Proton Transfer Coordinate Research Articles

Lactim–lactam tautomerism is favoured over enol–keto tautomerism in 2-hydroxy-5-(4-fluorophenyl)nicotinic acid: Experimental and quantum chemical approach

A model compound, 2-hydroxy-5-(4-fluorophenyl)nicotinic acid (HFPNA) has been synthesized and its ground and excited-state properties towards tautomerisation via possible two ways of proton transfer process have been elaborately examined by means of steady-state absorption, emission and time-resolved emission spectroscopy and quantum chemical calculations. The theme issue of the present contribution is to illustrate a direct competition between two potential excited-state intramolecular proton transfer (ESIPT) pathways within the same molecule. By a direct comparison of spectral characteristics of HFPNA with those of salicylic acid (SA) and 2-hydroxypyridine (2HP) under similar experimental conditions it has been demonstrated that lactim–lactam tautomerisation dominates over enol–keto tautomerisation in HFPNA. Experimental evidences and structural calculation at Density Functional Theory (DFT) (B3LYP/6-31G**) and Hartree–Fock (6-31G**) levels predict the existence of both lactim and lactam-forms in the ground state. The ground and excited-state theoretical potential energy surfaces (PES) of HFPNA along both the ways of proton transfer coordinate at DFT level reveal that PES of HFPNA resemble well with that of 2HP while there are prominent differences from that of SA. We also report on the possibility of application of the studied molecule as a sensor of medium-pH following its sensitive response towards pH of the medium.

Car–Parrinello simulation of hydrogen bond dynamics in sodium hydrogen bissulfate

We studied proton dynamics of a short hydrogen bond of the crystalline sodium hydrogen bissulfate, a hydrogen-bonded ferroelectric system. Our approach was based on the established Car-Parrinello molecular dynamics (CPMD) methodology, followed by an a posteriori quantization of the OH stretching motion. The latter approach is based on snapshot structures taken from CPMD trajectory, calculation of proton potentials, and solving of the vibrational Schrodinger equation for each of the snapshot potentials. The so obtained contour of the OH stretching band has the center of gravity at about 1540 cm(-1) and a half width of about 700 cm(-1), which is in qualitative agreement with the experimental infrared spectrum. The corresponding values for the deuterated form are 1092 and 600 cm(-1), respectively. The hydrogen probability densities obtained by solving the vibrational Schrodinger equation allow for the evaluation of potential of mean force along the proton transfer coordinate. We demonstrate that for the present system the free energy profile is of the single-well type and features a broad and shallow minimum near the center of the hydrogen bond, allowing for frequent and barrierless proton (or deuteron) jumps. All the calculated time-averaged geometric parameters were in reasonable agreement with the experimental neutron diffraction data. As the present methodology for quantization of proton motion is applicable to a variety of hydrogen-bonded systems, it is promising for potential use in computational enzymology.

Deciphering the photophysics of 5-chlorosalicylic acid: evidence for excited-state intramolecular proton transfer

A detailed photophysical study of a pharmaceutically important chlorine-substituted derivative of salicylic acid viz., 5-chlorosalicylic acid (5ClSA), has been carried out by steady-state absorption, emission and time-resolved fluorescence spectroscopy and compared with its parent molecule salicylic acid (SA). A large Stokes-shifted emission band with negligible solvent polarity dependency indicates the spectroscopic signature of excited-state intramolecular proton transfer reaction. Presence of various ground-state species has been confirmed by a thorough investigation in different solvents and by pH variation experiments. Quantum chemical calculation by ab initio Hartree-Fock (HF) and Density Functional Theory (DFT) methods yields results consistent with experimental findings. Particularly, evaluation of potential energy surfaces for the S(0) and S(1) states across the proton transfer coordinate reveals distinct theoretical support for the inoperativeness of the GSIPT reaction as well as the occurrence of ESIPT process. The less favourable ESIPT reaction in 5ClSA is due to reduction of ground-state intramolecular hydrogen bond strength and excited-state negative charge density at the acceptor (-COOH) oxygen atom and increase of the excited-state barrier with respect to SA.

Charge transfer by electronic excitation: Direct measurement by high resolution spectroscopy in the gas phase

We report a quantitative measurement of the amount of charge that is transferred when the single ammonia complex of the photoacid beta-naphthol (2HNA) is excited by light. The measurement was made by comparing the permanent electric dipole moments of cis-2HNA in its ground (S(0)) and excited (S(1)) states, determined by Stark-effect studies of its fully resolved S(1)<--S(0) electronic spectrum. While the increase in electron transfer from the donor (NH(3)) to the acceptor (2HN) upon excitation is small ( approximately 0.05e), it is sufficient to redshift the electronic spectrum of the complex by approximately 600 cm(-1) ( approximately 0.1 eV). Thereby explored is the incipient motion of the acid-base complex along the excited state (electron-coupled) proton transfer coordinate.

