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.     

Electron attachment induced proton transfer in a DNA nucleoside pair: 2'-deoxyguanosine-2'-deoxycytidine

To elucidate electron attachment induced damage in the DNA double helix, electron attachment to the 2'-deoxyribonucleoside pair dG:dC has been studied with the reliably calibrated B3LYP/DZP++ theoretical approach. The exploration of the potential energy surface of the neutral and anionic dG:dC pairs predicts a positive electron affinity for dG:dC [0.83 eV for adiabatic electron affinity (EAad) and 0.16 eV for vertical electron affinity (VEA)]. The substantial increases in the electron affinity of dG:dC (by 0.50 eV for EAad and 0.23 eV for VEA) compared to those of the dC nucleoside suggest that electron attachment to DNA double helices should be energetically favored with respect to the single strands. Most importantly, electron attachment to the dC moiety in the dG:dC pair is found to be able to trigger the proton transfer in the dG:dC- pair, surprisingly resulting in the lower energy distonic anionic complex d(G-H)-:d(C+H).. The negative charge for the latter system is located on the base of dC in the dG:dC- pair, while it is transferred to d(G-H) in d(G-H)-:d(C+H)., accompanied by the proton transfer from N1(dG) to N3(dC). The low energy barrier (2.4 kcal/mol) for proton transfer from dG to dC- suggests that the distonic d(G-H)-:d(C+H). pair should be one of the important intermediates in the process of electron attachment to DNA double helices. The formation of the neutral nucleoside radical d(C+H). is predicted to be the direct result of electron attachment to the DNA double helices. Since the neutral radical d(C+H). nucleotide is the key element in the formation of this DNA lesion, electron attachment might be one of the important factors that trigger the formation of abasic sites in DNA double helices.     

Double proton transfer in the isolated and DNA-embedded guanine-cytosine base pair

The energetics and dynamics of double proton transfer (DPT) is investigated theoretically for the Watson-Crick conformation of the guanine-cytosine (GC) base pair. Using semiempirical density functional theory the isolated and DNA-embedded GC pair is considered. Differences in the energetics and dynamics of DPT thus addresses the question of how relevant studies of isolated base pairs are for the understanding of processes occurring in DNA. Two-dimensional potential energy surfaces involving the transferring hydrogen atoms and the proton donors and acceptors are presented for both systems. The DPT reaction is accompanied by a contraction of the distance between the two bases with virtually identical energetic barriers being 18.8 and 18.7 kcal/mol for the isolated and DNA-embedded system, respectively. However, the transition state for DPT in the DNA-embedded GC pair is offset by 0.1 A to larger N-H separation compared to the isolated GC pair. Using activated ab initio molecular dynamics, DPT is readily observed for the isolated base pair with a minimal amount of 21.4 kcal/mol of initial average kinetic energy along the DPT normal mode vector. On a time scale of approximately 100 fs DPT has occurred and the excess energy is redistributed. For the DNA-embedded GC pair considerably more kinetic energy is required (30.0 kcal/mol) for DPT and the process is completed within one hydrogen vibration. The relevance of studies of isolated base pairs and base pair analogs in regard of reactions or properties involving DNA is discussed.     

Combined effect of stacking and solvation on the spontaneous mutation in DNA

In DNA, base pairs are involved in two reciprocal interactions: interbase hydrogen bonds and stacking. Furthermore, base pairs also undergo the effects of the external entities present in the biological environment, such as water molecules and cations. In this contribution, the double spontaneous mutation has been studied with hybrid theoretical tools in a DNA-embedded guanine-cytosine model accounting for the impact of the first hydration shell. According to our findings, the combination of the neighboring base pairs and surrounding water molecules plays a crucial role in the double proton transfer. Indeed, as a consequence of these interactions, the double proton transfer (DPT) mechanism is altered: on the one hand, stacking and hydration strongly affect the geometry of base pairs, and, on the other hand, vicinal water molecules may play an active role in the tautomeric equilibrium by catalyzing the proton transfer reaction.     

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.     

In search of excited-state proton transfer in the lumichrome dimer in the solid state: theoretical and experimental approach

Quantum chemical density functional theory (DFT) calculations and spectral data were employed to investigate the possibility of the excited-state double proton transfer (ESDPT) in lumichrome crystals. The calculations in a lumichrome dimer predict a transfer of a proton in the first excited state, leading to a cation-anion pair. The presently reported X-ray structure of 1,3-dimethyllumichrome and its complex solid-state luminescence indicate that also in this molecule intermolecular hydrogen bonds might be involved in the photophysics. The long-wavelength emission in lumichrome crystals peaked at 530 nm is attributed to excited-state proton transfer, whereas a wider emission band in methylated lumichrome derivatives peaked at 560 nm is attributed to ions formed upon photoexcitation of the crystals.     

