From Local Covalent Bonding to Extended Electric Field Interactions in Proton Hydration.

Seemingly simple yet surprisingly difficult to probe, excess protons in water constitute complex quantum objects with strong interactions with the extended and dynamically changing hydrogen-bonding network of the liquid. Proton hydration plays pivotal roles in energy transport in hydrogen fuel cells and signal transduction in transmembrane proteins. While geometries and stoichiometry have been widely addressed in both experiment and theory, the electronic structure of these specific hydrated proton complexes has remained elusive. Here we show, layer by layer, how utilizing novel flatjet technology for accurate x-ray spectroscopic measurements and combining infrared spectral analysis and calculations, we find orbital-specific markers that distinguish two main electronic-structure effects: Local orbital interactions determine covalent bonding between the proton and neigbouring water molecules, while orbital-energy shifts measure the strength of the extended electric field of the proton.

Electronic Structure Changes of an Aromatic Amine Photoacid along the Förster Cycle.

Photoacids show a strong increase in acidity in the first electronic excited state, enabling real-time studies of proton transfer in acid-base reactions, proton transport in energy storage devices and biomolecular sensor protein systems. Several explanations have been proposed for what determines photoacidity, ranging from variations in solvation free energy to changes in electronic structure occurring along the four stages of the Förster cycle. Here we use picosecond nitrogen K-edge spectroscopy to monitor the electronic structure changes of the proton donating group in a protonated aromatic amine photoacid in solution upon photoexcitation and subsequent proton transfer dynamics. Probing core-to-valence transitions locally at the amine functional group and with orbital specificity, we clearly reveal pronounced electronic structure, dipole moment and energetic changes on the conjugate photobase side. This result paves the way for a detailed electronic structural characterization of the photoacidity phenomenon.

Electron Flow Characterization of Charge Transfer for Carbonic Acid to Strong Base Proton Transfer in Aqueous Solution.

Protonation of the strong base methylamine CH3NH2 by carbonic acid H2CO3 in aqueous solution, HOCOOH···NH2CH3 → HOCOO-···+HNH2CH3, has been previously studied ( J. Phys. Chem. B 2016, 109, 2271-2280; J. Phys. Chem. B 2016, 109, 2281-2290) via Car-Parinnello molecular dynamics. This proton transfer (PT) reaction within a hydrogen (H)-bonded complex was found to be barrierless and very rapid, with key reaction coordinates comprising the proton coordinate, the H-bond separation RON, and a solvent coordinate, reflecting the water solvent rearrangement involved in the neutral to ion pair conversion. In the present work, the reaction's charge flow aspects are analyzed in detail, especially a description via Mulliken charge transfer for PT (MCTPT). A natural bond orbital analysis and some extensions of them are employed for the complex's electronic structure during the reaction trajectories. Results demonstrate that consistent with the MCTPT picture, the charge transfer (CT) occurs from a methylamine base nonbonding orbital to a carbonic acid antibonding orbital. A complementary MCTPT reaction product perspective of CT from the antibonding orbital of the HN+ moiety to the nonbonding orbital of the oxygen in the H-bond complex is also presented. σOH and σHN+ bond order expressions show this CT to occur within the H-bond OHN triad, an aspect key for simultaneous bond-breaking and -forming in the PT reaction.

Infrared and NMR Spectroscopic Fingerprints of the Asymmetric H7 + O3 Complex in Solution.

The front cover artwork is provided by the groups of Prof. Ehud Pines (BGU, Israel) and Dr. Benjamin Fingerhut (MBI, Berlin). The image shows a scientist integrating experiments with theory for resolving the structural diffusion of the aqueous proton in acetonitrile providing a novel view on the Grotthuss mechanism. Read the full text of the Article at 10.1002/cphc.202001046.

Infrared and NMR Spectroscopic Fingerprints of the Asymmetric H7+ O3 Complex in Solution.

Infrared (IR) absorption in the 1000-3700 cm-1 range and 1 H NMR spectroscopy reveal the existence of an asymmetric protonated water trimer, H7+ O3, in acetonitrile. The core H7+ O3 motif persists in larger protonated water clusters in acetonitrile up to at least 8 water molecules. Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations reveal irreversible proton transport promoted by propagating the asymmetric H7+ O3 structure in solution. The QM/MM calculations allow for the successful simulation of the measured IR absorption spectra of H7+ O3 in the OH stretch region, which reaffirms the assignment of the H7+ O3 spectra to a hybrid-complex structure: a protonated water dimer strongly hydrogen-bonded to a third water molecule with the proton exchanging between the two possible shared-proton Zundel-like centers. The H7+ O3 structure lends itself to promoting irreversible proton transport in presence of even one additional water molecule. We demonstrate how continuously evolving H7+ O3 structures may support proton transport within larger water solvates.

