The Nature of the Hydrated
Excess Proton and Its Unusual
Behavior
Protons Play a Key Role in Many Processes
Chemistry
Materials
Science
AEM fuel cells
• Acid-base chemistry
• Enzyme catalysis
• Drug interactions
• Atmospheric reactions
• Fuel cells and batteries
• Renewable energy materials
• Proton exchange membranes
• Anion exchange membranes
Proton transport in Nafion
Li-ion batteries
Proton channels in proteins
Protons in Biomolecular Systems
• Within a cell, moving protons across a membrane allows energy to be
stored as an electrochemical gradient
charge
separation
concentration
difference
• This potential energy can be used to power chemical processes,
such as:
• ATP synthesis and hydrolysis
• Photosynthesis
• Heat production
• Homeostasis
• Flagellar rotation
ATP synthase
Wikimedia Commons
Studying Chemical Systems
• In a molecular dynamics (MD) simulation, a set of interacting particles
move according to equations of motion defined by Newtonian mechanics
position at
later time
Newton’s
second law
• An MD simulation produces trajectory data, which consists of the
position, velocity, and energy of each particle at every time point
considered in the simulation
• Applying statistical mechanics allows us to derive information on
macroscopic observables from this microscopic data
• A force field consists of 1) a potential energy function describing interand intra-molecular interactions, and 2) a set of parameters which
ensure agreement with experimental results
• Selection of an appropriate force field is crucial to a successful MD
simulation
The Challenge of Proton Solvation and Transport
• The excess proton is a dynamic
Y. Wu, H. Chen , F. Wang, F. Paesani , and G. A. Voth, J. Phys. Chem. B (2008)
electrical charge defect delocalized
over several water molecules
• Despite what is taught in many
textbooks, the hydrated excess
proton does not exist as the
simple hydronium cation (H3O+).
• It is rather an “electron hole” with
one missing electron from the
excess proton and it is constantly
moving
• A model for proton solvation and transport (PS&T) must be able to
describe the continuously changing network of hydrogen-bonded
water molecules surrounding a hydrated proton
• Traditional force fields, however, are not reactive; they lack the
ability to describe the formation and cleavage of chemical bonds
Computer Modeling of Hydrated Protons
• A high-level treatment of chemical reactions requires explicitly treating
the involved electrons through quantum mechanics
• Due to their small size, electrons move much more quickly than atoms
• This difference in time scales makes it computationally expensive to
consider electrons and atoms together
• Nevertheless, traditional force field models can be extended to reactive
systems through special techniques
• The multiscale reactive molecular dynamics (MSRMD) methodology relies on a linear
combination of several different states to model
charge delocalization and dynamic bonding
environments
C. Knight and G. A. Voth, Acc. Chem. Res. (2012)
• Ab initio molecular dynamics (AIMD) simulations are extremely accurate
because they are based on quantum mechanics
• The MS-RMDmethod can be parametrized via AIMD data; combining these
technologies allows for the sampling of longer time and length scales than
would be feasible with AIMD alone
The Hydrated Proton has Two Predominant Forms
• The chemical identity of the hydrated proton is described by two
predominant solvation structures: the Eigen (E) and Zundel (Z) cations
• Excess proton transfer between
+
+
two water molecules occurs via
H
O
5
2
H9O4
the Zundel cation
• The Eigen cation is the most stable hydrated proton species in liquid
water, as shown by the probability distribution the two largest MS-RMD
amplitudes (L) and the free energy profile of the proton solvation
structure in bulk water (R)
E
Z
Z
E
J. M. J. Swanson, C. M. Maupin, H. Chen, M. K. Petersen, J. Xu, Y. Wu, and G. A. Voth, J. Phys. Chem. B, (2007)
Grotthuss Proton Shuttling
• The Grotthuss mechanism for proton transport was first proposed in
1806 by T. Grotthuss, even though he did not know the chemical
formula of water (Ann. Chim. LVIII, 54 (1806))
• According to this mechanism the excess proton
hops between adjacent water molecules in the
water wire through successive covalent bond
formation and breaking events
• Modern research suggests that Grotthuss
C. Knight and G. A. Voth, Acc. Chem. Res. (2012)
shuttling occurs by the Eigen-Zundel-Eigen
(EZE) mechanism, whereby one distorted Eigen
cation is converted into another with the Zundel
cation as an intermediate
• The EZE mechanism for proton transport has been statistically validated
through MS-RMD simulations, AIMD simulations, and photoelectron
spectroscopy
The Special-Pair Dance
• The ‘resting’ state of the solvated proton is best described as a distorted
Eigen cation
• Within this structure, the central hydronium ion forms strong hydrogen
bonds with the three surrounding water molecules which comprise its
first solvation shell
• In the special-pair (SP) dance, the length
C. Knight and G. A. Voth, Acc. Chem. Res. (2012)
of these hydrogen bonds fluctuates
rapidly over time, with any one of the
three bonds being shorter than the
remaining two
• This dance is a preparatory stage of
proton transfer, during which the central
hydronium ion searches for a partner
• The successful partner accepts only one
hydrogen bond, whereas most water
molecules accept two
The Special-Pair Dance and Proton Transfer
• Once a successful partner is identified, the proton transfer event occurs
between the special pair
• The partner transfers significant electronic charge to the hydronium cation
along the strong SP hydrogen bond
• As per the EZE mechanism, the Zundel cation corresponds to the transition
state of proton transfer
O. Markovitch, H. Chen, S. Izvekov, F.
Paesani, G.A. Voth, and N. Agmom, J.
