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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Heterogeneity in hydrophobic deep eutectic solvents: SAXS prepeak and local environments.

Recently, the introduction of novel deep eutectic solvents having a hydrophobic character with greener starting materials has motivated researchers to explore these water-immiscible solvents, owing to their new potential applications. In this regard, herein atomistic molecular dynamics simulations have been performed to understand the bulk phase morphology present in dl-menthol based hydrophobic deep eutectic solvents (HDESs) with organic acids of different chain lengths used as hydrogen bond donors. From the appearance of a prepeak in the simulated total X-ray scattering structure function (S(q)), we found an evidence of intermediate-range structural organization in these HDESs. We show that the prepeak originates from the self-segregation of dl-menthol and the polar hydroxyl groups of the acids, as witnessed from partitioning of the total S(q). Surprisingly, even for a very long tail containing HDES, the apolar-apolar component shows only nominal contribution to the prepeak. We show that the structure of these HDESs is dominated by a set of very strong intermolecular hydrogen bonding between menthol-menthol, acid-acid, and menthol-acid molecules. Our results show that there is competition between the hydroxyl hydrogen of the acids and menthol to form an intermolecular hydrogen bond with the carbonyl oxygen of the acids and hydroxyl oxygen of menthol.

Unique and generic structural features of cholinium amino acid-based biocompatible ionic liquids.

Cholinium amino acid-based (Ch-AA) biocompatible ionic liquids (bio-ILs) are synthesized from renewable components and are efficiently used for biomass processing. However, their microscopic structural features that lead to their application as biomass solvents remain undetermined. Herein, we use atomistic simulations to investigate the structures of six different Ch-AA bio-ILs up to the nanometer length scale and demonstrate that, depending on the anion side chain structure, the respective IL exhibits structural ordering at different length scales. All the six Ch-AA bio-ILs investigated here show a generic feature of having a strong hydrogen bonding network between the hydroxyl group of the cholinium cation and the carboxyl group of the amino acid anions. We illustrate that each of these bio-ILs also displays a unique feature. Distinctive intermediate range structural ordering leads to heterogeneity in methioninate- and phenylalaninate-based ILs caused by the anion side chain segregation. Intermediate range ordering is not observed in glutaminate- and glutamate-based ILs because significant anion side chain and backbone interactions hinder the formation of side chain clusters. Interestingly, for the cysteinate-based IL, the side chains do not interact with the backbones and the intermediate range ordering is not observed because of a shorter anionic side chain.

Design and synthesis of ß-carboline and combretastatin derivatives as anti-neutrophilic inflammatory agents.

A series of ß-carboline derivatives was synthesized by the Pictet-Spengler reaction with or without the combretastatin skeleton. The structures of these derivatives were elucidated by spectroscopic techniques. All synthesized compounds were evaluated for their anti-inflammatory activity in human neutrophils. Among them, two compounds, NTU-228 and HK-72, showed significant inhibitory effects on N-formyl-Met-Leu-Phe (fMLF)-induced superoxide anion generation in human neutrophils with IC50 values of 5.58 ± 0.56 and 2.81 ± 0.07 µM, respectively. Neither NTU-228 nor HK-72 caused cytotoxicity in human neutrophils. NTU-228 inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and intracellular Ca2+ levels ([Ca2+]i) in fMLF-activated human neutrophils. Additionally, HK-72 selectively inhibited the fMLF-induced phosphorylation of p38 and [Ca2+]i in human neutrophils. Molecular docking analysis showed a favorable binding affinity of HK-72 toward p38 MAPK. The proposed synthetic strategy opens up new opportunities for the synthesis of novel potential candidates against neutrophilic inflammation.

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.

Synthesis and Redox Properties of Superbenzene Porphyrin Conjugates.

Superbenzene porphyrin conjugates find wide range of applications from nonlinear optical materials to semiconductors. Herein, we report the synthesis and characterization of 5,15-bis(3,5-di-tert-butylphenyl)-10,20-bis(pentaphenylphenyl)phenylporphyrin and its Zinc-metallated complex. Oxidative planarization of 5,15-bis(3,5-di-tert-butylphenyl)-10,20-bis(pentaphenylphenyl)phenylporphyrin and its metallated complex was carried out by using NOBF4 as an oxidizing agent. The formation of superbenzene porphyrin conjugates validates its Scholl type reactions. The laboratory-synthesized porphyrin conjugates were characterized experimentally using spectroscopic techniques such as 1H NMR, 13C NMR, electron spin resonance, and ultraviolet-visible spectroscopy for structural conformation. In addition, density functional theory calculations were carried out to validate the experimental results. The theoretical and experimental results show that the 4-(pentaphenylphenyl)phenyl ligand increases the stability, optical properties, and rate of planarization of synthesized porphyrins. The conjugates exhibited intense and distant electronic communication between two hexabenzocoronene sites, taking advantage of porphyrin as a π-spacer. The π-radical cation has also been found to be an intermediate in oxidative C-C bond formation. NICS calculations support such a conclusion.

