT-Raman spectroscopic techniques. Their electronic effects are compared with the proficiency of frontier molecular orbital theory carried out by Gaussian 09 program. Global parameters are calculated to know the global reactivity and stability of the compounds. A multiwave function analyzer 3.6 is habituated to study and compare topological survey with the significance of Electron localization function (ELF), Local orbital locator (LOL), Electrostatic potential (ESP) and Total Density of states (TDOS) of ESP, BSP and FSP. ADME parameters are determined to know the viability of the compounds for its drug candidature. Molecular docking of ESP, BSP and FSP performed mutually with all the three PDB ID'S 4UGC, 5ZBH and 6UP8.

Performance and mechanism of lignin and quercetin as bio-based anti-aging agents for asphalt binder: A combined experimental and ab initio study

• FTIR is used to assess the inhibitory effect of anti-aging agents on asphalt aging. • The capability of lignin to inhibit asphalt aging is lower than that of quercetin. • AIMD simulation and DFT method are used to explore aging mechanism of asphalt. • Bond strength and electrostatic potential are important for anti-aging properties. The addition of lignin to petroleum asphalt as a bio-based anti-aging agent has attracted significant attention owing to its antioxidant property and similar molecular structure to asphalt. To guide the structural modification of lignin to improve its performance in inhibiting asphalt aging, we conducted a combined experimental and ab initio study to reveal the mechanism by which lignin competitively blocks the asphalt aging pathway and to identify the factors affecting the anti-aging property of lignin. Fourier transform infrared spectroscopy was used to evaluate the capability of lignin to prevent asphalt aging. Although lignin inhibited asphalt aging, its activity was significantly lower than that of quercetin, which is another natural phenolic antioxidant. To explain the different performances of lignin and quercetin, ab initio molecular dynamics and density functional theory methods were employed to investigate the aging mechanism of asphalt and the anti-aging mechanism of these two natural phenolics. The results indicate that the H abstraction by O 2 or free radicals is important in asphalt aging and triggers other reactions. Phenolic hydroxyls on lignin and quercetin have strong ability for H atom transfer and positive local electrostatic potential, and so they attract and react with oxidants to prevent the latter from abstracting H atoms from asphalt. Quercetin has a higher content of phenolic hydroxyls than lignin and therefore exhibits superior anti-aging activity. Based on these theoretical results, it is suggested to improve the anti-aging capability of lignin by modifying its structure to lower the molecular weight and increase the phenolic hydroxyl content.