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The antioxidative activity of natural product compound amurensin H (1) and its three synthetic compounds 5-(6-hydroxy-2-(4-hydroxyphenyl)benzofuran-3-yl)benzene-1,3-diol (2), (E)-2-(4-hydroxyphenyl)-4-(4-hydroxystyryl)benzofuran-6-ol (3), and (E)-5-(6-hydroxy-4-(4-hydroxystyryl)benzofuran-3-yl)benzene-1,3-diol (4) are extensively studied by DFT (density functional theory) method. At the theoretical B3LYP/6-311G(d,p) level, the HAT (hydrogen atom transfer) mechanism is assignable to compounds 1-4 in gas, but the SPL-ET (sequential proton loss-electron transfer) mechanism is the main way in water and methanol. The antioxidative actions of the studied compounds are mainly based on OH bond breakage, especially OH groups directly substituted at benzofuran nucleus. Amurensin H (1) is better than the remaining compounds due to 6-OH group. 1-6-OH induces the low bond BDE (bond dissociation enthalpy) and PA (proton affinity) values in thermal analysis. Importantly, the kinetic reaction of 1-6-OH + HOO• in methanol exerts the lowest ΔG# value of 5.6 kcal/mol and the highest K value of 1.983 x 1010 L/mol.s. At the B3LYP/6-311G(d,p)/LANL2DZ level, the successful formation of complex [Zn(compound 1)2(H2O)2] at 6-OH is confirmed by molecular orbital and UV-Vis spectroscopic analyses.

A systematic conformational search reveals three N- (amino) and eight O- (carbonyl) protonated glycine conformers with benchmark equilibrium(adiabatic) relative energies in the 0.00–7.51(0.00–7.37) and 25.91–31.61(24.45–30.28) kcal mol−1 ranges, respectively. Benchmark ab initio structures of the glycine conformers and its protonated species are obtained at the CCSD(T)-F12b/aug-cc-pVTZ level of theory and the relative energy computations consider basis-set effects up to aug-cc-pVQZ with CCSD(T)-F12b, electron correlation up to CCSDT(Q), core correlation corrections, scalar relativistic effects, and zero-point energy contributions. The best predictions for Boltzmann-averaged 0(298.15) K proton affinities and [298.15 K gas-phase basicities] of glycine are 211.00(212.43)[204.75] and 186.38(187.64)[180.21] kcal mol−1 for N- and O-protonation, respectively, in excellent agreement with experiments.

Accurate calculations of the structure and properties of analytes and their ions are of great interest to the theory and practice of mass spectrometry, ion mobility spectrometry, and related methods. In this work, using accurate quantum chemical methods, we computed the structure of neutral and protonated pyridine, 2-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, and 2,4,6-trimethylpyridine molecules and also of proton-bound dimers of pyridine and 2,4-dimethylpyridine. Two stable conformers of the 2,4-dimethylpyridine proton-bound dimer are found. An accurate and economical method is proposed for calculating proton affinity and gas-phase basicity with the calculation error close to the experimental one. The values of proton affinity and gas-phase basicity for 2,4,6-trimethylpyridine are computed. Reduced mobilities of protonated molecules and proton-bound dimers are calculated by the trajectory method in different versions. A calculation version is proposed that allows mobility computation with the error close to the experimental one and adequately reproduces small differences in the mobility of isomers. The versatility of the chosen B3PW91−D3BJ/def2−TZVP method of the density functional theory with the inclusion of dispersion correction is shown. The method (in combination with B2GP−PLYP−D3BJ/def2−TZVPPD calculations) ensures accurate calculations of the molecular structure, proton affinity, and gas-phase basicity, and also charges on atoms for computing ion mobility.

We present a convenient three-step synthesis of amino substituted phosphazenyl phosphines of the general formula (R2N)3P=N–P(NR2)2 [NR2 = N(CH2)4, N(CH2)5, N(CH2)6]. These easily accessible mixed valent compounds display a surprisingly high proton affinity and basicity in the same range as the corresponding Schwesinger diphosphazene (Me2N)3P=N–P=NEt(NMe2)2 (Et-P2) and Verkade’s proazaphosphatrane superbases. Within the central [PIII–N=PV] scaffold, the phosphine PIII and not the phosphazene NIII atom is the center of highest proton affinity, basicity and donor strength. As P-bases, the title compounds display calculated proton affinities between 265.8 (NR2 = NMe2) and 274.7 kcal·mol–1 [NR2 = N(CH2)4] and pKBH+ values between 26.4 (NR2 = NMe2) and 31.5 [NR2 = N(CH2)4] on the acetonitrile scale. As P- nucleophiles, they are key intermediates in the synthesis of hyperbasic bis(diphosphazene) proton sponges, chiral bis(diphosphazene) proton pincers, bisphosphazides, and superbasic P2- bisylides. Their Staudinger reactions as nucleophile towards 1, 8-diazidonaphthalene leading to 1, 8-naphthalene-bisphosphazides is described in detail. The donor strength of the title compounds towards fragments [Se] and [Ni(CO)3] is in the same range as that of N-heterocyclic carbenes.

The pKa is the standard measure used to describe the aqueous proton affinity of a compound, indicating the proton concentration (pH) at which two protonation states (e.g. A− and AH) have equal free energy. However, compounds can have additional protonation states (e.g. AH2+), and may assume multiple tautomeric forms, with the protons in different positions (microstates). Macroscopic pKas give the pH where the molecule changes its total number of protons, while microscopic pKas identify the tautomeric states involved. As tautomers have the same number of protons, the free energy difference between them and their relative probability is pH independent so there is no pKa connecting them. The question arises: What is the best way to describe protonation equilibria of a complex molecule in any pH range? Knowing the number of protons and the relative free energy of all microstates at a single pH, ∆G°, provides all the information needed to determine the free energy, and thus the probability of each microstate at each pH. Microstate probabilities as a function of pH generate titration curves that highlight the low energy, observable microstates, which can then be compared with experiment. A network description connecting microstates as nodes makes it straightforward to test thermodynamic consistency of microstate free energies. The utility of this analysis is illustrated by a description of one molecule from the SAMPL6 Blind pKa Prediction Challenge. Analysis of microstate ∆G°s also makes a more compact way to archive and compare the pH dependent behavior of compounds with multiple protonatable sites.

