Variation of atomic charges on proton transfer in strong hydrogen bonds: the case of anionic and neutral imidazole-acetate complexes

The variation of atomic charges upon proton transfer in hydrogen bonding complexes of 4-methylimidazole, in both neutral and protonated cationic forms, and acetate anion, is investigated. These complexes model the histidine (neutral and protonated)-aspartate pair present in active sites of proteases where strong N--H...O hydrogen bonds are formed. Three procedures (Merz-Kollman scheme, Natural Population Analysis, and Atoms in Molecules Method) are used to compute atomic charges and explore their variation upon H-transfer in the gas phase and in the presence of two continuum media with dielectric constants 5 (protein interiors) and 78.39 (water). The effect of electron correlation was also studied by comparing Hartree-Fock and MP2 results for both complexes in the gas phase. Greater net charge interchanged upon H-transfer is observed in the anionic complex with respect to the neutral complex. Raising the polarity of the medium increases the amount of net charge transfer in both complexes, although the neutral system exhibits a larger sensitivity to the presence of solvent. Charge transfer associated to N--H...O and N...H--O bonds reveal the ionic contribution to the interaction depending on the number of charged subunits but the presence of solvent affects little this quantity. The lack of electron correlation overestimates all the charges as well as their variations and so uncorrelated calculations should be avoided.     

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.     

Proton-coupled electron transfer from tyrosine: a strong rate dependence on intramolecular proton transfer distance

Proton-coupled electron transfer (PCET) was examined in a series of biomimetic, covalently linked Ru(II)(bpy)(3)-tyrosine complexes where the phenolic proton was H-bonded to an internal base (a benzimidazyl or pyridyl group). Photooxidation in laser flash/quench experiments generated the Ru(III) species, which triggered long-range electron transfer from the tyrosine group concerted with short-range proton transfer to the base. The results give an experimental demonstration of the strong dependence of the rate constant and kinetic isotope effect for this intramolecular PCET reaction on the effective proton transfer distance, as reflected by the experimentally determined proton donor-acceptor distance.     

Switching from ultrafast electron transfer to proton transfer in excited drug–protein complexes upon biotransformation

Photosensitization by drugs is directly related with the excited species and the photoinduced processes arising from interaction with UVA light. In this context, the ability of gefitinib (GFT), a tyrosine kinase inhibitor (TKI) used for the treatment of a variety of cancers, to induce phototoxicity and photooxidation of proteins has recently been demonstrated. In principle, photodamage can be generated not only by a given drug but also by its photoactive metabolites that maintain the relevant chromophore. In the present work, a complete study of O-desmorpholinopropyl gefitinib (GFT-MB) has been performed by means of fluorescence and ultrafast transient absorption spectroscopies, in addition to molecular dynamics (MD) simulations. The photobehavior of the GFT-MB metabolite in solution is similar to that of GFT. However, when the drug or its metabolite are in a constrained environment, i.e. within a protein, their behavior and the photoinduced processes that arise from their interaction with UVA light are completely different. For GFT in complex with human serum albumin (HSA), locally excited (LE) singlet states are mainly formed; these species undergo photoinduced electron transfer with Tyr and Trp. By contrast, since GFT-MB is a phenol, excited state proton transfer (ESPT) to form phenolate-like excited species might become an alternative deactivation pathway. As a matter of fact, the protein-bound metabolite exhibits higher fluorescence yields and longer emission wavelengths and lifetimes than GFT@HSA. Ultrafast transient absorption measurements support direct ESPT deprotonation of LE states (rather than ICT), to form phenolate-like species. This is explained by MD simulations, which reveal a close interaction between the phenolic OH group of GFT-MB and Val116 within site 3 (subdomain IB) of HSA. The reported findings are relevant to understand the photosensitizing properties of TKIs and the role of biotransformation in this type of adverse side effects.

The photoinduced processes from the protein-bound GFT result in electron transfer, while those related with the photoactive metabolite GFT-MB induce excited state proton transfer to form phenolate-like excited species.     

