Molecular dynamics simulation of a reverse micelle self assembly in supercritical CO2

In this communication we report on molecular dynamics computer simulations of self-assembly of reverse micelles in supercritical carbon dioxide. The reverse micelles contain perfluoropolyether ammonium carboxylate surfactants and an aqueous core. We observed a quick self-assembly of these micelles over time periods of approximately 5 ns, irrespective of initial conditions. In most cases, the self-assembled perfluorinated reverse micelles have a nice spherical shape and properties consistent with experiments. When the fluorinated surfactant is replaced by its hydrogenated analogue, the assembled aggregate contains a region of direct contact between water and carbon dioxide, indicating that hydrogenated surfactant is not a good agent for creation of microemulsions in water/carbon dioxide mixtures.     

Hydrogen bonding of methanol in supercritical CO2: comparison between 1H NMR spectroscopic data and molecular simulation results

Molecular dynamics simulation results on hydrogen bonding in mixtures of methanol with CO2 at supercritical, liquid-like conditions are compared to 1H NMR spectroscopic data that have recently become available. The molecular models are parametrized using vapor-liquid equilibrium data only, which they reliably describe. A new molecular model for methanol of Lennard-Jones plus point charge type is presented. This molecular methanol model is investigated in terms of its capability to yield hydrogen-bonding statistics. Simple assumptions are made regarding the assignment of NMR chemical shifts to the different types of hydrogen-bonded species. Only two state-independent parameters are fitted to the large NMR data set on the basis of hydrogen-bonding statistics from molecular simulations. Excellent agreement between the molecular simulation results and the NMR data is found. This shows that the molecular models of the simple type studied here cannot only describe thermodynamic properties but also structural effects of hydrogen bonding in solutions.     

Conformational study of fosinopril sodium in solution using NMR and molecular modeling

Two conformers of fosinopril sodium in methanol were unambiguously established using 2D NMR methods and variable‐temperature NMR experiments. Differences in their conformational structure were shown to be related to the rotational energy barrier about the amide bond and hydrophobic interaction. The relationship between the 3D structure and activity is discussed. It is suggested that the trans‐conformer may be more biologically active owing to its stacking structure and strong hydrophobic interaction and the cis‐conformer could be more easily hydrolyzed because of its extended structure. Copyright © 2003 John Wiley & Sons, Ltd.     

Molecular simulation of interaction between passivated gold nanoparticles in supercritical CO2

Molecular dynamics simulations have been performed to study the potential of mean force (PMF) between passivated gold nanoparticles (NPs) in supercritical CO(2) (scCO(2)). The nanoparticle model consists of a 140 atom gold nanocore and a surface self-assembled monolayer, in which two kinds of fluorinated alkanethiols were considered. The molecular origin of the thermodynamics interaction and the solvation effect has been comprehensively studied. The simulation results demonstrate that increasing the solvent density and ligand length can enhance the repulsive feature of the free energy between the passivated Au nanoparticles in scCO(2), which is in good agreement with previous experimental results. The interaction forces between the two passivated NPs have been decomposed to reveal various contributions to the free energy. It was revealed that the interaction between capping ligands and the interaction between the capping ligands and scCO(2) solvent molecules cooperatively determine the total PMF. A thermodynamic entropy-energy analysis for each PMF contribution was used to explain the density dependence of PMF in scCO(2) fluid. Our simulation study is expected to provide a novel microscopic understanding of the effect of scCO(2) solvent on the interaction between passivated Au nanoparticles, which is helpful to the dispersion and preparation of functional metal nanoparticles in supercritical fluids.     

