Lipopolysaccharides (LPS) are the primary constituent of the outer membrane of Gram-negative bacteria such as Pseudomonas aeruginosa. Gram-negative bacteria can synthesize modified forms of LPS in response to environmental stimuli or due to genetic mutations, a process known as outer membrane remodeling. Chemical modifications of the LPS modulate the integrity and antibiotic susceptibility of bacterial outer membranes. It also governs microbial adhesion to tissues and artificial material surfaces. We have extended a previous model of the rough LPS to include four novel chemotypes rmlC, galU, LPS Re, and Lipid-A. Atomistic molecular dynamics (MD) simulations were performed for outer membrane models constituted of each LPS chemotypes and 1,2-dipalmitoyl-3-phosphatidylethanolamine. It is shown that the decrease in the LPS polysaccharide chain length leads to a significant increase in the diffusion coefficients for the Ca(2+) counterions, increase in acyl chain packing (decrease in membrane fluidity), and attenuation of the negative potential across the LPS surface as positive counterions becomes more exposed to the solvent. The electrostatic potential on the LPS surfaces reflects heterogeneous charge distributions with increasingly larger patches of positive and negative potentials as the polysaccharide chain length decreases. Such a pattern originates from the spatial arrangement of charged phosphate-Ca(2+) clusters in the LPS inner-core that becomes exposed in the membrane surface as monosaccharide units are lost in the shortest chemotypes LPS Re and Lipid-A. These MD-derived conformational ensembles reproduce experimental trends and provide atom-level structural information on the rough LPS chemotypes that can help to rationalize antibiotic resistance and bacterial adhesion processes.

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Surfactants are molecular structures with remarkable physicochemical properties and applications. Most of their characteristics are due to their ability to promote aggregation and interactions with different interfaces. The scarcity of theoretical studies dedicated to evaluating the forces involved in these interactions prompted us to propose other models capable of reproducing the experimental data in better ways. We carried out molecular dynamics (MD) simulations to obtain a model for cetyltrimethylammonium bromide (CTAB), selected from gromos54a7 force field parameters, that better describes most of its behaviors in aqueous solution (micellar structure, counterion dissociation, etc.) and its adsorption pattern on a gold surface. The parameters adopted for one of the models were able to mimic several characteristics suggested by experimental measurements of the CTAB micelles, as well their adsorption pattern on a gold surface. Indeed, this model was able to obtain quasi-spherical micelles, as well as a pattern of adjacent cylindrical micelles with alkyl chain interactions on a gold surface.Keywords: molecular dynamics, micelles, interface interaction, cetyltrimethylammonium bromide, gold IntroductionSurfactants are a class of compounds containing a polar group, charged or neutral, attached to a long hydrophobic tail.1,2 These are remarkably versatile compounds with a broad variety of important applications in the pharmaceutical, medical, and food industries and for nanomaterial synthesis.3,4 Above a certain temperature in solution (the Krafft temperature), surfactants tend to aggregate to minimize unfavorable interactions between the surfactants and the surrounding environment. 5 The minimum concentration required for surfactant aggregation is defined as the critical micellar concentration (CMC), and most of the characteristics of these aggregates are controlled by factors such as the solvent type, chemical structure of the surfactant, and solution conditions (e.g., concentration, temperature, presence of additives, and ionic strength). 6Variations of these factors yield aggregates with different morphologies such as spherical or ellipsoidal micelles, cylindrical or thread-like micelles, disk-like micelle, membranes and vesicles.7 These self-assembled structures have been characterized by a number of techniques, such as dynamic light scattering (DLS), 8 nuclear magnetic resonance (NMR), 9,10 fluorescence spectroscopy, 11 quasielastic neutron scattering (QENS), 12,13 small-angle X-ray scattering (SAXS), 14,15 and small-angle neutron scattering (SANS). 16,17 Computational simulations have also been employed to explore the structures and dynamical behaviors of micelles for different surfactants. 18Considering that no holes exist within a micelle, its radius is estimated as the maximum extension of a hydrocarbon chain and can be evaluated by using the following equation:where l max is the maximum length in nm and n C is the number of carbon atoms in the chain. 19 Indeed, under the previously mentioned conditions, ...

