29 research outputs found

    Temperature Dependence and Energetics of Single Ions at the Aqueous Liquid–Vapor Interface

    No full text
    We investigate temperature-dependence of free energetics with two single halide anions, I<sup>–</sup> and Cl<sup>–</sup>, crossing the aqueous liquid–vapor interface through molecular dynamics simulations. The result shows that I<sup>–</sup> has a modest surface stability of 0.5 kcal/mol at 300 K and the stability decreases as the temperature increases, indicating the surface adsorption process for the anion is entropically disfavored. In contrast, Cl<sup>–</sup> shows no such surface state at all temperatures. Decomposition of free energetics reveals that water–water interactions provide a favorable enthalpic contribution, while the desolvation of ion induces an increase in free energy. Calculations of surface fluctuations demonstrate that I<sup>–</sup> generates significantly greater interfacial fluctuations compared to Cl<sup>–</sup>. The fluctuation is attributed to the malleability of the solvation shells, which allows for more long-ranged perturbations and solvent density redistribution induced by I<sup>–</sup> as the anion approaches the liquid–vapor interface. The increase in temperature of the solvent enhances the inherent thermally excited fluctuations and consequently reduces the relative contribution from anion to surface fluctuations, which is consistent with the decrease in surface stability of I<sup>–</sup>. Our results indicate a strong correlation with induced interfacial fluctuations and anion surface stability; moreover, resulting temperature dependent behavior of induced fluctuations suggests the possibility of a critical level of induced fluctuations associated with surface stability

    C(sp<sup>3</sup>)–C(sp<sup>3</sup>) Radical-Cross-Coupling Reaction via Photoexcitation

    No full text
    The photoexcitation of 4-alkyl-1,4-dihydropyridines (alkyl-DHPs) in the presence of a base triggers the single-electron-transfer-mediated desulfonative radical-cross-coupling (RCC) reaction without the need for any metal or photocatalyst. 4-Alkyl-substituted 1,4-DHPs as the electron donor (reductant) and alkyl sulfones as the electron acceptor (oxidant) are chosen strategically as the two best-matched modular radical precursors for the construction of C(sp3)–C(sp3) bonds. Ultraviolet light-emitting diodes (365 nm) have proven to be adequate for inducing single-electron transfer between two radical precursors in the excited state. Following this designed strategy, a diverse collection of primary, secondary, and tertiary persistent alkyl radicals from both radical precursors have been used to forge C(sp3)–C(sp3) bonds. This blueprint features good functional group compatibility, a broad scope, and detailed mechanistic investigation

    C(sp<sup>3</sup>)–C(sp<sup>3</sup>) Radical-Cross-Coupling Reaction via Photoexcitation

    No full text
    The photoexcitation of 4-alkyl-1,4-dihydropyridines (alkyl-DHPs) in the presence of a base triggers the single-electron-transfer-mediated desulfonative radical-cross-coupling (RCC) reaction without the need for any metal or photocatalyst. 4-Alkyl-substituted 1,4-DHPs as the electron donor (reductant) and alkyl sulfones as the electron acceptor (oxidant) are chosen strategically as the two best-matched modular radical precursors for the construction of C(sp3)–C(sp3) bonds. Ultraviolet light-emitting diodes (365 nm) have proven to be adequate for inducing single-electron transfer between two radical precursors in the excited state. Following this designed strategy, a diverse collection of primary, secondary, and tertiary persistent alkyl radicals from both radical precursors have been used to forge C(sp3)–C(sp3) bonds. This blueprint features good functional group compatibility, a broad scope, and detailed mechanistic investigation

    Free Energetics of Arginine Permeation into Model DMPC Lipid Bilayers: Coupling of Effective Counterion Concentration and Lateral Bilayer Dimensions

    No full text
    Mechanisms and underlying thermodynamic determinants of translocation of charged cationic peptides such as cell-penetrating peptides across the cellular membrane continue to receive much attention. Two widely held views include endocytotic and non-endocytotic (diffusive) processes of permeant transfer across the bilayer. Considering a purely diffusive process, we consider the free energetics of translocation of a monoarginine peptide mimic across a model DMPC bilayer. We compute potentials of mean force for the transfer of a charged monoarginine peptide unit from water to the center of a 1,2-dimyristoyl-<i>sn</i>-glycero-3-phosphocholine (DMPC) model lipid bilayer. We use fully atomistic molecular dynamics simulations coupled with the adaptive biasing force (ABF) method for free energy estimation. The estimated potential of mean force difference from bulk to bilayer center is 6.94 ± 0.28 kcal/mol. The order of magnitude of this prediction is consistent with past experimental estimates of arginine partitioning into physiological bilayers in the context of translocon-based experiments, though the correlation between the bench and computer experiments is not unambiguous. Moreover, the present value is roughly one-half of previous estimates based on all-atom molecular dynamics free energy calculations. We trace the differences between the present and earlier calculations to system sizes used in the simulations and the dependence of the contributions to the free energy from various system components (water, lipids, ions, peptide) on overall system size. By varying the bilayer lateral dimensions in simulations using only sufficient numbers of counterions to maintain overall system charge neutrality, we find the possibility of an inherent convergent transfer free energy value