Light-triggered proton and electron transfer in flavin cofactors

The pH dependent behavior of two flavin cofactors, flavin-adenine dinucleotide (FAD) and flavin mononucleotide (FMN), has been characterized using femtosecond transient absorption spectroscopy for the first time. The flavin excited state was characterized in three states of protonation (Fl(-), Fl, and FlH(+)). We found that Fl and Fl(-) exhibit the same excited state absorption but that the lifetime of Fl(-) is much shorter than that of Fl. The transient absorption spectrum of FlH(+) is significantly different from Fl and Fl(-), suggesting that the electronic properties of the flavin chromophore become appreciably modified by protonation. We further studied the excited state protonation of the flavin and found that the protonation sites of the flavin in the ground and excited state are not equivalent. In the case of FAD, its excited state dynamics are controlled by the two conformations it adopts. At low and high pH, FAD adopts an "open" conformation and behaves the same as FMN. In a neutral pH range, FAD undergoes a fast excited state deactivation due to the "stacked" conformer. The transition from stacked to open conformer occurs at pH ～ 3 (because of adenine protonation) and pH ～ 10 (because of flavin deprotonation).     

Self-assembly and heterogeneous electron transfer properties of metallo-octacarboxyphthalocyanine complexes on gold electrode

Electrochemical properties of redox-active self-assembled molecular films of novel metallo-octacarboxyphthalocyanine (MOCPc, M = Fe, Co and Mn) complexes integrated with cysteamine (Cys) monolayer on gold electrodes via amide bonds were investigated. X-Ray photoelectron spectroscopy confirmed the appearance of the various elements in their expected chemical environment upon immobilization of these species. The heterogeneous electron transfer properties of the Au-Cys-MOCPc molecular films using an outer-sphere ([Fe(CN)(6)](4-)/[Fe(CN)(6)](3-)) redox probe were studied using cyclic voltammetry and electrochemical impedance spectroscopy. The electron transfer rate constant (k(app)) depends markedly on the central metal of the metallophthalocyanine cores (k(app): Co > Mn > Fe). A strong pH dependence of the electron transport of the Au-Cys-MOCPc molecular films was found. The surface pK(a) values of the MOCPc complexes were essentially the same (ca. 7.5). The differences in the electron transports and ionization constants are discussed. The electrodes are sensitive to the electrooxidation of epinephrine in physiological pH conditions, peak potential (E(p)/V vs. Ag|AgCl, saturated KCl) decreasing as FeOCPc (0.20 V) < MnOCPc (0.26 V) < CoOCPc (0.34 V).     

Photoinduced electron transfer in bisporphyrin-diimide complexes

The bisporphyrin host ZnH was synthesized, and its complexation with two aromatic diimide guest molecules, bis(pyridyl)naphthalenediimide NIN and bis(pyridyl)phenyldiimide PIN, was investigated by (1)H NMR and UV/Vis spectroscopy. The diimide guests were complexed simultaneously with both metalloporphyrins of the host, with association constants on the order of 10(8)M(-1). The processes occurring in the complex after excitation of the porphyrinic host were studied by steady-state and time-resolved emission and transient absorption spectroscopy. Complexation alters the photophysical properties of the host ZnH; the luminescence bands shift to the red by 30 nm in the complexed forms, while the emission quantum yield and the lifetime decrease. Comparison of a complex between ZnH and a model guest unable to undergo photoinduced processes allowed us to establish that, in the diimide complexes, quenching of the porphyrinic luminescence occurs with a rate of 1.1 x 10(10)s(-1). The process is identified as an electron transfer from the excited singlet of the porphyrinic host to the imide guest, which yields charge-separated states with a lifetime of 710 ps for ZnH(+)-NIN(-) and 260 ps for ZnH(+)-PIN(-).     

Integral encounter theory of strong electron transfer

The integral encounter theory (IET) has been extended to the reactions limited by diffusion along the reaction coordinate to the level crossing points where either thermal or hot electron transfer occurs. IET describes the bimolecular ionization of the instantaneously excited electron donor D* followed by the hot geminate backward transfer which precedes the ion pair equilibration and its subsequent thermal recombination. We demonstrate that the fraction of ion pairs which avoids the hot recombination is much smaller than their initial number when the electron tunneling is strong.     

Synthesis, characterization and electron transfer properties of some picolinate complexes of ruthenium

