Stability of Cytoplasmic Membrane of Escherichia coli Bacteria in Aqueous and Ethanolic Environment.

The mechanism of action of any antibacterial agent or disinfectant depends largely on their interaction with the bacterial membrane. Herein, we use the SPICA (surface property fitting coarse graining) force-field and develop a coarse-grained (CG) model for the structure of the cytoplasmic membrane of Escherichia coli (E. coli) and its interaction with water and ethanol. We elucidate the impact of different concentrations of ethanol on the cytoplasmic membrane bilayers and vesicles of E. coli using the CG molecular dynamics (CG MD) simulations. Our modeling approach first focuses on the parametrization of the required force-field for POPG lipid and its interaction with water, ethanol, and POPE lipid. Subsequently, the structural stability of the E. coli bacterial membrane in the presence of high and low concentrations of ethanol is delineated. Both flat bilayers as well as vesicles of E. coli membrane were considered for the CG MD. Our results reveal that, at low ethanol concentrations (<30 mol %), the size of the E. coli vesicles increases with discernible deformations in their shapes. Because of ethanol-induced interdigitation, thinning of the E. coli vesicular membrane is also observed. However, at higher ethanol concentrations (>30 mol %), the integrity of the vesicles is lost because of deteriorating invasion of ethanol molecules into the vesicle bilayer and significant weakening of lipid-lipid interactions. At higher ethanol concentrations (40 and 70 mol %), both the multivesicle and single-vesicle bacterial membranes exhibit a similar rupturing pattern wherein the extraction of lipids from the membrane and formation of aggregates of the component lipids are observed. These aggregates consist of polar head groups of 3-5 POPE/POPG lipids with intertwined nonpolar tails.

Mechanism of hydrophobic gating in the acetylcholine receptor channel pore.

Neuromuscular acetylcholine receptors (AChRs) are hetero-pentameric, ligand-gated ion channels. The binding of the neurotransmitter acetylcholine (ACh) to two target sites promotes a global conformational change of the receptor that opens the channel and allows ion conduction through the channel pore. Here, by measuring free-energy changes from single-channel current recordings and using molecular dynamics simulations, we elucidate how a constricted hydrophobic region acts as a "gate" to regulate the channel opening in the pore of AChRs. Mutations of gate residues, including those implicated in congenital myasthenia syndrome, lower the permeation barrier of the channel substantially and increase the unliganded gating equilibrium constant (constitutive channel openings). Correlations between hydrophobicity and the observed free-energy changes, supported by calculations of water densities in the wild-type versus mutant channel pores, provide evidence for hydrophobic wetting-dewetting transition at the gate. The analysis of a coupled interaction network provides insight into the molecular mechanism of closed- versus open-state conformational changes at the gate. Studies of the transition state by "phi"(φ)-value analysis indicate that agonist binding serves to stabilize both the transition and the open state. Intersubunit interaction energy measurements and molecular dynamics simulations suggest that channel opening involves tilting of the pore-lining M2 helices, asymmetric outward rotation of amino acid side chains, and wetting transition of the gate region that lowers the barrier to ion permeation and stabilizes the channel open conformation. Our work provides new insight into the hydrophobic gate opening and shows why the gate mutations result in constitutive AChR channel activity.

Solvation Shell Anatomy of H2S and CO Dissolved in Reline and Ethaline Deep Eutectic Solvents.