    Liquid–Vapor Interfacial Properties of Aqueous Solutions of Guanidinium and Methyl Guanidinium Chloride: Influence of Molecular Orientation on Interface Fluctuations

    No full text
    The guanidinium cation (C­(NH<sub>2</sub>)<sub>3</sub><sup>+</sup>) is a highly stable cation in aqueous solution due to its efficient solvation by water molecules and resonance stabilization of the charge. Its salts increase the solubility of nonpolar molecules (“salting-in”) and decrease the ordering of water. It is one of the strongest denaturants used in biophysical studies of protein folding. We investigate the behavior of guanidinium and its derivative, methyl guanidinium (an amino acid analogue) at the air–water surface, using atomistic molecular dynamics (MD) simulations and calculation of potentials of mean force. Methyl guanidinium cation is less excluded from the air–water surface than guanidinium cation, but both cations show orientational dependence of surface affinity. Parallel orientations of the guanidinium ring (relative to the Gibbs dividing surface) show pronounced free energy minima in the interfacial region, while ring orientations perpendicular to the GDS exhibit no discernible surface stability. Calculations of surface fluctuations demonstrate that, near the air–water surface, the parallel-oriented cations generate significantly greater interfacial fluctuations compared to other orientations, which induces more long-ranged perturbations and solvent density redistribution. Our results suggest a strong correlation with induced interfacial fluctuations and ion surface stability. These results have implications for interpreting molecular-level, mechanistic action of this osmolyte’s interaction with hydrophobic interfaces as they impact protein denaturation (solubilization)

    Investigating Hydrophilic Pores in Model Lipid Bilayers Using Molecular Simulations: Correlating Bilayer Properties with Pore-Formation Thermodynamics

    No full text
    Cell-penetrating and antimicrobial peptides show a remarkable ability to translocate across physiological membranes. Along with factors such as electric-potential-induced perturbations of membrane structure and surface tension effects, experiments invoke porelike membrane configurations during the solute transfer process into vesicles and cells. The initiation and formation of pores are associated with a nontrivial free-energy cost, thus necessitating a consideration of the factors associated with pore formation and the attendant free energies. Because of experimental and modeling challenges related to the long time scales of the translocation process, we use umbrella sampling molecular dynamics simulations with a lipid-density-based order parameter to investigate membrane-pore-formation free energy employing Martini coarse-grained models. We investigate structure and thermodynamic features of the pore in 18 lipids spanning a range of headgroups, charge states, acyl chain lengths, and saturation. We probe the dependence of pore-formation barriers on the area per lipid, lipid bilayer thickness, and membrane bending rigidities in three different lipid classes. The pore-formation free energy in pure bilayers and peptide translocating scenarios are significantly coupled with bilayer thickness. Thicker bilayers require more reversible work to create pores. The pore-formation free energy is higher in peptide–lipid systems than in peptide-free lipid systems due to penalties to maintain the solvation of charged hydrophilic solutes within the membrane environment

    Free Energetics of Carbon Nanotube Association in Pure and Aqueous Ionic Solutions

