Cooks Kinetic Method 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.

Quantification of enantiomers by mass spectrometry based on chemical derivatization and spectral shape deformation quantitative theory

A facile mass spectrometric kinetic method for quantitative analysis of chiral compounds was developed by integrating mass spectrometry based on chemical derivatization and the spectral shape deformation quantitative theory. Chemical derivatization was employed to introduce diastereomeric environments to the chiral compounds of interest, resulting in different abundance distribution patterns of fragment ions of the derivatization products of enantiomers in mass spectrometry. The quantitative information of the chiral compounds of interest was extracted from complex mass spectral data by an advanced calibration model derived based on the spectral shape deformation quantitative theory. The performance of the proposed method was tested on the quantitative analysis of R-propranolol in propranolol tablets. Experimental results demonstrated that it could achieve accurate and precise concentration ratio predictions for R-propranolol with an average relative predictive error (ARPE) of about 4%, considerably better than the corresponding results of the mass spectrometric method based on chemical derivatization and the univariate ratiometric model (ARPE: about 12%). The limit of detection (LOD) and limit of quantification (LOQ) of the proposed method for the concentration ratio of R-propranolol were estimated to be 1.5% and 6.0%, respectively. The proposed method is complementary to the existing methods designed for the quantification of enantiomers such as the Cooks kinetic method.

Vitamin C: an experimental and theoretical study on the gas-phase structure and ion energetics of protonated ascorbic acid.

In order to investigate the gas-phase mechanisms of the acid catalyzed degradation of ascorbic acid (AA) to furan, we undertook a mass spectrometric (ESI/TQ/MS) and theoretical investigation at the B3LYP/6-31 + G(d,p) level of theory. The gaseous reactant species, the protonated AA, [C6 H8 O6 ]H+ , were generated by electrospray ionization of a 10-3 M H2 O/CH3 OH (1 : 1) AA solution. In order to structurally characterize the gaseous [C6 H8 O6 ]H+ ionic reactants, we estimated the proton affinity and the gas-phase basicity of AA by the extended Cooks's kinetic method and by computational methods at the B3LYP/6-31 + G(d,p) level of theory. As expected, computational results identify the carbonyl oxygen atom (O2) of AA as the preferred protonation site. From the experimental proton affinity of 875.0 ± 12 kJ mol-1 and protonation entropy ΔSp 108.9 ± 2 J mol-1 K-1 , a gas-phase basicity value of AA of 842.5 ± 12 kJ mol-1 at 298 K was obtained, which is in agreement with the value issuing from quantum mechanical computations. Copyright © 2016 John Wiley & Sons, Ltd.

Proton Affinity of Isomeric Dipeptides Containing Lysine and Non-Proteinogenic Lysine Homologues.

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.

Proton affinity of dipeptides containing alanine and diaminobutyric acid

Thermochemical properties, including the proton affinity, the gas-phase basicity, and the protonation entropy, were determined for the acetylated unnatural amino acid, 2,4-diaminobutyric acid, AcDab and two isomeric dipeptides containing alanine (Ala) and Dab, AcAlaDab and AcDabAla. The experiments were carried out using a triple quadrupole mass spectrometer. The extended Cooks kinetic method was applied to determine the values of the proton affinity. The proton affinities for the three compounds were determined to be 235.1±2.0kcal/mol (AcDab), 244.7±2.0kcal/mol (AcAlaDab), and 242.0±2.0kcal/mol (AcDabAla). The gas-phase basicities (GB) and the protonation entropies (ΔpS) for these peptides were determined accordingly. The results suggested that the dipeptides were more basic than the single amino acid by about 7kcal/mol, and the C-terminal Dab peptide, AcAlaDab, was more basic than the N-terminal Dab peptide, AcDabAla, by about 2.5kcal/mol. Computational studies were carried out via a series of steps including conformational search using the MMFF force field, followed by geometry optimization and energy calculations at the B3LYP/6-311++G(2d,p)//B3LYP/6-311+G(d) level of theory. Theoretically predicted proton affinities were in reasonably good agreement with the experiments. The higher basicity of the C-Dab dipeptide was likely due conformational effect that stabilized the charged C-Dab peptide more efficiently than the N-Dab peptide.

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.