Reversible intermolecular-coupled-intramolecular (RICI) proton transfer occurring on the reaction-radius a of 2-naphthol-6,8-disulfonate photoacid.

Steady-state and time-resolved fluorescence techniques were employed to study the excited-state proton transfer (ESPT) from a reversibly dissociating photoacid, 2-naphthol-6,8-disulfonate (2N68DS). The reaction was carried out in water and in acetonitrile-water solutions. We find by carefully analyzing the geminate recombination dynamics of the photobase-proton pair that follows the ESPT reaction that there are two targets for the proton back-recombination reaction: the original O- dissociation site and the SO3 - side group at the 8 position which is closest to the proton OH dissociation site. This observation is corroborated in acetonitrile-water mixtures of χwater < 0.14, where a slow intramolecular ESPT occurs on a time scale of about 1 ns between the OH group and the SO3 - group via H-bonding water. The proton-transferred R*O- fluorescence band in mixtures of χwater < 0.14 where only intramolecular ESPT occurs is red shifted by about 2000 cm-1 from the free R*O- band in neat water. As the water content in the mixture increases above χwater = 0.14, the R*O- fluorescence band shifts noticeably to the blue region. For χwater > 0.23 the band resembles the free anion band observed in pure water. Concomitantly, the ESPT rate increases when χwater increases because the intermolecular ESPT to the solvent (bulk water) gradually prevails over the much slower intramolecular via the water-bridges ESPT process.

Intact carbonic acid is a viable protonating agent for biological bases.

Carbonic acid H2CO3 (CA) is a key constituent of the universal CA/bicarbonate/CO2 buffer maintaining the pH of both blood and the oceans. Here we demonstrate the ability of intact CA to quantitatively protonate bases with biologically-relevant pKas and argue that CA has a previously unappreciated function as a major source of protons in blood plasma. We determine with high precision the temperature dependence of pKa(CA), pKa(T) = -373.604 + 16,500/T + 56.478 ln T. At physiological-like conditions pKa(CA) = 3.45 (I = 0.15 M, 37 °C), making CA stronger than lactic acid. We further demonstrate experimentally that CA decomposition to H2O and CO2 does not impair its ability to act as an ordinary carboxylic acid and to efficiently protonate physiological-like bases. The consequences of this conclusion are far reaching for human physiology and marine biology. While CA is somewhat less reactive than (H+)aq, it is more than 1 order of magnitude more abundant than (H+)aq in the blood plasma and in the oceans. In particular, CA is about 70× more abundant than (H+)aq in the blood plasma, where we argue that its overall protonation efficiency is 10 to 20× greater than that of (H+)aq, often considered to be the major protonating agent there. CA should thus function as a major source for fast in vivo acid-base reactivity in the blood plasma, possibly penetrating intact into membranes and significantly helping to compensate for (H+)aq's kinetic deficiency in sustaining the large proton fluxes that are vital for metabolic processes and rapid enzymatic reactions.

Hydrated Excess Protons in Acetonitrile/Water Mixtures: Solvation Species and Ultrafast Proton Motions.

The solvation structure of protons in aqueous media is highly relevant to electric properties and to proton transport in liquids and membranes. At ambient temperature, polar liquids display structural fluctuations on femto- to picosecond time scales with a direct impact on proton solvation. We use two-dimensional infrared (2D-IR) spectroscopy to follow proton dynamics in acetonitrile/water mixtures with the Zundel cation H5O2+ prepared in neat acetonitrile as a benchmark. The 2D-IR spectra of the proton transfer mode of H5O2+ demonstrate stochastic large-amplitude motions in the double-minimum proton potential, driven by fluctuating electric fields. In all cases, the excess proton is embedded in a water dimer, forming an H5O2+ complex as the major solvation species. This observation is rationalized by quantum mechanics/molecular mechanics molecular dynamics simulations including up to four water molecules embedded in acetonitrile. The Zundel motif interacts with its closest water neighbor in an H7O3+ unit without persistent proton localization.