In aqueous solution ruthenium trichloride reacted with picolinic acid (Hpic) in the presence of a base to afford [Ru(pic)₃]. In solution it shows intense ligand-to-metal charge transfer transitions near 310 and 370 nm, together with a low-intensity absorption near 2000 nm. [Ru(pic)₃] is one-electron paramagnetic and shows a rhombic ESR spectrum in 1:1 dimethylsulphoxide-methanol solution at 77 K. The distortions from octahedral symmetry have been calculated by ESR data analysis. The axial distortion is larger than the rhombic one. In acetonitrile solution it shows a reversible ruthenium(III)-ruthenium(II) reduction at −0.09 V vs. SCE and a reversible ruthenium(III)-ruthenium(IV) oxidation at 1.52 V vs. SCE. Chemical or electrochemical reduction of [Ru^III(pic)₃] gives [Ru^II(pic)₃]⁻, which in solution shows intense MLCT transitions near 360, 410 and 490 nm, and is converted back to [Ru(pic)₃] by exposure to air. Reaction of [Ru(pic)₃] with 8-quinolinol (HQ) in dimethylsulphoxide solution affords [RuQ₃]. [Ru(bpy)(pic)₂] (bpy = 2,2′-bipyridine) has been prepared by the reaction of Hpic with [Ru(bpy)(acac)₂]Cl (acac = acetylacetonate ion) in ethyleneglycol. It is diamagnetic and in solution shows intense MLCT transitions near 370, 410 and 530 nm. In acetonitrile solution it shows a reversible ruthenium(II)-ruthernium(III) oxidation at 0.44 V vs. SCE and a reversible one-electron reduction of bpy at − 1.64V vs. SCE.     

Mechanistic implications of proton transfer coupled to electron transfer.

The kinetics of electron transfer for the reactions cis-[Ru(IV)(bpy)2(py)(O)]2+ + H+ + [Os(II)(bpy)3]2+ <==> cis-[Ru(III)(bpy)2(py)(OH)]2+ + [Os(III)(bpy)3]3+ and cis-[Ru(III)(bpy)2(py)(OH)]2+ + H+ + [Os(II)(bpy)3]2+ <==> cis-[Ru(II)(bpy)2(py)(H2O)]2+ + [Os(III)(bpy)3]3+ have been studied in both directions by varying the pH from 1 to 8. The kinetics are complex but can be fit to a double "square scheme" involving stepwise electron and proton transfer by including the disproportionation equilibrium, 2cis-[Ru(III)(bpy)2(py)(OH)]2+ <==> (3 x 10(3) M(-1) x s(-1) forward, 2.1 x 10(5) M(-1) x s(-1) reverse) cis-[Ru(IV)(bpy)2(py)(O)]2+ + cis-[Ru(II)(bpy)2(py)(H2O)]2+. Electron transfer is outer-sphere and uncoupled from proton transfer. The kinetic study has revealed (1) pH-dependent reactions where the pH dependence arises from the distribution between acid and base forms and not from variations in the driving force; (2) competing pathways involving initial electron transfer or initial proton transfer whose relative importance depends on pH; (3) a significant inhibition to outer-sphere electron transfer for the Ru(IV)=O2+/Ru(III)-OH2+ couple because of the large difference in pK(a) values between Ru(IV)=OH3+ (pK(a) < 0) and Ru(III)-OH2+ (pK(a) > 14); and (4) regions where proton loss from cis-[Ru(II)(bpy)2(py)(H2O)]2+ or cis-[Ru(III)(bpy)2(py)(OH)]2+ is rate limiting. The difference in pK(a) values favors more complex pathways such as proton-coupled electron transfer.     

Simultaneous proton transfer along a linear water polymer

SCF CNDO calculations were performed for species H₃O⁺·(H₂O)_n·OH^? where n was varied from one to three. The position of the intervening protons was changed simultaneously while the oxygens and remaining hydrogens were kept fixed. It was found that only one minimum occurs when n is one or two while an asymmetric double minimum potential is found when n is equal to three. A barrier of 10.4 kcal/mole was found.     

Noise-assisted quantum electron transfer in photosynthetic complexes

Electron transfer (ET) between primary electron donor and acceptor is modeled in the photosynthetic complexes. Our model includes (i) two discrete energy levels associated with donor and acceptor, which are directly interacting and (ii) two continuum manifolds of electron energy levels (“sinks”), each interacting with the donor and acceptor. We also introduce external (classical) noise which acts on both donor and acceptor. We derive a closed system of integro-differential equations which describes the non-Markovian quantum dynamics of the ET. A region of parameters is found in which the ET dynamics can be simplified, and described by coupled ordinary differential equations. Using these simplified equations, both cases of sharp and flat redox potentials are analyzed. We analytically and numerically obtain the characteristic parameters that optimize the ET rates and efficiency in this system. In particular, we demonstrate that even for flat redox potential a simultaneous influence of sink and noise can significantly increase the efficiency of the ET. We discuss a relation between our approach and the Marcus theory of ET.     

