Experimental Gas-phase Acidities Research Articles

Experimental and computational gas-phase acidity of cyclic ureas

The gas-phase acidities (GA) of three cyclic ureas, imidazolidin-2-one (1H), benzoimidazolinone (2H) and parabanic acid (3H), have been experimentally determined. GA of 1H (1485.1 ± 8.4 kJ mol−1) was derived by equilibrium method using FT-ICR mass-spectrometer, while GAs of 2H (1413.7 ± 9.0 kJ mol−1) and 3H (1334.1 ± 9.0 kJ mol−1) were derived by the extended Cooks kinetic method (EKM) using ESI-TQ mass spectrometer. Quantum chemical calculations, at the Gaussian-n levels of theory (G3 and G4), shed light on structural and electronic effects on the intrinsic acidity of the studied compounds. These calculations confirmed the excellent consistency of our experimental results.

Validation and extension of the gas-phase superacidity scale.

In recent years it has become increasingly evident that the previously reported experimental gas-phase acidity (GA) values of several strong acids differ markedly from the corresponding high-level computational values. In this work, the superacidic part of the current gas-phase acidity scale was validated and extended. For that, the strongly acidic section of the gas-phase acidity scale was remeasured using the equilibrium Fourier transform ion cyclotron resonance (FTICR-MS) method, adding new compounds and introducing methodological changes. In particular, a novel approach for anchoring the scale was used - the results were anchored to the computational (W1BD) GA values of trifluoromethanesulfonic acid and bis(fluorosulfonyl)imide (291.3 and 286.2 kcal mol-1 , respectively). The newly measured section consists of 20 gas-phase superacids and its consistency standard deviation is 0.2 kcal mol-1 , indicating good consistency. In contrast to the previously reported experimental gas-phase acidities for a number of important superacids, the current results are consistent with high-level theoretical GA values. Structure-acidity relationships based on the current results as well as available MeCN and DCE acidity data were described and explained. The introduced methodological innovations were found to be adequate and strong evidence is presented in support of the current GA values of the strong acids.

DFT calculations in periodic boundary conditions of gas-phase acidities and of transition-metal anionic clusters: case study with carboxylate-stabilized ruthenium clusters

The first part of this study aims at evaluating the accuracy of DFT calculations of acids and their conjugate bases in periodic boundary conditions and plane-wave basis sets. The resulting gas-phase acidities are compared to experimental data. Calculations done with the PBE functional are accurate, with a $$\sim 4\,\hbox {kcal mol}^{-1}$$ mean average deviation (MAD) with respect to experiments and a $$\sim 1\,\hbox {kcal mol}^{-1}$$ MAD with respect to non-periodic DFT calculations done in the aug-cc-pvtz basis set with the same functional. In the second part, the relative stability of $$\mathrm{Ru}_{13}^{-}$$ isomers is also successfully compared to previous calculations done using local basis sets (Waldt et al. in J Chem Phys 142:024319, 2015). Finally, several carboxylic acids and their conjugate bases are adsorbed on two Ru $$_{13}$$ clusters, showing a linear correlation between adsorption energies and experimental gas-phase acidities.

Gas-Phase Acidities and Basicities of Alanines and N-Benzylalanines by the Extended Kinetic Method.

This paper reports an experimental determination of the gas-phase acidities and basicities of N-benzylalanines, in both their α and β forms, by means of the extended kinetic method (EKM). The experimental gas-phase acidity of β-alanine was also determined. Standard ab initio molecular orbital calculations at the G3 level were performed for alanines, and at the G3(MP2)//B3LYP level for N-benzylalanines. There is a very good agreement between the experimental and the calculated values. The more branched α-amino acids are more acidic and less basic than the linear β-amino acids.

Acidity of Strong Acids in Water and Dimethyl Sulfoxide.

Careful analysis and comparison of the available acidity data of HCl, HBr, HI, HClO4, and CF3SO3H in water, dimethyl sulfoxide (DMSO), and gas-phase has been carried out. The data include experimental and computational pKa and gas-phase acidity data from the literature, as well as high-level computations using different approaches (including the W1 theory) carried out in this work. As a result of the analysis, for every acid in every medium, a recommended acidity value is presented. In some cases, the currently accepted pKa values were revised by more than 10 orders of magnitude.