Intermolecular proton-transfer in acetic acid clusters induced by vacuum-ultraviolet photoionization

Infrared (IR) spectroscopy based on vacuum-ultraviolet one-photon ionization detection was carried out to investigate geometric structures of neutral and cationic clusters of acetic acid: (CH(3)COOH)(2), CH(3)COOH-CH(3)OH, and CH(3)COOH-H(2)O. All the neutral clusters have cyclic-type intermolecular structures, in which acetic acid and solvent molecules act as both hydrogen donors and acceptors, and two hydrogen-bonds are formed. On the other hand, (CH(3)COOH)(2) (+) and (CH(3)COOH-CH(3)OH)(+) form proton-transferred structures, where the acetic acid moiety donates the proton to the counter molecule. (CH(3)COOH-H(2)O)(+) has a non-proton-transferred structure, where CH(3)COOH(+) and H(2)O are hydrogen-bonded. The origin of these structural differences among the cluster cations is discussed with the relative sizes of the proton affinities of the cluster components and the potential energy curves along the proton-transfer coordinate.

Absorption and Emission of the Apigenin and Luteolin Flavonoids: A TDDFT Investigation

The absorption and emission properties of the two components of the yellow color extracted from weld (Reseda luteola L.), apigenin and luteolin, have been extensively investigated by means of DFT and TDDFT calculations. Our calculations reproduce the absorption spectra of both flavonoids in good agreement with the experimental data and allow us to assign the transitions giving rise to the main spectral features. For apigenin, we have also computed the electronic spectrum of the monodeprotonated species, providing a rationale for the red-shift of the experimental spectrum with increasing pH. The fluorescence emission of both apigenin and luteolin has then been investigated. Excited-state TDDFT geometry optimizations have highlighted an excited-state intramolecular proton transfer (ESIPT) from the 5-hydroxyl to the 4-carbonyl oxygen of the substituted benzopyrone moiety. By computing the potential energy curves at the ground and excited states as a function of an approximate proton transfer coordinate for apigenin, we have been able to trace an ESIPT pathway and thus explain the double emission observed experimentally.

Reconsideration of the excited-state double proton transfer (ESDPT) in 2-aminopyridine/acid systems: role of the intermolecular hydrogen bonding in excited states

In the present work, the excited-state double proton transfer (ESDPT) in 2-aminopyridine (2AP)/acid systems has been reconsidered using the combined experimental and theoretical methods. The steady-state absorption and fluorescence spectra of 2AP in different acids, such as formic acid, acetic acid, propionic acid, etc. have been measured. We demonstrated for the first time that the ESDPT reaction can take place between 2AP and all of these acids due to the formation of the intermolecular double hydrogen bonds. Furthermore, the vitally important role of the intermolecular double hydrogen bonds between 2AP and acids for ESDPT reaction has also been confirmed by the disappearance of ESDPT when we add the polar acetonitrile to the 2AP/acids systems. This may be due to that the respective polar solvation of 2AP and acids by the acetonitrile solvent disrupts the formation of intermolecular double hydrogen bonds between 2AP and acids. Moreover, the intermolecular double hydrogen bonds are demonstrated to be significantly strengthened in the electronic excited state of 2AP/acid systems using the time-dependent density functional theory (TDDFT) method. The ESDPT reaction is facilitated by the electronic excited-state hydrogen bond strengthening. In addition, potential energy curves of the electronic excited state along the proton transfer coordinate are also calculated by the TDDFT method. The stepwise mechanism of the ESDPT reaction in the 2AP/acid systems is theoretically reconfirmed, and the concerted mechanism is theoretically excluded. At the same time, the sequence of the double proton transfers is theoretically clarified for the first time using the potential energy curves calculated by TDDFT method.

Evidence of coupled photoinduced proton transfer and intramolecular charge transfer reaction in para-N,N-dimethylamino orthohydroxy benzaldehyde: Spectroscopic and theoretical studies

Steady state and time resolved fluorescence spectroscopy and quantum chemical calculations have been used to study excited state properties of para-N,N-dimethylamino orthohydroxy benzaldehyde (PDOHBA). Spectral characteristics of PDOHBA support the existence of both donor–acceptor charge transfer (CT) and proton transfer (PT) reaction in the excited state. Structural calculations at Hartree Fock and Density Functional Theory (DFT) levels and theoretical potential energy surfaces (PESs) along the proton transfer and donor twisting coordinates using DFT and Time Dependent Density Functional Theory point towards the possibility of barrierless PT and CT reaction in the first excited state of PDOHBA.