Determination of the Gas-phase Acidities of Oligopeptides

Amino acid residues located at different positions in folded proteins often exhibit different degrees of acidities. For example, a cysteine residue located at or near the N-terminus of a helix is often more acidic than that at or near the C-terminus (1-6). Although extensive experimental studies on the acid-base properties of peptides have been carried out in the condensed phase, in particular in aqueous solutions (6-8), the results are often complicated by solvent effects (7). In fact, most of the active sites in proteins are located near the interior region where solvent effects have been minimized (9,10). In order to understand intrinsic acid-base properties of peptides and proteins, it is important to perform the studies in a solvent-free environment. We present a method to measure the acidities of oligopeptides in the gas-phase. We use a cysteine-containing oligopeptide, Ala3CysNH2 (A3CH), as the model compound. The measurements are based on the well-established extended Cooks kinetic method (Figure 1) (11-16). The experiments are carried out using a triple-quadrupole mass spectrometer interfaced with an electrospray ionization (ESI) ion source (Figure 2). For each peptide sample, several reference acids are selected. The reference acids are structurally similar organic compounds with known gas-phase acidities. A solution of the mixture of the peptide and a reference acid is introduced into the mass spectrometer, and a gas-phase proton-bound anionic cluster of peptide-reference acid is formed. The proton-bound cluster is mass isolated and subsequently fragmented via collision-induced dissociation (CID) experiments. The resulting fragment ion abundances are analyzed using a relationship between the acidities and the cluster ion dissociation kinetics. The gas-phase acidity of the peptide is then obtained by linear regression of the thermo-kinetic plots (17,18). The method can be applied to a variety of molecular systems, including organic compounds, amino acids and their derivatives, oligonucleotides, and oligopeptides. By comparing the gas-phase acidities measured experimentally with those values calculated for different conformers, conformational effects on the acidities can be evaluated.

Gas‐phase basicity of 2‐furaldehyde

2-Furaldehyde (2-FA), also known as furfural or 2-furancarboxaldehyde, is an heterocyclic aldehyde that can be obtained from the thermal dehydration of pentose monosaccharides. This molecule can be considered as an important sustainable intermediate for the preparation of a great variety of chemicals, pharmaceuticals and furan-based polymers. Despite the great importance of this molecule, its gas-phase basicity (GB) has never been measured. In this work, the GB of 2-FA was determined by the extended Cooks's kinetic method from electrospray ionization triple quadrupole tandem mass spectrometric experiments along with theoretical calculations. As expected, computational results identify the aldehydic oxygen atom of 2-FA as the preferred protonation site. The geometries of O-O-cis and O-O-trans 2-FA and of their six different protomers were calculated at the B3LYP/aug-TZV(d,p) level of theory; proton affinity (PA) values were also calculated at the G3(MP2, CCSD(T)) level of theory. The experimental PA was estimated to be 847.9 ± 3.8 kJ mol(-1), the protonation entropy 115.1 ± 5.03 J mol(-1) K(-1) and the GB 813.6 ± 4.08 kJ mol(-1) at 298 K. From the PA value, a ΔH°(f) of 533.0 ± 12.4 kJ mol(-1) for protonated 2-FA was derived.

Can an Amine Be a Stronger Acid than a Carboxylic Acid? The Surprisingly High Acidity of Amine–Borane Complexes

The gas-phase acidity of a series of amine-borane complexes has been investigated through the use of electrospray mass spectrometry (ESI-MS), with the application of the extended Cooks kinetic method, and high-level G4 ab initio calculations. The most significant finding is that typical nitrogen bases, such as aniline, react with BH(3) to give amine-borane complexes, which, in the gas phase, have acidities as high as those of either phosphoric, oxalic, or salicylic acid; their acidity is higher than many carboxylic acids, such as formic, acetic, and propanoic acid. Indeed the complexation of different amines with BH(3) leads to a substantial increase (from 167 to 195 kJ mol(-1)) in the intrinsic acidity of the system; in terms of ionization constants, this increase implies an increase as large as fifteen orders of magnitude. Interestingly, this increase in acidity is almost twice as large as that observed for the corresponding phosphine-borane analogues. The agreement between the experimental and the G4-based calculated values is excellent. The analysis of the electron-density rearrangements of the amine and the borane moieties indicates that the dative bond is significantly stronger in the N-deprotonated anion than in the corresponding neutral amine-borane complex, because the deprotonated amine is a much better electron donor than the neutral amine. On the top of that, the newly created lone pair on the nitrogen atom in the deprotonated species, conjugates with the BN bonding pair. The dispersion of the extra electron density into the BH(3) group also contributes to the increased stability of the deprotonated species.

