Activation Barrier For Dissociation Research Articles

Bisaryloxime Ethers as Potent Inhibitors of Transthyretin Amyloid Fibril Formation

Amyloid fibril formation by the plasma protein transthyretin (TTR), requiring rate-limiting tetramer dissociation and monomer misfolding, is implicated in several human diseases. Amyloidogenesis can be inhibited through native state stabilization, mediated by small molecule binding to TTR's primarily unoccupied thyroid hormone binding sites. New native state stabilizers have been discovered herein by the facile condensation of arylaldehydes with aryloxyamines affording a bisarylaldoxime ether library. Of the library's 95 compounds, 31 were active inhibitors of TTR amyloid formation in vitro. The bisaryloxime ethers selectively stabilize the native tetrameric state of TTR over the dissociative transition state under amyloidogenic conditions, leading to an increase in the dissociation activation barrier. Several bisaryloxime ethers bind selectively to TTR in human blood plasma over the plethora of other plasma proteins, a necessary attribute for efficacy in vivo. While bisarylaldoxime ethers are susceptible to degradation by N-O bond cleavage, this process is slowed by their binding to TTR. Furthermore, the degradation rate of many of the bisarylaldoxime ethers is slow relative to the half-life of plasma TTR. The bisaryloxime ether library provides valuable structure-activity relationship insight for the development of structurally analogous inhibitors with superior stability profiles, should that prove necessary.

Kinetic Stabilization of the Native State by Protein Engineering: Implications for Inhibition of Transthyretin Amyloidogenesis

The amyloidogenic homotetrameric protein transthyretin (TTR) must undergo rate-limiting dissociation to partially denatured monomers in order to aggregate. TTR contains two distinct quaternary interfaces, one of which defines the binding sites for thyroxine and small-molecule amyloidogenesis inhibitors. Kinetic stabilization of the tetramer can be accomplished either by the binding of amyloidogenesis inhibitors selectively to the native state over the dissociative transition state or by the introduction of trans-suppressor subunits (T119M) into heterotetramers to destabilize the dissociative transition state. In each case, increasing the dissociation activation barrier prevents tetramer dissociation. Herein, we demonstrate that tethering two subunits whose quaternary interface defines the thyroxine binding site also dramatically increases the barrier for tetramer dissociation, apparently by destabilization of the dissociative transition state. The tethered construct (TTR-L-TTR)2 is structurally and functionally equivalent to wild-type TTR. Urea is unable to denature (TTR-L-TTR)2, yet it is able to maintain the denatured state once denaturation is achieved by GdnHCl treatment, suggesting that (TTR-L-TTR)2 is kinetically rather than thermodynamically stabilized, consistent with the identical wild-type TTR and (TTR-L-TTR)2 GdnHCl denaturation curves. Studies focused on a construct containing a single TTR-L-TTR chain and two normal monomer subunits establish that alteration of only one quaternary structural interface is sufficient to impose kinetic stabilization on the entire quaternary structure.

The dynamics of the dissociative adsorption of methane on Pt(533)

The influence of well-defined steps on the dynamics of the dissociative chemisorption of methane on Pt(533) has been investigated using molecular beam techniques. The initial dissociative chemisorption probability S0 has been determined as a function of incident energy Ei, angle of incidence θi, and surface temperature TS. For incident kinetic energies in the range 26<Ei(meV)<1450, the initial dissociation probability of CH4 on the Pt(533) surface is higher than on Pt(111), for all surface temperatures investigated. This enhancement in dissociation is associated with the additional direct sticking mediated by the step sites, with no evidence for any additional indirect dynamical channel to dissociation induced by the step sites in the range of energies studied. The Ei dependence can be separated into the contributions of the (111) terraces and the (100) steps. The latter exhibits an effective activation barrier for dissociation ≈300 meV lower than the (111) terraces. The angular dependence can also be interpreted as having two contributions, one associated with the (111) terraces, and the second associated with the steps. The angular dependence associated with the step sites is broader than the dependence expected for the (111) terraces, and has a maximum for incident trajectories with an angle between the angles corresponding to the normal directions of the (111) and (100) facets. An enhanced TS dependence is also observed on the Pt(533) surface over Pt(111). This is also associated with the influence of the step sites, and results either from the lower barrier to dissociation, or more likely a more effective coupling of the energy from the surface into the reaction coordinate.