A Theory−Experiment Conundrum for Proton Transfer

For the past 60 years, the framework for understanding the kinetic behavior of proton transfer has been transition state theory. Found throughout textbooks, this theory, along with the Bell tunneling correction, serves as the standard model for the analysis of proton/hydrogen atom/hydride transfer. In comparison, a different theoretical model has recently emerged, one which proposes that the transition state occurs within the solvent coordinate, not the proton transfer coordinate, and proton transfer proceeds either adiabatically or nonadiabatically toward product formation. This Account discusses the central tenets of the new theoretical model of proton transfer, contrasts these with the standard transition state model, and presents a discrepancy that has arisen between our experimental studies on a nonadiabatic system and the current understanding of proton transfer. Transition state theory posits that in the proton transfer coordinate, the proton must surmount an electronic barrier prior to the formation of the product. This process is thermally activated, and the energy of activation is associated with the degree of bond making and bond breaking in the transition state. In the new model, the reaction path involves the initial fluctuation of the solvent, serving to bring the reactant state and the product state into resonance, at which time the proton is transferred either adiabatically or nonadiabatically to form the product. If this theory is correct, then all of the deductions derived from the standard model regarding the nature of the proton transfer process are called into question. For weakly hydrogen-bonded complexes, two sets of experiments are presented supporting the proposal that proton transfer occurs as a nonadiabatic process. In these studies, the correlation of rate constants to driving force reveals both a normal region and an inverted region for proton transfer. Yet, the experimentally observed kinetic behavior does not align with the recent theoretical formulation for nonadiabatic proton transfer, underscoring the gap in the collective understanding of proton transfer phenomena.

A Systematic Comparison of Second-Order Polarization Propagator Approximation (SOPPA) and Equation-of-Motion Coupled Cluster Singles and Doubles (EOM-CCSD) Spin-Spin Coupling Constants for Selected Singly Bonded Molecules, and the Hydrides NH3, H2O, and HF and Their Protonated and Deprotonated Ions and Hydrogen-Bonded Complexes.

Second-order polarization propagator approximation (SOPPA) and equation-of-motion coupled cluster singles and doubles (EOM-CCSD) methods have been employed for the calculation of one-bond spin-spin coupling constants in series of small molecules and ions, and of one- and two-bond coupling constants across X-H···Y hydrogen bonds. For isolated molecules, one-bond SOPPA coupling constants (1)J(X-Y) involving (13)C, (15)N, (17)O, and (19)F have larger absolute values than corresponding EOM-CCSD coupling constants, with the EOM-CCSD values being in significantly better agreement with available experimental data. The difference between SOPPA and EOM-CCSD tends to increase as the number of nonbonding electrons on the coupled atoms increases, and the SOPPA values for O-F coupling are significantly in error. Similarly, the absolute values of SOPPA one-bond coupling constants (1)J(X-H) for the hydrides NH3, H2O, and FH and their protonated and deprotonated ions are greater than EOM-CCSD values, with the largest differences occurring for F-H coupling. One- and two-bond coupling constants (1)J(X-H), (1h)J(H-Y), and (2h)J(X-Y) across X-H···Y hydrogen bonds in neutral, protonated, and deprotonated complexes formed from the hydrides are similar at SOPPA and EOM-CCSD, with the largest differences again found for (1)J(F-H) in complexes with F-H as the proton donor, and (2h)J(F-F) for (FHF)(-). The signs of (1)J(X-H), (1h)J(H-Y), and (2h)J(X-Y) are the same at both levels of theory, as is their variation across the proton-transfer coordinate in F-H···NH3. SOPPA would appear to provide a reliable and more cost-effective alternative approach for computing coupling constants across hydrogen bonds, although couplings involving F may be problematic.