The anions pertechnetate, TcO4-, and perrhenate, ReO4-, exhibit very similar chemical and physical properties. Revealing and understanding disparities between them enhances fundamental understanding of both. Electrospray ionization generated the gas-phase proton bound dimer (TcO4-)(H+)(ReO4-). Collision induced dissociation of the dimer yielded predominantly HTcO4 and ReO4-, which according to Cooks' kinetic method indicates that the proton affinity (PA) of TcO4- is greater than that of ReO4-. Density functional theory computations agree with the experimental observation, providing PA[TcO4-] = 300.1 kcal mol-1 and PA[ReO4-] = 297.2 kcal mol-1. Attempts to rationalize these relative PAs based on elementary molecular parameters such as atomic charges indicate that the entirety of bond formation and concomitant bond disruption needs to be considered to understand the energies associated with such protonation processes. Although in both the gas and solution phases, TcO4- is a stronger base than ReO4-, it is noted that the significance of even such qualitative accordance is tempered by the very different natures of the underlying phenomena.

Sulfinamides, as an asymmetric synthesizer, especially in drug synthesis, play critical roles in organic chemistry. In this study, the gas phase ion energetics data including the topical proton affinities, topical gas phase basicities, adiabatic and vertical ionization energies (IE), and electron affinities of sulfinamides were calculated at B3LYP/6-311++G(d,p), G4MP2, and MP2/6-311++G(d,p) levels. Determination of the actual protonation sites of sulfinamides is an important challenging issue in the experimental investigations. Three significant centers, including oxygen atom, sulfur atom, and nitrogen atom of the amide functional group of the sulfinamides, can be protonated. Our calculations indicate that in most cases, oxygen center is the most probable protonation site of sulfinamides. Bond polarities and bond lengths of ionic species in comparison with the corresponding neutral molecules are investigated. The effect of these parameters on the calculated topical proton affinity and topical gas phase basicity values is discussed. The energy barriers for internal proton transfer of different sites in protonated sulfinamides were obtained and discussed at MP2/6-311++G(d,p) level of theory. Results show the IEs increase when the electron acceptor substituents are connected to the S—O group, while the electron donor functional groups reduce the IE values. The EAs were shifted to more positive values if the H atom of sulfinamide substitutes with an electron acceptor functional groups.

Photoactive yellow protein (PYP) is a small photoreceptor protein that has two unusually short hydrogen bonds between the deprotonated p-coumaric acid chromophore and two amino acids, a tyrosine and a glutamic acid. This has led to considerable debate as to whether the glutamic acid-chromophore hydrogen bond is a low barrier hydrogen bond, with conflicting results in the literature. We have modified the pK(a) of the tyrosine by amber suppression and of the chromophore by chemical substitution. X-ray crystal structures of these modified proteins are nearly identical to the wild-type protein, so the heavy atom distance between proton donor and acceptor is maintained, even though these modifications change the relative proton affinity between donor and acceptor. Despite a considerable change in relative proton affinity, the NMR chemical shifts of the hydrogen-bonded protons are only moderately affected. QM/MM calculations were used to explore the protons’ potential energy surface and connect the calculated proton position with empirically measured proton chemical shifts. The results are inconsistent with a low barrier hydrogen bond but in all cases are consistent with a localized proton, suggesting an ionic hydrogen bond rather than a low barrier hydrogen bond.

Alkylammonium cation affinities of 64 nitrogen-containing organobases, as well as the respective proton transfer processes from the alkylammonium cations to the base, have been computed in the gas phase by using DFT methods. The guanidine bases show the highest proton transfer values (191.9–233 kJmol􀀀 1) whereas the cis-2,2’-biimidazole presents the largest affinity towards the alkylammonium cations (> 200 kJmol􀀀 1) values. The resulting data have been compared with the experimentally reported proton affinities of the studied nitrogen-containing organobases revealing that the propensity of an organobase for the proton transfer process increases linearly with its proton affinity. This work can provide a tool for designing senors for bioactive compounds containing amino groups that are protonated at physiological pH., This work was carried out with financial support from the Spanish MICINN for financial support (projects CTQ2018-094644-B-C22 and CTQ2017-87231-P and PID2020-113686GB-I00), Comunidad de Madrid (P2018/EMT-4329 AIRTEC-CM), and the Fundación Seneca- CARM (Project 20811/PI/18).

Biological membranes are barriers to polar molecules, so membrane embedded proteins control the transfers between cellular compartments. Protein controlled transport moves substrates and activates cellular signaling cascades. In addition, the electrochemical gradient across mitochondrial, bacterial and chloroplast membranes, is a key source of stored cellular energy. This is generated by electron, proton and ion transfers through proteins. The gradient is used to fuel ATP synthesis and to drive active transport. Here the mechanisms by which protons move into the buried active sites of Photosystem II (PSII), bacterial RCs (bRCs) and through the proton pumps, Bacteriorhodopsin (bR), Complex I and Cytochrome c oxidase (CcO), are reviewed. These proteins all use water filled proton transfer paths. The proton pumps, that move protons uphill from low to high concentration compartments, also utilize Proton Loading Sites (PLS), that transiently load and unload protons and gates, which block backflow of protons. PLS and gates should be synchronized so PLS proton affinity is high when the gate opens to the side with few protons and low when the path is open to the high concentration side. Proton transfer paths in the proteins we describe have different design features. Linear paths are seen with a unique entry and exit and a relatively straight path between them. Alternatively, paths can be complex with a tangle of possible routes. Likewise, PLS can be a single residue that changes protonation state or a cluster of residues with multiple charge and tautomer states.