Rising atmospheric concentrations of anthropogenic hydrogen sulfide (H2S) and carbon monoxide (CO) as a result of industrialization have encouraged researchers to explore innovative technologies for capturing these gases. Deep eutectic solvents (DESs) are an alternative media for mitigating H2S and CO emissions. Herein, we have employed ab initio molecular dynamics simulations to investigate the structures of the nearest-neighbor solvation shells surrounding H2S and CO when they are dissolved in reline and ethaline DESs. We aim to delineate the structural arrangement responsible for favorable H2S and CO capture by analyzing the key interactions between H2S and CO solutes with various components of the DESs. We observe that in the reline-H2S system, chloride and carbonyl oxygen of urea are found to have the closest distance interaction with hydrogen atoms of the H2S solute. The sulfur atom of H2S is found to be predominantly solvated by hydrogen and oxygen atoms of urea molecules and the hydroxyl hydrogen of choline cations. The chloride ions and ethylene glycol molecules predominantly govern the solvation of H2S in the ethaline-H2S system. In both the DESs, H2S is solvated by the hydroxyl group of the choline cations rather than by their ammonium group. In the reline-CO system, all the atoms of urea along with chloride dominate the immediate solvation shell around CO. In the ethaline-CO system, hydroxyl oxygen and hydrogen atoms of ethylene glycol are found in the nearest solvation structure around CO. Both the DESs exhibit a stronger solvent-solute charge-transfer tendency toward the H2S solute compared to CO.

Origin of structural and dynamic heterogeneity in thymol and coumarin-based hydrophobic deep eutectic solvents as revealed by molecular dynamics.

Hydrophobic deep eutectic solvents (HDESs) have recently emerged as a class of water-immiscible solvents with greener starting materials and inherent hydrophobic character, opening the gates to various new promising applications. Herein, we have carried out all-atom molecular dynamics simulations to comprehend the bulk phase structural organization and dynamic behavior of thymol and coumarin-based HDESs at two molar ratios of the constituent components. The simulated X-ray and neutron scattering structure functions (S(q)s) indicate a prepeak signifying that these HDESs possess nanoscale heterogeneity or intermediate range ordering. The decomposition of the total S(q)s based on polarity reveals that clustering of the polar group present in thymol and coumarin leads to the presence of the prepeak which also has small contributions from the apolar-apolar correlations. The intermolecular hydrogen bonding network between thymol-coumarin and thymol-thymol mainly guides the arrangement of the HDESs. We find a stronger hydrogen bond between the carbonyl oxygen of coumarin and the hydroxyl hydrogen of thymol, marked by the longer hydrogen bond lifetime. In contrast, the shorter lifetime of the hydrogen bond between the hydroxyl oxygen and the hydroxyl hydrogen of thymol suggests a weaker hydrogen bonding. On changing the thymol : coumarin molar ratio from 1 : 1 to 2 : 1, the average lifetimes of both the hydrogen bonds decrease, suggesting stronger hydrogen bonds in the 1 : 1 HDES. The translational dynamics of thymol and coumarin become faster in the 2 : 1 thymol : coumarin HDES. A slightly stronger caging effect is observed for coumarin in comparison to thymol molecules. From the analysis of the non-Gaussian parameter, we observe the presence of heterogeneity in the translational displacements of thymol and coumarin molecules. Furthermore, the computed self-van Hove correlation functions reveal that thymol and coumarin molecules cover more distances than the ideal diffusive displacements, confirming the presence of dynamic heterogeneity.

Wrapping-Trapping versus Extraction Mechanism of Bactericidal Activity of MoS2 Nanosheets against Staphylococcus aureus Bacterial Membrane.

The promising broad-spectrum antibacterial activity of two-dimensional molybdenum disulfide (2D MoS2) has been widely recognized in the past decade. However, a comprehensive understanding of how the antibacterial pathways opted by the MoS2 nanosheets varies with change in lipid compositions of different bacterial strains is imperative to harness their full antibacterial potential and remains unexplored thus far. Herein, we present an atomistic molecular dynamics (MD) study to investigate the distinct modes of antibacterial action of MoS2 nanosheets against Staphylococcus aureus (S. aureus) under varying conditions. We observed that the freely dispersed nanosheets readily adhered to the bacterial membrane outer surface and opted for an unconventional surface directed "wrapping-trapping" mechanism at physiological temperature (i.e., 310 K). The adsorbed nanosheets mildly influenced the membrane structure by originating a compact packing of the lipid molecules present in its direct contact. Interestingly, these surface adsorbed nanosheets exhibited extensive phospholipid extraction to their surface, thereby inducing transmembrane water passage analogous to the cellular leakage, even at a slight increment of 20 K in the temperature. The strong van der Waals interactions between lipid fatty acyl tails and MoS2 basal planes were primarily responsible for this destructive phospholipid extraction. In addition, the MoS2 nanosheets bound to an imaginary substrate, controlling their vertical alignment, demonstrated a "nano-knives" action by spontaneously piercing inside the membrane core through their sharp corner, subsequently causing localized lipid ordering in their vicinity. The larger nanosheet produced a more profound deteriorating impact in all of the observed mechanisms. Keeping the existing knowledge about the bactericidal activity of 2D MoS2 in view, our study concludes that their antibacterial activity is strongly governed by the lipid composition of the bacterial membrane and can be intensified either by controlling the nanosheet vertical alignment or by moderately warming up the systems.