The effects of solute-solvent electrostatic interactions on solvation dynamics in supercritical CO2

We present here the results of molecular-dynamics simulation of solvation dynamics in supercritical CO(2) at a temperature of about 1.05T(c), where T(c) is the critical temperature, and at a series of densities ranging from 0.4 to 2.0 of the critical density rho(c). We focus on electrostatic solvation dynamics, representing the electronic excitation of the chromophore as a change in its charge distribution from a quadrupolar-symmetry ground state to a dipolar excited state. Two perturbations are considered, corresponding to different magnitudes of solute excited-state dipoles, denoted as d5 and d8. The d8 solute is more attractive, leading to a larger enhancement in CO(2) clustering upon solute electronic excitation. This has a large impact on solvation dynamics, especially at densities below rho(c). At these densities, solvation dynamics is much slower for the d8 than for the d5 solute. For both solutes, solvation dynamics becomes faster at densities above rho(c) at which solvent clustering diminishes. We show that the slowest solvation time scale is associated with solvent clustering and we relate it to solute-solvent mutual translational diffusion and the extent of change in effective local density resulting from solute electronic excitation.     

The effects of solute-solvent electrostatic interactions on solvatochromic shifts in supercritical CO2

Solvent clustering around attractive solutes is an important feature of supercritical solvation. We examine here the effects of the local density enhancement on solvatochromic shifts in electronic absorption and emission spectra in supercritical CO2. We use molecular dynamics (MD) simulation to study the spectral line shifts for model diatomic solutes that become more polar upon electronic excitation. The electronic transition is modeled as either a change from a quadrupolar to a dipolar solute charge distribution or as an increase in the magnitude of the solute dipole. Our main focus is on the density dependence of the line shifts at 320 K, which corresponds to about 1.05 times the solvent critical temperature, Tc, but results for higher temperatures are also obtained in order to determine the behavior of the line shifts in the absence of local density enhancement. We find that the extent of local density enhancement at 1.05Tc is strongly correlated with solute-solvent electrostatic attraction and that the density dependence of the emission line shifts resembles the behavior of the effective local densities, rho(eff), obtained from the first-shell coordination numbers. The differences that are seen are shown to be due to solute-solvent orientational correlations which provide an additional source of enhancement for electrostatic solvation energies and spectral line shifts.     

Oxazolidine-2-thiones: a molecular modeling study

Two oxazolidine-2-thiones, thio-analogs of linezolid, were synthesized and their antibacterial properties evaluated. Unlike oxazolidinones, the thio-analogs did not inhibit the growth of Gram positive bacteria. A molecular modeling study has been carried out to aid understanding of this unexpected finding.     

A combined spectroscopic and theoretical study of dibutyltin diacetate and dilaurate in supercritical CO2

Two organotin catalysts, namely, dibutyltin dilaurate (DBTDL) and dibutyltin diacetate (DBTDA), commonly used in the synthesis of polyurethanes, have been investigated combining vibrational spectroscopic measurements with molecular modeling. The structure and vibrational spectra of the DBTDA molecule have been simulated using density functional theory. Thus, because of the Sn...O interactions, the lowest energy conformer reveals an asymmetrically chelated structure of the acetate groups with a C2v symmetry. The experimental IR spectra of DBTDA and DBTDL diluted in carbon tetrachloride and in supercritical CO2 show unambiguously that these molecules adopt the asymmetrically chelated conformation in the solvent. A new attribution of the main peaks constituting the respective IR spectra of the catalysts could be carried out. Finally, from the IR spectra of the two catalysts diluted in supercritical CO2 reported as a function of time, it was found that both molecules react slightly with CO2. However, their spectrum remains unchanged at the earliest stage of the polymerization, indicating that these molecules preserve a catalytic activity similar to that noted in conventional organic solvent.     

Molecular interactions between lipid bilayers and a water-soluble polymer

Molecular interactions between lipid bilayers (liposomes) and chondroitin sulfate C (CS), a water soluble polymer, have been investigated in terms of zeta-potential, particle size, microscopic-viscosity, microscopic-polarity of liposomes and permeability of calcein. Microscopic morphology is dramatically changed by the addition of CS to the positively charged liposomes (Pos.L), while it is not changed by the addition to uncharged liposomes (Unc.L) or negatively charged liposomes (Neg.L). The absolute value of the particle size of Pos.L increases with the addition of CS, while the zeta- potential of Pos.L decreases. Permeability of Pos.L decreases with an increase in the concentration of CS. Phase transition temperature of Pos.L is changed after the addition of CS. These values, however, are not changed for the other liposomes by the addition of CS. The results of gel filtration chromatography show that CS is absorbed on the Pos.L surface. Microscopic viscosity is also increased by the addition of CS to Pos.L due to the adsorption of CS.     