    No full text
    Carbon nanotubes are a promising platform across a broad spectrum of applications ranging from separations technology, drug delivery, to bio­(electronic) sensors. Proper dispersion of carbon nanotube materials is important to retaining the electronic properties of nanotubes. Experimentally it has been shown that salts can regulate the dispersing properties of CNTs in aqueous system with surfactants (Niyogi, S.; Densmore, C. G.; Doorn, S. K. <i>J. Am. Chem. Soc.</i> <b>2009</b>, <i>131</i>, 1144–1153); details of the physicochemical mechanisms underlying such effects continue to be explored. We address the effects of inorganic monovalent salts (NaCl and NaI) on dispersion stability of carbon nanotubes.We perform all-atom molecular dynamics simulations using nonpolarizable interaction models to compute the potential of mean force between two (10,10) single-walled carbon nanotubes (SWNTs) in the presence of NaCl/NaI and compare to the potential of mean force between SWNTs in pure water. Addition of salts enhances stability of the contact state between two SWNT’s on the order of 4 kcal/mol. The ion-specific spatial distribution of different halide anions gives rise to starkly different contributions to the free energy stability of nanotubes in the contact state. Iodide anion directly stabilizes the contact state to a much greater extent than chloride anion. The enhanced stability arises from the locally repulsive forces imposed on nanotubes by the surface-segregated iodide anion. Within the time scale of our simulations, both NaI and NaCl solutions stabilize the contact state by equivalent amounts. The marginally higher stability for contact state in salt solutions recapitulates results for small hydrophobic solutes in NaCl solutions (Athawale, M. V.; Sarupria, S.; Garde, S. <i>J. Phys. Chem. B</i> <b>2008</b>, <i>112</i>, 5661–5670) as well as single-walled carbon nanotubes in NaCl and CaCl<sub>2</sub> aqueous solutions

    Investigating Hydrophilic Pores in Model Lipid Bilayers Using Molecular Simulations: Correlating Bilayer Properties with Pore-Formation Thermodynamics

    No full text
    Cell-penetrating and antimicrobial peptides show a remarkable ability to translocate across physiological membranes. Along with factors such as electric-potential-induced perturbations of membrane structure and surface tension effects, experiments invoke porelike membrane configurations during the solute transfer process into vesicles and cells. The initiation and formation of pores are associated with a nontrivial free-energy cost, thus necessitating a consideration of the factors associated with pore formation and the attendant free energies. Because of experimental and modeling challenges related to the long time scales of the translocation process, we use umbrella sampling molecular dynamics simulations with a lipid-density-based order parameter to investigate membrane-pore-formation free energy employing Martini coarse-grained models. We investigate structure and thermodynamic features of the pore in 18 lipids spanning a range of headgroups, charge states, acyl chain lengths, and saturation. We probe the dependence of pore-formation barriers on the area per lipid, lipid bilayer thickness, and membrane bending rigidities in three different lipid classes. The pore-formation free energy in pure bilayers and peptide translocating scenarios are significantly coupled with bilayer thickness. Thicker bilayers require more reversible work to create pores. The pore-formation free energy is higher in peptide–lipid systems than in peptide-free lipid systems due to penalties to maintain the solvation of charged hydrophilic solutes within the membrane environment

    Exploring Ion Permeation Energetics in Gramicidin A Using Polarizable Charge Equilibration Force Fields

    No full text
    Exploring Ion Permeation Energetics in Gramicidin A Using Polarizable Charge Equilibration Force Field

    Protein Denaturants at Aqueous–Hydrophobic Interfaces: Self-Consistent Correlation between Induced Interfacial Fluctuations and Denaturant Stability at the Interface

    No full text
    The notion of direct interaction between denaturing cosolvent and protein residues has been proposed in dialogue relevant to molecular mechanisms of protein denaturation. Here we consider the correlation between free energetic stability and induced fluctuations of an aqueous–hydrophobic interface between a model hydrophobically associating protein, HFBII, and two common protein denaturants, guanidinium cation (Gdm<sup>+</sup>) and urea. We compute potentials of mean force along an order parameter that brings the solute molecule close to the known hydrophobic region of the protein. We assess potentials of mean force for different relative orientations between the protein and denaturant molecule. We find that in both cases of guanidinium cation and urea relative orientations of the denaturant molecule that are parallel to the local protein–water interface exhibit greater stability compared to edge-on or perpendicular orientations. This behavior has been observed for guanidinium/methylguanidinium cations at the liquid–vapor interface of water, and thus the present results further corroborate earlier findings. Further analysis of the induced fluctuations of the aqueous–hydrophobic interface upon approach of the denaturant molecule indicates that the parallel orientation, displaying a greater stability at the interface, also induces larger fluctuations of the interface compared to the perpendicular orientations. The correlation of interfacial stability and induced interface fluctuation is a recurring theme for interface-stable solutes at hydrophobic interfaces. Moreover, observed correlations between interface stability and induced fluctuations recapitulate connections to local hydration structure and patterns around solutes as evidenced by experiment (Cooper et al., <i>J. Phys. Chem. A</i> <b>2014</b>, <i>118</i>, 5657.) and high-level ab initio/DFT calculations (Baer et al., <i>Faraday Discuss</i> <b>2013</b>, <i>160</i>, 89)
    corecore