Solvation Shell Structures of Ammonia in Reline and Ethaline Deep Eutectic Solvents.

Because of increasing atmospheric anthropogenic ammonia (NH3) emission, researchers are devising new techniques to capture NH3. Deep eutectic solvents (DESs) are found as potential media for NH3 mitigation. In the present study, we have carried out ab initio molecular dynamics (AIMD) simulations to decipher the solvation shell structures of an ammonia solute in reline (1:2 mixture of choline chloride and urea) and ethaline (1:2 mixture of choline chloride and ethylene glycol) DESs. We aim to resolve the fundamental interactions which help stabilize NH3 in these DESs, focusing on the structural arrangement of the DES species in the nearest solvation shell around NH3 solute. In reline, the hydrogen atoms of NH3 are preferentially solvated by chloride anions and the carbonyl oxygen atoms of urea. The nitrogen atom of NH3 renders hydrogen bonding with hydroxyl hydrogen of the choline cation. The positively charged head groups of the choline cations prefer to stay away from NH3 solute. In ethaline, strong hydrogen bonding interaction exists between the nitrogen atom of NH3 and hydroxyl hydrogen atoms of ethylene glycol. The hydrogen atoms of NH3 are found to be solvated by hydroxyl oxygen atoms of ethylene glycol and choline cation. While ethylene glycol molecules play a crucial role in solvating NH3, the chloride anions remain passive in deciding the first solvation shell. In both the DESs, choline cations approach NH3 from their hydroxyl group side. We observe slightly stronger solute-solvent charge transfer and hydrogen bonding interaction in ethaline than those in reline.

How NaFTA salt affects the structural landscape and transport properties of Pyrr1,3FTA ionic liquid.

Recently, it has been demonstrated that ionic liquids (ILs) with an asymmetric anion render a wider operational temperature range and can be used as a solvent in sodium ion batteries. In the present study, we examine the microscopic structure and dynamics of pure 1-methyl-1-propylpyrrolidinium fluorosulfonyl(trifluoromethylsulfonyl)amide (Pyrr1,3FTA) IL using atomistic molecular dynamics simulations. How the addition of the sodium salt (NaFTA) having the same anion changes the structural landscape and transport properties of the pure IL has also been explored. The simulated x-ray scattering structure functions reveal that the gradual addition of NaFTA salt (up to 1.2 molal) suppresses the charge alternating feature of the pure IL because of the replacement of the Pyrr+ cations with the Na+ ions. The Na+ ions are majorly found near the oxygen atoms of the anions, but the probability of finding the Na+ ions near these atoms slightly decreases with increasing salt concentration. As expected, the Na+ ions stay away from the Pyrr+ cations. However, the probability of finding the anions around anions increases with increasing salt concentration. The simulated self-diffusion coefficients of the ions in the pure IL reveal slightly faster diffusion of the Pyrr+ cations as compared to the FTA- anions. Interestingly, in the salt solution, despite having smaller size, the diffusion of the Na+ ions is found to be lesser than the Pyrr+ cations and the FTA- anions. The analysis of the ionic conductivity and transport numbers reveals that the fractional contribution of the FTA- anion to the overall conductivity remains nearly constant with increasing salt concentration, but the contribution of Pyrr+ cation decreases and Na+ ion increases.

Microstructures of Choline Amino Acid based Biocompatible Ionic Liquids.