Dissociative chemisorption of CH4 on a cesiated Pt(111) surface studied by supersonic molecular beam scattering techniques

We have clarified the dynamics and mechanism of CH4 dissociative chemisorption processes on a cesiated Pt(111) surface by means of molecular beam scattering techniques. A comparison is made of similar processes on a Pt(111) surface. It is found that the CH4 molecules with enough energy to overcome the activation barrier for dissociation can no longer dissociate on a cesiated surface of Pt(111). Time-of-flight and angular intensity distribution measurements of the reflected CH4 molecules have revealed a similarity in inelastic collision dynamics both on the Pt(111) and the cesiated Pt(111) surfaces. Even a low concentration of the Cs layer as 0.06 of coverage is found to modify the surface electronic structure such that the activation barrier is enhanced as a result of an increased Pauli repulsive potential component in the potential energy surface. It is also found from time-of-flight measurements that direct dissociation is the only pass way and precursor mediated dissociation is not possible both on the Pt(111) and the cesiated Pt(111) surfaces in our experimental conditions.

Activated dissociation via a trapping precursor: O2/Cu(001)-(2√×√)-O

Dissociative adsorption of O2 on Cu(001)-(2√×√)-O was shown to induce Cu2O epitaxial islands on the surface. The initial dissociative sticking probability of O2 on Cu(001)-(2√×√)-O scaled with the total translational energy of incident O2, suggesting that the interaction potential was highly corrugated. The sticking probability decreased with increasing translational energy of incidence and increased with increasing surface temperature. For lower translational energy of incident O2 (⩽130 meV), the velocity distribution of the scattered molecules was of nonshifted Maxwellian-type, indicating trapping desorption. The translational temperature of the trapping desorption was lower than the surface temperature and increased linearly with surface temperature, suggesting that there was no barrier for desorption. Neither thermal desorption experiments nor velocity distribution analysis of the trapping desorption showed any evidences of recombination desorption. These results were interpreted as an activated dissociation via a trapping precursor. The activation barrier for dissociation was estimated as 330 meV. The angular distribution of the trapping desorption was fitted well by cos2 θ, which was in contrast to the expectation of a cosine angular distribution based on the detailed balance arguments. The discrepancy may have been attributable to preferential consumption of the parallel momentum of the trapped O2 for dissociation and imbalance between adsorbing and desorbing O2 flux.

Intrinsic activation barriers and coadsorption effects for reactions on metal surfaces: unified formalism within the UBI-QEP approach

We present a unified formulation of the unity bond index-quadratic exponential potential method (UBI-QEP, formerly known as the BOC-MP method) of determining metal surface reaction energetics. We give a unified treatment of enthalpies and intrinsic activation barriers for dissociation and recombination reactions as particular cases of disproportionation reactions. We discuss numerous examples of elementary reactions, which form a database for various reaction mechanisms. We start with the zero coverage limit and then focus on coadsorption effects on reaction energetics on monometallic and bimetallic (alloy) surfaces. We consider first the full treatment and then develop the “uniform scaling” approximation, with guidelines (and examples) where it may be efficiently used. We provide tables of numerical values covering most of practically important cases of coadsorption effects on fcc(111) and fcc(100) surfaces, which allow one to easily estimate coverage effects on activation barriers by simple interpolation. We also clarify the nature of basic UBI-QEP parameters and correlation between local and global adsorbate coverage. These developments, illustrated by various examples, make applications of the UBI-QEP method much easier for practitioners, particularly those who have no UBI-model computer program and make calculations by hand.