Anchoring the Gas-Phase Acidity Scale from Hydrogen Sulfide to Pyrrole. Experimental Bond Dissociation Energies of Nitromethane, Ethanethiol, and Cyclopentadiene.

A meta-analysis of experimental information from a variety of sources is combined with statistical thermodynamics calculations to refine the gas-phase acidity scale from hydrogen sulfide to pyrrole. The absolute acidities of hydrogen sulfide, methanethiol, and pyrrole are evaluated from literature R-H bond energies and radical electron affinities to anchor the scale. Relative acidities from proton-transfer equilibrium experiments are used in a local thermochemical network optimized by least-squares analysis to obtain absolute acidities of 14 additional acids in the region. Thermal enthalpy and entropy corrections are applied using molecular parameters from density functional theory, with explicit calculation of hindered rotor energy levels for torsional modes. The analysis reduces the uncertainties of the absolute acidities of the 14 acids to within ±1.2 to ±3.3 kJ/mol, expressed as estimates of the 95% confidence level. The experimental gas-phase acidities are compared with calculations, with generally good agreement. For nitromethane, ethanethiol, and cyclopentadiene, the refined acidities can be combined with electron affinities of the corresponding radicals from photoelectron spectroscopy to obtain improved values of the C-H or S-H bond dissociation energies, yielding D298(H-CH2NO2) = 423.5 ± 2.2 kJ mol(-1), D298(C2H5S-H) = 364.7 ± 2.2 kJ mol(-1), and D298(C5H5-H) = 347.4 ± 2.2 kJ mol(-1). These values represent the best-available experimental bond dissociation energies for these species.

Acidities of closo-1-COOH-1,7-C2B10H11 and Amino Acids Based on Icosahedral Carbaboranes

Carborane clusters are not found in Nature and are exclusively man-made. In this work we study, both experimentally and computationally, the gas-phase acidity (measured GA = 1325 kJ·mol(-1), computed GA = 1321 kJ·mol(-1)) and liquid-phase acidity (measured pKa = 2.00, computed pKa = 1.88) of the carborane acid closo-1-COOH-1,7-C2B10H11. The experimental gas-phase acidity was determined with electrospray tandem mass spectrometry (ESI/MS), by using the extended Cooks kinetic method (EKM). Given the similar spatial requirements of the title icosahedral cage and benzene and the known importance of aminoacids as a whole, such a study is extended, within an acid-base context, to corresponding ortho, meta, and para amino acids derived from icosahedral carborane cages, 1-COOH-n-NH2-1, n-R with {R = C2B10H10, n = 2, 7, 12}, and from benzene {R = C6H4, n = 2, 3, 4}. A remarkable difference is found between the proportion of neutral versus zwitterion structures in water for glycine and the carborane derived amino acids.

Electronic Effects of 11β Substituted 17β-Estradiol Derivatives and Instrumental Effects on the Relative Gas Phase Acidity

Numerous studies have highlighted the role of the proton donor characteristics of the phenol group of 17β-estradiol (E(2)) in its association with the estrogen receptor alpha (ERα). Since the substitutions at position C((11)) have been reported to modulate this association, we hypothesized that such substitutions may modify the phenol acidity. Hence, phenol gas-phase acidity of nine C((11))-substituted E(2)-derivatives were evaluated using the extended Cooks' kinetic method, which is a method widely used to determine thermochemical properties by mass spectrometry. To enhance accuracy in data collection we recorded data from several instruments, including quadrupole ion trap, triple quadrupole, and hybrid QqTOF. Indeed, we report for the first time the use of the QqTOF instrument to provide a novel means to improve data accuracy by giving access to an intermediate effective temperature range. All experimental gas-phase acidity values were supported by theoretical calculations. Our results confirmed the ability of distant substituents at C((11)) to modulate the phenol acidity through electrostatic interactions, electron withdrawing inductive effects, and mesomeric effects. However, no relationship was found between the phenol gas-phase acidity of investigated steroids and their binding affinity for ERα assessed in solution. Thus, our results highlight that the intrinsic properties of the hormone do not influence sufficiently the stabilization of the hormone/ERα complex. It is more likely that such stabilization would be more related to factors depending on the environment within the binding pocket such as hydrophobic, steric as well as direct intermolecular electrostatic effects between ERα residues and the substituted steroidal estrogens.

