Slide 1

The Nature of the Hydrated Excess Proton and Its Unusual Behavior

Protons Play a Key Role in Many ProcessesChemistryAcid-base chemistryEnzyme catalysisDrug interactionsAtmospheric reactionsMaterials ScienceFuel cells and batteriesRenewable energy materialsProton exchange membranesAnion exchange membranes

AEM fuel cellsLi-ion batteries

Proton transport in Nafion

Proton channels in proteins

Protons in Biomolecular SystemsThis potential energy can be used to power chemical processes, such as:Within a cell, moving protons across a membrane allows energy to be stored as an electrochemical gradientcharge separationconcentrationdifferenceATP synthesis and hydrolysisPhotosynthesisHeat productionFlagellar rotationHomeostasis

ATP synthaseWikimedia Commons

Studying Chemical SystemsIn a molecular dynamics (MD) simulation, a set of interacting particles move according to equations of motion defined by Newtonian mechanics

An MD simulation produces trajectory data, which consists of the position, velocity, and energy of each particle at every time point considered in the simulationApplying statistical mechanics allows us to derive information on macroscopic observables from this microscopic dataA force field consists of 1) a potential energy function describing inter- and intra-molecular interactions, and 2) a set of parameters which ensure agreement with experimental resultsSelection of an appropriate force field is crucial to a successful MD simulation position at later timeNewtons second law

The Challenge of Proton Solvation and TransportThe excess proton is a dynamic electrical charge defect delocalized over several water moleculesDespite 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 protonTraditional force fields, however, are not reactive; they lack the ability to describe the formation and cleavage of chemical bondsY. Wu, H. Chen , F. Wang, F. Paesani , and G. A. Voth, J. Phys. Chem. B (2008)

Computer Modeling of Hydrated ProtonsA high-level treatment of chemical reactions requires explicitly treating the involved electrons through quantum mechanicsDue to their small size, electrons move much more quickly than atomsThis difference in time scales makes it computationally expensive to consider electrons and atoms togetherNevertheless, traditional force field models can be extended to reactive systems through special techniquesThe multiscale reactive molecular dynamics (MS-RMD) methodology relies on a linear combination of several different states to model charge delocalization and dynamic bonding environmentsC. Knight and G. A. Voth, Acc. Chem. Res. (2012) Ab initio molecular dynamics (AIMD) simulations are extremely accurate because they are based on quantum mechanicsThe 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 FormsThe chemical identity of the hydrated proton is described by two predominant solvation structures: the Eigen (E) and Zundel (Z) cations

H9O4+

H5O2+Excess proton transfer between two water molecules occurs via the Zundel cationThe 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)

EZ

EZJ. 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 ShuttlingThe 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 eventsThe EZE mechanism for proton transport has been statistically validated through MS-RMD simulations, AIMD simulations, and photoelectron spectroscopyC. Knight and G. A. Voth, Acc. Chem. Res. (2012) Modern research suggests that Grotthuss 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 Special-Pair DanceThe resting state of the solvated proton is best described as a distorted Eigen cationWithin this structure, the central hydronium ion forms strong hydrogen bonds with the three surrounding water molecules which comprise its first solvation shellIn the special-pair (SP) dance, the length of these hydrogen bonds fluctuates rapidly over time, with any one of the three bonds being shorter than the remaining twoThis dance is a preparatory stage of proton transfer, during which the central hydronium ion searches for a partnerThe successful partner accepts only one hydrogen bond, whereas most water molecules accept twoC. Knight and G. A. Voth, Acc. Chem. Res. (2012)

The Special-Pair Dance and Proton TransferOnce a successful partner is identified, the proton transfer event occurs between the special pairThe 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 transferThe SP dance demonstrates the sensitive coupling between the excess proton and its surrounding hydrogen bond networkProton transfer, therefore, occurs via a cooperative, diffusive process rather than by simple hoppingThe study of these mechanisms was accomplished by combining the efficiency of the MS-RMDmethod and the accuracy of AIMD

O. Markovitch, H. Chen, S. Izvekov, F. Paesani, G.A. Voth, and N. Agmom, J. Phys. Chem. B (2008)Hydrated Proton Dynamics and Charge Defect DelocalizationA 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.

The Special Pair DanceO. 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). Excess Proton Charge Defect:Center of Excess Charge (CEC)(Position shown by yellow ball)CEC

11

Acid Dissociation in Water: A Complex ProcessAspartic Acid pKa: 3.7Eigen-like structures are most stable at larger values of RCZundel-like structures occur at transitionsAn ion pair is evident around RC = 3Shown 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

Amphiphilic Character of the Hydrated ProtonOne might expect that two hydrated protons would repel each other because of their net positive chargesHowever, the interactions between hydrated protons are not so straightforwardAt 0.430.85 M concentrations, hydronium cations are found to form unusually stable contact ion pairs by positioning the hydronium oxygen lone pair sides toward one anotherThis 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 moleculesThe three H-atoms of the hydronium form strong H-bonds within the Eigen cation, thus imparting hydrophilic characterHowever, 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 bondJ. Xu, S. Izvekov, and G. A. Voth, J. Phys. Chem. B (2010)C. Knight and G. A. Voth, Acc. Chem. Res. (2012)

Hydrated Protons at the Water-Vacuum InterfaceConventional analysis of ion solvation near the dielectric boundary at the liquid-vapor interface holds that ions should be expelled from the interfaceThe 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 clustersHydronium cationDangling O-H bondThis 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 waterThese theoretical predictions were subsequently verified through agreement with experimental results

Hydronium cationDangling O-H bondM. K. Petersen, S. S. Iyengar, T. J. F. Day, and G. A. Voth, J. Phys. Chem. B, (2004)

Hydrophobic InteractionsThe aggregation and dispersion of hydrophobic particles in water is principally determined by the interplay between enthalpy and entropyAlthough the aggregation of hydrophobic particles is typically favored entropically, it is more complicated enthalpically since H-bonding rearrangements in the surrounding solvent must be consideredAs 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 concentrationThe present results taken together reveal that the enhanced solubility of hydrophobic species in acidic aqueous solutions largely originates from the existence of associated hydrophobe- hydrated proton structures. Although a hydronium cation has a similar radius to the salting-out cations K+ and NH4+, hydrophobic soluble in acidic solution than in salt solution of the same concentration

H. Chen, J. Xu, and G. A. Voth, J. Phys. Chem. B (2009) Hydrophobic particles (light) in salt solutionHydrophobic particles (light) in acidic solutionThis behavior can be explained by the existence of associated hydrophobe- hydrated proton structures, which form as a result of hydroniums unusual amphiphilic character

Hydrophobic particles (light) in salt solutionHydrophobic particles (light) in acidic solution

Applications

PS&T in biomolecular systems has presented the most challenging and arguably important application for the MS-RMD simulation methodology to dateComputer simulations have been applied to the following systemsCytochrome c oxidaseAquaporin channelsInfluenza A M2 proton channelCarbonic anhydrasePhospholipid membranesMutated aquaporins

AcknowledgementsThis research has been supported by the National Science Foundation