Proton transfer from Bronsted acid sites (BASs) to alcohol molecules ignites the acid-catalyzed alcohol dehydration reactions. For aqueous phase dehydration reactions in zeolites, the coexisting water molecules around BASs in the zeolite pores significantly affect the alcohol dehydration activity. In the present work, proton transfer processes among the BASs of H-BEA zeolites, the adsorbed cyclohexanol and surrounding water clusters with different sizes up to 8 water molecules were investigated using ab initio molecular dynamics (AIMD) simulations combined with the multiple-walker well-tempered metadynamics algorithm. The plausible proton locations and proton transfer processes were characterized using two/three-dimensional free energy landscapes. The strong proton affinity makes the protonated cyclohexanol stable species until a water trimer is formed. The proton either is shared between protonated cyclohexanol and the water trimer or remains with the water trimer (H7O3+). With a further increase in water concentrations, the proton prefers to remain with the water clusters.

The structure, stability, and bonding character of fifteen (Ng-H-Ng)+ and (Ng-H-Ng')+ (Ng, Ng' = He-Xe) compounds were explored by theoretical calculations performed at the coupled cluster level of theory. The nature of the stabilizing interactions was, in particular, assayed using a method recently proposed by the authors to classify the chemical bonds involving the noble-gas atoms. The bond distances and dissociation energies of the investigated ions fall in rather large intervals, and follow regular periodic trends, clearly referable to the difference between the proton affinity (PA) of the various Ng and Ng'. These variations are nicely correlated with the bonding situation of the (Ng-H-Ng)+ and (Ng-H-Ng')+. The Ng-H and Ng'-H contacts range, in fact, between strong covalent bonds to weak, non-covalent interactions, and their regular variability clearly illustrates the peculiar capability of the noble gases to undergo interactions covering the entire spectrum of the chemical bond.

Hypothesis Charge descriptors of aquatic nanoparticles (NPs) are evaluated from proton titration curves measured at different salt concentrations and routinely analysed by the Non-Ideal Competitive Adsorption-Donnan (NICAD) model. This model, however, suffers from approximations regarding particle electrostatics, which may bias particle charge estimation. Implementation of Poisson-Boltzmann (PB) theory within consistent treatment of NPs protolytic data is expected to address NICAD shortcomings. Experiments An alternative to NICAD is elaborated on the basis of nonlinearized PB equation for soft particle electrostatics to properly unravel the electrostatic and chemical components of proton binding to NPs. A numerical package is developed for automated analysis of proton titration curves and proton affinity spectra at different salt concentrations. The performance of the method is illustrated for humic matter nanoparticles with different charge and size, and compared to that of NICAD. Findings Unlike NICAD, PB-based treatment successfully reproduces particle charge dependence on pH for practical salt concentrations from the thin to thick electric double layer limit. Donnan representation in NICAD leads to moderate to dramatic misestimations of proton affinity and binding heterogeneity depending on particle size to Debye layer thickness ratio. Interpretation of NPs protolytic properties with PB theory further avoids adjustment of the ‘particle Donnan volume’ empirically introduced in NICAD.

We report the proton affinities (PAs) and gas-phase basicities (GBs) of pyrogallol (1,2,3-trihydroxybenzene) and phloroglucinol (1,3,5-trihydroxybenzene), as determined by high level quantum chemical calculations and a series of isodesmic proton transfer reactions. These yet unmeasured values have relevance to release of active species from nanocarriers derived from the calixarene family of macrocycles. The PAs and GBs obtained for these two trihydroxybenzene isomers are compared and contrasted with those obtained previously for the third isomer, hydroxyquinol (1,2,4-trihydroxybenzene). Preferred protonation sites and relative thermochemical values are analyzed in terms of electron delocalization effects and the consequent disruption of intramolecular hydrogen bonding.

Cytochrome c Oxidase (CcO) is the terminal electron acceptor in aerobic respiratory chain, reducing O2 to water. The released free energy is stored by pumping protons through the protein, maintaining the transmembrane electrochemical gradient. Protons are held transiently in a proton loading site (PLS) that binds and releases protons driven by the electron transfer reaction cycle. Multi-Conformation Continuum Electrostatics (MCCE) was applied to crystal structures and Molecular Dynamics snapshots of the B-type Thermus thermophilus CcO. Six residues are identified as the PLS, binding and releasing protons as the charges on heme b and the binuclear center are changed: the heme a3 propionic acids, Asp287, Asp372, His376 and Glu126B. The unloaded state has one proton and the loaded state two protons on these six residues. Different input structures, modifying the PLS conformation, show different proton distributions and result in different proton pumping behaviors. One loaded and one unloaded protonation states have the loaded/unloaded states close in energy so the PLS binds and releases a proton through the reaction cycle. The alternative proton distributions have state energies too far apart to be shifted by the electron transfers so are locked in loaded or unloaded states. Here the protein can use active states to load and unload protons, but has nearby trapped states, which stabilize PLS protonation state, providing new ideas about the CcO proton pumping mechanism. The distance between the PLS residues Asp287 and His376 correlates with the energy difference between loaded and unloaded states.

Infrared spectra for a series of asymmetric proton-bound dimers with protonated trimethylamine (TMA-H+ ) as the proton donor were recorded and analyzed. The frequency of the N-H+ stretching mode is expected to red shift as the proton affinity of proton acceptors increases. The observed band, however, shows a peculiar splitting of approximately 300 cm-1 with the intensity shifting pattern resembling a two-level system. Theoretical investigation reveals that the observed band splitting and its extraordinarily large gap of around 300 cm-1 is a result of strong coupling between the fundamental of the proton stretching mode and overtone states of the two proton bending modes, that is commonly known as Fermi resonance (FR). We also provide a general theoretical model to link the strong FR coupling to the quasi-two-level system. Since the model does not depend on the molecular specification of TMA-H+ , the strong coupling we observed is an intrinsic property associated with proton motions.