Structures and energetics of the deprotonated adenine-uracil base pair, including proton-transferred systems

The B3LYP/DZP++ level of theory has been employed to investigate the structures and energetics of the deprotonated adenine-uracil base pairs, (AU-H)-. Formation of the lowest-energy structure, [A(N9)-U]- (which corresponds to deprotonation at the N9 atom of adenine), through electron attachment to the corresponding neutral is accompanied by proton transfer from the uracil N3 atom to the adenine N1 atom. The driving force for this proton transfer is a significant stabilization from the base pairing in the proton transferred form. Such proton transfer upon electron attachment is also observed for the [A(N6b)-U]- and [A(C2)-U]- anions. Electron attachment to the A-U(N3) radical causes strong lone pair repulsion between the adenine N1 and the uracil N3 atoms, driving the two bases apart. Similarly, lone pair repulsion in the anion A(N6a)-U causes the loss of coplanarity of the two base units. The computed adiabatic electron attachment energies for nine AU-H radicals range from 1.86 to 3.75 eV, implying that the corresponding (AU-H)- anions are strongly bound. Because of the large AEAs of the (AU-H) radicals, the C-H and N-H bond dissociation in the AU- base pair anions requires less energy than the neutral AU base pair. The computed C-H and N-H bond dissociation energies for the AU- anion (i.e., the AU base pair plus one electron) are in the range 1.0-3.2 eV, while those for neutral AU are 4.08 eV or higher.     

Ultrafast deactivation of an excited cytosine-guanine base pair in DNA

Multiconfigurational ab initio calculations and QM/MM molecular dynamics simulations of a photoexcited cytosine-guanine base pair in both gas phase and embedded in the DNA provide detailed structural and dynamical insights into the ultrafast radiationless deactivation mechanism. Photon absorption promotes transfer of a proton from the guanine to the cytosine. This proton transfer is followed by an efficient radiationless decay of the excited state via an extended conical intersection seam. The optimization of the conical intersection revealed that it has an unusual topology, in that there is only one degeneracy-lifting coordinate. This is the central mechanistic feature for the decay both in vacuo and in the DNA. Radiationless decay occurs along an extended hyperline nearly parallel to the proton-transfer coordinate, indicating the proton transfer itself is not directly responsible for the deactivation. The seam is displaced from the minimum energy proton-transfer path along a skeletal deformation of the bases. Decay can thus occur anywhere along the single proton-transfer coordinate, accounting for the remarkably short excited-state lifetime of the Watson-Crick base pair. In vacuo, decay occurs after a complete proton transfer, whereas in DNA, decay can also occur much earlier. The origin of this effect lies in the temporal electrostatic stabilization of dipole in the charge-transfer state in DNA.     

Detection and automatic repair of nucleotide base-pair mutations by coherent light

We show that phase-coherent optical techniques allow for the detection and automatic repair of mutations in nucleotide pairs. We demonstrate computationally that there is a laser pulse sequence that can detect the occurrence of a mutation caused by a double proton transfer between hydrogen-bonded nucleotide pairs and automatically repair it by converting the mutated nucleotide pair to the nonmutated one. The specific system chosen for this demonstration is the hydrogen-bonded 2-pyridone.2-hydroxypyridine dimer at typical internucleotide distances, a well-established model for tautomeric acid base pairs.     

Excited-state double proton transfer of 7-azaindole dimers in a low-temperature organic glass

The excited-state double proton transfer of model DNA base pairs, 7-azaindole (7AI) dimers, is explored in a low-temperature organic glass of n-dodecane using picosecond time-resolved fluorescence spectroscopy. Reaction mechanisms are found to depend on the conformations of 7AI dimers at the moment of excitation; whereas planar conformers tautomerize rapidly (<10 ps), twisted conformers undergo double proton transfer to form tautomeric dimers on the time scale of 250 ps at 8 K. The proton transfer is found to consist of two orthogonal steps: precursor-configurational optimization and intrinsic proton transfer via tunneling. The rate is almost isotope independent at cryogenic temperatures because configurational optimization is the rate-determining step of the overall proton transfer. This optimization is assisted by lattice vibrations below 150 K or by librational motions above 150 K.     