Bio-compatible ionic liquids (Bio-ILs) represent a class of solvents with peculiar properties and exhibit huge potential for their applications in different fields of chemistry. Ever since they were discovered, researchers have used bio-ILs in diverse fields such as biomass dissolution, CO2 sequestration, and biodegradation of pesticides. This review highlights the ongoing research studies focused on elucidating the microscopic structure of bio-ILs based on cholinium cation ([Ch]+ ) and amino acid ([AA]- ) anions using the state-of-the-art a b i n i t i o ${ab\hskip0.25eminitio}$ and classical molecular dynamics (MD) simulations. The microscopic structure associated with these green ILs guides their suitability for specific applications. ILs of this class differ in the side chain of the amino acid anions, and varying the side chain significantly affects the structure of these ILs and thus helps in tuning the efficiency of biomass dissolution. This review demonstrates the central role of the side chain on the morphology of choline amino acid ([Ch][AA]) bio-ILs. The seemingly matured field of bio-ILs and their employment in various applications still holds significant potential, and the insights on their microscopic structure would steer the field of target specific application of these green ILs.

MoS2 nanosheet induced destructive alterations in the Escherichia coli bacterial membrane.

Two dimensional molybdenum disulfide (MoS2) nanosheets have recently gained wide recognition for their efficient broad-spectrum antibacterial activity complemented with great biocompatibility and minimal bacterial resistance inducing capabilities. However, despite the numerous investigations, the molecular level interactions at the nano-bio interface responsible for their bactericidal activity remain obscure. Herein, through an atomistic molecular dynamics study, we attempt to seek an in-depth understanding of the atomic level details of the underlying mechanism of their antibacterial action against the Escherichia coli (E. coli) bacterial membrane. Our study reveals a two-step MoS2 nanosheet interaction pathway with the bacterial membrane. The nanosheets spontaneously adhere to the membrane surface and prompt vigorous phospholipid extraction majorly via strong van der Waals interactions with lipid hydrophobic tails. The lipid extraction process originates a significant water intrusion in the bilayer hydrophobic region, signifying the onset of cytoplasmic leakage under realistic conditions. Further, a synergistic effect of lipid-lipid self-interactions and lipid-MoS2 dispersion interactions drags the nanosheet to completely immerse in the bilayer hydrophobic core. The embedded nanosheets induce a layerwise structural rearrangement of the membrane lipids in their vicinity, thus altering the structural and dynamic features of the membrane in a localized manner by (i) increasing the lipid fatty acyl tail ordering and (ii) alleviating the lipid lateral dynamics. The detrimental efficacy of the nanosheets can be magnified by enlarging the nanosheet size or by increasing the nanosheet concentration. Our study concludes that the MoS2 nanosheets can exhibit their antibacterial action through destructive phospholipid extraction as well as by altering the morphology of the membrane by embedding in the membrane core.

Solvent Organization around Methane Dissolved in Archetypal Reline and Ethaline Deep Eutectic Solvents as Revealed by AIMD Investigation.

Because of the rising concentration of harmful greenhouse gases like methane in the atmosphere, researchers are striving for developing novel techniques for capturing these gases. Recently, neoteric liquids such as deep eutectic solvents (DESs) have emerged as an efficient means of sequestration of methane. Herein, we have performed ab initio molecular dynamics (AIMD) simulations to elucidate the solvation structure around a methane molecule dissolved in reline and ethaline DESs. We aim to elicit the structural organization of different constituents of the DESs in the vicinity of methane, particularly highlighting the key interactions that stabilize such gases in DESs. We observe quite different solvation structures of methane in the two DESs. In ethaline, chloride ions play an active role in solvating methane. Instead, in reline, chloride ions do not interact much with the methane molecule in the first solvation shell. In reline, choline cations approach the methane molecule from their hydroxyl group side, whereas urea molecules approach methane from their carbonyl oxygen as well as amide group sides. In ethaline, ethylene glycol and Cl- dominate the nearest neighbor solvation structure around the methane molecule. In both the DESs, we do not observe any significant methane-DES charge transfer interactions, apart from what is present between choline cation and Cl- anion.