Intermolecular interactions in polymer blends: 1D and 2D NMR studies

Most mixtures of high molecular weight polymers are not miscible in the absence of specific intermolecular interactions. We have used two dimensional NMR in solutions and in the solid state to probe these interactions and to gain a molecular level understanding of the forces that control polymer blend formation. The results show that weak, but specific intermolecular interactions often control the phase structure of polymer blends.     

Coupling between a fluorinated olefin and a perfluorinated iodide: a model study on the reaction mechanism of perfluorinated polymer cross-linking

In a model study, , , - and - correlated NMR techniques confirm a Markovnikov type reaction intermediate for the major coupling products between a short, low MW perfluorinated iodide C₂F₅I (I) and a short, low MW fluorinated olefin CF₃(CF₂)₇CHCH₂ (II). The reaction is peroxide induced (di-t-butyl peroxide, DTBP) and is conducted at 140 °C for a 3 h reaction time in a sealed glass ampoule. Side reaction products due to the reaction of DTBP with radical reaction intermediates were also observed and identified. The study aimed to mimic as closely as possible the peroxide-initiated coupling reaction between an iodine terminated fluoropolymer (model compound I) and its fluorinated di-olefin coupling agent (model compound II). A mono-olefin was chosen to simplify the model reaction.     

Conformational analysis of sulfur-containing 6-deoxy-l-hexose derivatives by molecular modeling and NMR spectroscopy. A theoretical study and experimental evidence of intramolecular nonbonded interactions between sulfur and oxygen

6-Deoxy-l-mannose diphenyldithioacetal (1) unexpectedly gave the rearranged products phenyl 3,4-di-O-acetyl-2-S-phenyl-1,2-dithio-6-deoxy-beta-l-glucopyranoside (9) and 3,4-di-O-acetyl-2,5-anhydro-6-deoxy-l-glucose diphenyldithioacetal (10) upon treatment with acetyl chloride, while 6-deoxy-l-mannose ethylenedithioacetal (3) yielded (4aR,6S,7S,8R,8aS)-7,8-diacetyloxy-6-methylhexahydro-4aH-[1,4]dithiino[2,3b]pyran (11), whose structure was further confirmed by X-ray diffraction, and 3,4-di-O-acetyl-2,5-anhydro-l-rhamnose ethylenedithioacetal (12). The geometry of the four rearranged products as well as that of 1-thio-6-deoxy-l-mannopyranosides 5 and 7 and their acetyl derivatives 6 and 8 was studied by density functional theory (B3LYP/6-31G) molecular models, in combination with a Karplus-type analysis of the NMR vicinal coupling constants, revealing that the six-membered ring of pyranosides 5-9 and 11 exists in a slightly distorted chair conformation (6-13% distortion) and that the conformational behavior of the 2,5-anhydro-6-deoxy-l-glucose dithioacetals 10 and 12 is strongly influenced by the presence of stabilizing intramolecular nonbonded sulfur-oxygen 1,4- and 1,5-interactions. Compounds 9-12 were formed by a molecular rearrangement via sulfonium ion intermediates followed by stereoselective intramolecular cyclizations as formulated by the quantum chemical calculations performed in the present study.     

Solvation structure and dynamics for passivated Au nanoparticle in supercritical CO2: a molecular dynamic simulation

All-atomic molecular dynamics simulations have been performed to study the interfacial structural and dynamical properties of passivated gold nanoparticles in supercritical carbon dioxide (scCO(2)). Simulations were conducted for a 55-atom gold nanocore with thiolated perfluoropolyether as the packing ligands. The effect of solvent density and surface coverage on the structural and dynamical properties of the self-assembly monolayer (SAM) has been discussed. The simulation results demonstrate that the interface between nanoparticle and scCO(2) solvent shows a depletion region due to the preclusion of SAM. The presence of scCO(2) solvent around the passivated Au nanoparticle can lead to an enhanced extension of the surface SAM. Under full coverage, the structure and conformation of SAM are insensitive to the density change of scCO(2) fluid. This simulation results clarify the microscopic solvation mechanism of passivated nanoparticles in supercritical fluid medium and is expected to be helpful in understanding the scCO(2)-based nanoparticle dispersion behavior.     