Computational Studies of the Interactions of Oxygen with Platinum Clusters

Density functional theory is used to compute electronic and thermodynamic interactions between atomic and molecular oxygen and small Ptn clusters (n = 2−6). Binding energies, vibrational frequencies, and charge distributions are reported. Two states are identified for the adsorption of molecular oxygen: the superoxo species (O2δ-) and the peroxo species (O22δ-) formed by charge transfer from the metal cluster to the O2 molecule. An analysis of the adsorbed O2 dissociation on Pt clusters illustrates the dependence of the activation barrier for dissociation on the metal cluster size.

Molecularly chemisorbed intermediates to oxygen adsorption on Pt(111): A molecular beam and electron energy-loss spectroscopy study

High translational energy adsorption of oxygen on the (111) surface of platinum was examined with electron energy loss spectroscopy (EELS) and molecular beam techniques. EEL spectra indicate that over an incident energy range of 0.2–1.37 eV and on a Pt(111) surface held at 77 K, oxygen adsorbs in an associative chemisorbed state—yielding to the dissociated state only after sufficient substrate heating. Simple direct dissociation appears negligible for all incident kinetic energies studied. At near-zero surface coverages, exclusive population of the peroxolike molecular precursor is observed for adsorption at these high translational energies, while both superoxolike and peroxolike forms are detected for low energy adsorption (0.055 eV). This peculiarity represents evidence that translational energy is effective in differentially populating reaction intermediates and provides better quantification of potential energy barriers to dissociation. We estimate the activation barrier for dissociation from the peroxolike precursor to be approximately 0.29 eV. Initial adsorption probability measurements over a wide range of surface temperatures and high incident kinetic energies corroborate a molecular chemisorption mediated mechanism.

Binding Energies of Proton-Bound Dimers of Imidazole and n-Acetylalanine Methyl Ester Obtained by Blackbody Infrared Radiative Dissociation

The dissociation kinetics of protonated n-acetyl-L-alanine methyl ester dimer (AcAlaME(d)), imidazole dimer, and their cross dimer were measured using blackbody infrared radiative dissociation (BIRD). Master equation modeling of these data was used to extract threshold dissociation energies (E(o)) for the dimers. Values of 1.18 +/- 0.06, 1.11 +/- 0.04, and 1.12 +/- 0.08 eV were obtained for AcAlaME(d), imidazole dimer, and the cross dimer, respectively. Assuming that the reverse activation barrier for dissociation of the ion-molecule complex is negligible, the value of E(o) can be compared to the dissociation enthalpy (DeltaH(d) degrees ) from HPMS data. The E(o) values obtained for the imidazole dimer and the cross dimer are in agreement with HPMS values; the value for AcAlaME(d) is somewhat lower. Radiative rate constants used in the master equation modeling were determined using transition dipole moments calculated at the semiempirical (AM1) level for all dimers and compared to ab initio (RHF/3-21G*) calculations where possible. To reproduce the experimentally measured dissociation rates using master equation modeling, it was necessary to multiply semiempirical transition dipole moments by a factor between 2 and 3. Values for transition dipole moments from the ab initio calculations could be used for two of the dimers but appear to be too low for AcAlaME(d). These results demonstrate that BIRD, in combination with master equation modeling, can be used to determine threshold dissociation energies for intermediate size ions that are in neither the truncated Boltzmann nor the rapid energy exchange limit.

Effect of surface segregation on the catalytic activity of alloys: CO hydrogenation on Pd–Ni(111) surface

A semi-empirical model has been presented for studying the effect of surface segregation and local environment on the catalytic activity of the PdNi(111) surface for CO hydrogenation. Large Pd segregation to the surface has been found to affect the activation barrier for dissociation of molecules on the surface. It also affects the activation barriers for different reaction steps in the CO hydrogenation process to form methanol on the Pd–Ni surface. It is argued that for the Pd–Ni system, hydrogenation of the adsorbed HCO s species is the rate-limiting step. It has then been shown that an addition of even 5 at% of Pd in bulk Ni may increase the activity by as much as four orders of magnitude. So far as the local environmental effect is concerned, it is found that the most active centres for the HCO s hydrogenation step are the centre hollow sites having three-fold symmetry with 3 Pd atoms as nearest neighbours followed by centre hollow sites with two Pd atoms and one Ni atom as nearest neighbours.

