Double Proton Transfer Reaction Research Articles

A TDDFT study on the excited-state double proton transfer reaction of 8-hydroxyquinoline along a hydrogen-bonded bridge

The mechanism of excited-state multiple proton transfer reaction is demonstrated to be controlled by a hydrogen-bonded bridge.

How was the proton transfer process in bis-3, 6-(2- benzoxazolyl)-pyrocatechol, single or double proton transfer?

A theoretical analysis of proton transfer process for the symmetric systems with two intramolecular hydrogen bonds, bis-3,6-(2-benzoxazolyl)-pyrocatechol(BBPC) in hexane solvent, has been researched. In this study, we utilized ωB97X-D/ 6-311 + g (d,p) and B3LYP/6-31 + G(d) two procedures calculating the foremost bond length and bond angle, respectively. Our calculations demonstrate the two intramolecular hydrogen bonds were strengthened in S1 state, thus the proton transfer reaction can be facilitated. Furthermore, the calculated IR vibrational spectra confirmed hydrogen bonds were enhanced in S1 state. We found three local minima A B and C from the potential energy surfaces (PESs) on the S1 state, and the energy of B point and C point are identical. A new ESIPT mechanism has been proposed that was not equal to the previous conclusions. The new ESIPT mechanism elucidates that single proton transfer more likely occurs in the symmetric BBPC molecule in comparison with the double proton transfer reaction. And the frontier molecular orbitals(MOs) further illustrate the trend of ESIPT reaction.

Role of intramolecular hydrogen bonding in the excited-state intramolecular double proton transfer (ESIDPT) of calix[4]arene: A TDDFT study

Abstract The time-dependent density functional theory (TDDFT) method was performed to investigate the excited-state intramolecular double proton transfer (ESIDPT) reaction of calix[4]arene (C4A) and the role of the intramolecular hydrogen bonds in the ESIDPT process. The geometries of C4A in the ground state and excited states (S1, S2 and T1) were optimized. Four intramolecular hydrogen bonds formed in the C4A are strengthened or weakened in the S2 and T1 states compared to those in the ground state. Interestingly, upon excitation to the S1 state of C4A, two protons H1 and H2 transfer along the two intramolecular hydrogen bonds O1-H1···O2 and O2-H2···O3, while the other two protons do not transfer. The ESIDPT reaction breaks the primary symmetry of C4A in the ground state. The potential energy curves of proton transfer demonstrate that the ESIDPT process follows the stepwise mechanism but not the concerted mechanism. Findings indicate that intramolecular hydrogen bonding is critical to the ESIDPT reactions in intramolecular hydrogen-bonded systems.

Optically Triggered Stepwise Double-Proton Transfer in an Intramolecular Proton Relay: A Case Study of 1,8-Dihydroxy-2-naphthaldehyde

1,8-Dihydroxy-2-naphthaldehyde (DHNA), having doubly intramolecular hydrogen bonds, was strategically designed and synthesized in an aim to probe a long-standing fundamental issue regarding synchronous versus asynchronous double-proton transfer in the excited state. In cyclohexane, DHNA shows the lowest lying S0 →S1 (π-π*) absorption at ∼400 nm. Upon excitation, two large Stokes shifted emission bands maximized at 520 and 650 nm are resolved, which are ascribed to the tautomer emission resulting from the first and second proton-transfer products, denoted by TA* and TB*, respectively. The first proton transfer (DHNA* → TA*) is ultrafast (< system response of 150 fs), whereas the second proton transfer is reversible, for which the rates of forward (TA* → TB*) and backward (TA* ← TB*) proton transfer were determined to be (1.7 ps)(-1) and (3.6 ps)(-1), respectively. The fast equilibrium leads to identical population lifetimes of ∼54 ps for both TA* and TB* tautomers. Similar excited-state double-proton transfer takes place for DHNA in a single crystal, resulting in TA* (560 nm) and TB* (650 nm) dual-tautomer emission. A comprehensive 2D plot of reaction potential energy surface further proves that the sequential two-step proton motion is along the minimum energetic pathway firmly supporting the experimental results. Using DHNA as a paradigm, we thus demonstrate unambiguously a stepwise, proton-relay type of intramolecular double-proton transfer reaction in the excited state, which should gain fundamental understanding of the multiple proton transfer reactions.