Kinetic measurements, competitive hydrogenation, and H–D kinetic isotopic studies confirm the prevalence of proton–electron transfer events during the catalytic reduction of aliphatic carbonyls (C3–C6) at protic solvent and transition-metal (Ru, Pt, and Pd) interfaces. Polar protic solvents assist with the initial, rapid H-adatom ionization, which forms a proton and an electron pair. The proton shuffles through the solvent matrix and attacks the carbonyl oxygen in a quasi-equilibrated step, resulting in the formation of a charged hydroxy intermediate as the most abundant reactive intermediate. Subsequently, this intermediate undergoes a kinetically relevant H-adatom addition on the carbon atom that forms the charged alcohol, which then recombines with the electron and desorbs as the alcohol product. As a direct consequence of the initial, quasi-equilibrated proton transfer, the first-order rate coefficient increases exponentially as the gas-phase proton affinity of the carbonyls increases or as the invers...

Density functional calculations have been carried out to investigate the protonation pathways of phosphatranes, also known as Verkade bases, as a function of different equatorial substituents. The most favorable site of protonation is found to be at the phosphorus atom rather than the equatorial atom. The strength of transannular P⋯Nax interaction is responsible for the higher proton affinity of these bases. The proton transfer pathway from the phosphorus atom to the equatorial atom is kinetically very difficult owing to a high activation barrier. The initial deprotonation from the equatorial nitrogen atom is also favored by the presence of transannular interaction. The computed stabilization energies are found to depend largely on the phosphorus–equatorial bond strengths.

The proton affinity (PA) of a neutral molecule is defined as the negative of the enthalpy change for the gas-phase reaction between a proton and the neutral molecule to produce the (charged) conjugate acid of the molecule. PA is a fundamental property that is related to the structure of a molecule and affects its reactivity. Very few PA values are available for basic organic monoradicals and none for biradicals. Here, the PA values for several σ-type carbon-centered pyridine-based monoradicals and biradicals have been experimentally determined by monitoring proton transfer from the protonated mono- and biradicals to reference bases with known proton affinities as a function of time in Fourier-transform ion cyclotron resonance (FT-ICR) and linear quadrupole ion trap (LQIT) mass spectrometers. A procedure was developed for both instruments that permits differentiation between exo- and endothermic proton transfer reactions. The PA values of all the (bi)radicals studied were found to be lower than that of pyridine. This is rationalized based on the electron-withdrawing nature of the radical site(s). Thus, the PA values decrease in the order: pyridine > monoradicals > biradicals. The PA values of the monoradicals were also found to increase (making the protonated radicals less acidic) as the distance between the basic nitrogen atom and the radical site increases. Similar behavior was found for the biradicals, with one exception: 3,5-didehydropyridine has a larger PA (215.3 ± 3.3 kcal mol-1) than 3,4-didehydropyridine (PA = 213.4 ± 3.3 kcal mol-1) even though the latter biradical has one radical site farther away from the basic nitrogen atom. Quantum chemical calculations of the PAs of the (bi)radicals are in reasonably good agreement with the experimentally determined values. At the DFT (B3LYP), CCSD(T), and CASPT2 levels of theory, the mean unsigned errors are 2.3, 1.7, and 2.1 kcal mol-1.

The interaction of trans-W(N2)2(dppe)2 (1; dppe = 1,2-bis(diphenylphosphino)ethane) with relatively weak acids (p-nitrophenol, fluorinated alcohols, CF3COOH) was studied by means of variable temperature IR and NMR spectroscopy and complemented by DFT/B3PW91-D3 calculations. The results show, for the first time, the formation of a hydrogen bond to the coordinated dinitrogen, W–N≡N···H–O, that is preferred over H-bonding to the metal atom, W···H–O, despite the higher proton affinity of the latter. Protonation of the core metal—the undesirable side step in the conversion of N2 to NH3—can be avoided by using weaker and, more importantly, bulkier acids.

Ion-molecule reactions of Me2S2 with a wide range of aliphatic carbanions differing by structure and proton affinity values have been studied in the gas phase using mass spectrometry techniques and DFT calculations. The analysis of the spectra shows a variety of product ions formed via different reaction mechanisms, depending on the structure and proton affinity of the carbanion. Product ions of thiophilic reaction (m/z 47), SN2 (m/z 79), and E2 elimination – addition sequence of reactions (m/z 93) can be observed. Primary products of thiophilic reaction can undergo subsequent SN2 and proton transfer reactions. Gibbs free energy profiles calculated for experimentally observed reactions using PBE0/6-311+G(2d,p) method show good agreement with experimental results. Graphical Abstractᅟ Electronic supplementary material The online version of this article (10.1007/s13361-017-1858-x) contains supplementary material, which is available to authorized users.

Proton transfer reactions have been a topic of fundamental interest in several areas of chemistry and biology. However, such reactivity has not been explored in detail for nanoscale materials. In this article, we present a unique reaction of an atomically precise monolayer-protected silver nanocluster, [Ag29(BDT)12]3−, with a proton (H+). Under controlled conditions, the strong proton affinity facilitated a complete conversion of the cluster to its protonated form, [Ag29(BDT)12H]2−. Moreover, binding of alkali metal ions (Li+, Na+, K+, Rb+ and Cs+) induced specific structural changes and also favored dimerization of the cluster. In this case, the cations acted as a bridge between the two clusters and the degree of dimerization was specific to the size of the cations. The conformational changes and separation of the alkali–metal ion bound dimers from their respective monomers have been investigated by ion mobility mass spectrometry (IM MS) and tandem mass spectrometric studies. Density functional theory (DFT) calculations have been used to determine the possible structures of the monomers and the dimers. Similar reactivity of the cluster can also be extended to other metal ions. While the present study helps to expand the ion-chemistry of atomically precise clusters, gas-phase basicity of the molecule can be explored in further detail and this can find applications in the areas of sensing and materials in general.