A coarse-grained model of dimethyl sulfoxide for molecular dynamics simulations with lipid membranes.

Enhanced permeability of biomembranes upon the application of small amphiphiles is of vital importance to biologists and pharmacists, as their physiochemical interactions open new pathways for transdermal drug transportation and administration. Amphiphilic dimethyl sulfoxide (DMSO) is known to alter biomembrane permeability. Atomistic simulation-based studies to explore the impact of amphiphilic molecules on the model lipid membranes are of immense importance. These studies provide molecular details on how the membrane physical properties, such as fluidity and thickness, are modulated by amphiphile-lipid interactions. However, such approaches are usually limited to short simulation time and length scales. To circumvent such limitations, the use of coarse-grained (CG) models is a current computational strategy. In this article, we have presented a new CG force-field for DMSO for molecular dynamics (MD) simulations. The model is designed to reproduce experimental bulk properties of DMSO and its aqueous mixtures, molecular-level structure of liquid DMSO, and the phase transfer energy of a single DMSO molecule from the aqueous phase to the lipid bilayer hydrophobic interior. The current CG DMSO model successfully mimics the structural variation in phospholipid bilayer systems (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) including alteration in bilayer thickness, lipid tail ordering, lipid lateral packing, and electron density profiles at various DMSO concentrations when compared to those obtained from parallel atomistic simulations.

Molecular dynamics investigation of wetting-dewetting behavior of reline DES nanodroplet at model carbon material.

Deep eutectic solvents (DESs) have emerged as a promising class of solvents for application in nanotechnology, particularly for designing new functional nanomaterials based on carbon. Here, we have employed molecular dynamics simulations to understand the structuring of choline chloride and urea-based DES, reline, nanodroplets on carbon sheets with varying strength of the DES-sheet interaction potentials. The wetting-dewetting nature of reline has been investigated by analyzing simulated contact angles formed by its nanodroplets on the carbon sheets. Through this investigation, we find that at the lowest DES-sheet interaction strength, the contact angle formed by the reline nanodroplet on the carbon surface exceeds 150°, indicating that the surface is supersolvophobic. On the other hand, at the higher interaction potentials, reline DES wets the surface of the sheets, forming an adlayer primarily consisting of urea molecules. The choline cation and urea molecules are observed to exhibit stronger interactions with the carbon surface as compared to that of chloride anions. At the supersolvophobic carbon surface, the urea molecules have relatively higher density in the bulk of the nanodroplet, whereas the choline cation and chloride have major contributions to the outer layers of the droplets. Moreover, at the solvophilic surfaces, urea molecules are present in the adlayer, as well as in the bulk of the droplets, whereas the reline-vapor interface majorly consists of choline and chloride ions.

DMSO induced dehydration of heterogeneous lipid bilayers and its impact on their structures.

Recently, we have reported that higher concentrations of dimethyl sulfoxide (DMSO) exhibit an enhancement in the structural ordering of the homogeneous N-palmitoyl-sphingomyelin (PSM) bilayer, whereas the presence of DMSO at lower concentrations leads to minor destabilization of the PSM bilayer structure. In this study, we aim to understand how these two modes of action of DMSO diversify for heterogeneous bilayers by employing atomistic molecular dynamic simulations. A binary bilayer system comprising PSM and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and a ternary bilayer system consisting of cholesterol along with PSM and POPC are the two heterogeneous biomimetic bilayers studied herein. We have simulated both the mixed lipid bilayer systems at 323 K, which is above the main phase transition temperature of the PSM lipid. This study reveals that DMSO exerts contrasting effects on the structure and stability of mixed bilayer systems, depending on its concentration. At 5 mol% of DMSO, the binary bilayer system shows slight disordering of lipid tails in conjunction with an appreciable increase in the area per lipid (APL), whereas for the ternary bilayer system, the orientational ordering of the lipid tails does not alter much; however, a slight expansion in the APL is observed. On the other hand, at 20 mol% of DMSO, an appreciable increase in the ordering of lipid tails for both the mixed bilayer systems occurs, depicting an enhancement in the structural stability of the bilayers. Furthermore, the H-bond analysis reveals that water-lipid H-bonding interaction decreases with increasing concentration of DMSO. We also observe contraction of the water-lipid interfacial region, pointing out DMSO induced dehydration at the lipid head-group region, and the dehydration effect is prominent for 20 mol% of DMSO. Furthermore, the computed free energies suggest that the free energy required for the transfer of a DMSO molecule from the lipid head-group region to the lipid head-tail interface is higher for the cholesterol containing ternary bilayer.