Gas phase acidity of a cysteine residue in small oligopeptides

The conformational effects on the gas-phase acidities of small cysteine-containing peptides were examined using ten oligopeptides. The gas-phase deprotonation enthalpies were measured using the extended Cooks kinetic method with full entropy analysis. The experiments were carried out using a triple quadrupole mass spectrometer. The values of ΔacidH were determined to be 335.6±1.7kcal/mol (AlaCysNH2), 334.6±1.8kcal/mol (Ala2CysNH2), 331.2±1.8kcal/mol (CysAlaNH2), 330.5±2.0kcal/mol (CysAla2NH2), 329.7±1.8kcal/mol (AlaCysAlaNH2), 335.3±1.8kcal/mol (GlyCysNH2), 334.6±1.7kcal/mol (Gly2CysNH2), 330.4±1.8kcal/mol (CysGlyNH2), 329.7±1.8kcal/mol (CysGly2NH2), and 327.3±2.0kcal/mol (GlyCysGlyNH2). The gas-phase acidities (ΔacidG) and the deprotonation entropies (ΔacidS) for these peptides were determined accordingly. These results suggested that the tripeptides were more acidic than the corresponding dipeptides by about 1kcal/mol, and the N-cysteine peptides were more acidity than the isomeric C-cysteine peptides by about 4kcal/mol. The initial conformations of the peptides were modeled via a conformational search using the MMFF method. The final geometries and energies were calculated at the B3LYP/6-31++G(d,p) level of theory. The calculated enthalpies of deprotonation agreed reasonably well with the experimental results. The conformations of the deprotonated N-cysteine peptides were more compact than those of the C-cysteine analogues. The more compact conformations allowed more efficient multiple hydrogen-bonding interactions between the thiolate anion and the nearby NH bonds. The greater acidities of the N-cysteine peptides were likely the results of the more favorable hydrogen-bonding and charge–amide dipole interactions that stabilized the thiolate anions more efficiently.

Gas-Phase Acid-Base Properties of Melamine and Cyanuric Acid

The thermochemical properties of melamine and cyanuric acid were characterized using mass spectrometry measurements along with computational studies. A triple-quadrupole mass spectrometer was employed with the application of the extended Cooks kinetic method. The proton affinity (PA), gas-phase basicity (GB), and protonation entropy (Δ(p)S) of melamine were determined to be 226.2 ± 2.0 kcal/mol, 218.4 ± 2.0 kcal/mol, and 26.2 ± 2.0 cal/mol K, respectively. The deprotonation enthalpy (Δ(acid)H), gas-phase acidity (Δ(acid)G), and deprotonation entropy (Δ(acid)S) of cyanuric acid were determined to be 330.7 ± 2.0 kcal/mol, 322.9 ± 2.0 kcal/mol, and 26.1 ± 2.0 cal/mol K, respectively. The geometries and energetics of melamine, cyanuric acid, and related ionic species were calculated at the B3LYP/6-31+G(d) level of theory. The computationally predicted proton affinity of melamine (225.9 kcal/mol) and gas-phase deprotonation enthalpy of cyanuric acid (328.4 kcal/mol) agree well with the experimental results. Melamine is best represented as the imide-like triazine-triamine form and the triazine nitrogen is more basic than the amino group nitrogen. Cyanuric acid is best represented as the keto-like tautomer and the N-H group is the most probable proton donor.

Gas-Phase Acidities of Cysteine-Polyglycine Peptides: The Effect of the Cysteine Position