A systematic investigation on the potential basicity of the novel hyperlithiated species Li3F2O and Li3F2(OH)n (n = 1, 2) based upon the superalkali cluster Li3F2 was conducted using high-level ab initio techniques. Equilibrium structures for both the neutral and anionic states in the gas-phase were identified and their relative stabilities using atomization enthalpies are analysed and compared with their respective proton affinities and gas-phase basicities. Our calculations, using a modified form of the CBS-QB3 composite method, identified several unique structures that possess superbase potential comparable to the proton affinity of Roger Alder's canonical Proton Sponge. The calculations show that, in general, as the number of hydroxide groups increase, so too does the proton affinity.

The optical properties of flavins strongly depend on the charge and oxidation states as well as the environment. Herein, the electronic spectrum of cold protonated lumichrome, the smallest flavin molecule, is recorded by means of photodissociation in the visible range (VISPD) in a cryogenic ion trap tandem mass spectrometer coupled to an electrospray ionization source. The vibronic spectrum is assigned to the S1 ← S0 (ππ*) transition of the most stable N5-protonated isomer by comparison with quantum chemical calculations at the PBE0/cc-pVDZ level in combination with multidimensional Franck-Condon simulations. Analysis of the geometric and electronic structures of neutral and protonated lumichrome explains the large red shift of the band origin upon protonation (ΔS1 ∼ -6000 cm-1), which corresponds to the increase in proton affinity upon S1 excitation as a result of charge transfer. N5 protonation greatly modifies the structure of the central pyrazine ring of the chromophore. The orbitals involved in S1 ← S0 excitation include an important fraction of the probability at the central ring and they are, hence, largely influenced by the positive charge of the attached proton. The rich vibronic spectrum indicates the large geometry change upon S1 excitation. This combined experimental and computational approach is shown to be suitable to determine the optical properties of flavins as a function of oxidation, protonation, metalation, and microsolvation state.

A new class of superbases was designed using cycloheptatriene derivatives and their basicities were assessed theoretically by B3LYP/6–311++G(d,p) method in gas phase. The superbasicity of these compounds is due to formation of an aromatic 7-membered ring upon protonation which stabilizes the protonated structure. Other fragments such as guanidine and phosphazene groups were also added to these compounds to enhance their basicities. The computed proton affinities (PA) for these superbases were 245–288 kcal/mol. Cycloheptatriene was also used in the design of some proton sponges to increase their basicities. The computed PAs of the proton sponges were 256–279 kcal/mol.

Proton affinities of a number of alkyl acetates (CH3–C(=O)–OR) and of methyl alkanoates (R–C(=O)–OCH3, R=H, alkyl) have been assembled from the literature or measured using the kinetic method. It was observed that the proton affinities for the isomeric species CH3–C(=O)–OR and R–C(=O)–OCH3 are almost identical, an unexpected result as the charge in these protonated ester molecules is largely at the keto carbon atom and so this site should be more sensitive to alkyl substitution. Analysis of the data, including those from lone pair ionisation and core-electron ionisation experiments available from the literature, indicate that after protonation, extensive charge relaxation (or polarisation) takes place (as is also the case, according to the literature, after core-electron ionisation). By contrast, after lone pair ionisation, which results in radical cations, such relaxation processes are relatively less extensive. As a consequence, changes in ion enthalpies of these protonated molecules follow more closely the changes in neutral enthalpies, compared with changes in enthalpies of the corresponding radical cations, formed by electron detachment. Preliminary analyses of published energetic data indicate that the above finding for organic esters may well be another example of a more general phenomenon.

Cytochrome c oxidase (CcO) catalyzes the reduction of oxygen to water and uses the released free energy to pump protons against the transmembrane proton gradient. To better understand the proton-pumping mechanism of the wild-type (WT) CcO, much attention has been given to the mutation of amino acid residues along the proton translocating D-channel that impair, and sometimes decouple, proton pumping from the chemical catalysis. Although their influence has been clearly demonstrated experimentally, the underlying molecular mechanisms of these mutants remain unknown. In this work, we report multiscale reactive molecular dynamics simulations that characterize the free-energy profiles of explicit proton transport through several important D-channel mutants. Our results elucidate the mechanisms by which proton pumping is impaired, thus revealing key kinetic gating features in CcO. In the N139T and N139C mutants, proton back leakage through the D-channel is kinetically favored over proton pumping due to the loss of a kinetic gate in the N139 region. In the N139L mutant, the bulky L139 side chain inhibits timely reprotonation of E286 through the D-channel, which impairs both proton pumping and the chemical reaction. In the S200V/S201V double mutant, the proton affinity of E286 is increased, which slows down both proton pumping and the chemical catalysis. This work thus not only provides insight into the decoupling mechanisms of CcO mutants, but also explains how kinetic gating in the D-channel is imperative to achieving high proton-pumping efficiency in the WT CcO.

This work presents a structural approach for determination of proton affinities of molecules. In proton-bound dimer [X…H…M]+, M and X compete with each other to capture the proton. The correlation between proton affinities of a series of molecules, M, and X…H bond length was studied while X was a common molecule in the all proton-bound dimers. Linear relationships were observed between proton affinities of a series of alcohols, ethers, aldehydes, ketones and amines and X…H bond length, where H2O and HF were used as X. The method was employed for the measurement of proton affinities of (HF)1–10 clusters using NH3 and H2O as common molecules, [NH3…H…(HF)n]+ and [H2O…H…(HF)n]+. A linear correlation was observed for the PAs of (HF)n clusters versus N…H bond length.

