Influence of Ions on Aqueous Acid–Base Reactions

We study the effects of bromide salts on the rate and mechanism of the aqueous proton/deuteron‐transfer reaction between the photoacid 8‐hydroxy‐1,3,6‐pyrenetrisulfonic acid (HPTS) and the base acetate. The proton/deuteron release is triggered by exciting HPTS with 400 nm femtosecond laser pulses. Probing the electronic and vibrational resonances of the photoacid, the conjugate photobase, the hydrated proton/deuteron and the accepting base with femtosecond visible and mid‐infrared pulses monitors the proton transfer. Two reaction channels are identified: 1) direct long‐range proton transfer over hydrogen‐bonded water bridges that connect the acid and base and 2) acid dissociation to produce fully solvated protons followed by proton scavenging from solution by acetate. We observe that the addition of salt affects the long‐range reaction pathway, and reduces both the rate at which protons are released to solution by HPTS and the rate at which solvated protons are scavenged from solution by acetate. We study the dependence of these effects on the nature and concentration of the dissolved salt.     

Long-range proton transfer in aqueous Acid-base reactions

We study the mechanism of proton transfer (PT) in the aqueous acid-base reaction between the photoacid 8-hydroxy-1,3,6-pyrenetrisulfonic acid (HPTS) and acetate by probing the vibrational resonances of HPTS, acetate, and the hydrated proton with femtosecond mid-infrared laser pulses. We find that PT takes place in a distribution of hydrogen-bound reaction complexes that differ in the number of water molecules separating the acid and the base. The number of intervening water molecules ranges from 0 to 5, which, together with a strongly distance-dependent PT rate, explains the observed highly nonexponential reaction kinetics. The kinetic isotope effect for the reaction is determined to be 1.5, indicating that tunneling does not play a significant role in the transfer of the proton. Rather, the transfer mechanism is best described in terms of the adiabatic PT picture as it has been formulated by Hynes and co-workers [Staib, A.; Borgis, D.; Hynes, J. T. J. Chem. Phys. 1995, 102, 2487. Ando, K.; Hynes, J. T. J. Phys. Chem. B 1997, 101, 10464.], where solvent fluctuations play an essential role in forming the correct hydrogen-bond configuration and solvent polarization to facilitate PT.     

On the role of water in intermolecular proton-transfer reactions

We study the mechanism of proton transfer (PT) between the photoacid (8-hydroxy-1,3,6-pyrenetrisulfonic acid (HPTS)) and the base acetate in aqueous solution using femtosecond vibrational spectroscopy. By probing the vibrational resonances of the photoacid, the accepting base, and the hydrated proton we find that intermolecular PT in this model system involves the transfer of the proton across several water molecules linking the donor-acceptor pair by hydrogen bonds (H-bonds). We find that at high base concentration the rate of PT is not determined by the mutual diffusion of acid and base but rather by the rate of Grotthuss-like conduction of the proton between molecules. This long-range PT requires an activated solvent configuration to facilitate the charge transfer.     

Bimodal proton transfer in acid-base reactions in water

We investigate one of the fundamental reactions in solutions, the neutralization of an acid by a base. We use a photoacid, 8-hydroxy-1,3,6-trisulfonate-pyrene (HPTS; pyranine), which upon photoexcitation reacts with acetate under transfer of a deuteron (solvent: deuterated water). We analyze in detail the resulting bimodal reaction dynamics between the photoacid and the base, the first report on which was recently published. We have ascribed the bimodal proton-transfer dynamics to contributions from preformed hydrogen bonding complexes and from initially uncomplexed acid and base. We report on the observation of an additional (6 ps)(-1) contribution to the reaction rate constant. As before, we analyze the slower part of the reaction within the framework of the diffusion model and the fastest part by a static, sub-150 fs reaction rate. Adding the second static term considerably improves the overall modeling of the experimental results. It also allows to connect experimentally the diffusion controlled bimolecular reaction models as defined by Eigen-Weller and by Collins-Kimball. Our findings are in agreement with a three-stage mechanism for liquid phase intermolecular proton transfer: mutual diffusion of acid and base to form a "loose" encounter complex, followed by reorganization of the solvent shells and by "tightening" of the acid-base encounter complex. These rearrangements last a few picoseconds and enable a prompt proton transfer along the reaction coordinate, which occurs faster than our time resolution of 150 fs. Alternative models for the explanation of the slower "on-contact" reaction time of the loose encounter complex in terms of proton transmission through a von Grotthuss mechanism are also discussed.     