Inductive effects in radicals calculated from DFT energies; substituted bicyclo[2.2.2]octan‐1‐yloxy radicals

Energies of a series of 4-substituted 1-oxybicyclo[2.2.2]octan-1-yloxy radicals with 18 various substituents were calculated within the framework of the DFT theory at the levels UB3LYP/6-311+G(d,p)//UB3LYP/6-311+G(d,p) and UB3LYP/6-311++G(2df,p)//UB3LYP/6-311+G(d,p) and compared with similar series of the parent alcohols, their deprotonated and protonated forms calculated at the levels B3LYP/6-311+G(d,p)//B3LYP/6-311+G(d,p) and B3LYP/6-311++G(2df,p)//B3LYP/6-311+G(d,p). The two levels are of the same performance and both are sufficient for molecules of this type according to comparison with scarce experimental gas-phase acidities and basicities. The substituent effects were analyzed in terms of isodesmic equations. In addition to strong dependence on the substituent inductive effect, a slight dependence on the electronegativity of the first atom of the substituent was proven in certain cases. In all aspects, there is no qualitative difference between the effects on radicals and on similar closed shell species. Radicals behave as slightly electron deficient; the substituent effect is weaker than that on the ions but stronger than on neutral molecules.

Ab Initio Prediction of the Gas- and Solution-Phase Acidities of Strong Brønsted Acids: The Calculation of pKa Values Less Than −10

The intrinsic gas-phase acidities of a series of 21 Brønsted acids have been predicted with G3(MP2) theory. The G3(MP2) results agree with high level CCSD(T)/CBS acidities for H(2)SO(4), FSO(3)H, CH(3)SO(3)H, and CF(3)SO(3)H to within 1 kcal/mol. The G3(MP2) results are in excellent agreement with experimental gas-phase acidities in the range 342-302 kcal/mol to within <1 kcal/mol for 14 out of 15 acids. Five of the six acids in the range of 302-289 kcal/mol had an average deviation of 5.5 kcal/mol and the strongest acid, (CF(3)SO(2))(3)CH, deviated by 15.0 kcal/mol. These high-level calculations strongly suggest that the experimental acidities in this very acidic part of the scale need to be remeasured. The CCSD(T)/CBS (mixed exponential Gaussian) additive approach for CH(3)CO(2)H, HNO(3), H(2)SO(4), CH(3)SO(3)H, FSO(3)H, and CF(3)SO(3)H gives excellent agreement (+/-1 kcal/mol) with experiment for the DeltaH(f)(0)'s of non-sulfur containing species, and supports the low end of the experimental values for H(2)SO(4) and FSO(3)H. Use of a larger basis set (aug-cc-pV5Z) in the CBS extrapolation improves the agreement with experiment for both H(2)SO(4) and FSO(3)H. The G3(MP2) heats of formation for RSO(3)H molecules tend to be underestimated as compared to the CCSD(T)/CBS approach by 2.5-7.0 kcal/mol. COSMO solvation calculations were used to predict solution free energies and pK(a) values with pK(a)'s up to -17.4. Including the solvation of the proton gives good agreement with experimental pK(a) values in the very acidic regime, whereas it is less reliable for weaker acids. The use of CH(3)CO(2)H and HNO(3) as reference acids in the less acidic and more acidic regions of the scale, respectively, provided improved results to within +/-2 pK(a) units in nearly all cases (+/-3 kcal/mol accuracy).