The state of deprotonation/protonation of surfaces has far-ranging implications in chemistry, from acid–base catalysis1 and the electrocatalytic and photocatalytic splitting of water2, to the behaviour of minerals3 and biochemistry4. An entity’s acidity is described by its proton affinity and its acid dissociation constant pKa (the negative logarithm of the equilibrium constant of the proton transfer reaction in solution). The acidity of individual sites is difficult to assess for solids, compared with molecules. For mineral surfaces, the acidity is estimated by semi-empirical concepts, such as bond-order valence sums5, and increasingly modelled with first-principles molecular dynamics simulations6,7. At present, such predictions cannot be tested—experimental measures, such as the point of zero charge8, integrate over the whole surface or, in some cases, individual crystal facets9. Here we assess the acidity of individual hydroxyl groups on In2O3(111)—a model oxide with four different types of surface oxygen atom. We probe the strength of their hydrogen bonds with the tip of a non-contact atomic force microscope and find quantitative agreement with density functional theory calculations. By relating the results to known proton affinities of gas-phase molecules, we determine the proton affinity of the different surface sites of In2O3 with atomic precision. Measurements on hydroxylated titanium dioxide and zirconium oxide extend our method to other oxides. Non-contact atomic force microscopy measurements are used to probe the hydrogen bond strength of individual surface hydroxyl groups and determine their acidity with atomic precision.

Antioxidants can reveal their activity through several different but similar reaction mechanisms such as hydrogen atom transfer (HAT), proton-coupled electron transfer (PCET), single-electron transfer (SET), single-electron transfer followed by proton transfer (SET-PT), sequential proton loss electron transfer (SPLET), sequential proton loss hydrogen atom transfer (SPLHAT), and radical adduct formation (RAF). The antioxidative properties of natural phenolic compounds (quercetin, gallic acid, and dihydroxybenzoic acids) were examined applying the density functional theory (DFT). The potency of free radical scavenging of the mentioned compounds was analyzed using the thermodynamic parameters: bond dissociation enthalpy, ionization potential, proton dissociation enthalpy, proton affinity, and electron-transfer enthalpy. The influence of different radicals was estimated on the bases of reactions enthalpies between antioxidants and free radical species. The effect of free radicals on HAT, PCET, and SPLET mechanisms is explained by means of a mechanistic approach. The obtained results contribute to the elucidation and understanding of the complex processes involved in the antioxidative action.

The spectral behavior of some p-nitro-p-substituted benzoylhydrazones in the perchloric acid media was followed, applying the UV spectroscopy. The position of the absorption maximum in the spectra was defined in acidic media and the electronic transitions were discussed, as well (7

In this study, we present reactions of NH4+ with a series of analytes (A): acetone (C3H6O), methyl vinyl ketone (C4H6O), methyl ethyl ketone (C4H8O), and eight monoterpene isomers (C10H16) using a Selective Reagent Ionization Time-of-Flight Mass Spectrometer (SRI-ToF-MS). We studied the ion-molecule reactions at collision energies of 55 and 80 meV. The ketones, having a substantially lower proton affinity than NH3, produce only cluster ions NH4+ (A) in detectable amounts at 55 meV. At 80 meV, no cluster ions were detected meaning that these adduct ions are formed by strongly temperature dependent association reactions. Bond energies of cluster ions and proton affinities for most monoterpenes are not known and were estimated by high level quantum chemical calculations. The calculations reveal monoterpene proton affinities, which range from slightly smaller to substantially higher than the proton affinity of NH3. Proton affinities and cluster bond energies allow to group the monoterpenes as a function of the enthalpy for the dissociation reaction NH4+A→AH++NH3 . We find that this enthalpy can be used to predict the NH4+ (A) cluster ion yield. The present study explains product ion formation involving NH4+ ion chemistry. This is of importance for chemical ionization mass spectrometry (CIMS) utilizing NH4+ as well as NH4+ (H2O) as reagent ions to quantitatively detect atmospherically important organic compounds in real-time.

1,8-bis-(dimethylamino)-naphthalene, the first ever reported proton sponge, has been snatching much attention with its spectacular proton affinity (PA) for decades. This manuscript discusses the affinities of DMAN towards s-block metal ions Li+, Na+, K+, Be++, Mg++ and Ca++ and compare with PA. We report that the affinity of DMAN towards Be++ is higher than PA. It was observed that increasing methylation at the peri-nitrogen atoms increases the beryllium ion affinity like PA. In light of all these discussions, this manuscript discusses if DMAN can better be termed as a beryllium ion sponge.

We investigate the gas phase proton transfer reactivity of the dianionic molybdenum oxysulfide clusters [Mo2O2S6]2– and [Mo2O2S5]2– in binary collisions in an FT-ICR mass spectrometer in combination with quantum chemical calculations. The proton transfer reactions are probed with a series of acids with increasing proton affinity, namely trifluoroacetic acid, difluoroacetic acid, pyruvic acid and formic acid. Proton transfer followed by Coulomb explosion is observed for both dianions with all acids except for formic acid. The calculations predict a proton affinity of 16.1(1) and 16.5(1) eV for [Mo2O2S6]2– and [Mo2O2S5]2–, respectively, significantly higher than the proton affinities of tri- and difluoroacetate as well as pyruvate and formate, which range from 14.00(18)–14.98(10) eV. Calculated reaction potential energy surfaces explain the observations. A Coulomb barrier separating the collision complex from the products is present in all cases. The barrier lies well below the entrance channel for trifluoroacetic acid, difluoroacetic acid and pyruvic acid. For formic acid, however, the barrier lies near the entrance channel.