Understanding the Role of Water in Aqueous Ruthenium‐Catalyzed Transfer Hydrogenation of Ketones.

We report an accurate computational study of the role of water in transfer hydrogenation of formaldehyde with a ruthenium‐based catalyst using a water‐specific model. Our results suggest that the reaction mechanism in aqueous solution is significantly different from that in the gas phase or in methanol solution. Previous theoretical studies have shown a concerted hydride and proton transfer in the gas phase (M. Yamakawa, H. Ito, R. Noyori, J. Am. Chem. Soc. 2000 , 122, 1466–1478;J.‐W. Handgraaf, J. N. H. Reek, E. J. Meijer, Organometallics 2003 , 22, 3150–3157; D. A. Alonso, P. Brandt, S. J. M. Nordin, P. G. Andersson, J. Am. Chem. Soc. 1999 , 121, 9580–9588; D. G. I. Petra, J. N. H. Reek, J.‐W. Handgraaf, E. J. Meijer, P. Dierkes, P. C. J. Kamer, J. Brussee, H. E. Schoemaker, P. W. N. M. van Leeuwen, Chem. Eur. J. 2000 , 6, 2818–2829), whereas a delayed, solvent‐mediated proton transfer has been observed in methanol solution (J.‐W. Handgraaf, E. J. Meijer, J. Am. Chem. Soc. 2007 , 129, 3099–3103). In aqueous solution, a concerted transition state is observed, as in the previous studies. However, only the hydride is transferred at that point, whereas the proton is transferred later by a water molecule instead of the catalyst.     

Solvent-dependent photoacidity state of pyranine monitored by transient mid-infrared spectroscopy.

We investigate with femtosecond mid-infrared spectroscopy the vibrational-mode characteristics of the electronic states involved in the excited-state dynamics of pyranine (HPTS) that ultimately lead to efficient proton (deuteron) transfer in H2O (D2O). We also study the methoxy derivative of pyranine (MPTS), which is similar in electronic structure but does not have the photoacidity property. We compare the observed vibrational band patterns of MPTS and HPTS after electronic excitation in the solvents: deuterated dimethylsulfoxide, deuterated methanol and H2O/D2O, from which we conclude that for MPTS and HPTS photoacids the first excited singlet state appears to have charge-transfer (CT) properties in water within our time resolution (150 fs), whereas in aprotic dimethylsulfoxide the photoacid appears to be in a non-polar electronic excited state, and in methanol (less polar and less acidic than water) the behaviour is intermediate between these two extremes. For the fingerprint vibrations we do not observe dynamics on a time scale of a few picoseconds, and with our results obtained on the O-H stretching vibration we argue that the dynamic behaviour observed in previous UV/Vis pump-probe studies is likely to be related to solvation dynamics.     

Proton-coupled electron transfer from tryptophan: a concerted mechanism with water as proton acceptor