Ultrafast Dynamics of a "Super" Photobase.

Molecular reactivity can change dramatically with the absorption of a photon due to the difference of the electronic configurations between the excited and ground states. Here we report on the discovery of a modular system (Schiff base formed from an aldehyde and an amine) that upon photoexcitation yields a more basic imine capable of intermolecular proton transfer from protic solvents. Ultrafast dynamics of the excited state conjugated Schiff base reveals the pathway for proton transfer, culminating in a 14-unit increase in pKa to give the excited state pKa * >20 in ethanol.

Large-amplitude transfer motion of hydrated excess protons mapped by ultrafast 2D IR spectroscopy.

Solvation and transport of excess protons in aqueous systems play a fundamental role in acid-base chemistry and biochemical processes. We mapped ultrafast proton excursions along the proton transfer coordinate by means of two-dimensional infrared spectroscopy, both in bulk water and in a Zundel cation (H5O2)+ motif selectively prepared in acetonitrile. Electric fields from the environment and stochastic hydrogen bond motions induce fluctuations of the proton double-minimum potential. Within the lifetime of a particular hydration geometry, the proton explores a multitude of positions on a sub-100-femtosecond time scale. The proton transfer vibration is strongly damped by its 20- to 40-femtosecond population decay. Our results suggest a central role of Zundel-like geometries in aqueous proton solvation and transport.

Reversible Excited-State Proton Geminate Recombination: Revisited.

About three decades ago, Pines and Huppert found that the excited-state proton transfer to water from a photoacid (8-hydroxy-1,3,6-pyrene trisulfonate (HPTS)) is followed by an efficient diffusion-assisted reversible geminate-recombination of the proton. To model the reaction, Pines, Huppert, and Agmon used the Debye-Smoluchowski equation with boundary conditions appropriate for reversible contact reaction kinetics. This reaction model has been used successfully to quantitatively fit the experimental data of the time-resolved fluorescence of HPTS and several commonly used photoacids. A consequence of the reversibility of this reaction is an apparent long-time tail of the photoacid fluorescence signal, obeying (after lifetime correction) a t-3/2 power law asymptotics. Recently, Lawler and Fayer reported that in bulk water the observed power-law decay of the long-time fluorescence tail of HPTS is -1.1 rather than -1.5, as expected from the spherically symmetric diffusion model. In the current study, we reaffirm our previous reports of the power-law behavior of HPTS fluorescence. We also demonstrate that molecular-level complications such as the deviation from spherical symmetry, rotational dynamics, competitive proton binding to the sulfonate moieties of HPTS, distance-dependent diffusion coefficient, and the initial starting point of the proton can affect the observed kinetics only at intermediate times, but not at asymptotically long times. Theoretically, we analyze the rebinding kinetics in terms of the number of extrema of the logarithmic derivative, showing subtle effects on the direction of approach to the asymptotic line (whether from above or below), which also appears to be corroborated experimentally.

The Hydrated Excess Proton in the Zundel Cation H5 O2 (+) : The Role of Ultrafast Solvent Fluctuations.

The nature of the excess proton in liquid water has remained elusive after decades of extensive research. In view of ultrafast structural fluctuations of bulk water scrambling the structural motifs of excess protons in water, we selectively probe prototypical protonated water solvates in acetonitrile on the femtosecond time scale. Focusing on the Zundel cation H5 O2 (+) prepared in room-temperature acetonitrile, we unravel the distinct character of its vibrational absorption continuum and separate it from OH stretching and bending excitations in transient pump-probe spectra. The infrared absorption continuum originates from a strong ultrafast frequency modulation of the H(+) transfer vibration and its combination and overtones. Vibrational lifetimes of H5 O2 (+) are found to be in the sub-100 fs range, much shorter than those of unprotonated water. Theoretical results support a picture of proton hydration where fluctuating electrical interactions with the solvent and stochastic thermal excitations of low-frequency modes continuously modify the proton binding site while affecting its motions.

How Acidic Is Carbonic Acid?