TDDFT Potential Energy Functions for Excited State Intramolecular Proton Transfer of Salicylic Acid, 3-Aminosalicylic Acid, 5-Aminosalicylic Acid, and 5-Methoxysalicylic Acid

We report the application of time-dependent density functional theory (TDDFT) to the calculation of potential energy profile relevant to the excited state intramolecular proton transfer (ESIPT) processes in title molecules. The TDDFT single point energy calculations along the reaction path have been performed using the CIS optimized structure in the excited state. In addition to the Stokes shifts, the transition energies including absorption, fluorescence, and 0-0 transition are estimated from the TDDFT potential energy profiles along the proton transfer coordinate. The excited state TDDFT potential energy profile of SA and 3ASA resulted in very flat function of the OH distance in the range ROH = 1.0-1.6 A, in contrast to the relatively deep single minimum function in the ground state. Furthermore, we obtained very shallow double minima in the excited state potential energy profile of SA and 3ASA in contrast to the single minimum observed in the previous work. The change of potential energy profile along the reaction path induced by the substitution of electron donating groups (-NH2 and -OCH3) at different sites has been investigated. Substitution at para position with respect to the phenolic OH group showed strong suppression of excited state proton dislocation compared with unsubstitued SA, while substitution at ortho position hardly affected the shape of the ESIPT curve. The TDDFT results are discussed in comparison with those of CASPT2 method.

Probing the proton‐transfer coordinate of complexes with FH…P hydrogen bonds using one‐ and two‐bond spin–spin coupling constants

Scalar coupling constants have been computed using the EOM-CCSD method for equilibrium structures of complexes stabilized by F--H...P hydrogen bonds, as well as structures along the proton-transfer coordinates of these complexes. Variations in the signs and absolute values of (1)J(F--H), (1h)J(H--P) and (2h)J(F--P) have been analyzed and interpreted in terms of changing hydrogen bond type. Of the three phosphorus bases (phosphine, trimethylphosphine and phosphinine) investigated in this study, trimethylphosphine forms the strongest complex with FH, and has the largest two-bond F--P coupling constant. Among the relatively simple phosphorus bases, it would appear to be a leading candidate for experimental NMR study. Similarities and differences are noted between the corresponding coupling constants (J) and the reduced coupling constants (K) across F--H...P and F--H...N hydrogen bonds.

Complexes with N−H+−P Hydrogen Bonds: Structures, Binding Energies, and Spin−Spin Coupling Constants

Ab-initio MP2/aug'-cc-pVTZ calculations have been performed to determine the structures and binding energies of proton-bound complexes stabilized by N-H+-P hydrogen bonds and to investigate the nature of the proton-transfer coordinate in these systems. Double minima are found only when the difference between the protonation energies of the N and P bases is less than about 4 kcal/mol. The isomer in which the protonated nitrogen base is the donor lies lower on the potential surface and also has a greater binding energy relative to the corresponding isolated monomers. Equation-of-motion coupled cluster singles and doubles (EOM-CCSD) calculations have been employed to obtain one- and two-bond spin-spin coupling constants across these hydrogen bonds. Two-bond coupling constants (2h)J(N-P) correlate with N-P distances, irrespective of whether the donor ion is N-H+ or P-H+. One-bond coupling constants (1)J(N-H) and (1h)J(H-P) for complexes stabilized by N-H+...P hydrogen bonds correlate with corresponding distances, but similar correlations are not found for (1)J(P-H) and (1h)J(H-N) for complexes with P-H+...N hydrogen bonds. Negative values of (1h)K(H-N) and (1h)K(H-P) indicate that the hydrogen bonds in these complexes are traditional. Comparisons are made with complexes stabilized by N-H+-N and P-H+-P hydrogen bonds.

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.

Probing P−H+−P Hydrogen Bonds: Structures, Binding Energies, and Spin−Spin Coupling Constants

Ab initio MP2/aug'-cc-pVTZ calculations have been performed to determine the structures and binding energies of 22 open and 3 cyclic complexes formed from the sp2 [H(2)C=PH and HP=PH (cis and trans)] and sp3 [PH2(CH3) and PH3] hybridized phosphorus bases and their corresponding protonated ions. EOM-CCSD calculations have been carried out to obtain (31)P-(31)P and (31)P-(1)H coupling constants across P-H+-P hydrogen bonds. Two equilibrium structures with essentially linear hydrogen bonds have been found along the proton-transfer coordinate, except for complexes with P(CH3)H3+ as the proton donor to the sp2 bases. Although the isomer having the conjugate acid of the stronger base as the proton donor lies lower on the potential energy surface, it has a smaller binding energy relative to the corresponding isolated monomers than the isomer with the conjugate acid of the weaker base as the donor. The hydrogen bond of the latter has increased proton-shared character. All of the complexes are stabilized by traditional hydrogen bonds, as indicated by positive values of the reduced coupling constants (2h)K(P-P) and (1)K(P-H), and negative values of (1h)K(H-P). (2h)J(P-P) correlates with the P-P distance, a correlation determined primarily by the nature of the proton donor. For open complexes, (1)J(P-H) always increases relative to the isolated monomer, while (1h)J(H-P) is relatively small and negative. (2h)J(P-P) values are quite large in open complexes, but are much smaller in cyclic complexes in which the P-H+-P hydrogen bonds are nonlinear. Thus, experimental measurements of (2h)J(P-P) should be able to differentiate between open and cyclic complexes.