Theory of Substituent Effects: Recent Advances

The review reports recent progress in the studies of substituent effects in isolated molecules, i. e. based either on the experimental gas-phase acidities (basicities), or on quantum chemical calculations. Attention was focused on cases when the results differed from or exceeded the traditional views: redefinition of the inductive effect, quantitative estimation of resonance, validity of the Hammett equation, interpretation of the ortho effect, additivity of the enthalpies of formation, acidity of carboxylic acids. Keywords: basicities, Gas-Phase Acidities, Enthalpy, Quantum Chemical Calculations, Inductive Effect

Are calculated enthalpies of formation sometimes more reliable than experimental? A test on alkyl substituted benzoic acids

Energies of 20 alkyl-substituted benzoic acids were calculated at the levels B3LYP/6-311+G(d,p)//B3LYP/6-311+G(d,p) and MP2/6-311+G(d,p)//MP2/6-311+G(d,p); the pertinent enthalpies at 298 K were calculated at the same levels. Comparison with experimental enthalpies of formation Delta(f)H degrees (g)(298) was carried out in terms of isodesmic reactions, that is, in the relative values. Of the four calculated quantities, the DFT enthalpies yielded best correlation with the standard deviation of 2.1 kJ mol(-1), near to the experimental uncertainty; the DFT energies are only slightly worse and the MP2 enthalpies or energies much worse. However, the DFT method overestimated systematically the substituent effects and had to be calibrated. Comparison with the experimental gas-phase acidities was less telling and the fit was worse because both methods overestimated the substituent effects. Extending the base in selected examples did not give better results. Although the systematic deviations are evidently due to the imperfections of the theoretical models, individual big deviations should be attributed to experimental errors or to the abnormal behavior of certain compounds at the experimental conditions. From this point of view, three examples of the so-called long-range effect claimed in the case of different benzoic acid derivatives, always for substituents in the meta position, must be refused as unproven because the experimental energies were not confirmed by calculations.

Polar Substituent Effects in the Bicyclo[1.1.1]pentane Ring System: Acidities of 3-Substituted Bicyclo[1.1.1]pentane-1-carboxylic Acids

Experimental gas-phase acidities are reported for a series of 3-substituted (X) bicyclo [1.1.1]pent-1-yl carboxylic acids (1, Y = COOH). A comparison with available calculated data (MP2/6-311++G**// B3LYP/6-311+G**) reveals good agreement. The relative substituent effects are shown to be adequately described by a much lower level of theory (B3LYP/6-31+G*). Various correlations are presented which clearly point to polar field effects as being the origin of the relative acidities.

Electrostatic calculation of the substituent effect: an efficient test on isolated molecules.

The energy of a disubstituted molecule has often been approximated by simple electrostatic formulas that represent the substituents as poles or dipoles. Herein, we test this approach on a new model system that is more direct and more efficient than testing on acid-base properties. The energies of 27 1,4-derivatives of bicyclo[2.2.2]octane were calculated within the framework of the density functional theory at the B3LYP/6-311+G(d,p) level; interaction of the two substituents was evaluated in terms of isodesmic homodesmotic reactions. This interaction energy, checked previously on some experimental gas-phase acidities, was considered to be accurate and served as reference to test the electrostatic approximation. This approximation works well in the qualitative sense as far as the sign and the order of magnitude are concerned: beginning with the strongest interaction between two poles, a weaker interaction between pole and dipole, and the weakest between two dipoles. However, all the electrostatic calculations yield energies that are too small, particularly for weak interaction, and this fundamental defect is not remedied by some possible improvements. In particular, variation of the effective permittivity would require a physically impossible value less than unity. The explanation must lie in a more complex distribution of electron density than anticipated in the electrostatic model. It also follows that possible conclusions about the transmission of substituent effects "through space" have little validity.

Background of the Hammett equation as observed for isolated molecules: meta- and para-substituted benzoic acids.

Fundamental model compounds for the Hammett equation, meta- and para-substituted benzoic acids, were investigated by the density functional theory at the B3LYP/6-311+G(d,p) level. Energies of 25 acids and of their anions were calculated in all possible conformations and from them the energies of the assumed mixture of conformers. Relative acidities correlated with the experimental gas-phase acidities almost within the experimental uncertainty, much more precisely than in the case of previous calculations at lower levels. Dissection of the substituent effects into those operating in the acid molecule and in the anion was carried out by means of isodesmic reactions starting from monosubstituted benzenes. Both effects are cooperating in the resulting effect on the acidity; those in the acid molecule are smaller but not negligible. They are also responsible for some deviations from the Hammett equation (through-resonance of para donor substituents) and for the weaker resonance in the acid molecule in meta derivatives; in the anions the inductive and resonance effects are almost equal. On the other hand, the cooperation of effects in the acid and in the anion makes the relative acidity more sensitive to electron withdrawing and is probably one of the reasons why the Hammett equation is so generally valid.