Electron donor-acceptor interactions in ethanol-CO2 mixtures: an ab initio molecular dynamics study of supercritical carbon dioxide

The nature of interactions between ethanol and carbon dioxide has been characterized using simulations via the Car-Parrinello molecular dynamics (CPMD) method. Optimized geometries and energetics of free-standing ethanol-CO2 clusters exhibit evidence for a relatively more stable electron donor-acceptor (EDA) complex between these two species rather than a hydrogen-bonded configuration. This fact has also been confirmed by the higher formation rate of the EDA complex in supercritical carbon dioxide-ethanol mixtures. The probability density distribution of CO2 molecules around ethanol in the supercritical state shows two high probability regions along the direction of the lone pairs on the oxygen atom of ethanol. The EDA interaction between ethanol and CO2 as well as that between CO2 molecules themselves leads to significant deviations from linearity in the geometry of the CO2 molecule. The vibrational spectra of carbon dioxide obtained from the atomic velocity correlation functions in the bulk system as well as from isolated complexes show splitting of the nu2 bending mode that arises largely from CO2-CO2 interactions, with ethanol contributing only marginally because of its low concentration in the present study. The stretching frequency of the hydroxyl group of ethanol is shifted to lower frequencies in the bulk mixture when compared to its gas-phase value, in agreement with experiments.     

Molecular mechanism of HIV-1 integrase-vDNA interactions and strand transfer inhibitor action: a molecular modeling perspective

Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an essential enzyme for splicing a viral DNA (vDNA) replica of its genome into host cell chromosomal DNA (hDNA) and has been recently recognized as a promising therapeutic target for developing anti-AIDS agents. The interaction between HIV-1 IN and vDNA plays an important role in the integration process of the virus. However, a detailed understanding about the mechanism of this interactions as well as the action of the anti-HIV drug raltegravir (RAL, approved by FDA in 2007) targeting HIV-1 IN in the inhibition of the vDNA strand transfer is still absent. In the present work, a molecular modeling study by combining homology modeling, molecular dynamics (MD) simulations with molecular mechanics Poisson-Boltzmann surface area (MM-PBSA), and molecular mechanics Generalized-Born surface area (MM-GBSA) calculations was performed to investigate the molecular mechanism of HIV-1 IN-vDNA interactions and the inhibition action of vDNA strand transfer inhibitor (INSTI) RAL. The structural analysis showed that RAL did not influence the interaction between vDNA and HIV-1 IN, but rather targeted a special conformation of HIV-1 IN to compete with host DNA and block the function of HIV-1 IN by forcing the 3'-OH of the terminal A17 nucleotide away from the three catalytic residues (Asp64, Asp116, and Glu152) and two Mg(2+) ions. Thus, the obtained results could be helpful for understanding of the integration process of the HIV-1 virus and provide some new clues for the rational design and discovery of potential compounds that would specifically block HIV-1 virus replication.     

Adsorption and self-assembly of surfactant/supercritical CO2 systems in confined pores: a molecular dynamics simulation

A coarse-grained molecular dynamics simulation has been carried out to study the adsorption and self-organization for a model surfactant/supercritical CO2 system confined in the slit-shape nanopores with amorphous silica-like surfaces. The solid surfaces were designed to be CO2-philic and CO2-phobic, respectively. For the CO2-philic surface, obviously surface adsorption is observed for the surfactant molecules. The various energy profiles were used to monitor the lengthy dynamics process of the adsorption and self-assembly for surfactant micelles or monomers in the confined spaces. The equilibrium properties, including the morphologies and micelle-size distributions of absorbed surfactants, were evaluated based on the equilibrium trajectory data. The interaction between the surfactant and the surface produces an obvious effect on the dynamics rate of surfactant adsorption and aggregation, as well as the final self-assembly equilibrium structures of the adsorbed surfactants. However, for the CO2-phobic surfaces, there are scarcely adsorption layers of surfactant molecules, meaning that the CO2-phobic surface repels the surfactant molecules. It seems to conclude that the CO2 solvent depletion near the interfaces determines the surface repellence to the surfactant molecules. The effect of the CO2-phobic surface confinement on the surfactant micelle structure in the supercritical CO2 has also been discussed. In summary, this study on the microscopic behaviors of surfactant/Sc-CO2 in confined pores will help to shed light on the surfactant self-assembly from the Sc-CO2 fluid phase onto solid surfaces and nanoporous media.     