Chemisorption of Hydrogen on Stepped Surfaces of Ni and Cu

The chemisorption of hydrogen on stepped (410) surfaces of Ni and Cu has been studied using the embedded-atom method (EAM). First, contours of potential energy surface (PES) for atomic H on the stepped (410) surface of Ni, Cu are presented and compared with those of flat (100) surfaces. It is found that stepped surfaces have more active adsorption sites and the binding energy of H is larger at the step sites. Then, the dissociation of the hydrogen molecule on the stepped (410) surfaces of Ni and Cu is also investigated. The activation barrier Ea, adsorption heat qad and corresponding H–metal bond length R for different H2 dissociation pathways are calculated and the associated potential energy surfaces are obtained. The calculated results show that in the process of H2 approaching the concave site at the bottom of a step, the activation barrier for H2 dissociation is lowest; while for H2 approaching the outside edge of the terrace, the activation barrier is highest. Compared with that of H2 on perfect (100) surfaces of Ni, Cu, the presence of steps can significantly lower the activation barrier for dissociation of H2.

Chemisorption of hydrogen on stepped (410) surfaces of Ni and Cu

The chemisorption of hydrogen on stepped (410) (in step notation, (s)-[4(100) × (010)] surfaces of Ni and Cu has been studied using the embedded-atom method (EAM). First, contours of the potential-energy surface (PES) for atomic H on stepped (410) surfaces of Ni, Cu are presented and compared with that of the flat (100) surfaces. It is found that stepped surfaces have more active adsorption sites and the binding energy of H is larger at the step sites. Then, the dissociation of the hydrogen molecule on the stepped (410) surfaces of Ni and Cu is also investigated. The activation barrier E a, adsorption heat q ad and corresponding H-metal bond length R for different H 2 dissociation pathways are calculated and the associated potential-energy surfaces are obtained. The calculated results show that in the process of H 2 approaching the concave site at the bottom of a step, the activation barrier for H 2 dissociation is lowest; while for H 2 approaching the outside edge of the terrace, the activation barrier is highest. Compared with that of H 2 on perfect (100) surfaces of Ni, Cu, the presence of steps can significantly lower the activation barrier for dissociation of H 2.

Decomposition and reduction of NO on transition metal surfaces: bond order conservation Morse potential analysis

Periodic trends in the decomposition of NO and its reduction to N 2 and NH 3 by CO and H 2 on transition metal surfaces have been analyzed theoretically using the bond order conservation Morse potential (BOCMP) method. The analysis is based on calculations of the energetics, the reaction enthalpies ΔH and activation barriers ΔH ∗ , of elementary steps thought to comprise the mechanisms of the NO transformations. As the periodic series, the close-packed surfaces Pt(111), Rh(111), Ru(001), and Re(001) were chosen. The calculated heats of chemisorption Q of NH 3, NH 2, NH, NO, H 2O and OH are in good agreement with experiment. The activation barriers for dissociation of NO from a chemisorbed state, ΔE NO s ∗ were found to decrease in the order Pt > Rh > Ru > Re. For reasonable values of Q N and Q O, in the zero-coverage extreme these activation barriers were calculated to be much smaller than the relevant heats of chemisorption Q NO, so that dissociation of No upon heating is projected for all the surfaces studied with the possible exception of Pt(111). The presence of adsorbed N S and O S atoms may dramatically increase the values of ΔE NO S ∗ , for example, from 7–9 to 24–27 kcal/mol for Rh(100) and Rh(100)c(2 × 2)O,N, respectively. This sensitiv the values of ΔE NO s ∗ to NO S coverage may explain the diversity of experimental results obtained for different coverages (exposu and temperatures even for the same single crystal face. The anisotropy of the values of Q X(X = NO, N, O) for different surfaces and possible reconstructions of these surfaces also contribute to the balance between dissociation and desorption of NO. Of the two channels for recombinative desorption of N 2, 2N S→ N 2,g and N S + NO S→ N 2,g + O S, the latter has the smaller activati barrier. Because the N 2 formation barriers rapidly increase in the order Pt ∼ Rh ⪡ Ru ⪡ Re, Rh or Rh-Pt surfaces are projected to be the most efficient catalysts for NO reduction by CO (to N 2 and CO 2). Similarly, Pt surfaces are projected to be the most efficient catalysts for NO reduction by H 2 (to NH 3 and H 2O). The general mechanistic picture emerging from the BOCMP analysis concurs with experimental data. Some apparent inconsistencies, particularly concerning the dissociation of NO, are discussed and some model conclusions to be verified by future experiments are noted.