A new smoothing function to introduce long-range electrostatic effects in QM/MM calculations.

A new method to account for long range electrostatic contributions is proposed and implemented for quantum mechanics/molecular mechanics long range electrostatic correction (QM/MM-LREC) calculations. This method involves the use of the minimum image convention under periodic boundary conditions and a new smoothing function for energies and forces at the cutoff boundary for the Coulomb interactions. Compared to conventional QM/MM calculations without long-range electrostatic corrections, the new method effectively includes effects on the MM environment in the primary image from its replicas in the neighborhood. QM/MM-LREC offers three useful features including the avoidance of calculations in reciprocal space (k-space), with the concomitant avoidance of having to reproduce (analytically or approximately) the QM charge density in k-space, and the straightforward availability of analytical Hessians. The new method is tested and compared with results from smooth particle mesh Ewald (PME) for three systems including a box of neat water, a double proton transfer reaction, and the geometry optimization of the critical point structures for the rate limiting step of the DNA dealkylase AlkB. As with other smoothing or shifting functions, relatively large cutoffs are necessary to achieve comparable accuracy with PME. For the double-proton transfer reaction, the use of a 22 Å cutoff shows a close reaction energy profile and geometries of stationary structures with QM/MM-LREC compared to conventional QM/MM with no truncation. Geometry optimization of stationary structures for the hydrogen abstraction step by AlkB shows some differences between QM/MM-LREC and the conventional QM/MM. These differences underscore the necessity of the inclusion of the long-range electrostatic contribution.

Energy Barrier Reduction for the Double Proton-Transfer Reaction in Guanine–Cytosine DNA Base Pair on a Gold Surface

We investigate, by means of first-principles calculations, the impact of a gold surface on the proton-transfer of the guanine–cytosine (GC) DNA base pair. Our calculations employ density functional improvements to correct van der Waals interactions and properly treat a weakly bound GC pair at an Au(111) surface. We adopted the simultaneous double proton-transfer (SDPT) mechanism proposed by Löwdin, which may lead to a spontaneous mutation in the structure of DNA from specific tautomerization involving the base pairs. Our calculated differences in the energetics and kinetics of the SDPT in the GC pair, when in contact with an inert gold surface, indicate a reduction of about 31% in the activation energy barrier of the GC/Au(111) tautomeric equilibrium. This finding gives strong evidence that tautomerism of DNA base pairs, binding to a noble surface, may be indeed relevant for the assessment of a possible point mutation, which could be induced by the presence of gold nanoparticles during DNA replication.

Direct and solvent-assisted thione–thiol tautomerism in 5-(thiophen-2-yl)-1,3,4-oxadiazole-2(3H)-thione: Experimental and molecular modeling study

The compound has been synthesized and characterized by IR, NMR and X-ray diffraction. Quantum chemical calculations at B3LYP/6−311++G(d,p) level were performed to study the molecular and spectroscopic properties, conformational equilibrium, thione↔thiol tautomerism and intermolecular double proton transfer reaction of the compound. The obtained structural and spectroscopic results are well in agreement with the experimental data. The solvent effect on the proton transfer reaction was investigated in three solvents using the polarizable continuum model approximation and solvent-assisted mechanism. The anti-thione tautomer is the most stable isomer among the four possible structural forms both in the gas phase and in solution phase. A high tautomeric energy barrier is found for the tautomerism between the anti and syn forms of the compound, indicating a quite disfavored process. Although the presence of one methanol or water solvent molecule significantly lowers the energy barrier, it is not adequate for the reaction to occur.