Heterogeneity and Nanostructure of Superconcentrated LiTFSI-EmimTFSI Hybrid Aqueous Electrolytes: Beyond the 21 m Limit of Water-in-Salt Electrolyte.

Ionic liquids such as EmimTFSI (1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide) have been found to improve the solubility of LiTFSI salt in water-in-salt electrolyte (WiSE) from 21 to 60 m. However, the molecular origin of such enhancement in the solubility is still unknown. In the present work, we elucidate the microscopic structures of LiTFSI-EmimTFSI-based hybrid aqueous electrolytes and compare them with the structure of LiTFSI-based WiSE using molecular dynamics simulations. Our analysis reveals the presence of alternating water-rich clusters and TFSI-rich extended domains in the WiSE. In these clusters and domains, the Li+ ions reside such that the total number of oxygen atoms around them is conserved to four, where water contributes about three oxygen atoms. The addition of EmimTFSI in the WiSE results in removal of water from the nearest-neighbor solvation shell of TFSI- ions but not from the Li+ ions. Significant structural changes are observed when LiTFSI salt is further added to LiTFSI-EmimTFSI aqueous solution. In both the hybrid electrolytes, water and Emim+ cations are found to avoid each other. The simulated X-ray scattering structure factor reveals the presence of larger length-scale heterogeneity in the most concentrated solution of the hybrid aqueous electrolyte. We observe that this nanoscale heterogeneity originates from a water-TFSI-Emim-TFSI-water-TFSI-Emim-TFSI-like arrangement in which Li+ ions are dispersed such that the coordination number of oxygen atoms around them is enhanced to five, wherein the major contribution comes from the TFSI- ions. We envision that the enhanced LiTFSI solubility originates from the replacement of water molecules with TFSI- ions in the first solvation shell of Li+ ions.

An Overview of Structure and Dynamics Associated with Hydrophobic Deep Eutectic Solvents and Their Applications in Extraction Processes.

Recent development of novel water-immiscible green solvents known as hydrophobic deep eutectic solvents (HDESs) has opened the gates for applications requiring media where the presence of water is undesirable. Ever since they were prepared, researchers have used HDESs in diverse fields such as extraction processes, CO2 sequestration, membrane formation, and catalysis. The structure and dynamics associated with the species comprising HDESs guide their suitability for specific applications. For example, varying the alkyl tail length of the HDES components significantly affects the dynamics of the components and thus helps in tuning the efficiency of extraction processes. However, the development of HDESs is still in infancy, and very few theoretical studies are available in the literature that help in understanding the structure and dynamics of HDESs. This review highlights the recent studies focused on the microscopic structure and dynamics of HDESs and their potential applications, particularly in extraction processes. We have also provided a glimpse of how the integration of experiments and computational techniques can help delineate the mechanism of extraction processes.

Anionic Lipid Clustering-Mediated Bactericidal Activity and Selective Toxicity of Quaternary Ammonium-Substituted Polycationic Pullulan against the Staphylococcus aureus Bacterial Membrane.

Non-amphiphilic polycations have recently been recognized to hold excellent antimicrobial potential with great mammalian cell compatibility. In a recent study, the excellent broad-spectrum bactericidal efficacy of a quaternary ammonium-substituted cationic pullulan (CP4) was demonstrated. Their selective toxicity and nominal probability to induce the acquisition of resistance among pathogens fulfill the fundamental requirements of new-generation antibacterials. However, there have been exiguous attempts in the literature to understand the antimicrobial activity of polycations against Gram-positive bacterial membranes. Here, for the first time, we have scrutinized the molecular level interactions of CP4 tetramers with a model Staphylococcus aureus membrane to understand their probable antibacterial function using molecular dynamics simulations. Our analysis reveals that the hydrophilic CP4 molecules are spontaneously adsorbed onto the membrane outer leaflet surface by virtue of strong electrostatic interactions and do not penetrate into the lipid tail hydrophobic region. This surface binding of CP4 is strengthened by the formation of anionic lipid-rich domains in their vicinity, causing lateral compositional heterogeneity. The major outcomes of the asymmetric accumulation of bulky polycationic CP4 on one leaflet are (i) anionic lipid segregation at the interaction site and (ii) a decrease in the cationic lipid acyl tail ordering and ease of water translocation across the lipid hydrophobic barrier. The membrane-CP4 interactions are strongly monitored by the ionic strength; a higher salt concentration weakens the binding of CP4 on the membrane surface. In addition, our study also substantiates the non-interacting behavior of CP4 oligomers with biomimetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane, indicating their cell selectivity and specificity against pathogenic membranes.