Protic ionic liquids (PIL) are promising anhydrous proton conductors for fuel cell applications especially at higher temperature. In this study, quantum chemistry calculations using density functional theory (DFT) were performed to investigate proton conduction in imidazolium methanesulfonate (IMMSA) PIL on interaction with varying imidazole (IM) concentration. These investigations include the extent of proton transfer (PT) from methanesulfonic acid to the imidazole base and calculation of various energy barriers of PT. The results show that the difference in gas phase proton affinity (ΔPA) of the anion and base is a reliable predictor of the extent of proton transfer from acid to base, and ΔPA values

A method is developed for the prediction of mass spectral ion counts of drug-like molecules using in silico calculated chemometric data. Various chemometric data, including polar and molecular surface areas, aqueous solvation free energies, and gas-phase and aqueous proton affinities were computed, and a statistically significant relationship between measured mass spectral ion counts and the combination of aqueous proton affinity and total molecular surface area was identified. In particular, through multilinear regression of ion counts on predicted chemometric data, we find that log10(MS ion counts) = -4.824 + c 1•PA + c 2•SA, where PA is the aqueous proton affinity of the molecule computed at the SMD(aq)/M06-L/MIDI!//M06-L/MIDI! level of electronic structure theory, SA is the total surface area of the molecule in its conjugate base form, and c 1 and c 2 have values of -3.912 × 10-2 mol kcal-1 and 3.682 × 10-3 A-2. On a 66-molecule training set, this regression exhibits a multiple R value of 0.791 with p values for the intercept, c 1, and c 2 of 1.4 × 10-3, 4.3 × 10-10, and 2.5 × 10-6, respectively. Application of this regression to an 11-molecule test set provides a good correlation of prediction with experiment (R = 0.905) albeit with a systematic underestimation of about 0.2 log units. This method may prove useful for semiquantitative analysis of drug metabolites for which MS response factors or authentic standards are not readily available. Graphical Abstract ᅟ.

Proton, lithium and sodium cations affinities and gas phase basicities toward them were calculated for 60 organic compounds including alcohols, ethers, aldehydes, ketones and amines using B3LYP and CBS-Q methods. The proton affinities (PA) computed by the both methods were in good agreement with the experimental PAs. In the case of lithium cation basicities (LCB) and sodium cation basicities (SCB), the CBS-Q method reproduced the experimentally obtained values while the B3LYP overestimated them by about 1–2 kcal/mol. There was a linear relationship between lithium cation affinities (LCA) and sodium cation affinities (SCA), regardless of the molecules type, while the PA-LCA and PA-SCA correlations were linear only for homogeneous families.

Proton affinities (PA) of non-hydrated, M, and hydrated forms, M(H2O)1,2,3, of 20 organic molecules including alcohols, ethers, aldehydes, ketones and amines were calculated by the B3LYP/6-311++G(d,p) method. For homogeneous families, linear correlations were observed between PAs of the M(H2O)1,2,3 and the PAs of the non-hydrated molecules. Also, the absolute values of the hydration enthalpies of the protonated molecules decreased linearly with the PAs. The correlation functions predicted that for an amine with PA 1100 kJ/mol the PA(M(H2O)) is smaller than the PA.

Conformational effects on the proton affinity of oligopeptides have been studied using six alanine (A)-based acetylated dipeptides containing a basic probe that is placed closest to either the C- or the N-terminus. The basic probe includes Lysine (Lys) and two nonproteinogenic Lys-homologues, ornithine (Orn) and 2,3-diaminopropionic acid (Dap). The proton affinities of the peptides have been determined using the extended Cooks kinetic method in a triple quadrupole mass spectrometer. Computational studies have been carried out to search for the lowest energy conformers and to calculate theoretical proton affinities as well as various molecular properties using the density functional theory. The dipeptides containing a C-terminal probe, ALys, AOrn, and ADap, were determined to have a higher proton affinity by 1-4 kcal/mol than the corresponding dipeptides containing an N-terminal probe, LysA, OrnA, and DapA. For either the C-probe peptides or the N-probe peptides, the proton affinity reduces systematically as the side-chain of the probe residue is shortened. The difference in the proton affinities between isomeric peptides is largely associated with the variation of the conformations. The peptides with higher values of the proton affinity adopt a relatively compact conformation such that the protonated peptides can be stabilized through more efficient internal solvation.

Protonation of the anion in an ionic liquid plays a key role in the hypergolic reaction between ionic liquids and oxidizers such as white fuming nitric acid. To investigate the influence of the cation on the protonation reaction, the deprotonation energy of a set of cations has been calculated at the MP2 level of theory. Specifically, guanidinium, dimethyltriazanium, triethylamine, N-ethyl-N-methyl-pyrrolidinium, N-ethyl-pyridinium, 1,4-dimethyl-1,2,4-triazolium, 1-ethyl-4-methyl-1,2,4-triazolium, and 1-butyl-4-methyl-1,2,4-triazolium were studied. In addition, the net proton transfer energies from the cations to a set of previously studied anions was calculated, demonstrating an inverse correlation between the net proton transfer energy and the likelihood that the cation/anion combination will react hypergolically with white fuming nitric acid. It is suggested that this correlation occurs due to a balance between the energy released by the proton transfer and the rate of proton transfer as determined by the ionicity of the ionic liquid.

The ionicity and transport properties of a series of diethylmethylamine (DEMA) based protic ionic liquids (PILs) were characterized, principally utilizing nuclear magnetic resonance (NMR) spectroscopy. PILs were formed via the protonation of DEMA by an array of acids spanning a large range of acidities. A correlation between the (1)H chemical shift of the exchangeable proton and the acidity of the acid used for the synthesis of the PIL was observed. The gas phase proton affinity of the acid was found to be a better predictor of the extent of proton transfer than the commonly used aqueous ΔpKa. Pulsed field gradient (PFG) NMR was used to determine the diffusivity of the exchangeable proton in a subset of the PILs. The exchangeable proton diffuses with the acid if the PIL is synthesized with a weak acid, and with the base if a strong acid is used. The ionicity of the PILs was characterized using the Walden analysis and by comparing to the ideal Nernst-Einstein conductivity predicted from the (1)H PFG-NMR results.

Photosystem II (PSII) uses water as the terminal electron donor, producing oxygen in the Mn4CaO5 oxygen evolving complex (OEC), while cytochrome c oxidase (CcO) reduces O2 to water in its heme⁻Cu binuclear center (BNC). Each protein is oriented in the membrane to add to the proton gradient. The OEC, which releases protons, is located near the P-side (positive, at low-pH) of the membrane. In contrast, the BNC is in the middle of CcO, so the protons needed for O2 reduction must be transferred from the N-side (negative, at high pH). In addition, CcO pumps protons from N- to P-side, coupled to the O2 reduction chemistry, to store additional energy. Thus, proton transfers are directly coupled to the OEC and BNC redox chemistry, as well as needed for CcO proton pumping. The simulations that study the changes in proton affinity of the redox active sites and the surrounding protein at different states of the reaction cycle, as well as the changes in hydration that modulate proton transfer paths, are described.