Theoretical studies on proton transfer reaction of 3(5)-substituted pyrazoles

The inter and intra molecular proton transfer reactions of a series of pyrazole derivatives have been studied by using density functional theory (DFT) and MP2 methods implementing 6-311++G(d,p) atomic basis set. The substituents have been selected to cover a wide range of electronic effects. Proton transfer process was studied for mechanisms including single proton transfer, double proton transfer and proton transfer assisted by a water or ammonia molecule. The results showed single proton transfer reactions for interconversion pyrazole derivatives need highest activation energies in the range of 45.7 − 51.59 and 49.4 − 53.96 kcal/mol at B3LYP and MP2 levels, respectively. It was found that for the 3–substituted pyrazoles, electron withdrawing groups form stronger dimers but in the 5-substituted tautomers electron donating groups form stronger hydrogen bond. The double proton transfer reactions between dimers were studied and transition states calculated. The ranges of activation energies were found to be 17.51 − 19.36 and 17.02 − 17.80 kcal/mol for the C→E and D→D reactions respectively. In addition, the activation energies for the proton transfer reaction assisted by water or ammonia molecules were found to be in the range of 26.62−31.78 and 17.25 − 22.46 kcal/mol, respectively, calculated at MP2/6-311++G(d,p) level of theory. DFT and MP2 methods have been employed to study of proton transfer reaction of substituted pyrazoles. Activation energy of monomers are in the range of 45.7–51.59 kcal/mol at MP2 levels. The double proton transfer reaction was studied for all dimers and activation energies were found to be in the range of 17.51–19.36 kcal/mol.

Intermolecular hydrogen-bonding effects on photophysics and photochemistry

Intermolecular hydrogen bonding, as an important site-specific interaction between hydrogen donor and acceptor molecules both in the gas phase and in solution, plays a significant role and has a remarkable influence on the photophysics and photochemistry of chromophores in the hydrogen-bonding surroundings. In recent years, the excited-state structures and dynamics of the intermolecular hydrogen bonding have been widely investigated by using both the experimental and theoretical methods. This review article focuses on the recent research progress of the important intermolecular hydrogen-bonding effects on the non-adiabatic photophysical processes and photochemical reactions. Firstly, the corresponding relationship between electronic spectral red-shift or blue-shift and excited-state intermolecular hydrogen bond strengthening or weakening has been clarified. A dynamic equilibrium induced by the intermolecular hydrogen bond strengthening in the electronically excited state of fluorenone chromophore was used to explain the steady-state spectral features. The stepwise mechanism of excited-state double proton transfer reaction for the 2-aminopyridine/acid systems was demonstrated. The role of intermolecular hydrogen bonding on the excited-state proton transfer in the sensing mechanism of fluorescent probes has also been discussed. Moreover, a dihydrogen-bonded complex formed by borane-trimethylamine and phenol showed interesting geometric structures and infared spectrum in electronically excited state.

Theoretical investigation of thione-thiol tautomerism, intermolecular double proton transfer reaction and hydrogen bonding interactions in 4-ethyl-5-(2-hydroxyphenyl)-2H-1,2,4-triazole-3(4H)-thione

The thione-thiol tautomerism and intermolecular double proton transfer reaction for the title triazole compound were studied at the B3LYP level of theory using 6-311++G(d,p) basis function. The solvent effect on the proton transfer reactions was investigated in three solvents (chloroform, methanol and water) using the polarizable continuum model (PCM) approximation (direct solvent effect) and solvent-assisted mechanism. The results show that the thione-enol tautomer is the most stable isomer among the four possible tautomeric forms of the compound both in the gas phase and in solution phase. A very high tautomeric energy barrier is found for the thione-thiol tautomerism between the enol and keto forms of the compound both in the gas phase and in solution phase, indicating a quite disfavored process. The direct solvent effect is found to be sizable with increasing polarity of the solvents. Even though the presence of the solvent molecules significantly lowers the barrier of the proton transfer, it is not adequate for the reaction to occur. The energetic and thermodynamic parameters of the double proton transfer process show that the double proton exchange from thione-enol dimer to thiol-enol dimer is thermodynamically unfavored. However, the exchange from thiol-enol dimer to thione-enol dimer for the gas phase and methanol phase seems to be feasible with a low barrier height, and is supported by negative values in enthalpy and free energy changes. The intermolecular hydrogen bonding interactions were analyzed in the gas phase regarding their geometries and energies. The stability of the H-bonds comes in the order of O1H1⋯N1>S1H2⋯N2>N2H2⋯S1>N2H2⋯N1.