Computation of pKafrom Dielectric Continuum Theory

This work considers calculation of pKa for a series of related alcohols, carboxylic acids, and ammonium ions spanning a wide range of acidities, using quantum mechanical treatment of solute electronic structure in conjunction with a dielectric continuum model for solvation of each bare solute. The electronic structure methods used are of sufficiently high quality to give very good agreement with experimental gas phase acidities. Dielectric continuum theory of solvation is used in a recently developed form that accurately takes account of solute charge density penetrating outside the solvent cavity that nominally encloses it. The cavity surface is defined by a single parameter characterizing an electronic isodensity contour, and contours are examined at and near the value 0.001 e/ that has previously led to a good account of solvation effects on properties of neutral solutes in various solvents. In water, the pKa values calculated for alcohols and carboxylic acids are generally much higher than experiment, while for ammonium ions they are comparable to experiment. Good results in water can be obtained from linear correlations that describe the effects of different substituents in solutes sharing the same acidic functional group, but different correlations apply for different acidic functional groups. For the polar nonprotic solvents DMSO and MeCN, pKa values close to experimental results are obtained, and very good linear correlations are found that simultaneously describe well all the solutes considered. It is argued this indicates that dielectric continuum theory properly accounts for long-range bulk solvent effects on pKa without the need for special parameterization of the cavity. To achieve good pKa results in water, further account must be taken of specific short-range effects such as hydrogen bonding. Rather than distort the cavity from the physical solute−solvent interface region in order to artificially force dielectric continuum theory to serve this purpose, as is commonly done through detailed parameterization schemes, it is recommended that other complementary approaches more appropriate for describing short-range interactions should be sought to complete the treatment of solvation effects in water.

Substituent effects on the acidity of weak acids. 2. Calculated gas-phase acidities of substituted benzoic acids.

To investigate the origin of substituent effects on the acidity of benzoic acids, the structures of a series of substituted benzoic acids and benzoates have been calculated at the B3LYP/6-311+G* and MP2/6-311+G* theoretical levels. The vibrational frequencies were calculated using B3LYP/6-311+G* and allowed corrections for the change in zero-point energies on ionization, and the change in energy on going from 0 K (corresponding to the calculations) to 298 K. A more satisfactory agreement with the experimental values was obtained by energy calculations at the MP2/ 6-311++G* level using the above structures. The resulting Delta H(acid) values agree very well with the experimental gas-phase acidities. The energies of compounds with pi-electron-accepting or -releasing substituents, rotated to give the transition state geometries, provided rotational barriers that could be compared with those found for the corresponding substituted benzenes. Isodesmic reactions allowed the separate examination of the substituent effects on the energies of the acids and on the anions. Electron-withdrawing groups stabilize the benzoate anions more than they destabilize the benzoic acids. Electron-donating groups stabilize the acids and destabilize the anions by approximately equal amounts. The gas-phase acidities of meta- and para-substituted benzoic acids are linearly related. This is also found for the acidities of substituted phenylacetic acids and benzoic acids. Since direct pi-electron interactions are not possible with the phenylacetic acids, this indicates that the acidities are mainly controlled by a field effect interaction between the charge distribution in the substituted benzene ring and the negative charge of the carboxylate group. The Hammett sigma(M) and sigma(P) values are also linearly related for many small substituents from NO(2) through the halogens and to OH and NH(2). Most of the other substituents fall on a line with a different slope

Geometries, Acidities, and Dissociation Reactions of the Gaseous Superacids H2S2O3, H2SO5, HSO3F, and HSO3Cl