Energetics and dynamics of electron transfer and proton transfer in dissociation of metal(III)(salen)-peptide complexes in the gas phase

Time- and collision energy-resolved surface-induced dissociation (SID) of ternary complexes of Co(III)(salen)+, Fe(III)(salen)+, and Mn(III)(salen)+ with several angiotensin peptide analogues was studied using a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially equipped to perform SID experiments. Time-resolved fragmentation efficiency curves (TFECs) were modeled using an RRKM-based approach developed in our laboratory. The approach utilizes a very flexible analytical expression for the internal energy deposition function that is capable of reproducing both single-collision and multiple-collision activation in the gas phase and excitation by collisions with a surface. The energetics and dynamics of competing dissociation pathways obtained from the modeling provides important insight on the competition between proton transfer, electron transfer, loss of neutral peptide ligand, and other processes that determine gas-phase fragmentation of these model systems. Similar fragmentation behavior was obtained for various Co(III)(salen)-peptide systems of different angiotensin analogues. In contrast, dissociation pathways and relative stabilities of the complexes changed dramatically when cobalt was replaced with trivalent iron or manganese. We demonstrate that the electron-transfer efficiency is correlated with redox properties of the metal(III)(salen) complexes (Co > Fe > Mn), while differences in the types of fragments formed from the complexes reflect differences in the modes of binding between the metal-salen complex and the peptide ligand. RRKM modeling of time- and collision-energy-resolved SID data suggests that the competition between proton transfer and electron transfer during dissociation of Co(III)(salen)-peptide complexes is mainly determined by differences in entropy effects while the energetics of these two pathways are very similar.     

Photoinduced electron and proton transfer in the hydrogen-bonded pyridine-pyrrole system

We present here a detailed analysis of the mechanism of photoinduced electron and proton transfer in the planar pyrrole-pyridine hydrogen-bonded system, a model for the photochemistry of hydrogen bonds in DNA base pairs. Two different crossings, an avoided crossing and a conical intersection, are the key steps for forward and backward electron and proton transfer providing to the system photostability against UV radiation by restoring the system in its initial electronic and geometric structure.     

Moderate and advanced intramolecular proton transfer in urea-anion hydrogen-bonded complexes

The study of the interactions of the three urea-based receptors AH, BH(+) and CH(2+) with a variety of anions, in MeCN, has made it possible to verify the current view that hydrogen bonding is frozen proton transfer from the donor (the urea N-H fragment in this case) to the acceptor (the anion X(-)). The poorly acidic, neutral receptor AH establishes two equivalent hydrogen bonds N-H···X(-), with all anions, including CH(3)COO(-) and F(-), in which moderate proton transfer from N-H to the anion takes place. The strongly acidic, dicationic receptor CH(2+) forms, with most anions, complexes in which two inequivalent hydrogen bonds are present: one involving moderate proton transfer (N-H···X(-)) and one in which advanced proton transfer has taken place, described as N(-)···H-X. The degree of proton advancement is directly related to the basic tendencies of the anion. The cationic receptor BH(+) of intermediate acidic properties only forms complexes with two inequivalent hydrogen bonds (moderate+advanced proton transfer) with CH(3)COO(-) and F(-), and complexes with two equivalent hydrogen bonds (moderate proton transfer) with all the other anions. Moreover, [B···HF] and [C···HF](+), on addition of a second F(-) ion, lose the bound HF molecule to give HF(2)(-). Release of CH(3)COOH, with the formation of [CH(3)COOH···CH(3)COO](-), also takes place with the [B···CH(3)COOH] complex in the presence of a large excess of anion.     

Pyridine as proton acceptor in the concerted proton electron transfer oxidation of phenol

Taking pyridine as a prototypal example of biologically important nitrogen bases involved in proton-coupled electron transfers, it is shown with the example of the photochemically triggered oxidation of phenol by Ru(III)(bpy)(3) that this proton acceptor partakes in a concerted pathway whose kinetic characteristics can be extracted from the overall kinetic response. The treatment of these data, implemented by the results of a parallel study carried out in heavy water, allowed the determination of the intrinsic kinetic characteristics of this proton acceptor. Comparison of the reorganization energies and of the pre-exponential factors previously derived for hydrogen phosphate and water (in water) as proton acceptors suggests that, in the case of pyridine, the proton charge is delocalized over a primary shell of water molecules firmly bound to the pyridinium cation.     