Four chemotypes of the Rough lipopolysaccharides (LPS) membrane from Pseudomonas aeruginosa were investigated by a combined approach of explicit water molecular dynamics (MD) simulations and Poisson-Boltzmann continuum electrostatics with the goal to deliver the distribution of the electrostatic potential across the membrane. For the purpose of this investigation, a new tool for modeling the electrostatic potential profile along the axis normal to the membrane, MEMPOT, was developed and implemented in DelPhi. Applying MEMPOT on the snapshots obtained by MD simulations, two observations were made: (a) the average electrostatic potential has a complex profile, but is mostly positive inside the membrane due to the presence of Ca2+ ions which overcompensate for the negative potential created by lipid phosphate groups; and (b) correct modeling of the electrostatic potential profile across the membrane requires taking into account the water phase, while neglecting it (vacuum calculations) results in dramatic changes including a reversal of the sign of the potential inside the membrane. Furthermore, using DelPhi to assign different dielectric constants for different regions of the LPS membranes, it was investigated whether a single frame structure before MD simulations with appropriate dielectric constants for the lipid tails, inner, and the external leaflet regions, can deliver the same average electrostatic potential distribution as obtained from the MD-generated ensemble of structures. Indeed, this can be attained by using smaller dielectric constant for the tail and inner leaflet regions (mostly hydrophobic) than for the external leaflet region (hydrophilic) and the optimal dielectric constant values are chemotype-specific.

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In this work, we have applied Density Functional Theory calculations to investigate the electronic and spacial effects of different phosphorus ligands on the selectivity of the olefin (propene and styrene) insertion reaction into the RhAH bond of the complexes HRh(PR 3 )(CO) 2 (olefin), where the modified ligand PR 3 , is a phosphine (R ¼ H, F, Et, Ph) or phosphite (R ¼ OEt, OPh). M06/SBKJC/cc-pVDZ calculations revealed that the olefin coordination and insertion reaction are dominated by the electronic effects of the phosphorus ligands. A very good correlation between the Tolman electronic factor, v, with the backdonated charges from the metallic center to the olefin and also with the interaction energy of the olefin with the four-coordinated HRh(CO) 2 (PR 3 ) catalyst was found. Using the propene as the substrate and for all the phosphorus ligands investigated, the insertion always proceeds through the reaction path leading to the linear metal-alkyl intermediate. However, when styrene is used, the branched metal-alkyl intermediate is always favored. The structural results obtained for the transition states do not support the existence of a p-allilic intermediates. The regioselectivity obtained for the insertion reaction of styrene results from thermodynamic aspects of the reaction in which the branched metal-alkyl intermediate is always favored by $5 kcal/mol. The M06/SBKJC/cc-pVDZ results are in good agreement with the experimental findings.

Full quantum mechanical calculations at the DFT level were carried out to study the full catalytic cycle for the hydroformylation of propene, catalyzed by the heterobimetallic catalyst trans-[HPt(PPh3)2(SnCl3)] with real triphenylphosphine ligands. All intermediates and transition states along the elementary steps of the entire catalytic cycle were located and the energies involved in the catalytic cycle calculated using the BP86 functional. The solvent effects along the entire catalytic cycle were evaluated using the polarizable continuum model. The regioselectivity of the hydroformylation is set at the olefin insertion step, with the aldehyde reductive elimination being the rate-determining step of the entire cycle, with an activation free energy of 18.1 kcal mol–1, in line with the experimental findings. The trans effect of the SnCl3 ligand seems to be pronounced only in the first step of the catalytic cycle, facilitating the insertion of the olefin into the Pt–H bond trans to it. The BP86 calculations predict a diasteroselectivity ratio of 95:5 in favor of the linear aldehyde product, which it is in excellent agreement with the experimental value.

ABSTRACT:In this work we have applied Quantum Mechanical calculations to investigate the first two elementary steps (olefin insertion and carbonylation) in the hydroformylation of styrene, using the model catalysts of the type [HRh(CO) x (PMe 3 ) 3Ϫx ] (x ϭ 1, 2), which are supposed to be the catalytic species that will be present depending on the CO pressure. The migratory styrene insertion reaction and CO insertion reaction into the metal-alkyl bond were investigated at the MP4(SDQ) level using the BP86 optimized geometries. Additionally the Spin Component Scale procedure on the MP2 and MP3 energies (SCS-MP2 and SCS-MP3) was also applied. It is shown that, at normal hydroformylation conditions and normal CO and H 2 pressure, the active catalytic species is preferentially formed in trans arrangement, trans-[HRh-(CO)(PMe 3 ) 2 ], 2b. Because of the greater steric hindrance around the rhodium atom, the electronic effects of the phosphine do not contribute significantly to the stability of the catalyst. The MPn calculations overestimate the stability of the -complexes, in comparison with the BP86 value, as much as 25 kcal/mol, with large fluctuations along the perturbation series. The activation energies predicted by the BP86 method, in comparison with the MPn results, are underestimated about 5 kcal/mol. The reaction and the coordination energies are very sensitive to the theoretical level employed. Our results indicate that the competitive trapping of the styrene by different catalytic species, one leading to the branched and the other leading to the linear species, as was experimentally proposed to explain the selectivity, only seems to hold if we consider the subsequent CO insertion step. This assumption based only on the olefin insertion reaction, as the selectivity determining step, does not apply since the branched product will always preferentially be formed. All methods employed here predict the selectivity in good agreement with the experimental selectivity of 70-95% in favor of the branched product.