Structural adaptations in the bovine serum albumin protein in archetypal deep eutectic solvent reline and its aqueous mixtures.

The global concern over the environmental impact and challenges associated with the use of conventional solvents in biotransformation processes have pushed the search for alternative solvents. Recently, deep eutectic solvents (DESs) have appeared as a promising replacement with better biocompatibility and have been postulated to hold great potential in protein engineering and crystallization processes. In this context, herein, we have investigated the effect of reline (a choline chloride : urea mixture in 1 : 2 proportion) DES in its pure and hydrated forms on the structural stability and conformation of the bovine serum albumin (BSA) protein using all-atom molecular dynamics simulations. We observe a substantial overall expansion of the BSA structure with a simultaneous increment in the solvent accessible surface area, signifying the influence of reline on the BSA tertiary structure. These induced structural perturbations are quite pronounced in reline-water mixtures. Concomitantly, a notable reline concentration-dependent disruption of the BSA secondary structure through the melting of α-helices, mainly driven by H-bonding interactions, is observed. In the presence of pure reline, significant rigidity in the protein backbone is also observed. Thus, despite the expansion, the BSA tertiary structure in pure reline is found to be most close to the native protein structure and remains in a partially folded state at all the studied reline concentrations. In pure reline, BSA-urea hydrogen bonding is more prevalent than BSA-[Ch]+. We also observe that in aqueous reline systems, the BSA-water hydrogen bonds are mostly compensated by BSA-urea hydrogen bonds. The aqueous re-equilibration of these partially denatured protein conformations showed a significant recovery of secondary and tertiary structures, where the recovery is most profound for the BSA conformation extracted from pure reline.

Deciphering Ethanol-Driven Swelling, Rupturing, Aggregation, and Fusion of Lipid Vesicles Using Coarse-Grained Molecular Dynamics Simulations.

Traditionally, liquid ethanol is known to enhance the permeability of lipid membranes and causes vesicle aggregation and fusion. However, how the amphiphilic ethanol molecules perturb the lipid vesicles to facilitate their aggregation or fusion has not been addressed at any level of molecular simulations. Herein, not only have we developed a coarse-grained (CG) model for liquid ethanol, its aqueous mixture, and hydrated lipid membranes for molecular dynamics (MD) simulations, but also utilized it to delineate the aggregation and fusion of lipid vesicles using CG-MD simulations with multimillion particles. We have systematically parametrized the force-field for pure ethanol and its interactions with hydrated POPC and POPE model lipid membranes. In this process, we have successfully reproduced the bulk ethanol structure and concentration-dependent density of aqueous ethanol. To quantify the interaction of ethanol with lipid membranes, we have reproduced the transfer free energy of the ethanol molecule across the hydrated bilayers, and the concentration-dependent distribution of ethanol molecules across the lipid bilayers. After having acceptable force-field parameters for ethanol-membrane interactions, we have checked the effect of ethanol toward the vesicles comprising POPC lipids. We observe a rapid increase in the size of the POPC lipid vesicles with increasing amounts of ethanol up to 30 mol %. We unambiguously observe swelling and decrease in the thickness of the POPC vesicles with increasing amounts of ethanol up to 30 mol %, beyond which the vesicles begin to lose their integrity and rupture at higher mol % of ethanol. The fusion study of two vesicles demonstrates that fused vesicles can be obtained from 20 to 30 mol % of ethanol provided that they are brought closer than a critical distance at a particular mol %. The multivesicle simulations show that along with the increase in the sizes of vesicles the propensity of vesicle aggregation increases as the mol % of ethanol increases.