Multicomponent density functional theory (DFT) allows the consistent quantum mechanical treatment of both electrons and nuclei. Recently the epc17 electron-proton correlation functional was derived using a multicomponent extension of the Colle-Salvetti formalism and was implemented within the nuclear-electronic orbital (NEO) framework for treating electrons and specified protons quantum mechanically. Herein another electron-proton correlation functional, denoted epc18, is derived using a different form for the functional parameter interpreted as representing the correlation length for electron-proton interactions. The epc18 functional is shown to perform similarly to the epc17 functional for predicting three-dimensional proton densities and proton affinities. Both functionals are shown to be transferable for use with a series of diverse electronic exchange-correlation functionals, indicating that any reasonable electronic exchange-correlation functional may be used in tandem with the epc17 and epc18 electron-proton correlation functionals. Understanding the impact of different forms of the electron-proton correlation functional, as well as the interplay between electron-proton and electron-electron correlation, is critical for the general applicability of NEO-DFT.

Molecular wires are functional molecules applicable in the field of transfer processes in technological and biochemical applications. Besides molecular wires with the ability to transfer electrons, research is currently focused on molecular wires with high proton affinity and proton transfer ability. Recently, proposed peptidic proton wires (H wires) are one example. Their ability to mediate the transport of protons from aqueous solutions onto the surface of a Hg electrode in a catalytic hydrogen evolution reaction was investigated by constant-current chronopotentiometric stripping. However, elucidating the structure of H wires and rationalizing their stability are key requirements for their further research and application. In this article, we focus on the His (H) and Ala (A)-containing peptidic H wire A3-(H-A2)6 in solution and after its immobilization onto the electrode surface in the presence of the secondary structure stabilizer 2,2,2-trifluoroethanol (TFE). We found that the solvent containing more ...

LiO − (proton affinity = 1785 kJ/mol) is the strongest base reported in the literature, followed by CH 3 − (proton affinity = 1743 kJ/mol). Using ab initio and DFT calculations, we propose the design of a novel base OLi 3 O − , by interacting OLi 3 superalkali with O atom, which is even more basic than LiO − . The proton affinity of OLi 3 O − isomers lies in the range 1803–1928 kJ/mol. This strongest base is kinetically and thermodynamically stable, which can be synthesized by reacting Li 2 O with LiO − at least in gas phase. This study may provide suitable path to the experimentalists to further explore this novel species.

Extended hydrogen bond networks are a common structural motif of enzymes. A recent analysis proposed quantum delocalization of protons as a feature present in the hydrogen bond network spanning a triad of tyrosines (Y(16), Y(32), and Y(57)) in the active site of ketosteroid isomerase (KSI), contributing to its unusual acidity and large isotope shift. In this study, we utilized amber suppression to substitute each tyrosine residue with 3-chlorotyrosine to test the delocalization model and the proton affinity balance in the triad. X-ray crystal structures of each variant demonstrated that the structure, notably the O-O distances within the triad, was unaffected by 3-chlorotyrosine substitutions. The changes in the cluster's acidity and the acidity's isotope dependence in these variants were assessed via UV-vis spectroscopy and the proton sharing pattern among individual residues with (13)C nuclear magnetic resonance. Our data show pKa detuning at each triad residue alters the proton delocalization behavior in the H-bond network. The extra stabilization energy necessary for the unusual acidity mainly comes from the strong interactions between Y(57) and Y(16). This is further enabled by Y(32), which maintains the right geometry and matched proton affinity in the triad. This study provides a rich picture of the energetics of the hydrogen bond network in enzymes for further model refinement.

A theoretical study on antioxidant properties of fourteen xanthones extracted from the pericarp of G. Mangostana has been performed. Three main reaction mechanisms are investigated: hydrogen atom transfer (HAT), single electron transfer–proton transfer (SETPT) and sequential proton loss electron transfer (SPLET). The O H bond dissociation enthalpy (BDE), ionization energy (IE), proton affinity (PA) and electron transfer energy (ETE) parameters were computed in gas phase and water. The results show that HAT would be the most favorable mechanism for explaining antioxidant activity of xanthones in gas phase, whereas the SPLET mechanism is thermodynamically favored in water.

Quantum theoretical studies show that the extremely high proton affinity at the metal center of the unusual T-shaped (LXL)AuI -pincer complex, consisting of a carbazole framework and two mesoionic carbenes, is caused by relativistic effects. This brings the basicity of the AuI center in line with the electron-rich nitrogen atom of the carbazole ring system, resulting in one of the highest proton affinities for a neutral molecule.

In proteins, proton exchange is caused due to the changes in the proton affinity (pKa) of ionizable groups that are engaged in conformational changes induced by the binding of a ligand. In addition, knowledge regarding the type and number of such ionizable groups is very important to understand the pH-dependent changes of the thermodynamic parameters. Therefore, in this study, we performed a comprehensive analysis of proton exchange by using beta lactoglobulin (Blg), a representative of the lipocalin family of proteins. We used isothermal titration calorimetry to evaluate the proton exchange during binding with sodium dodecyl sulfate (SDS) at different pHs ranging from 2 to 9. SDS binds to Blg in all studied range of pHs and enthalpy-driven reactions are observed in acidic pH, whereas enthalpy-entropy driven reactions are observed in neutral and basic pHs. Enthalpy-entropy compensation leads to relatively small changes in the association constants with the maximal value at pH = 8.0. The simultaneous analysis of the number of exchanged protons, the binding constants, and the enthalpy was performed in the range pH 5.5-9. At least 4 residues that change their ionization pattern are needed to explain the observed pH dependence.