The mechanism of proton-coupled electron transfer (PCET) from tyrosine in enzymes and synthetic model complexes is under intense discussion, in particular the pH dependence of the PCET rate with water as proton acceptor. Here we report on the intramolecular oxidation kinetics of tryptophan derivatives linked to [Ru(bpy)(3)](2+) units with water as proton acceptor, using laser flash-quench methods. It is shown that tryptophan oxidation can proceed not only via a stepwise electron-proton transfer (ETPT) mechanism that naturally shows a pH-independent rate, but also via another mechanism with a pH-dependent rate and higher kinetic isotope effect that is assigned to concerted electron-proton transfer (CEP). This is in contrast to current theoretical models, which predict that CEP from tryptophan with water as proton acceptor can never compete with ETPT because of the energetically unfavorable PT part (pK(a)(Trp(?)H(+)) = 4.7 ? pK(a)(H(3)O(+)) ≈ -1.5). The moderate pH dependence we observe for CEP cannot be explained by first-order reactions with OH(-) or the buffers and is similar to what has been demonstrated for intramolecular PCET in [Ru(bpy)(3)](3+)-tyrosine complexes (Sjo?din, M.; et al. J. Am. Chem. Soc.2000, 122, 3932. Irebo, T.; et al. J. Am. Chem. Soc.2007, 129, 15462). Our results suggest that CEP with water as the proton acceptor proves a general feature of amino acid oxidation, and provide further experimental support for understanding of the PCET process in detail.     

Testing the three step excited state proton transfer model by the effect of an excess proton

In a previous work, we proposed an extended model for intermolecular excited-state proton transfer to the solvent. The model invoked an intermediate species, the contact ion-pair RO(-)...H(3)O(+), where a proton is strongly hydrogen bonded to the conjugated photabase RO(-). In this study we tested the extended model by measuring the transient absorption and emission of 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) in an aqueous solution in the presence of a large concentration of mineral acids. In a neutral pH solution, the pump-probe signal consists of three time components, <1, 4, and 100 ps. The 4 ps time component, with a relative amplitude of about 0.3, was attributed to the formation of the contact ion-pair and the long 100 ps component to the dissociation of the ion-pair to a free proton and RO(-). In the presence of acid, the recombination of an excess proton competes with the geminate recombination. At a high acid concentration, the recombination process alters the time-dependent concentrations of the reactant, product and intermediate contact ion-pair. We observed that when the acid concentration increases, the amplitude of both the long and intermediate time components decreases. At about 3 M of acid, both components almost disappear. Model calculations of the acid effect on the transient HPTS signal indeed showed that the amplitude of the intermediate time component decreases as the excess proton concentration increases.     

Excited-state proton transfer from pyranine to acetate in gamma-cyclodextrin and hydroxypropyl gamma-cyclodextrin

Excited-state proton transfer (ESPT) from pyranine (8-hydroxypyrene-1,3,6-trisulfonate, HPTS) to acetate has been studied by picosecond and femtosecond emission spectroscopy in gamma-cyclodextrin (gamma-CD) and 2-hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) cavities. In both the CDs, ESPT from HPTS to acetate is found to be very much slower (90 and 200 ps) than that in bulk water (0.15 and 6 ps). From molecular modeling, it is shown that in the cyclodextrin cavity the acetate is separated from the OH group of HPTS by water bridges. As a result, proton transfer in the cavity requires rearrangement of the hydrogen-bond network involving the cyclodextrin. This is responsible for the marked slowdown of ESPT. ESPT of HPTS in substituted gamma-CD is found to be slower than that in the unsubstituted one. This is attributed to the hydroxypropyl groups, which prevent close approach of acetate to HPTS.     

Effect of electrolytes on the excited-state proton transfer and geminate recombination

Time-resolved emission and steady-state fluorescence techniques are used to study the excited-state intermolecular proton transfer from 8-hydroxypyrene-1,3,6-trisulfonate (HPTS or pyranine) to water in the presence of inert salts, NaCl and MgCl(2). At low salt concentrations, up to about 0.5 M MgCl(2) or about 0.8 M NaCl, the time-resolved emission of both the photoacid and conjugate base can be quantitatively fitted by our diffusion-assisted geminate recombination model. In this concentration range, the proton transfer and geminate recombination rate constants are almost independent of the salt concentrations whereas the proton diffusion constant decreases as the salt concentration increases. At higher salt concentrations, the proton-transfer rate constant decreases while the recombination rate constant increases slightly. For the saturated solution of MgCl(2) (about 5 M at room temperature), the steady-state emission consists of only a single band of the protonated photoacid. Careful examination of the time-resolved emission of HPTS in the presence of a large concentration of MgCl(2) shows that the quality of the fit to the geminate recombination model is rather poor and we fail to find adjustable parameters for a good quality fitting. For this large concentration range of MgCl(2) we were able to get a good fit of the experimental data with a model based on a distribution of proton-transfer rates. The model is consistent with an inhomogeneous water environment next to the excited HPTS molecule in such concentrated solutions.     