Quaternary ammonium substituted pullulan accelerates wound healing and disinfects Staphylococcus aureus infected wounds in mouse through an atypical 'non-pore forming' pathway of bacterial membrane disruption.

The emergence of multi-drug resistant pathogens has fueled the search for alternatives to the existing line of antibiotics that can eradicate pathogens without inducing resistance development. Here, we report the accelerated wound healing and disinfection potential of a non-amphiphilic quaternized fungal exopolysaccharide, pullulan, without resistance generation in pathogens. The quaternary ammonium substituted pullulan (CP) derivatives showed excellent bactericidal activity against both Gram negative (MBC90 = 1.5 µg mL-1) and Gram positive (MBC90 = 0.25 µg mL-1) bacteria at very low concentrations without showing any toxicity towards mammalian cells. A combined approach of atomistic molecular dynamics simulation and experimental assays revealed that CP exerts a membrane directed bactericidal action through an atypical "non-pore forming" pathway which is not yet established for any known antibacterial polysaccharides. This involves an increase in membrane roughness, disorder among anionic lipid tails, formation of localized anionic lipid clusters and membrane depolarization, finally leading to physical disruption of the membrane integrity. Moreover, CP also displayed biofilm eradication abilities and emerged as an excellent therapeutic material for disinfection and healing of infected wounds. The present work shows the potential of exploiting polysaccharides as next-generation broad-spectrum antimicrobials and provides a platform for further development of rationally designed pullulan-based functional materials for biomedical applications.

Mechanistic Insight on BioIL-Induced Structural Alterations in DMPC Lipid Bilayer.

The emerging application risks of traditional ionic liquids (ILs) toward the ecosystem have changed the perception regarding their greenness. This resulted in the exploration of their more biocompatible alternatives known as biocompatible ILs (BioILs). Here, we have investigated the impact of two such biocompatible cholinium amino acid-based ILs on the structural behavior of model homogeneous DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) lipid bilayer using all-atom molecular dynamics simulation technique. Two classic cholinium-amino acid-based ILs, cholinium glycinate ([Ch][Gly]) and cholinium phenylalaninate ([Ch][Phe]), which differ only by the side chain lengths and hydrophobicity of the anions, have been utilized in the present work. Simultaneous analysis of the bilayer structural properties reveals that the existence of [Ch][Gly] BioIL above a particular concentration induces phase transition from fluid phase to gel phase in the DMPC lipid bilayer. Such a freezing of lipid bilayer upon the exposure to concentrated aqueous solution of [Ch][Gly] BioIL indicates the harmfulness of this BioIL toward the cell membranes majorly containing DMPC lipids, as the cell freezing can negatively affect its stability and functionality. Despite having a more hydrophobic amino acid side chain of [Phe]- anion in [Ch][Phe], in the case of bilayer-[Ch][Phe] systems we observe the minimal impact of [Ch][Phe] BioIL on the DMPC bilayer properties up to 10 mol % concentration. In the presence of these BioIL, we observe the thickening of the bilayer and accumulation of the cations and anions of the BioILs at the interface of DMPC lipid heads and tails. The transfer free-energy profile of a [Phe]- anion from aqueous phase to membrane center also indicates the anion partitioning at lipid head-tail interface and its inability to penetrate in the lipid membrane tail region. In contrast, the free-energy profile for a [Gly]- anion offers a very high energy barrier to the insertion of [Gly]- into the membrane interior, leading to accumulation of [Gly]- anions at the lipid head-water region.

Multiple evidences of dynamic heterogeneity in hydrophobic deep eutectic solvents.