The gas-phase geometries, dipole moments, enthalpies, and Gibbs free energies of thiosulfuric acid H2S2O3, peroxosulfuric acid H2SO5, fluorosulfuric acid HSO3F, and chlorosulfuric acid HSO3Cl as well as of their monoanions have been determined by ab initio MO calculations at various levels of theory. The most stable conformations of the four acid molecules are all of C1 symmetry. The acidities, defined as ΔG°298 of the deprotonation reaction, obtained by the G2 method are as follows [kJ mol−1]: HO−SO2−SH 1251 and HO−SO2−SH 1276, HO−SO(=S)−OH 1241, HO−SO2−OOH 1239, HO−SO2−F 1229, HO−SO2−Cl 1219. Good agreement of the calculated acidities of HSO3F and HSO3Cl is observed with the experimental gas-phase acidities, which are the only experimental values available. The OH acidities of all five species are higher than that of sulfuric acid (1268 kJ mol−1). Therefore, these compounds may be termed as superacids. In contrast to the liquid state, chlorosulfuric acid is a stronger proton donor than fluorosulfuric acid in the gas phase. The dissociation of the acid molecules HSO3X (X = SH, OOH, F, Cl) into SO3 and HX is endothermic and endergonic in all cases. The same holds for the dissociation of the anions SO3X− into SO3 and X−. From these dissociation enthalpies and literature data the enthalpies of formation of the mentioned sulfonic acids and their anions are calculated.

Gas-Phase Ion Chemistry of Borazine, an Inorganic Analogue of Benzene

The gas-phase reactivity of selected ionic species with borazine and of borazine-derived ions with selected neutrals has been studied by FT-ICR and ab initio computations and related to the corresponding ion chemistry of benzene. The most basic site of borazine is at nitrogen, and its conjugate acid, H3B3N3H4+, is similar in structure to the benzenium ion, as shown by ab initio calculations. H3B3N3H4+ ions undergo H/D exchange of up to four hydrogens with CD3OD and do not isomerize by stepwise 1,2-hydrogen shifts. Protonation at boron is calculated to be unfavored by 28 kcal/mol with respect to protonation at nitrogen. The H4B3N3H3+ ions show the features of a [B3N3H5···H2]+ complex, prone to dissociation at room temperature. The experimental gas-phase basicity of borazine is equal to 185.0 ± 1 kcal/mol. The Lewis basicity toward Me3Si+ places borazine into a linear correlation pertaining to model aromatic compounds. The experimental gas-phase acidity is 365.4 ± 1.5 kcal/mol. The reactions of neutral borazine with protonating, alkylating, and nitrating ions have been characterized and compared with the corresponding reactions of benzene. B3N3H5+ ions, retaining a cyclic structure, react similarly, in some respects, as phenylium ions, C6H5+.

Modulation of the proton-transfer equilibrium of the adducts between 2-hydroxy- p-quinones and 4-( N, N-dimethyl)aminopyridine: a semiempirical MO study

AM1 and PM3 semiempirical calculations were performed on the adducts between 2,5-dihydroxy-1, 4-benzoquinone ( DHpQ) or 2-hydroxy-5-methyl-1, 4-benzoquinone (HMQ) and 4-( N, N-dimethyl)aminopyridine (DAPY). Such systems can be employed as a model for the active site of copper-containing amine oxidases. The present paper shows that the DHpQ-DAPY (or HMQ-DAPY) adduct can exist in two tautomeric forms, namely a hydrogen-bonded (OH···N) and a proton transfer one (O − ··· HN +). According to semiempirical calculations, the former is more stable in vacuum but, as an increasing number of proton-donor molecules are coordinated to the system through hydrogen bonding, a progressive stabilisation of the latter species is obtained. The proton-donors examined were, besides water, different alcohols, chloroform and methylene chloride. Their efficiency in hydrogen bonding to the solute was compared and turned out to vary linearly with the solvatochromic parameter α of Kamlet and Taft (M.J. Kamlet, R. Taft, J.C.S. Perkin II, (1979) 349). It was also shown that, in general, the α-scale of solvent hydrogen-bond-donor ability linearly correlates with the AM1 or PM3 calculated charge density on the proton engaged in the hydrogen bond. For a limited number of solvents (water and alcohols), α also linearly correlates with the experimental gas-phase acidity.