The sequence and conformational effects on the gas-phase acidities of peptides have been studied by using two pairs of isomeric cysteine-polyglycine peptides, CysGly(3,4)NH(2) and Gly(3,4)CysNH(2). The extended Cooks kinetic method was employed to determine the gas-phase acidities using a triple quadrupole mass spectrometer with an electrospray ionization source. The ion activation was achieved via collision-induced dissociation experiments. The deprotonation enthalpies (Delta(acid)H) were determined to be 323.9 +/- 2.5 kcal/mol (CysGly(3)NH(2)), 319.2 +/- 2.3 kcal/mol (CysGly(4)NH(2)), 333.8 +/- 2.1 kcal/mol (Gly(3)CysNH(2)), and 321.9 +/- 2.8 kcal/mol (Gly(4)CysNH(2)), respectively. The corresponding deprotonation entropies (Delta(acid)S) of the peptides were estimated. The gas-phase acidities (Delta(acid)G) were derived to be 318.4 +/- 2.5 kcal/mol (CysGly(3)NH(2)), 314.9 +/- 2.3 kcal/mol (CysGly(4)NH(2)), 327.5 +/- 2.1 kcal/mol (Gly(3)CysNH(2)), and 317.4 +/- 2.8 kcal/mol (Gly(4)CysNH(2)), respectively. Conformations and energetic information of the neutral and anionic peptides were calculated through simulated annealing (Tripos), geometry optimization (AM1), and single point energy calculations (B3LYP/6-31+G(d)), respectively. Both neutral and deprotonated peptides adopt many possible conformations of similar energies. All neutral peptides are mainly random coils. The two C-cysteine anionic peptides, Gly(3,4)(Cys-H)(-)NH(2), are also random coils. The two N-cysteine anionic peptides, (Cys-H)(-)Gly(3,4)NH(2), may exist in both random coils and stretched helices. The two N-cysteine peptides, CysGly(3)NH(2) and CysGly(4)NH(2), are significantly more acidic than the corresponding C-terminal cysteine ones, Gly(3)CysNH(2) and Gly(4)CysNH(2). The stronger acidities of the former may come from the greater stability of the thiolate anion resulting from the interaction with the helix-macrodipole, in addition to the hydrogen bonding interactions.

Gas-Phase Acidities of Cysteine-Polyalanine Peptides I: A3,4CSH and HSCA3,4

The gas-phase acidities of four cysteine-polyalanine peptides, A(3,4)CSH and HSCA(3,4), were determined using the extended Cooks kinetic method with full entropy analysis. A triple-quadrupole mass spectrometer with an electrospray interface was employed for the experimental study. The ion activation was achieved via collision-induced dissociation (CID) experiments. The deprotonation enthalpies (Delta(acid)H) of the peptides were determined to be 332.2 +/- 2.0 kcal/mol (A(3)CSH), 325.9 +/- 2.0 kcal/mol (A(4)CSH), 319.3 +/- 3.0 kcal/mol (HSCA(3)), and 319.2 +/- 4.0 kcal/mol (HSCA(4)). The deprotonation entropies (Delta(acid)S) of the peptides were estimated based on the entropy term (Delta(DeltaS)) and the deprotonation entropies of the reference acids. By using the deprotonation enthalpies and entropies, the gas-phase acidities (Delta(acid)G) of the peptides were derived: 325.0 +/- 2.0 kcal/mol (A(3)CSH), 320.2 +/- 2.0 kcal/mol (A(4)CSH), 316.3 +/- 3.0 kcal/mol (HSCA(3)), and 315.4 +/- 4.0 kcal/mol (HSCA(4)). Conformations and energetic information of the peptides were calculated through simulated annealing (Tripos), geometry optimization (AM1), and single-point energy calculations (B3LYP/6-31+G(d)), respectively. The calculated theoretical deprotonation enthalpies (Delta(acid)H) of 334.2 kcal/mol (A(3)CSH), 327.7 kcal/mol (A(4)CSH), 320.6 kcal/mol (HSCA(3)), and 318.6 kcal/mol (HSCA(4)) are in good agreement with the experimentally determined values. Both the experimental and computational studies suggest that the two N-terminal cysteine peptides, HSCA(3,4), are significantly more acidic than the corresponding C-terminal ones, A(3,4)CSH. The high acidities of the former are likely due to the helical conformational effects for which the thiolate anion may be strongly stabilized by the interaction with the helix macrodipole.

Gas-Phase Thermochemical Properties of the Damaged Base O6-Methylguanine versus Adenine and Guanine