Adsorption of H 2 and CO on Mn/Fe(110) surfaces

Mn-covered Fe(1101) surfaces were prepared by vapor-deposition at 130 K and annealing at 635 K for 15 s. H 2 and CO were adsorbed on these Mn/Fe(110) surfaces at 130 K and analyzed by thermal desorption spectroscopy (TDS) and O 1s X-ray photoelectron spectroscopy (XPS). Compared to pure Fe(110), Mn caused a drastic decrease in the sticking probability of H 2, indicative of an increase in the barrier for H 2 dissociation. Near Mn monolayer coverage there was a slight increase in the adsorption energy of hydrogen. For CO a lowering of the activation barrier of dissociation due to Mn was observed. Although molecular CO adsorbed on Mn/Fe(110) at a rate equal to that on Fe(110), the dissociation of CO started already at 223 K on Mn-covered Fe compared to ⪢ 373 K on clean Fe(110). The amount of dissociated CO at 523 K was 14 and 80% of the initial coverage for Fe(110) and Mn/Fe(110), respectively. Mn/Fe synergism on CO adsorption was most clearly noted at submonolayer Mn coverage. Changes in the peak temperature of the molecular CO state coupled to the increased amount of dissociated CO are suggestive of a significantly altered molecular adsorption well and weakened metal-CO bonding.

Evidence of isomerization during ion isolation in the quadrupole ion trap

Evidence of ion isomerization during isolation in an ion trap mass spectrometrer is presented. An ion—molecule reaction that is specific for the tolyl cation was used to monitor the relative abundance of this species. In particular, it has been observed that ion isolation in the ion trap can impart sufficient energy to the tolyl cation to cause it to isomerize to a form (presumably either the benzyl or the tropylium ion) that is not reactive with the neutral reagent. These results are important to consider in ion trap applications involving ion species having activation barriers for isomerization lower than the activation barriers for dissociation.

Synthesis and decomposition of ammonia on transition metal surfaces: bond-order-conservation-Morse-potential analysis

The mechanism of ammonia synthesis and decomposition on transition metal surfaces has been analyzed using the BOC-MP (bond-order-conservation-Morse-potential) method. The analysis is based on calculations of the heats of chemisorption, Q, for all adsorbed species and activation barriers, ΔE ∗ , for all elementary reactions believed to be involved in the reaction N 2 + H 2 ↔ NH 3 over Pt(111), Ru(001), Fe(110), Re(001). The relevant experimental values of Q and ΔE ∗ agree well with the BOC-MP estimates. It is shown that along the periodic series Pt, Ru, Fe, Re, the dissociation activation barriers decrease but the recombination and desorption barriers increase. In particular, we find that on all the surfaces the largest activation barrier corresponds to the recombinative desorption 2N s → N 2. This step is projected to be the rate-determining process for ammonia decomposition, and Pt is projected to be the most efficient catalyst. For the dissociation N 2 → 2N s, we find that the activation barrier sharply increases in the order Re ≤ Fe ⪡ Pt, which makes Pt surfaces incapable of catalyzing ammonia synthesis. These and other BOC-MP projections are in agreement with the results of mechanistic studies on Pt(111), Ru(001), and Fe(110).

