Proton Dissociation Energies Research Articles

Structural Character and Energetics of Tyrosyl Radical Formation by Electron/Proton Transfers of a Covalently Linked Histidine-Tyrosine: A Model for Cytochrome c Oxidase

The structural, energetic, and electronic and IR spectroscopic properties for a model of the cross-linked histidine-tyrosine (His-Tyr) residues as found in cytochrome c oxidase (CcO) are investigated by ab initio methods. The formation of a His-Tyr radical is studied by two paths: proton release followed by electron release and vice versa. The energetics for the proton/electron releases of the Tyr depend modestly on the cross-linked His substituent and, more sensitively, on the charge of the cation attached to the imino N site of the His residue. Protonation of the imino N site significantly increases the electron ionization potential and decreases the proton dissociation energy, making them competitive processes. A positive charge placed at the imino N site, whose value is scanned from zero to one, shows a continuous increase in ionization potential and a decrease in proton dissociation energy, with the +1 limit agreeing well with the protonated imino N site result, indicating a dominant electrostatic effect. The charge populations and the spin density distributions of the His-Tyr model, the radical cation formed by electron ionization, the anion formed by proton dissociation, and the final His-Tyr radical depend sensitively on the substituents, implying a modulation role on the charge transfer between the phenol and imidazole rings, especially for the charged species. His-Tyr and protonated His-Tyr exhibit differences among their respective structural isomers with consequences on their IR absorptions. Small barriers between their pseudo-cis and pseudo-trans rotamers demonstrate the relative flexibility between the two rings, and these may facilitate proton release and charge transfer. The cation effect demonstrates that the cationized cross-linked His-Tyr should be the best candidate to mimic the covalently ring-linked histidine-tyrosine structure in CcO.

Solvent Effects are Important in Elucidating Radical-Scavenging Mechanisms of Antioxidants. A Case Study on Genistein

In two recent researches on antioxidant mechanisms of flavonoids and isoflavonoids, quantum chemical method was employed to calculate the proton dissociation energies, the bond dissociation energies and the ionization potentials for the phenols and derived radicals to help determine the radical-scavenging mechanisms. As the solvent effect was left out of consideration, the conclusion drawn from the calculation incurred some controversies. In the current study, we re-calculated the parameters for genistein and its anion by employing a B3LYP/6–311+G(d,p)//6–31G(d,p) method with solvent effect. Accordingly, a more reasonable explanation on the experimentally observed behavior of genistein as a radical scavenger was obtained. Therefore, solvent effect should be considered in the investigation of radical-scavenging mechanisms of antioxidants in polar solvents.

A Theoretical Study of Imidazole- and Thiol-Based Zinc Binding Groups Relevant to Inhibition of Metzincins

In this report, we present a quantum chemical/density functional theory (DFT) study of possible zinc binding modes for five imidazole- and thiol-based ligands relevant to metzincin (MMP and ADAM) inhibitor design. The gas-phase DFT calculations show that, while the imidazole-based ligands may bind zinc in either a five-coordinate bidentate or a four-coordinate monodentate manner, the deprotonated thiolate-containing mercaptoketone and mercapto alcohol ligands are not strongly bidentate, in agreement with recently reported model complex structures. On the basis of modeling of ligand−water exchange reactions, we estimate that the free energy released upon coordination of these zinc binding groups to metzincins decreases in the order mercaptoketone > mercapto alcohol > imidazole-based. The range of binding free energies, however, is only about a few kcal/mol, in the gas phase. In addition, calculated proton dissociation energies show that the driving force for deprotonation of coordinated thiol is greater than that for either imidazole or water. In other words, the Zn−SRH moieties are generally more acidic than their or Zn−ImH or Zn−OH2 counterparts. These results suggest feasibility of imidazole-based chelating moieties as zinc binding groups in the design of MMP and ADAM inihibitors.

Effects of Donors and Acceptors on the Energetics and Mechanism of Proton, Hydrogen, and Hydride Release from Imidazole

The mechanism and energetics of H-unit (proton, hydrogen, hydride) release from the N−H site of imidazole (IM) is explored on the basis of B3LYP/6-311++G** calculations. Of the three H-unit release modes of IM, H-atom release is strongly favored in the gas phase. Protonation of the bare N-site, positive charge injection over the whole IM ring, and water coupled to the N−H site can each significantly decrease the proton dissociation energy but separately do not change the relative release priority of the proton and H-atom. Their cooperative effect not only significantly decreases the proton dissociation energy but also makes proton release more favorable than H-atom release. A point charge of variable-magnitude placed at the bare N-site leads to a crossover between proton and H-atom dissociation to favor proton release around 1.8 charge units. When a hydrogen-bonded water is added to the N−H site, the crossover that favors proton release falls to a much smaller value (∼0.4 charge units). Thus, proton release, which is dominant in many normal biological processes, may result from a combination of positive charge or positively-charged particle catalysis at the bare N-site and a basic species assisting at the N−H site.