The gas phase acidity (DeltaH(acid) and DeltaG(acid)) and proton affinity (PA, and gas phase basicity (GB)) of adenine, guanine, and O(6)-methylguanine (OMG) have been examined using both theoretical (B3LYP/6-31+G*) and experimental (bracketing, Cooks kinetic) methods. We previously measured the acidity of adenine using bracketing methods; herein we measure the acidity of adenine by the Cooks kinetic method (DeltaH(acid) = 335 +/- 3 kcal mol(-1); DeltaG(acid) = 329 +/- 3 kcal mol(-1)). We also measured the PA/GB of adenine using both bracketing and Cooks methods (PA = 224 and 225 kcal mol(-1); GB = 216 and 217 kcal mol(-1)). Guanine is calculated to have several stable tautomers in the gas phase, in contrast to in solution, where the canonical tautomer predominates. Experimental measurements of gas phase guanine properties are difficult due to its nonvolatility; using electrospray and the Cooks kinetic method, we are able to measure a DeltaH(acid) of 335 +/- 3 kcal mol(-1) (DeltaG(acid) = 328 +/- 3 kcal mol(-1)). The proton affinity is 227 +/- 3 kcal mol(-1) (GB = 219 +/- 3 kcal mol(-1)). Comparison of these values to calculations indicates that we may have a mixture of the keto and enol tautomers under our conditions in the gas phase, although it is also possible that we only have the canonical form since in the Cooks method, we form the proton-bound dimers via electrospray of an aqueous solution, which should favor guanine in the canonical form. We also examined O(6)-methylguanine (OMG), a highly mutagenic damaged base that arises from the alkylation of guanine. Our calculations indicate that OMG may exist as both the "N9" (canonical) and "N7" (proton on N7 rather than N9) tautomers in the gas phase, as both are calculated to be within 3 kcal mol(-1) in energy. We have bracketed the acidity and proton affinity of OMG, which were previously unknown. The more acidic site of OMG has a DeltaH(acid) value of 338 +/- 3 kcal mol(-1) (DeltaG(acid) = 331 +/- 3 kcal mol(-1)). We have also bracketed the less acidic site (DeltaH(acid) = 362 +/- 3 kcal mol(-1), DeltaG(acid) = 355 +/- 3 kcal mol(-1)) and the PA (229 +/- 4 kcal mol(-1) (GB = 222 +/- 4 kcal mol(-1))). We confirmed these results through Cooks kinetic method measurements as well. Our ultimate goal is to understand the intrinsic reactivity of nucleobases; gas phase acidic and basic properties are of interest for chemical reasons and also possibly for biological purposes, since biological media can be quite nonpolar. We find that OMG is considerably less acidic at N9 than adenine and guanine and less basic at O6 than guanine; the biological implications of these differences are discussed.

Gas-Phase Thermochemical Properties of Pyrimidine Nucleobases

The gas-phase acidity and proton affinity of thymine, cytosine, and 1-methyl cytosine have been examined using both theoretical (B3LYP/6-31+G*) and experimental (bracketing, Cooks kinetic) methods. This paper represents a comprehensive examination of multiple acidic sites of thymine and cytosine and of the acidity and proton affinity of thymine, cytosine, and 1-methyl cytosine. Thymine exists as the most stable "canonical" tautomer in the gas phase, with a DeltaH(acid) of 335 +/- 4 kcal mol(-1) (DeltaG(acid) = 328 +/- 4 kcal mol(-1)) for the more acidic N1-H. The acidity of the less acidic N3-H site has not, heretofore, been measured; we bracket a DeltaH(acid) value of 346 +/- 3 kcal mol(-1) (DeltaG(acid) = 339 +/- 3 kcal mol(-1)). The proton affinity (PA = DeltaH) of thymine is measured to be 211 +/- 3 kcal mol(-1) (GB = DeltaG = 203 +/- 3 kcal mol(-1)). Cytosine is known to have several stable tautomers in the gas phase in contrast to in solution, where the canonical tautomer predominates. Using bracketing methods in an FTMS, we measure a DeltaH(acid) for the more acidic site of 342 +/- 3 kcal mol(-1) (DeltaG(acid) = 335 +/- 3 kcal mol(-1)). The DeltaH(acid) of the less acidic site, previously unknown, is 352 +/- 4 kcal mol(-1) (345 +/- 4 kcal mol(-1)). The proton affinity is 228 +/- 3 kcal mol(-1) (GB = 220 +/- 3 kcal mol(-1)). Comparison of these values to calculations indicates that we most likely have a mixture of the canonical tautomer and two enol tautomers and possibly an imine tautomer under our conditions in the gas phase. We also measure the acidity and proton affinity of cytosine using the extended Cooks kinetic method. We form the proton-bound dimers via electrospray of an aqueous solution, which favors cytosine in the canonical form. The acidity of cytosine using this method is DeltaH(acid) = 343 +/- 3 kcal mol(-1), PA = 227 +/- 3 kcal mol(-1). We also examined 1-methyl cytosine, which has fewer accessible tautomers than cytosine. We measure a DeltaH(acid) of 349 +/- 3 kcal mol(-1) (DeltaG(acid) = 342 +/- 3 kcal mol(-1)) and a PA of 230 +/- 3 kcal mol(-1) (GB = 223 +/- 3 kcal mol(-1)). Our ultimate goal is to understand the intrinsic reactivity of nucleobases; gas-phase acidic and basic properties are of interest for chemical reasons and also possibly for biological purposes because biological media can be quite nonpolar.