Why the tautomerization of the G·C Watson–Crick base pair via the DPT does not cause point mutations during DNA replication? QM and QTAIM comprehensive analysis

The ground-state tautomerization of the G·C Watson–Crick base pair by the double proton transfer (DPT) was comprehensively studied in vacuo and in the continuum with a low dielectric constant (ϵ = 4), corresponding to a hydrophobic interface of protein–nucleic acid interactions, using DFT and MP2 levels of quantum-mechanical (QM) theory and quantum theory “Atoms in molecules” (QTAIM). Based on the sweeps of the electron-topological, geometric, polar, and energetic parameters, which describe the course of the G·C ↔ G∗·C∗ tautomerization (mutagenic tautomers of the G and C bases are marked with an asterisk) through the DPT along the intrinsic reaction coordinate (IRC), it was proved that it is, strictly speaking, a concerted asynchronous process both at the DFT and MP2 levels of theory, in which protons move with a small time gap in vacuum, while this time delay noticeably increases in the continuum with ϵ = 4. It was demonstrated using the conductor-like polarizable continuum model (CPCM) that the continuum with ϵ = 4 does not qualitatively affect the course of the tautomerization reaction. The DPT in the G·C Watson–Crick base pair occurs without any intermediates both in vacuum and in the continuum with ϵ = 4 at the DFT/MP2 levels of theory. The nine key points along the IRC of the G·C base pair tautomerization, which could be considered as electron-topological “fingerprints” of a concerted asynchronous process of the tautomerization via the DPT, have been identified and fully characterized. These key points have been used to define the reactant, transition state, and product regions of the DPT reaction in the G·C base pair. Analysis of the energetic characteristics of the H-bonds allows us to arrive at a definite conclusion that the middle N1H⋯N3/N3H⋯N1 and the lower N2H⋯O2/N2H⋯O2 parallel H-bonds in the G·C/G∗·C∗ base pairs, respectively, are anticooperative, that is, the strengthening of the middle H-bond is accompanied by the weakening of the lower H-bond. At that point, the upper N4H⋯O6 and O6H⋯N4 H-bonds in the G·C and G∗·C∗ base pairs, respectively, remain constant at the changes of the middle and the lower H-bonds at the beginning and at the ending of the G·C ↔ G∗·C∗ tautomerization. Aiming to answer the question posed in the title of the article, we established that the G∗·C∗ Löwdin’s base pair satisfies all the requirements necessary to cause point mutations in DNA except its lifetime, which is much less than the period of time required for the replication machinery to forcibly dissociate a base pair into the monomers (several ns) during DNA replication. So, from the physicochemical point of view, the G∗·C∗ Löwdin’s base pair cannot be considered as a source of point mutations arising during DNA replication.

Deuteration effect on the NH/ND stretch band of the jet-cooled 7-azaindole and its tautomeric dimers: Relation between the vibrational relaxation and the ground-state double proton-transfer reaction

Infrared spectra of NH and ND stretch bands of the 7-azaindole (7-AI) dimer and its tautomeric dimer are observed to investigate a deuteration effect on the spectra and also a ground-state double proton-transfer (DPT) reaction. We examined the three isotopic species for each dimers; undeuterated one (NH–NH) and one or two hydrogen atom(s) of the NH groups is deuterated ones (NH–ND and ND–ND, respectively). It is found that the ND stretch band profiles of the NH–ND and ND–ND tautomeric dimers are very similar with each other. This result is very distinct from the result of the comparison of the NH stretch band profiles of the NH–NH and NH–ND dimers in our previous paper. For a further discussion, we examined the deuteration effect in the case of the 7-AI dimer. It is found that band profiles of the NH stretch of the NH–NH and the NH–ND dimers and also the ND stretch of the NH–ND and the ND–ND dimers exhibit similar patterns, respectively. These facts indicates that the vibrational relaxation from the NH/ND stretch level of the dimer basically proceed within a monomer unit. The large deuteration effect of the NH stretch band profile observed previously is found to be characteristic of the tautomeric dimer. This behavior is related to a large anharmonicity of the potential energy surface originating from an existence of the double-proton transfer reaction barrier.