Correlating proton transfer dynamics to probe location in confined environments

The dramatic impact of differing environments on proton transfer dynamics of the photoacid HPTS prompted us to investigate these systems with two highly complementary methods: ultrafast time-resolved transient absorption and two-dimensional NMR spectroscopies. Both ultrafast time-resolved transient absorption spectroscopy and time-resolved anisotropy decays demonstrate the proton transfer dynamics depend intimately on the specific reverse micellar system. For w(0) = 10 reverse micelles formed with anionic AOT surfactant, the HPTS proton transfer dynamics are similar to dynamics in bulk aqueous solution, and the corresponding (1)H 2D NOESY NMR spectra display no cross peaks between HPTS and AOT consistent with the HPTS residing well hydrated by water in the interior of the reverse micelle water pool. In contrast, ultrafast transient absorption experiments show no evidence for HPTS photoinduced proton transfer reaction in reverse micelles formed with the cationic CTAB surfactant. In CTAB reverse micelles, clear cross peaks between HPTS and CTAB in the 2D NMR spectra show that HPTS embeds in the interface. These results indicate that the environment strongly impacts the proton transfer reaction and that complementary experimental techniques develop understanding of how location critically affects molecular responses.     

Periodicity in proton conduction along a H‐bonded chain. Application to biomolecules

Molecular complexes are constructed to simulate proton transfer channels of the influenza A virus and of the active site of carbonic anhydrase. These complexes consist of proton donor and acceptor groups connected by a chain of water molecules. Quantum chemical calculations on the methylimidazole(H⁺)? H₂O? CH₃COO^? model of the M2 virus channel indicate free translational motion of the water molecule between donor and acceptor, as well as concerted transfer of both H‐bond protons. The proton transfer barrier does not depend on the position of the bridged water molecule and varies linearly with the difference of electrostatic potentials between the donor and acceptor. When the water chain is elongated, and with various donor and acceptor models, periodicity appears in the H‐bond lengths and the progression of proton transfer in each link. This “wave” is shown to propagate along the chain, as it is driven by the displacement of a single proton. One can thereby estimate the velocity of the proton wave and proton conduction time. Computations are performed to examine the influence of immersing the system within a polarizable medium. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008     

Excited-state proton transfer: indication of three steps in the dissociation and recombination process

A femtosecond pump-probe, with approximately 150 fs resolution, as well as time-correlated single photon counting with approximately 10 ps resolution techniques are used to probe the excited-state intermolecular proton transfer from HPTS to water. The pump-probe signal consists of two ultrafast components (approximately 0.8 and 3 ps) that precede the relatively slow (approximately 100 ps) component. From a comparative study of the excited acid properties in water and methanol and of its conjugate base in basic solution of water, we propose a modified mechanism for the ESPT consisting of two reactive steps followed by a diffusive step. In the first, fast, step the photoacid dissociates at about 10 ps to form a contact ion pair RO-*...H3O+. The contact ion pair recombines efficiently to re-form the photoacid with a recombination rate constant twice as large as the dissociation rate constant. The first-step equilibrium constant value is about 0.5 and thus, at short times, <10 ps, only approximately 30% of the excited photoacid molecules are in the form of the conjugated base-proton contact ion pair. In the second, slower, step, of about 100 ps, the proton is separated by at least one water molecule from the conjugate base RO-. The separated proton and the conjugated base can recombine geminately as described by our previous diffusion-assisted model. The new two-step reactive model predicts that the population of the ROH form of HPTS will decrease with two time constants and the RO- population will increase by the same time constants. The proposed model fits the experimental data of this study as well as previous published experimental data.     