Synthesis and decomposition of ammonia on transition metal surfaces: bond-order-conservation-Morse-potential analysis

The mechanism of ammonia synthesis and decomposition on transition metal surfaces has been analyzed using the BOC-MP (bond-order-conservation-Morse-potential) method. The analysis is based on calculations of the heats of chemisorption, Q, for all adsorbed species and activation barriers, ΔE∗, for all elementary reactions believed to be involved in the reaction N2 + H2 NH3 over Pt(111), Ru(001), Fe(110), Re(001). The relevant experimental values of Q and ΔE∗ agree well with the BOC-MP estimates. It is shown that along the periodic series Pt, Ru, Fe, Re, the dissociation activation barriers decrease but the recombination and desorption barriers increase. In particular, we find that on all the surfaces the largest activation barrier corresponds to the recombinative desorption 2Ns → N2. This step is projected to be the rate-determining process for ammonia decomposition, and Pt is projected to be the most efficient catalyst. For the dissociation N2 → 2Ns, we find that the activation barrier sharply increases in the order Re ⩽ Fe ⪡ Pt, which makes Pt surfaces incapable of catalyzing ammonia synthesis. These and other BOC-MP projections are in agreement with the results of mechanistic studies on Pt(111), Ru(001) and Fe(110).

Analysis of the thermochemistry of C 2 hydrocarbons on transition metal surfaces using a refined BOC-MP approach

A refined version of the BOC-MP (bond-order-conservation Morse-potential) approach has been used to calculate the heats of adsorption and the activation barriers for dissociation and recombination of C 2H x species on transition metal surfaces, such as Fe/W(110), Ni(111), and Pt(111). The calculations reveal distinct periodic patterns of C 2H x transformations. In particular, it is found that most of the decomposition routes of ethylene and acetylene are strongly exothermic on Fe and W, but are mildly endothermic on Pt. Accordingly, the calculations predict that C-H and C-C bond cleavage from the gas phase occurs practically without activation on Fe and W, but with finite activation barriers on Ni and especially Pt. The conceivable pathways of C 2H x decompositions are discussed in detail. The projections of the refined BOC-MP approach are in much better agreement with experiment, as compared with our previous calculations.

Energetics of metal-surface reactions: back-of-the-envelope theoretical modeling

The slow progress of quantum mechanical modeling of surface energetics makes it necessary to develop working alternatives. One of them is a phenomenological analytic approach based on bond-order conservation (BOC) and making use of Morse potentials (MP). This paper highlights the ‘back-of-the-envelope’ formalism of the BOC-MP model, and provides representative examples of calculations of the heats of chemisorption and the dissociation activation barriers for diatomic and some polyatomic adsorbates. The model findings are in good agreement with experiment. It appears that the BOC-MP model is well suited to treat the energetics of metal-surface reactions.

Coadsorption, promotion, and poisoning effects: Analytic modeling based on bond-order conservation

Our bond-order conservation model [ J. Am. Chem. Soc. 106 (1984) 6479; Surface Sci. 150 (1985) L115, 163 (1985) L645, L730] has been extended to treat effects of an atomic modifier D, either electronegative or electropositive, on coadsorbed atoms A and diatomic molecules AB. Taking a fcc(100) surface as an example, explicit formulas have been obtained for the relevant heats of chemisorption Q A and Q AB as a function of the D coverage θ D when D occupies the hollow site, for three typical cases: (i) a single D; (ii) a p(2 × 2) structure, θ D = 1 4 ; (iii) a c(2 × 2) structure, θ D = 1 2 . The values of Q A and ( Q AB) been estimated for various on-top, bridge, and hollow sites for a realistic range of the parameter r = Q D Q A (Q AB) . Possible corrections due to direct D-A and D-AB interactions, both attractive and repulsive, are discussed. We consider coadsorption effects on the stretch frequency ν AB and dissociation activation barrier Δ E ∗ AB and project a variety of patterns depending on the nature of D, coverages θ D and θ AB, and some other parameters. The results obtained are in encouraging agreement with experiment. The complex nature of coadsorption effects is stressed.