Theoretical studies on the effect of substituent in the proton transfer reaction of 4-substituted pyrazoles

Density functional theory (B3LYP and CAM-B3LYP) and MP2 methods have been employed to study of proton transfer in annular tautomerism and double proton transfer reaction of a series of pyrazoles substituted at the 4 position (NH2, OH, CH3, F, H, Cl, CN, NO2, CHO, NO). It was found that activation energy for monomers of pyrazole derivatives via tautomerism process is in the range of 47.8–55.5kcal/mol. In addition the pyrazole with electron releasing groups have lower activation energy than electron withdrawing ones. Moreover it was found that formation of dimers favored, and corrected interaction energies were found in the range of 11.4–12.0, 10.0–10.6 and 12.2–12.8kcal/mol using CAM-B3LYP, B3LYP and MP2 methods, using 6-311++G(d,p) basis function, respectively. The double proton transfer reaction was studied for dimers and the obtained results showed that corrected activation energies vary in the range of 13.0–15.0 and 11.4–12.6kcal/mol at DFT and MP2 levels of theory, respectively. A good correlation between B3LYP and CAM-B3LYP results for prediction of hydrogen bond strength was observed.

Polarizability, chemical hardness and ionization potential as descriptors to understand the mechanism of double proton transfer in acetamide dimer

The double proton transfer mechanism in the acetamide dimer is examined in terms of the energy profile, reaction force, chemical hardness, average polarizability, ionization potential, chemical potential and interaction energies using HF as well as density functional theory based approach. The energy profile for the activation process of acetamide dimer to the imino ether product is obtained using B3LYP function and is in agreement with the results of the other methods. To test the validity of the reaction mechanism, the intrinsic reaction coordinate (IRC) calculation is performed at the B3LYP level of theory. The results show that the reaction starts with a structural rearrangement, where the two dimers approach each other, and through the transition state (TS) product is obtained. This structural rearrangement to the activation barrier steers the activation process. During the course of double proton transfer reaction in acetamide dimer (AAD) we observe that the ionization potential (IP) is inversely related with average polarizability (αav) and linearly related with chemical hardness (η). We also observe that the use of NH distance as proton transfer co-ordinate nicely explain the reaction energy profile and it is computationally less expensive than the IRC method.

Quantum chemical investigation of the intra- and intermolecular proton transfer reactions and hydrogen bonding interactions in 4-amino-5-(2-hydroxyphenyl)-2H-1,2,4-triazole-3(4H)-thione

The intramolecular thione-thiol tautomerism and intermolecular double proton transfer reaction of the hydrogen-bonded thione and thiol dimers in the title triazole compound were studied at the B3LYP level of theory using 6-311++G(d,p) basis function. The influence of the solvent on the single and double proton transfer reactions was examined in three solvents (chloroform, methanol and water) using the polarizable continuum model (PCM) approximation. The computational results show that the thione tautomer is the most stable isomer with a very high tautomeric energy barrier both in the gas phase and in solution phase, indicating a quite disfavored process. The solvent effect is found to be sizable with increasing polarity. In the double proton transfer reaction, the thione dimer is found to be more stable than thiol dimer both in the gas phase and in solution phase. The energetic and thermodynamic parameters of the double proton transfer process show that the double proton exchange from thione dimer to thiol dimer is thermodynamically unfavored. However, the exchange from thiol dimer to thione dimer for the gas phase and water phase seems to be feasible with a low barrier height and with a negative value in enthalpy and free energy changes. In addition, the hydrogen bonding interactions were analyzed in the gas phase regarding their geometries and energies. It is found that all complex formations are enthalpically favored, and the stability of the H-bonds comes in the order of S1-H2···N2>N2-H2···S1>N3-H3B···O1. Finally, non-linear optical properties were carried out at the same calculation level in the gas phase.