Excited-state double proton transfer dynamics of model DNA base pairs: 7-hydroxyquinoline dimers

The excited-state double proton transfer of model DNA base pairs, 7-hydroxyquinoline dimers, in benzene has been investigated using picosecond time-resolved fluorescence spectroscopy. Upon excitation, whereas singly hydrogen-bonded noncyclic dimers do not go through tautomerization within the relaxation time of 1400 ps, doubly hydrogen-bonded cyclic dimers undergo excited-state double proton transfer on the time scale of 25 ps to form tautomeric dimers, which subsequently undergo a conformational change in 180 ps to produce singly hydrogen-bonded tautomers. The rate constant of the double proton transfer reaction is temperature-independent, showing a large kinetic isotope effect of 5.2, suggesting that the rate is governed mostly by tunneling.     

Effects of protonation on proton transfer processes in Watson–Crick adenine–thymine base pair

Intermolecular proton transfer processes in the Watson and Crick adenine–thymine neutral and protonated base pairs have been studied using the density functional theory (DFT) with the non-local hybrid B3LYP density functional. Protonated systems subject to study are those resulting from protonation at the main basic sites of the base pair model, namely N₇ and N₃ of adenine and O₂^′ and O₄^′ of thymine. Protonation of adenine induces a strengthening by about 4–5 kcal/mol of the base pair and does not significantly modify the double proton transfer energy profile obtained for the unprotonated system. On the other hand, protonation at the O₄^′ and O₂^′ thymine moiety causes thymine’s N₃ proton to spontaneously transfer to adenine while non-transferred minima disappear at this level of theory. The different behaviour between protonated adenine– thymine and protonated guanine–cytosine is discussed. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Contribution to the Fernando Bernardi Memorial Issue.     

Structure of adducts of the intermolecular interaction of dimethylpyrazole and diphenylformamidine with hydrogen halides in the solution

The structure of adducts forming in the solution due to the interaction of bifunctional azo compounds (dimethylpyrazole (DMP) and diphenylformamidine (DPFA)) with hydrogen halides (HF, HCl, and HBr) is found from the data of the IR absorption spectra and quantum chemical calculations. It is shown that in the interaction with HCl or HBr proton donors, proton transfer via the hydrogen bond to the basic N atom of the azo compound occurs with the formation of an NH⁺…Hal⁻ ionic pair. Strong evidences of proton transfer and the anion-cation pair formation are not found for the DMP-_F structure, and complexes with the molecular N…HF hydrogen bond are the dominant structures. Geometric parameters of the formed structures are calculated. The formation of trimers, containing two molecules of the azo compound and one HHal molecule, with an increase in the nitrogenous base concentration is experimentally proved, and the trimer structure is determined.     

Probing irradiation induced DNA damage mechanisms using excited state Car-Parrinello molecular dynamics

Photoinduced proton transfer in the Watson-Crick guanine (G)-cytosine (C) base pair has been studied using Car-Parrinello molecular dynamics (CP-MD). A flexible mechanical constraint acting on all three hydrogen bonds in an unbiased fashion has been devised to explore the free energy profile along the proton transfer coordinate. The lowest barrier has been found for proton transfer from G to C along the central hydrogen bond. The resulting charge transfer excited state lies energetically close to the electronic ground state suggesting the possibility of efficient radiationless decay. It is found that dynamic, finite temperature fluctuations significantly reduce the energy gap between the ground and excited states for this charge transfer product, promoting the internal conversion process. A detailed analysis of the internal degrees of freedom reveals that the energy gap is considerably reduced by out-of-plane molecular vibrations, in particular. Consequently, it appears that considering only the minimum energy path provides an upper-bound estimate of the associated energy gap compared to the full-dimension dynamical reaction coordinate. Furthermore, the first CP-MD simulations of the G-C base pair in liquid water are presented, and the effects of solvation on its electronic structure are analyzed.     

Cu2+/+ cation coordination to adenine--thymine base pair. Effects on intermolecular proton-transfer processes

Intermolecular proton-transfer processes in the Watson & Crick adenine-thymine Cu+ and Cu2+ cationized base pairs have been studied using the density functional theory (DFT) methods. Cationized systems subject to study are those resulting from cation coordination to the main basic sites of the base pair, N7 and N3 of adenine and O2 of thymine. For Cu+ coordinated to N7 or N3 of adenine, only the double proton-transferred product is found to be stable, similarly to the neutral system. However, when Cu+ interacts with thymine, through the O2 carbonyl atom, the single proton transfer from thymine to adenine becomes thermodynamically spontaneous, and thus rare forms of the DNA bases may spontaneously appear. For Cu2+ cation, important effects on proton-transfer processes appear due to oxidation of the base pair, which stabilizes the different single proton-transfer products. Results for hydrated systems show that the presence of the water molecules interacting with the metal cation (and their mode of coordination) can strongly influence the ability of Cu2+ to induce oxidation on the base pair.     