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.

Photo-physical properties of 1-hydroxy-2-naphthaldehyde: A combined fluorescence spectroscopy and quantum chemical calculations

The ground and excited state properties of 1-hydroxy-2-naphthaldehyde (HN12) towards proton transfer reaction have been elaborately investigated on the basis of steady state absorption and emission, time-resolved fluorescence spectroscopy and quantum chemical calculations by ab initio (Hartree–Fock) and density functional theory (DFT) methods. The molecule HN12 exists as closed (intramolecular hydrogen bonded) and open conformer and their anions, and the hydrogen bonded solvated cluster in the ground state. The closed conformer on excitation undergoes photo-induced keto-enol tautomerism across the pre-existing intramolecular hydrogen bond (IMHB) and shows a red shifted emission band for the keto tautomer. Theoretically a significant change of some structural parameters such as O d–H 1 bond length, O d⋯H 1⋯O a bond angle and charge distribution at the proton translocation site in the excited state favours intramolecular proton transfer process. Calculated potential energy curves along the proton transfer coordinate at the pre-existing hydrogen bonding site by DFT level account well for the feasibility of a barrierless ultrafast excited state intramolecular proton transfer reaction in HN12 molecule.

Charge-Transfer ππ* Excited State in the 7-Azaindole Dimer. A Hybrid Configuration Interactions Singles/Time-Dependent Density Functional Theory Description

The hybrid configuration interaction singles/time dependent density functional theory approach of Dreuw and Head-Gordon [Dreuw, A.; Head-Gordon, M. J. Am. Chem. Soc. 2004, 126, 4007] has been applied to study the potential energy landscape and accessibility of the charge-transfer pipi* excited state in the dimer of 7-azaindole, which has been traditionally considered a model for DNA base pairing. It is found that the charge-transfer pipi* excited state preferentially stabilizes the product of a single proton transfer. In this situation, the crossing between this state and the photoactive electronic state of the dimer is accessible. It is found that the charge-transfer pipi* excited state has a very steep potential energy profile with respect to any single proton-transfer coordinate and, in contrast, an extremely flat potential energy profile with respect to the stretch of the single proton-transfer complex. This is predicted to bring about a pair of rare fragments of the 7-azaindole dimer, physically separated and hence having very long lifetimes. This could have implications in the DNA base pairs of which the system is an analogue, in the form of replication errors.

Predicted Signs of One-Bond Spin−Spin Coupling Constants (1hJH-Y) across X−H−Y Hydrogen Bonds for Complexes with Y = 15N, 17O, and 19F

Ab initio equation-of-motion coupled cluster (EOM-CCSD) calculations have been performed on a set of 44 complexes to obtain one-bond H−Y spin−spin coupling constants (1hJH-Y) across X−H−Y hydrogen bonds, with Y as the second-period elements 15N, 17O, and 19F. For complexes with traditional hydrogen bonds, the reduced Fermi-contact terms and the reduced one-bond spin−spin coupling constants (1hKH-Y) are negative. Since 1KX-H has been shown previously to be positive, a change of sign of these two coupling constants must occur along the proton-transfer coordinate. For complexes with symmetric X−H−X hydrogen bonds, the two reduced X−H coupling constants are equal and positive at equilibrium. For complexes stabilized by hydrogen bonds that have some proton-shared character, both 1hKH-Y and 1KX-H are also positive. The signs of all three reduced coupling constants (1hKH-Y, 2hKX-Y, and 1KX-H) that can arise between pairs of hydrogen-bonded atoms are interpreted in terms of the nuclear magnetic resonance triplet wave function model (NMRTWM). Determination of the signs of 1hKH-Y and 1KX-H could be useful for confirming the presence or absence of a proton-shared hydrogen bond.

Photoinduced proton transfer from the green fluorescent protein chromophore to a water molecule: analysis of the transfer coordinate

The proton transfer from the green fluorescent protein chromophore to a nearby water molecule is studied by means of CASSCF, CASPT2 and TDDFT calculations. A 1πσ* electronic state is found to intersect with the photoactive 1ππ* electronic state along the proton transfer coordinate. This state crossing constitutes a possible non-radiative deactivation pathway of the photoexcited neutral form of the chromophore. A discussion on the performance of the different levels of theory employed is also given, focusing in the ability to correctly describe the 1πσ* electronic state.