Hydrogen-Bonded Double-Proton Transfer in Five Guanine–Cytosine Base Pairs after Hydrogen Atom Addition

The double-proton transfer reactions in Watson-Crick guanine-cytosine (GC) base pairs after hydrogen atom addition are studied theoretically. The structural changes and energy differences among the structures are compared to explore the double-proton transfer mechanisms, concerted and stepwise. The concerted mechanism is found in all five radicals (GC+H)(•) considered, while the stepwise mechanism is predicted only for structures G-H(•)C(C6) and H(•)G(N7)-C. The geometrical features have been found to change regularly in the concerted double-proton transfer. This is different from the single-proton transfer, for which the structural perturbations are dispersed throughout the GC base pair. The energy analyses demonstrate that the concerted double-proton transfer mechanism is more favorable in the gas phase, while the stepwise mechanism dominates in water. The structures of proton transfer products become less favored energetically.

Use of polarizability and chemical hardness to locate the transition state and the potential energy curve for double proton transfer reaction: A DFT based study

Density functional theory (DFT) based calculations on a series of double and single proton-transfer reactions e.g. formamide (FA), acetamide (AA) and trifluoro acetamide (TFA) dimmers are performed to understand the potential energy surfaces during proton transfer processes. Apart from using the N–H distances as proton transfer co-ordinate we have computed the variations in polarizations and chemical hardnesses of the species involved to locate the transition state structures during the double proton transfer reactions. The average polarizability (αav) and the chemical hardness (η) show their optimum value at the same N–H distance and it corresponds to the transition state for all the three titled complexes. The maximum polarizability and minimum chemical hardness at the transition state (TS) are due to maximal charge separation at TS. We observe that computation of maximum polarizability and minimum chemical hardness along the reaction co-ordinate are the easiest way to locate the transition state during the proton transfer processes.

The reaction force constant: an indicator of the synchronicity in double proton transfer reactions

Earlier work, both experimental and computational, has drawn attention to the transition region in a chemical reaction, which includes the traditional transition state but extends along the intrinsic reaction coordinate ξ from perturbed forms of the reactants to perturbed forms of the products. The boundaries of this region are defined by the reaction force F(ξ), which is the negative gradient of the potential energy V(ξ) of the system along ξ. The reaction force constant κ(ξ), the second derivative of V(ξ), is negative throughout the transition region. We have now demonstrated, for a series of twelve double proton transfer processes, that the profile of κ(ξ) in the transition region is an indicator of the synchronicity of the two proton migrations in each case. When they are fully or nearly fully synchronous, κ(ξ) has a single minimum in the transition region. When the migrations are considerably nonsynchronous, κ(ξ) has two minima separated by a local maximum. Such an assessment of the degree of synchronicity cannot readily be made from an examination of the transition state alone, nor it is easily detected in the profiles of V(ξ) and F(ξ).

1,4-bis-(3-hydroxy-4-oxo-4H-chromen-2-yl)-benzene (bis-flavonol): synthesis, spectral properties and principle possibility of the excited state double proton transfer reaction

Abstract Synthesis and systematic investigation of the spectral-luminescent properties of “bis-flavonol” {1,4-bis-(3-hydroxy-4-oxo-4H-chromen-2-yl)-benzene} were performed. Hypothetical possibility for the double excited-state proton transfer reaction in bis-flavonol is discussed based on both quantum-chemical modeling and experimental data. Consecutive S1*-state transfer of the two protons of the title molecule is shown to be energetically unfavorable, however, still preserving a possibility for the concerted double proton transfer in the excited dienol form.

Proton transfer reaction and intermolecular interactions in associates of 2,5-dihydroxy-1,8-naphthyridine

Tautomerism in monomers/dimers and association of 2,5-dihydroxy-1,8-naphthyridine was studied at the DFT level recently recommended for studies of non-covalent interactions. Studied dimers are stabilized by double and triple hydrogen-bonding. In some associates the intermolecular proton transfer may take place. Transition state related to the double proton transfer reactions were calculated and discussed in terms of energetics, changes in atomic charges upon association, aromaticity (HOMA), properties of hydrogen bond critical point (QTAIM methodology) and geometry change during this reaction. It was found that double proton transfer is supported by third hydrogen bond or by weak secondary interaction. Some protons in transition states are shared between two basic atoms, while other are covalently bound only to one of them. The said process leads to replacement of secondary interactions of attractive character to repulsive and vice versa. Overall, results suggest that in subjected compound the triple hydrogen-bonded associate may be in equilibrium with double hydrogen-bonded dimer.