Interplay between spin crossover and proton migration along short strong hydrogen bonds

The iron(ii) salt [Fe(bpp)₂](isonicNO)₂·HisonicNO·5H₂O (1) (bpp = 2,6-bis(pyrazol-3-yl)pyridine; isonicNO = isonicotinate N-oxide anion) undergoes a partial spin crossover (SCO) with symmetry breaking at T₁ = 167 K to a mixed-spin phase (50% high-spin (HS), 50% low-spin (LS)) that is metastable below T₂ = 116 K. Annealing the compound at lower temperatures results in a 100% LS phase that differs from the initial HS phase in the formation of a hydrogen bond (HB) between two water molecules (O4W and O5W) of crystallisation. Neutron crystallography experiments have also evidenced a proton displacement inside a short strong hydrogen bond (SSHB) between two isonicNO anions. Both phenomena can also be detected in the mixed-spin phase. 1 undergoes a light-induced excited-state spin trapping (LIESST) of the 100% HS phase, with breaking of the O4W⋯O5W HB and the onset of proton static disorder in the SSHB, indicating the presence of a light-induced activation energy barrier for proton motion. This excited state shows a stepped relaxation at T₁(LIESST) = 68 K and T₂(LIESST) = 76 K. Photocrystallography measurements after the first relaxation step reveal a single Fe site with an intermediate geometry, resulting from the random distribution of the HS and LS sites throughout the lattice.

A proton migration across a short strong hydrogen bond can be triggered by spin crossover of a remote Fe²⁺ cation, with the onset of a photoinduced activation energy barrier for proton motion at low temperatures.     

Variation of atomic charges during proton transfer in hydrogen bonds

The point atomic charges in a number of ionic H-bonded systems are studied by ab initio calculations as functions of the proton transfer coordinate. In the proton-bound complexes of water–water, ammonia–ammonia, formamide–water, formamide–ammonia, and dimethylether–ammonia, the net atomic charges were obtained using Mulliken population analysis and from the diagonal elements of the atomic polar tensors calculated at the HF/4–31G and MP2/6–31 + G** levels. The dependence of the atomic charges upon the coordinate of the transferring proton was found to be close (within an error of 0.02 e) to a linear function for intermolecular distances in the 2.5–2.8 Å range. The obtained charge and charge flux dependencies highlight the electron redistribution during the proton transfer process and provide insights into the source of the high infrared (IR) intensities of stretching modes of N? H and O? H bonds undergoing hydrogen bonding. © 1994 by John Wiley & Sons, Inc.     

Hydrated alizarin complexes: hydrogen bonding and proton transfer

We investigated the hydrogen bonding structures and proton transfer for the hydration complexes of alizarin (Az) produced in a supersonic jet using fluorescence excitation (FE), dispersed laser induced fluorescence (LIF), visible-visible hole burning (HB), and fluorescence detected infrared (FDIR) spectroscopy. The FDIR spectrum of bare Az with two O-H groups exhibits two vibrational bands at 3092 and 3579 cm(-1), which, respectively, correspond to the stretching vibration of O1-H1 that forms a strong intramolecular hydrogen bond with the C9=O9 carbonyl group and the stretching vibration of O2-H2 that is weakly hydrogen-bonded to O1-H1. For the 1:1 hydration complex Az(H(2)O)(1), we identified three conformers. In the most stable conformer, the water molecule forms hydrogen bonds with the O1-H1 and O2-H2 groups of Az as a proton donor and proton acceptor, respectively. In the other conformers, the water binds to the C10=O10 group in two nearly isoenergetic configurations. In contrast to the sharp vibronic peaks in the FE spectra of Az and Az(H(2)O)(1), only broad, structureless absorption was observed for Az(H(2)O)(n) (n≥ 2), indicating a facile decay process, possibly due to proton transfer in the electronic excited state. The FDIR spectrum with the wavelength of the probe laser fixed at the broad band exhibited a broad vibrational band near the O2-H2 stretching vibration frequency of the most stable conformer of Az(H(2)O)(1). With the help of theoretical calculations, we suggest that the broad vibrational band may represent the occurrence of proton transfer by tunnelling in the electronic ground state of Az(H(2)O)(n) (n≥ 2) upon excitation of the O2-H2 vibration.     

On the theory of tunnelling in electron and proton transfer reactions

The concept of tunnelling in the theory of electron and proton transfer reactions has recently been questioned on the ground that the situation is a non-stationary one. It has been suggested that time-dependent perturbation theory should be applied to obtain the quantum mechanical transition probability. We have done this for a square barrier. The result for most reactions is the same as obtained by the WKB approximation.