Theoretical study of proton coupled electron transfer reaction in the light state of the AppA BLUF photoreceptor

The BLUF (blue light sensor using flavin adenine dinucleotide) domain is widely studied as a prototype for proton coupled electron transfer (PCET) reactions in biological systems. In this work, the photo-induced concerted PCET reaction from the light state of the AppA BLUF domain is investigated. To model the simultaneous transfer of two protons in the reaction, two-dimensional potential energy surfaces for the double proton transfer are first calculated for the locally excited and charge transfer states, which are then used to obtain the vibrational wave function overlaps and the vibrational energy levels. Contributions to the PCET rate constant from each pair of vibronic states are then analyzed using the theory based on the Fermi's golden rule. We show that, the recently proposed light state structure of the BLUF domain with a tautomerized Gln63 residue is consistent with the concerted transfer of one electron and two protons. It is also found that, thermal fluctuations of the protein structure, especially the proton donor-acceptor distances, play an important role in determining the PCET reaction rate. © 2018 Wiley Periodicals, Inc.     

B型DNA中鸟嘌呤-胞嘧啶碱基对内双质子转移反应

采用ONIOM(M06-2X/6-31G^*:PM3)方法研究了单个鸟嘌呤-胞嘧啶(GC)碱基对和含GC碱基对的四种排序的DNA三聚体(dATGCAT, dGCGCGC, dTAGCTA, dCGGCCG)的双质子转移反应. 通过分析其双质子转移方式、质子转移过程中各结构的能量和氢键变化, 总结出环境因素对GC碱基对双质子转移机理的影响. 气相中, dCGGCCG三聚体中发生分步双质子转移, 其它四种模型中均发生协同双质子转移. 分析发现质子转移方式受上下相邻碱基对的静电相互作用和质子接受位的质子亲和势影响, dATGCAT和dGCGCGC排序有助于质子H4a转移, 而dTAGCTA和dCGGCCG排序有助于质子H1转移, 胞嘧啶的N3位较高的质子亲和势有助于质子H1转移. 水溶剂中, 上下相邻碱基对的静电相互作用被减弱, 水溶剂稳定了分步转移过程中的单质子转移产物, 因此分步转移机理占据优势, 五种模型中均出现分步双质子转移, 在此过程中能量变化趋势相似. 溶剂效应有利于单质子转移, 却增加了双质子转移反应的反应能.     

The Protonated Guanine–Cytosine Base Pair

Protonated base pairs were recently implicated in the context of DNA proton transfer and charge migration. The effects of protonating different sites of the guanine–cytosine (GC) base pair are studied here by using the DZP++ B3LYP density functional method. Optimized structures for the protonated GC base pair are compared with those of parent GC and the neutral hydrogenated GC radical (GCH). Proton and hydrogen‐atom additions significantly disturb the structure of the GC base pair. However, the structural perturbations arising from protonation are often less than those arising from hydrogenation of GC. Protonation of the GC base pair causes significant strengthening of the interstrand hydrogen bonds and a concomitant increase in the base dissociation energies. The adiabatic ionization potentials (AIPs), vertical ionization potentials (VIPs), and proton affinities (PAs) for the different protonation sites of the GC base pair are predicted. The N7 site of guanine is the preferred site for protonation of the GC base pair.     

PROTON TRANSFER IN THE PRIMARY PROCESS OF VISION

Abstract— Proton transfer was theoretically examined as a possible primary process of vision. The motion of protons in the adiabatic potential of the Schiff base hydrogen bond was investigated in terms of quantum mechanics. The probability of proton transfer from the Schiff base nitrogen (i.e. the unprotonation of Schiff base) was found to increase as the retinal rotated around 11–12. double bond by 90°. The results also suggested that the proton transfer can take place before or during the transition from the excited to ground state (excited state proton transfer). We proposed that such excited state proton transfer is one of the elementary processes in primary visual photochemistry, and this process leads to the unprotonated visual pigment, hyposorhodopsin, which has been experimentally verified as one of the primary photoproducts of rhodopsin. The probability of this process could be comparable to the conventional process leading to the protonated intermediate, bathorhodopsin. The relation of these results with the recent experimental data is discussed.