Dynamics of proton transfer in bacteriorhodopsin

Proton transfer in bacteriorhodopsin from the cytoplasm to the extracellular side is initiated from protonated asp96 in the cytoplasmic region toward the deprotonated Schiff base. This occurs in the transition from the photocycle late M state to the N state. To investigate this proton-transfer process, a quantum mechanics/molecular mechanics (QM/MM) model is constructed from the bacteriorhodopsin E204Q mutant crystal structure. Three residues, asp96, asp85, and thr89, as well as most of the retinal chromophore and the Schiff base link of lys216 are treated quantum mechanically and connected to the remaining classical protein through linker atom hydrogens. Structural transformation in the M state results in the formation of a water channel between the Schiff base and asp96. Since a part of this channel is lined with hydrophobic residues, there has been a question on the mechanism of proton transfer in a hydrophobic channel. Ab initio dynamics using the CHARMM/GAMESS methodology is used to simulate the transfer of the proton through a partially hydrophobic channel. Once sufficient water molecules are added to the channel to allow the formation of a single chain of waters from asp96 to the Schiff base, the transfer occurs as a fast (less than a picosecond) concerted event irrespective of the protonation state of asp85. Dynamic transfer of the proton from asp96 to the nearest water initiates the organization of a strongly bonded water chain conducive to the transfer of the proton to the Schiff base nitrogen.     

Excited-state intermolecular proton transfer of firefly luciferin V. Direct proton transfer to fluoride and other mild bases

We studied the direct proton transfer (PT) from electronically excited D-luciferin to several mild bases. The fluorescence up-conversion technique is used to measure the rise and decay of the fluorescence signals of the protonated and deprotonated species of D-luciferin. From a base concentration of 0.25 M or higher the proton transfer rates to the fluoride, dihdyrogen phosphate or acetate bases are fast and comparable. The fluorescence signals are nonexponential and complex. We suggest that the fastest decay component arises from a direct proton transfer process from the hydroxyl group of D-luciferin to the mild base. The proton donor and acceptor molecules form an ion pair prior to photoexcitation. Upon photoexcitation solvent rearrangement occurs on a 1 ps time-scale. The PT reaction time constant is ～2 ps for all three bases. A second decay component of about 10 ps is attributed to the proton transfer in a contact pair bridged by one water molecule. The longest decay component is due to both the excited-state proton transfer (ESPT) to the solvent and the diffusion-assisted PT process between a photoacid and a base pair positioned remotely from each other prior to photoexcitation.     

Charge redistribution and photoacidity: neutral versus cationic photoacids

A series of pyrene photoacids is used to investigate excited-state proton transfer with time-dependent pump-probe spectroscopy. The deprotonation dynamics of a cationic photoacid, 8-aminopyrene-1,3,6-trisulfonic acid trisodium salt (APTS), shows single exponential dynamics( approximately 30 ps) in water. This is in contrast to what is observed for the neutral photoacids 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) and 8-hydroxy-N,N,N',N',N",N"-hexamethylpyrene-1,3,6-trisulfonamide, which display biexponential dynamics. For the cationic photoacid, the vast majority of the intramolecular charge redistribution does not occur in the protonated state. Instead, the charge redistribution, which is responsible for the photoacidity and the observed spectroscopic changes, occurs primarily following the excited-state proton transfer. The lack of charge redistribution prior to proton transfer causes APTS to display single exponential kinetics. In contrast, the dynamics for the neutral photoacids are multiexponential because major charge redistribution precedes proton transfer followed by additional charge redistribution that accompanies proton transfer. Previous studies of HPTS in water are discussed in terms of the results presented here.     

Effects of the anion salt nature on the rate constants of the aqueous proton exchange reactions

The proton-transfer ground-state rate constants of the xanthenic dye 9-[1-(2-methyl-4-methoxyphenyl)]-6-hydroxy-3H-xanthen-3-one (TG-II), recovered by Fluorescence Lifetime Correlation Spectroscopy (FLCS), have proven to be useful to quantitatively reflect specific cation effects in aqueous solutions (J. M. Paredes, L. Crovetto, A. Orte, J. M. Alvarez-Pez and E. M. Talavera, Phys. Chem. Chem. Phys., 2011, 13, 1685-1694). Since these phenomena are more sensitive to anions than to cations, in this paper we have accounted for the influence of salts with the sodium cation in common, and the anion classified according to the empirical Hofmeister series, on the proton transfer rate constants of TG-II. We demonstrate that the presence of ions accelerates the rate of the ground-state proton-exchange reaction in the same order than ions that affect ion solvation in water. The combination of FLCS with a fluorophore undergoing proton transfer reactions in the ground state, along with the desirable feature of a pseudo-dark state when the dye is protonated, allows one unique direct determination of kinetic rate constants of the proton exchange chemical reaction.     