Can mass dissociation patterns of transition‐metal complexes be predicted from electrochemical data?

The Cooks kinetic method has been very convenient to correlate the relative dissociation rates obtained by collision-induced fragmentation experiments with the energies of two related bonds in molecules and complexes in the gas phase. Reliable bond energy data are, however, not always available, particularly for polynuclear transition-metal complexes, such as the triruthenium acetate clusters of the general formula [Ru(3) (micro(3)-O)(micro-CH(3)COO)(6)(py)(2)(L)](+), where L = ring substituted N-heterocyclic ligands. Accordingly, their gas-phase collision-induced tandem mass spectrometry (CID MS/MS) dissociation patterns have been analyzed pursuing a relationship with the more easily accessible redox potentials (E(1/2)) and Lever's E(L) parameters. In fact, excellent linear correlations of ln(1/2A(L)/A(py)), where A(py) and A(L) are the abundance of the fragments retaining the pyridine (py) and L ligand, respectively, with E(1/2) and E(L) were found. This result shows that those electrochemical parameters are correlated with bond energies and can be used in the analysis of the dissociation data. Such modified Cooks method can be used, for example, to determine the electronic effects of substituents on the metal-ligand bonds for a series of transition-metal complexes.

Electrospray Ionization Tandem Mass Spectrometry of Polymetallic μ-Oxo- and Carboxylate-Bridged [Ru3O(CH3COO)6(Py)2(L)]+Complexes: Intrinsic Ligand (L) Affinities with Direct Access to Steric Effects

[Ru 3 O(CH3COO) 6 (py) 2 (L)]+ (1 + ) are polymetallic singly charged cationic complexes with a unique structural arrangement in which three neutral ligands are bound via ruthenium atoms to a highly delocalized symmetrical triangular tridentate [Ru 3 O(CH 3 COO) 6 ] + core bonded by a μ-oxo and six carboxylate bridges. Several 1(PF 6 ) complexes with various terminal ligands (L) and two pyridines (py) used as reference ligands were synthesized. These complexes were directly transferred from a methanol solution to the gas phase and characterized by electrospray ionization mass spectrometry (ESI-MS) and subsequently dissociated by gentle collisions with argon molecules via ESI-MS/MS. The applicability of Cooks' kinetic method (CKM) to rank the binding affinities of a set of L to the [Ru 3 O(CH 3 COO) 6 ] + core was demonstrated by the good linear correlation (R = 0.98) observed in a CKM plot for which the relative peak intensities of the two fragment ions arising from the competitive loss of py or L as well as L affinities predicted by PM3(tm) calculations were used. Steric effects greatly affect L affinities, as evidenced by the values measured for ortho-substituted pyridines. The gaseous 1 + were found to display a relatively high effective temperature of 1258 K. We have therefore extended CKM to investigate metal-ligand interactions, showing its usefulness to order and measure intrinsic (no solvent or counterion effects) ligand affinities to large and structurally intricate polymetallic complexes.

Gaseous Supramolecules of Imidazolium Ionic Liquids: “Magic” Numbers and Intrinsic Strengths of Hydrogen Bonds