Phys. Chem. B (2008)
• The SP dance demonstrates the sensitive coupling between the excess
proton and its surrounding hydrogen bond network
• Proton transfer, therefore, occurs via a cooperative, diffusive process
rather than by simple hopping
• The study of these mechanisms was accomplished by combining the
efficiency of the MS-RMDmethod and the accuracy of AIMD
Hydrated Proton Dynamics and Charge Defect
Delocalization
•
A “stable” resonating hydrated
proton structure exists for 1-2 ps.
•
This structure involves a single
central oxygen atom, but several
transient Zundel-like structures.
•
This structure is best characterized
as a “distorted” Eigen cation.
Excess Proton Charge Defect:
Center of Excess Charge (CEC)
(Position shown by yellow ball)
CEC
The “Special Pair Dance”
O. Markovitch, H. Chen, S. Izvekov, F. Paesani, G. A. Voth, and N.
Agmon, “Statistical Identification of the Mechanism of Proton
Mobility”, J. Phys. Chem. B 112, 9456 (2008).
Acid Dissociation in Water: A Complex Process
• Shown at right is the so-called
“potential of mean force” or free
energy curve for the
dissociation of the hydrated
proton center of excess charge
(CEC) from the aspartic acid in
water along the reaction
coordinate (RC)
• The colored regions reflect the
distribution functions from the
MS-RMD simulations as a
function of CEC distance from
the Asp carbonyl oxygens
• A vertical slice as a function of
the RC gives the hydrated
proton distribution function
like in slide 7
•
•
•
•
Aspartic Acid pKa: 3.7
Eigen-like structures are most
stable at larger values of RC
Zundel-like structures occur at
transitions
An ion pair is evident around RC = 3
Amphiphilic Character of the Hydrated Proton
• One might expect that two hydrated protons would repel each other because
of their net positive charges
• However, the interactions between hydrated protons are not so
straightforward
• At 0.43−0.85 M concentrations, hydronium cations are found to form
unusually stable contact ion pairs by positioning the hydronium oxygen lone
pair sides toward one another
• This unexpected behavior can be attributed to the
amphiphilic nature of the hydrated excess proton,
which arises from the directionally asymmetric
ability of the core hydronium entity to form
hydrogen bonds with neighboring water molecules
C. Knight and G. A. Voth, Acc. Chem. Res. (2012)
• The three H-atoms of the hydronium form strong H-bonds within the
Eigen cation, thus imparting hydrophilic character
• However, the lone pair of the hydronium is a hydrophobic region, because
it is energetically unfavorable for the net-positive hydronium ion to
accept a hydrogen bond
J. Xu, S. Izvekov, and G. A. Voth, J. Phys. Chem. B (2010)
Hydrated Protons at the Water-Vacuum Interface
• Conventional analysis of ion solvation near the dielectric boundary at the
liquid-vapor interface holds that ions should be expelled from the interface
M. K. Petersen, S. S. Iyengar, T. J. F. Day, and G. A.
Voth, J. Phys. Chem. B, (2004)
Hydronium
cation
Hydronium
cation
‘Dangling’ O-H bond
‘Dangling’ O-H bond
• The amphiphilic nature of the hydrated
proton disrupts the hydrogen-bonding
network in bulk water
• As predicted by MS-RMD simulations,
this results in an enhanced hydronium
concentration near the water-vapor
interface in acidic aqueous solution and
at the surface of water clusters
• This unusual behavior stems from the fact that the hydrophobic lone pair
at the interface can be oriented toward the vapor region to minimize its
disturbance in the bulk water
• These theoretical predictions were subsequently verified through
agreement with experimental results
Hydrophobic Interactions
• The aggregation and dispersion of hydrophobic particles in water is
principally determined by the interplay between enthalpy and entropy
• Although the aggregation of hydrophobic particles is typically favored
entropically, it is more complicated enthalpically since H-bonding
rearrangements in the surrounding solvent must be considered
• As demonstrated in MS-RMD simulations, the solubility of hydrophobic
molecules is enhanced by low pH conditions
• Although a hydronium cation has a similar radius to the salting-out
cations K+ and NH4+, hydrophobic particles are more soluble in acidic
solution than in salt solution of the same concentration
Hydrophobic
particles
(light)
Hydrophobic
Hydrophobic
particles
(light)
in in
Hydrophobic particles
particles (light)
(light) in
in
• This behavior can be
salt
solution
acidic
solution
salt solution
acidic solution
explained by the existence of
associated hydrophobehydrated proton structures,
which form as a result of
hydronium’s unusual
amphiphilic character
H. Chen, J. Xu, and G. A. Voth, J. Phys. Chem. B (2009)
Applications
• PS&T in biomolecular systems has presented the most challenging and
arguably important application for the MS-RMD simulation
methodology to date
• Computer simulations have been applied to the following systems
Phospholipid membranes
Aquaporin channels
Cytochrome c oxidase
Influenza A M2
proton channel
Mutated aquaporins
Carbonic anhydrase
Acknowledgements
This research has been supported by
the National Science Foundation