Carbonic, lactic, and pyruvic acids have been generated in aqueous solution by the transient protonation of their corresponding conjugate bases by a tailor-made photoacid, the 6-hydroxy-1-sulfonate pyrene sodium salt molecule. A particular goal is to establish the pK(a) of carbonic acid H2CO3. The on-contact proton transfer (PT) reaction rate from the optically excited photoacid to the carboxylic bases was derived, with unprecedented precision, from time-correlated single-photon-counting measurements of the fluorescence lifetime of the photoacid in the presence of the proton acceptors. The time-dependent diffusion-assisted PT rate was analyzed using the Szabo-Collins-Kimball equation with a radiation boundary condition. The on-contact PT rates were found to follow the acidity order of the carboxylic acids: the stronger was the acid, the slower was the PT reaction to its conjugate base. The pK(a) of carbonic acid was found to be 3.49 ± 0.05 using both the Marcus and Kiefer-Hynes free energy correlations. This establishes H2CO3 as being 0.37 pK(a) units stronger and about 1 pK(a) unit weaker, respectively, than the physiologically important lactic and pyruvic acids. The considerable acid strength of intact carbonic acid indicates that it is an important protonation agent under physiological conditions.

Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution I: Acid and Base Coordinate and Charge Dynamics.

Protonation by carbonic acid H2CO3 of the strong base methylamine CH3NH2 in a neutral contact pair in aqueous solution is followed via Car-Parrinello molecular dynamics simulations. Proton transfer (PT) occurs to form an aqueous solvent-stabilized contact ion pair within 100 fs, a fast time scale associated with the compression of the acid-base hydrogen-bond (H-bond), a key reaction coordinate. This rapid barrierless PT is consistent with the carbonic acid-protonated base pKa difference that considerably favors the PT, and supports the view of intact carbonic acid as potentially important proton donor in assorted biological and environmental contexts. The charge redistribution within the H-bonded complex during PT supports a Mulliken picture of charge transfer from the nitrogen base to carbonic acid without altering the transferring hydrogen's charge from approximately midway between that of a hydrogen atom and that of a proton.

Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution II: Solvent Coordinate-Dependent Reaction Path.

The protonation of methylamine base CH3NH2 by carbonic acid H2CO3 within a hydrogen (H)-bonded complex in aqueous solution was studied via Car-Parrinello dynamics in the preceding paper (Daschakraborty, S.; Kiefer, P. M.; Miller, Y.; Motro, Y.; Pines, D.; Pines, E.; Hynes, J. T. J. Phys. Chem. B 2016, DOI: 10.1021/acs.jpcb.5b12742). Here some important further details of the reaction path are presented, with specific emphasis on the water solvent's role. The overall reaction is barrierless and very rapid, on an ∼100 fs time scale, with the proton transfer (PT) event itself being very sudden (<10 fs). This transfer is preceded by the acid-base H-bond's compression, while the water solvent changes little until the actual PT occurrence; this results from the very strong driving force for the reaction, as indicated by the very favorable acid-protonated base ΔpKa difference. Further solvent rearrangement follows immediately the sudden PT's production of an incipient contact ion pair, stabilizing it by establishment of equilibrium solvation. The solvent water's short time scale ∼120 fs response to the incipient ion pair formation is primarily associated with librational modes and H-bond compression of water molecules around the carboxylate anion and the protonated base. This is consistent with this stabilization involving significant increase in H-bonding of hydration shell waters to the negatively charged carboxylate group oxygens' (especially the former H2CO3 donor oxygen) and the nitrogen of the positively charged protonated base's NH3(+).

Controlling reactivity by remote protonation of a basic side group in a bifunctional photoacid.

6-Hydroxy-2-naphthoic acid and its sulfonate derivatives belong to a family of bifunctional photoacids where the -OH group acts as a proton donor and the -COO(-) group acts as a proton acceptor. Upon electronic excitation, the -OH group becomes more acidic and the -COO(-) group turns more basic. Change in the ionization state of one functional group causes a change (switch) in the reactivity of the other functional group. Using picosecond time-resolved and steady state spectroscopy, we find clear evidence for an ultrafast reactivity switch caused by a diffusional proton transfer through the water solvent between the two functional groups with no evidence of a concerted proton transfer.

Effect of Solvent Dielectric Constant and Acidity on the OH Vibration Frequency in Hydrogen-Bonded Complexes of Fluorinated Ethanols.