Theoretical study of electron, proton, and proton-coupled electron transfer in iron bi-imidazoline complexes.

A comparative theoretical investigation of single electron transfer (ET), single proton transfer (PT), and proton-coupled electron transfer (PCET) reactions in iron bi-imidazoline complexes is presented. These calculations are motivated by experimental studies showing that the rates of ET and PCET are similar and are both slower than the rate of PT for these systems (Roth, J. P.; Lovel, S.; Mayer, J. M. J. Am. Chem. Soc. 2000, 122, 5486). The theoretical calculations are based on a multistate continuum theory, in which the solute is described by a multistate valence bond model, the transferring hydrogen nucleus is treated quantum mechanically, and the solvent is represented as a dielectric continuum. For electronically nonadiabatic electron transfer, the rate expressions for ET and PCET depend on the inner-sphere (solute) and outer-sphere (solvent) reorganization energies and on the electronic coupling, which is averaged over the reactant and product proton vibrational wave functions for PCET. The small overlap of the proton vibrational wave functions localized on opposite sides of the proton transfer interface decreases the coupling for PCET relative to ET. The theory accurately reproduces the experimentally measured rates and deuterium kinetic isotope effects for ET and PCET. The calculations indicate that the similarity of the rates for ET and PCET is due mainly to the compensation of the smaller outer-sphere solvent reorganization energy for PCET by the larger coupling for ET. The moderate kinetic isotope effect for PCET arises from the relatively short proton transfer distance. The PT reaction is found to be dominated by solute reorganization (with very small solvent reorganization energy) and to be electronically adiabatic, leading to a fundamentally different mechanism that accounts for the faster rate.     

General acid catalysis in benzoic acid–Crystal Violet carbinol base reactions in toluene

Kinetics of benzoic acid–dye carbinol base reactions in an apolar aprotic solvent exhibit a complex dependence on the concentration of the acid, indicating the occurrence of general acid catalysis, the acid playing the dual role of the substrate and the catalyst. The complex kinetic behavior observed for 23 ortho‐ and meta‐substituted benzoic acids has been traced to overlapping participations of the monomer acid, hyperacidic open chain homoconjugated complex (dimeric and trimeric) acids, and nonreactive cyclic dimer and trimer acids. It has been found that although the degree of proton transfer in the transition state is 50–60% when the acid acts exclusively in the monomeric form, it gets enhanced to as high as more than 90% when the role of homoconjugated complex acids is taken into consideration. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 570–576, 2012     

Mechanistic aspects of proton chain transfer in the green fluorescent protein. Part II. A comparison of minimal quantum chemical models

In this paper we report the results of extensive quantum chemical reaction pathway calculations for the electronic ground state of several different cluster models that mimic the proton chain transfer path within the green fluorescent protein (GFP). Our principal objective is to establish the robustness with respect to variations in the model of our recent mechanistic inferences for the ground state proton chain transfer [S. Wang and S. C. Smith, J. Phys. Chem. B, 2006, 110, 5084]. Additionally, comparison of our ground state results with the excited state proton transfer (ESPT) study by Vendrell et al. [O. Vendrell, R. Gelabert, M. Moreno and J. M. Lluch, J. Am. Chem. Soc., 2006, 128, 3564] leads to the conclusion that the mechanism of proton chain transfer may be expected to be analogous in ground and excited states, principally because in both cases the loss of the chromophore's phenolic proton contributes strongly to the reaction coordinate only late in the reaction path.