29 research outputs found
Temperature Dependence and Energetics of Single Ions at the Aqueous Liquid–Vapor Interface
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
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
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
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
The
guanidinium cation (CÂ(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
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
Carbon nanotubes are a promising platform across a broad
spectrum
of applications ranging from separations technology, drug delivery,
to bioÂ(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
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
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
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)