Electronic Effects on O−H Proton Dissociation Energies of Phenolic Cation Radicals: A DFT Study

The electronic effects on O-H proton dissociation energies (PDEs) of para- and meta-substituted phenolic cation radicals have been investigated by density functional theory (DFT) using B3LYP function on a 6-31G(d, p) basis set. The calculation results indicate that electron-donating groups raise the O-H PDE and electron-withdrawing groups reduce the parameter, which are opposite to the electronic effects on O-H bond dissociation energies (BDEs). In addition, the electronic effects on O-H PDE are much stronger than those on O-H BDE. The differences result from the distinct electronic effects on stabilities of phenolic cation radicals and parent phenols. The finding also implies the proton-transfer process is unlikely a rate-controlling step for phenolic antioxidants to scavenge free radicals. Moreover, like O-H BDE, O-H PDE correlate better with the resonance parameter R+ than with field/inductive parameter F. Therefore, O-H PDEs of para-substituted phenolic cation radicals are mainly governed by the resonance effect.

Calculation of aqueous dissociation constants of 1,2,4-triazole and tetrazole: A comparison of solvation models

The aqueous acidity constants of 1,2,4-triazole and tetrazole have been calculated using quantum chemical methods with four solvation models. Gas-phase proton transfer reaction energies and enthalpies of formation were calculated at the G3 level of theory. For tetrazole, the G3 energies all differ from the experimental values by more than 10 kJ mol−1, while for 1,2,4-triazole the agreement is significantly better. Solvation energies were calculated using the semi-empirical quantum mechanical method SM5.42R/A, the iterative Langevin dipole method iLD, the ab initio quantum mechanical polarisable continuum method IEF-PCM and the Poisson–Boltzmann method PB. The PB method consistently provided better agreement with experiment than the other methods when applied to the G3 energies, although the difference in pKa was as large as 2.6 for tetrazole. The acidity constants obtained using PB and iLD solvation energies applied to the experimental gas-phase proton dissociation energies are in good agreement with experiment.

Comparison of DFT, Møller–Plesset, and coupled cluster calculations of the proton dissociation energies of imidazole and N-methylacetamide in the presence of zinc(II)

We report herein a comparison of DFT, Møller–Plesset, and coupled cluster calculations of the proton dissociation energies of imidazole and N-methylacetamide in the presence of the zinc divalent cation. Despite the MP2 calculation showing that the proton dissociation energy of the zinc-bound imidazole was 4kcal/mol higher than that of the zinc-bound N-methylacetamide, all the higher-level Møller–Plesset, DFT, and coupled-cluster calculations revealed that the proton dissociation energy of the zinc-bound imidazole was 4–10kcal/mol lower than that of the zinc-bound N-methylacetamide. The results support the reported hypothesis of imidazolate as a zinc ligand in proteins.

Zinc's Affect on Proton Transfer between Imidazole and Acetate Predicted by ab Initio Calculations

We have recently reported proton dissociation energies of common zinc coordinates, in the presence and absence of the zinc divalent cation, that were obtained from large basis set density functiona...

Proton Dissociation Energies of Zinc-Coordinated Hydroxamic Acids and Their Relative Affinities for Zinc: Insight into Design of Inhibitors of Zinc-Containing Proteinases

Hydroxamic acids, known as iron chelators, have recently been widely used as a key functional group of potential therapeutics targeting at zinc proteinases such as matrix metalloproteinases involve...

Ab Initio Calculations of Proton Dissociation Energies of Zinc Ligands: Hypothesis of Imidazolate as Zinc Ligand in Proteins

Despite intensive studies of zinc's role in proteins and recent growing appreciation of zinc in modern biology, the knowledge of the protonation state of common zinc ligands in proteins remains con...

O- versus F-protonation in (CF 3CF 2) 2O and CF 3OCF(CF 3) 2: a preliminary theoretical study

The relative modifications induced in the structure of perfluorodiethyl ether (CF 3CF 2) 2O and perfluoroisopropyl methyl ether CF 3OCF(CF 3) 2 by oxygen and fluorine protonation are studied at the RHF level with the 3–21G basis and correlated with their proton affinities and dissociation energies.

Photoionization mass spectroscopy with synchrotron radiation of hydrogen-bonded alkylamine clusters produced in supersonic beams

Hydrogen-bonded clusters of methyl, ethyl-, dimethyl-, and diethylamines are synthesized in a seeded supersonic expansion for a mass spectroscopic study. The mass spectra are compared by ionizing either with 21-eV electrons or with photons from dispersed synchrotron radiation. Photoionization efficiency curves are measured to determine threshold energies for the ionization and fragmentation of the clusters. The threshold values yield gas-phase proton affinities, association, and dissociation energies by thermochemical calculations. The derived thermochemical quantities of cluster ions depend on the amount of the association energies of the neutral clusters. The association energy data found in this study are compared with previously calculated values. Lower bounds to the bond dissociation energies of alkylamine cluster ions are presented. The absolute proton affinity values of CH/sub 3/NH/sub 2/ (930 +/- 15 kJ/mol), C/sub 2/H/sub 5/NH/sub 2/ (940 +/- 15 kJ/mol), (CH/sub 3/)/sub 2/NH (955 +/- 15 kJ/mol), and (C/sub 2/H/sub 5/)/sub 2/NH (965 +/- 15 kJ/mol) determined in this study are about 30 kJ/mol higher than the currently recommended reference data. The proton affinities of molecular aggregates are determined in order to quantify the first steps of gas-phase proton solvation energetics.