Molecular simulation of swelling and interlayer structure for organoclay in supercritical CO(2)

In this work, Monte Carlo simulations have been carried out to investigate the swelling stability and interlayer structures of alkylammonium-modified montmorillonite both in vacuum and in supercritical CO(2) (scCO(2)) fluid. In the vacuum (dry) condition, the stable spacing for this kind of organoclay was determined based on the energy minimum. In the stable spacing, the corresponding interlayer structure of dry organoclay is the monolayer arrangement with the intercalated surfactant chains lying parallel to the silicate surface. In scCO(2) fluid medium, the normal pressures within the organoclay gallery and the swelling free energy have been obtained from Gibbs ensemble Monte Carlo simulation. The mechanically and thermodynamically stable spacings of the organoclay have been determined. As compared with the case in vacuum, the simulation shows that the swelling of the organoclay is thermodynamically favorable in the environment of scCO(2) fluid. The interlayer structure and conformation have been used to analyze the mechanism of swelling. The headgroups of surfactant cations are distributed close to the clay surfaces. The presence of CO(2) molecules within the clay gallery can cause a specific steric arrangement of the long-chain alkylammonium cations.     

Microstructure of supercritical CO2-in-water microemulsions: a systematic contrast variation study

Microemulsions of the type H(2)O-scCO(2)-surfactant are potential candidates for novel solvent mixtures in the field of green chemistry. Furthermore, scCO(2)-microemulsions are highly interesting from a fundamental point of view since their properties such as the bending elastic constants can be strongly influenced solely by varying the pressure without changing the components. With this motivation we studied the phase behavior and the microstructure of water-rich scCO(2)-microemulsions. Such microemulsions were formulated using the technical grade non-ionic surfactants Zonyl FSO 100 and Zonyl FSN 100. At elevated pressures the temperature dependent phase behavior of these systems follows the general patterns of non-ionic microemulsions. Small angle neutron scattering experiments were conducted to determine the length scales and the topology of the microstructure of these systems. Having determined the exact scattering length densities and the composition of the respective sub-phases by a systematic contrast variation we could show that these systems consist of CO(2)-swollen microemulsion droplets that are dispersed in a continuous aqueous-phase. The scattering data were analyzed using a newly derived form factor for polydisperse, spherical core/shell particles with diffuse interfaces. The underlying analytical density profiles could be confirmed applying the model-free Generalized Indirect Fourier Transformation (GIFT) to the scattering data. Following the general patterns of non-ionic microemulsions the radius of the microemulsion droplets is found to increase almost linearly upon the addition of CO(2).     

FTIR study on the formation of TiO2 nanostructures in supercritical CO2

TiO(2) nanospherical and fibered structures were obtained via a one-step sol-gel method in supercritical carbon dioxide (scCO(2)) involving polycondensation of the alkoxide monomers titanium isopropoxide (TIP) and titanium butoxide (TBO) with acetic acid (HAc). The resulting materials were characterized by means of electron microscopy (SEM and TEM), X-ray diffraction (XRD), thermal analysis (TGA), and attenuated total reflection Fourier transmission infrared (ATR-FTIR) analysis. Depending on the experimental conditions, TiO(2) anatase nanospheres with a diameter of 20 nm or TiO(2) anatase/rutile nanofibers with a diameter of 10-100 nm were obtained. Fiber formation was enhanced by a higher HAc/Ti ratio and the use of the titanium isopropoxide (TIP) monomer. The mechanism of the microstructure formation was studied using in situ FTIR analysis in scCO(2). The FTIR results indicated that the formation of nanofibers was favored by a titanium hexamer that leads to one-dimensional condensation, while nanospheres were favored by a hexamer that permits three-dimensional condensation.