Infrared spectroscopy measurements were used to characterize the OH stretching vibrations in a series of similarly structured fluoroethanols, RCH2OH (R = CH3, CH2F, CHF2, CF3), a series which exhibits a systematic increase in the molecule acidity with increasing number of F atoms. This study, which expands our earlier efforts, was carried out in non-hydrogen-bonding solvents comprising molecules with and without a permanent dipole moment, with the former solvents being classified as polar solvents and the latter designated as nonpolar. The hydrogen bond interaction in donor-acceptor complexes formed in solution between the fluorinated ethanol H-donors and the H-acceptor base DMSO was investigated in relation to the solvent dielectric and to the differences ΔPA of the gas phase proton affinities (PAs) of the conjugate base of the fluorinated alcohols and DMSO. We have observed that νOH decreases as the acidity of the alcohol increases (ΔPA decreases) and that νOH varies inversely with ε, exhibiting different slopes for nonpolar and polar solvents. These 1/ε slopes tend to vary linearly with ΔPA, increasing with increasing acidity. These experimental findings, including the ΔPA trends, are described with our recently published two-state Valence Bond-based theory for acid-base H-bonded complexes. Lastly, the correlation of the alcohol's conjugate base PAs with Taft σ* values of the fluorinated ethyl groups CH(n)F(3-n)CH2- provides a connection of the inductive effects for these groups with the acidity parameter ΔPA associated with the H-bonded complexes.

Solvent-induced O-H vibration red-shifts of oxygen-acids in hydrogen-bonded O-H···base complexes.

Infrared spectroscopy has been used to characterize the solvent effect on the OH stretching vibrations νOH of phenol, 1-naphthol, 2-naphthol, 1-hydroxypyrene, and ethanol. We distinguish the dielectric (nonspecific) effect of the solvent on ΔνOH, the observed red-shifts in νOH, from the much larger red-shift caused by direct hydrogen (H)-bonding interactions with the solvents. To isolate the solvent dielectric constant ε effect on νOH, the OH oscillator was also studied when it is already H-bonded with an invariant oxygen base, dimethyl sulfoxide. We find that ΔνOH depends importantly on ΔPA, the difference between the proton affinities of the conjugate base of the proton donor and the proton acceptor. For a given H-bonded complex, νOH tends to vary inversely with ε, exhibiting different slopes for polar and nonpolar solvents, i.e., solvents comprising molecules with and without a permanent dipole moment, respectively. We use a two-state valence-bond-based theory to analyze our experimental data. This demonstrates that the OH oscillator acquires a more ionic-like character in the vibrational excited state, i.e., charge transfer; this results in a stronger H-bond in a more anharmonic potential for the OH vibration. The theory distinguishes between nonpolar and polar solvents and successfully accounts for the observed 1/ε and ΔPA variations.

Bifunctional photoacids: remote protonation affecting chemical reactivity.

Reversible protonation (deprotonation) of a side-group is a useful and convenient way to affect the reactivity of large organic and biological molecules. We use bifunctional photoacids to demonstrate how the protonation state of a basic side-group (COO(-)) controls the reactivity of the main acidic group of the photoacid (OH), both in the ground and the electronic excited state of 6-carboxy derivatives of 2-naphthol.

Solvent-induced red-shifts for the proton stretch vibrational frequency in a hydrogen-bonded complex. 1. A valence bond-based theoretical approach.

A theory is presented for the proton stretch vibrational frequency νAH for hydrogen (H-) bonded complexes of the acid dissociation type, that is, AH···B ⇔ A(-)···HB(+)(but without complete proton transfer), in both polar and nonpolar solvents, with special attention given to the variation of νAH with the solvent's dielectric constant ε. The theory involves a valence bond (VB) model for the complex's electronic structure, quantization of the complex's proton and H-bond motions, and a solvent coordinate accounting for nonequilibrium solvation. A general prediction is that νAH decreases with increasing ε largely due to increased solvent stabilization of the ionic VB structure A(-)···HB(+) relative to the neutral VB structure AH···B. Theoretical νAH versus 1/ε slope expressions are derived; these differ for polar and nonpolar solvents and allow analysis of the solvent dependence of νAH. The theory predicts that both polar and nonpolar slopes are determined by (i) a structure factor reflecting the complex's size/geometry, (ii) the complex's dipole moment in the ground vibrational state, and (iii) the dipole moment change in the transition, which especially reflects charge transfer and the solution phase proton potential shapes. The experimental proton frequency solvent dependence for several OH···O H-bonded complexes is successfully accounted for and analyzed with the theory.