Electrospray ionization mass spectrometry (ESI-MS) is found to gently and efficiently transfer small to large as well as singly to multiply charged [X+]n[A-]m supramolecules of imidazolium ion (X+) ionic liquids to the gas phase, and to reveal "magic numbers" for their most favored assemblies. Tandem mass spectrometric experiments (ESI-MS/MS) were then used to dissociate, via low-energy collision activation, mixed and loosely bonded [A- - - -X- - - -A']- and [X- - - -A- - - -X']+ gaseous supramolecules, as well as their higher homologues, and to estimate and order via Cooks' kinetic method (CKM) and B3LYP/6-311G(d,p) calculations the intrinsic solvent-free magnitude of hydrogen bonds. For the five anions studied, the relative order of intrinsic hydrogen-bond strengths to the 1-n-butyl-3-methylimidazolium ion [X1]+ is: CF3CO2- (zero) > BF4- (-3.1) > PF6- (-10.0) > InCl4- (-16.4) and BPh4- (-17.6 kcal mol(-1)). The relative hydrogen-bond strength for InCl4- was measured via CKM whereas those for the other anions were calculated and used as CKM references. A good correlation coefficient (R=0.998) between fragment ion ratios and calculated hydrogen-bond strengths and an effective temperature (Teff) of 430 K demonstrate the CKM reliability for measuring hydrogen-bond strengths in gaseous ionic liquid supramolecules. Using CKM and Teff of 430 K, the intrinsic hydrogen-bond strengths of BF4- for the three cations investigated is: 1-n-butyl-3-methyl-imidazolium ion (0) > 1,3-di-[(R)-3-methyl-2-butyl]-imidazolium ion (-2.4) > 1,3-di-[(R)-alpha-methylbenzyl]-imidazolium ion (-3.0 kcal mol(-1)). As evidenced by "magic" numbers, greater stabilities are found for the [(X1)2(BF4)3]- and [(X1)5A4]+ supramolecules (A not equal InCl4-).

The Na + affinities of α-amino acids: side-chain substituent effects

Na +-bound heterodimers of amino acids (AA) are produced in the gas phase by electrospray ionization (ESI). The dissociation kinetics of these AA 1Na +AA 2 ions are determined by collisionally activated dissociation (CAD) and converted to a ladder of relative Na + affinities via the Cooks kinetic method. The affinities derived follow the order (kJ mol −1, relative to Gly): Gly (0), Ala (6), Val (12), Leu (13), Cys (14), Ile (15), Ser (31), Pro (35), Thr (36), Phe (37), Tyr (40), Asp (42), Glu (43), Asn (45), Trp (49), Gln (51), His (57). Absolute Na + binding energies are estimated by anchoring the relative values to the Na + affinity of Ala (167 kJ mol −1), measured by the same approach using Na +-bound dimers of Ala and a series of acetamide derivatives. The Na + binding energies of the acetamide reference bases and of representative aliphatic and side-chain functionalized amino acids (Gly, Ala, Pro, Cys and Ser) are determined by ab initio theory. Experimental and ab initio affinities agree very well. The combined data show that functional side chains increase the AANa + bond strength by providing an extra ligand to the metal ion. Aromatic and carbonyl substituents in the side chain bring about substantial increases in the Na + binding energy, with particularly large increments observed for amide and electron-rich (N-containing) aromatic groups. A poor correlation is found between sodium ion and proton affinities, strongly suggesting that the Na + complexes do not have salt-bridge structures involving zwitterionic amino acids (in which the most basic site is protonated).

Determination of the electron affinities of α‐ and β‐naphthyl radicals using the kinetic method with full entropy analysis. The C — H bond dissociation energies of naphthalene

The C - H bond dissociation energies for naphthalene were determined using a negative ion thermochemical cycle involving the gas-phase acidity (Delta H (acid)) and electron affinity (EA) for both the alpha- and beta-positions. The gas-phase acidity of the naphthalene alpha- and beta-positions and the EAs of the alpha- and beta-naphthyl radicals were measured in the gas phase in a flowing after glow-triple quadrupole apparatus. A variation of the Cooks kinetic method was used to measure the EAs of the naphthyl radicals by collision-induced dissociation of the corresponding alpha- and beta-naphthylsulfinate adducts formed by reactions in the flow tube portion of the instrument. Calibration references included both pi and sigma radicals, and full entropy analysis was performed over a series of calibration curves measured at collision energies ranging from 3.5 to 8 eV (center-of-mass). The measured EAs are 33.0 +/- 1.4 and 31.4 +/- 1.0 kcal mol(-1) (1 kcal = 4.184 kJ) for the alpha- and beta-naphthyl radicals, respectively. The gas-phase acidities for naphthalene were measured by the DePuy silane cleavage method, which utilizes the relative abundances of aryldimethylsiloxides and trimethylsiloxide that result from competitive cleavages from a proposed penta coordinate hydroxysiliconate intermediate. The measured acidities are 394.0 +/- 5.0 and 397.6 +/- 4.8 kcal mol(-1) for the alpha- and beta- positions, respectively. The C - H bond dissociation energies calculated from the thermochemical cycle are 113.4 +/- 5.2 and 115.4 +/- 4.9 kcal mol(-1) for the alpha- and beta-positions, respectively. These energies are, to within experimental error, indistinguishable and are approximately the same as the first bond dissociation energy for benzene.