Hydrophobic deep eutectic solvents (HDESs) have gained immense popularity because of their promising applications in extraction processes. Herein, we employ atomistic molecular dynamics simulations to unveil the dynamics of DL-menthol (DLM) based HDESs with hexanoic (C6), octanoic (C8), and decanoic (C10) acids as hydrogen bond donors. The particular focus is on understanding the nature of dynamics with changing acid tail length. For all three HDESs, two modes of hydrogen bond relaxations are observed. We observe longer hydrogen bond lifetimes of the inter-molecular hydrogen bonding interactions between the carbonyl oxygen of the acid and hydroxyl oxygen of menthol with hydroxyl hydrogen of both acids and menthol. We infer strong hydrogen bonding between them compared to that between hydroxyl oxygen of acids and hydroxyl hydrogens of menthol and acids, marked by a faster decay rate and shorter hydrogen bond lifetime. The translational dynamics of the species in the HDES becomes slower with increasing tail length of the organic acid. Slightly enhanced caging is also observed for the HDES with a longer tail length of the acids. The evidence of dynamic heterogeneity in the displacements of the component molecules is observed in all the HDESs. From the values of the α-relaxation time scale, we observe that the molecular displacements become random in a shorter time scale for DLM-C6. The analysis of the self-van Hove function reveals that the overall distance covered by DLM and acid molecules in the respective HDES is more than what is expected from ideal diffusion. As marked by the shorter time scale associated with hole filling, the diffusion of the oxygen atom of menthol and the carbonyl oxygen of acid from one site to the other is fastest for hexanoic acid containing HDES.

Structure of cholinium glycinate biocompatible ionic liquid at graphite electrode interface.

We use constant potential molecular dynamics simulations to investigate the interfacial structure of the cholinium glycinate biocompatible ionic liquid (bio-IL) sandwiched between graphite electrodes with varying potential differences. Through number density profiles, we observe that the cation and anion densities oscillate up to ∼1.5 nm from the nearest electrode. The range of these oscillations does not change significantly with increasing electrode potential. However, the amplitudes of the cation (anion) density oscillations show a notable increase with increasing potential at the negative (positive) electrode. At higher potential differences, the bulkier N(CH3)3CH2 group of cholinium cations ([Ch]+) overcomes the steric barrier and comes closer to the negative electrode as compared to oxygen atom (O[Ch]+ ). We observe an increase in the interaction between O[Ch]+ and the positive electrode with a decrease in the distance between them on increasing the potential difference. We also observe hydrogen bonding between the hydroxyl group of [Ch]+ cations and oxygens of glycinate anions through the simulated tangential radial distribution function. Orientational order parameter analysis shows that the cation (anion) prefers to align parallel to the negative (positive) electrode at higher applied potential differences. Charge density profiles show a positive charge density peak near the positive electrode at all the potential differences because of the presence of partially positive charged hydrogen atoms of cations and anions. The differential capacitance (Cd) of the bio-IL shows two constant regimes, one for each electrode. The magnitude of these Cd values clearly suggests potential application of such bio-ILs as promising battery electrolytes.

First-principles based theoretical investigation of impact of polyolefin structure on photooxidation behavior.

Despite their mass production and large applications, polyolefins' stability and durability toward the air, moisture, and weather resistance is a challenge for the ecosystem. After long-term exposure to ultraviolet (UV) radiation or high-temperature or erosion, polyolefins undergo degradation generating microplastics (MPs). The MPs generated after the degradation of these polyolefins are hazardous for the ecosystem. In the present work, we have carried out density functional theory (DFT) studies to investigate the photodegradation of six different polyolefins ranging from polyethylene to polydecene, differing in side-chain. Herein, we have investigated photooxidized derivatives of different polyolefins and analyzed their relative stability, conformations, UV-visible spectral behavior, and carbonyl index. The photooxidized derivatives of various polyolefins formed during degradation are examined. The time-dependent density functional theory analysis confirms that the carbonyl groups of photooxidized products show absorption peak in Infrared (IR) and visible region, acting as light-absorbing species. The relative stabilities of hydroperoxide formed during photo/thermal oxidation of different polyolefins have been evaluated to explain the degradation behavior. The oligomerization and stabilization energies of their corresponding hydroperoxide's were computed and analyzed to explain the degradation behavior of the polyolefins. The computed results suggest that polyolefins in their pristine state are stable toward photooxidation, but chemical impurities like carbonyl, unsaturated carbonyl, carboxylic acid, and hydroperoxide derivatives make them prone to undergo degradation, a fundamental process leading to generation of MPs. The comparative results confirmed that the side-chain length affects the stability and degradation of different polyolefins toward photooxidation.