Reformation Of Bonds Research Articles

Ruthenium-Catalyzed C-H Bond Activation Approach to Azolyl Aminals and Hemiaminal Ethers, Mechanistic Evaluations, and Isomer Interconversion.

C(sp3)-N bond-forming reactions between benzotriazole and 5,6-dimethylbenzotriazole with N-methylpyrrolidinone, tetrahydrofuran, tetrahydropyran, diethyl ether, 1,4-dioxane, and isochroman have been conducted using RuCl3•3H2O/t-BuOOH in 1,2-dichloroethane. In all cases, N1 and N2 alkylation products were obtained, and these are readily separated by chromatography. One of these products, 1-(isochroman-1-yl)-5,6-dimethyl-1H-benzotriazole, was examined by X-ray crystallography. It is the first such compound to be analyzed by this method, and notably, the benzotriazolyl moiety is quasi-axially disposed, consistent with the anomeric effect. This has plausible consequences, not observed previously. In contrast to other hemiaminal ether-forming reactions, which proceed via radicals, this Ru-catalyzed process is not suppressed in the presence of a radical inhibitor. Therefore, an oxoruthenium-species-mediated rapid formation of an oxocarbenium intermediate is believed to occur. In the radical-trapping experiment, previously unknown products containing both the benzotriazole and the TEMPO unit have been identified. In these products, it is likely that the benzotriazole is introduced via a Ru-catalyzed C-N bond formation, whereas C-O bond-formation with TEMPO occurs via a radical reaction. We show that reactions of THF with TEMPO are influenced by ambient light. A competitive reaction of THF and THF-d8 with benzotriazole indicated that C-H bond cleavage occurs ca. 5 times faster than C-D cleavage. This is comparable to other metal-mediated radical reactions of THF, but lower than that observed for a reaction catalyzed by n-Bu4N+I-. Detailed mechanistic experiments and comparisons are described. The catalytic system was also evaluated for reactions of benzimidazole, imidazole, 1,2,4-triazole, and 1,2,3-triazole with THF, and successful reactions were achieved in each case. In the course of our studies, we discovered an unexpected but significant isomerization of some of the benzotriazolyl hemiaminal ethers. This is plausibly attributable to the pseudoaxial orientation of the heterocycle in the products and the stability of oxocarbenium ions, both of which can contribute to C-N bond cleavage and reformation. Predominantly, the N2-isomers rearrange to the N1-isomers even upon storage at low temperature! This previously unknown phenomenon has also been studied and described.

Linking Mechanochemistry to Protein Folding at the Single Bond Level

The impact of post translational modifications (PTM) on protein folding remains elusive. S-sulfenylation is the first oxidation step of cysteinyl thiols to create sulfenic acid. This PTM has emerged as a key sensor that modulates protein function and redox signalling. Here we use single molecule force clamp spectroscopy to create a stable sulfenic acid conformation by promoting an OH- nucleophilic attack on a single disulfide bond embedded within the core of the 27th immunoglobulin domain of titin (I27). By applying a tailor-designed force protocol, we set out to study the effect of S-sulfenylation on the oxidative folding of the I27 protein. We observe that sulfenic acid is a necessary precursor that facilitates enzymatic-free disulfide bond reformation. Furthermore, this disulfide reformation mechanism competes with the evolution of sulfenic acid to higher oxidation state species, which ultimately triggers protein misfolding. These results demonstrate that the oxidation state of a single amino acid within a protein has the power to completely alter the outcome of protein folding.

Functional, Dynamic and Structural Understanding of M2 Proton Channel from Influenza A and its Inhibition

While it has long been agreed that the M2 proton channel functions by shuttling protons on and off of the histidine tetrad near the mid plane of the lipid bilayer, the details have been hotly debated. Now details of the shuttling mechanism have been elucidated from solid state NMR spectroscopy. Short hydrogen bonds between the imidazole-imidazolium pairs are confirmed as well as their disruption by aqueous attack followed by N-H exchange and imidazolium-imidazole hydrogen bond reformation by either a deprotonation to the aqueous pore connected to the viral external environment (a futile proton cycle) or by deprotonation to a waters in the internal cavity between the His37 and Trp41 tetrads. For this latter option when the Trp41 gate opens the proton can be conducted into the viral interior (conductance cycle). The dynamics of the Trp41 residues and those of the secondary conductance gate (Val27) have been evaluated by wide-line solid state NMR.Solid state NMR REDOR and NCA experiments of the full length wild type M2 channel in complex with rimantadine enantiomers. The binding of these enantiomers to M2 shows a difference in binding affinity and a different set of binding interactions implying that stereospecific drugs may have biomedical benefits.M2 has multiple functions, among them is the facilitation of viral budding that takes advantage of the pyramidal shape of the M2 structure to induce membrane curvature. This shape is caused by the insertion of the juxtamembrane amphipathic helix in the lipid bilayer interface. We have now shown that the stability of this helix in the membrane is the result of cholesterol binding to this helix.

An adhesive zone model for polymeric interfaces

In this work we develop an adhesive zone model for polymeric interfaces, which describes the kinetics of dissociation and association of polymer chains bridging the interface. Compared with previous works on interfacial bond rupture, our adhesive zone model includes two novel features: possibility of bond reforming and a highly nonlinear force–extension relationship for the polymer chain motivated by previous experimental measurements. The absence of these two features was demonstrated in an earlier work to cause unphysical crack propagation under zero load as well as overextension of the chains beyond their full contour length. Using the rate dependent crack propagation in a double cantilever beam, which may be elastic or viscoelastic, as an example, the new adhesive zone model is shown to correct the unphysical results obtained earlier. Specifically, it leads to a significantly increased adhesive fracture energy, i.e., the energy per unit area required to rupture the chains on the interface, for slow crack propagation, owing to the ability to achieve a dynamic equilibrium of bond dissociation and association. Furthermore, the nonlinear chain model predicts a near-catastrophic decrease in chain density as the finite extensibility limit is approached. This results in an adhesive fracture energy which is orders of magnitude smaller than that predicted by the linear chain model for fast crack propagation. Although the adhesive zone model has only been applied to a double cantilever beam in this work, it is a generic model for polymeric interface, and can be implemented in finite element models to simulate fracture in bulk polymers in general.

Initial hydrogen-bonding dynamics of photoexcited coumarin in solution with femtosecond stimulated Raman spectroscopy

The ultrafast hydrogen bond breaking and reformation dynamics at the carbonyl site of a coumarin 102 dye molecule in ethanol is captured by femtosecond stimulated Raman spectroscopy (FSRS) on the femtosecond and picosecond timescales.

Rapid Protein Digestion and Purification with Membranes Attached to Pipet Tips.

This paper presents rapid protein purification and proteolysis methods that integrate membrane technology and pipet tips. Pushing a protein-containing solution through a protease-modified membrane at the end of a pipet tip digests proteins in 30 s or less, and the short proteolysis time avoids reformation of disulfide bonds to enable tryptic digestion without alkylation of cysteine residues. Moreover, proteolysis is more complete than digestion for 30 min in solution. Antibody digestion at the end of a pipet tip leads to 100% peptide coverage in MS analyses. Similarly, when membranes contain Ni(2+) complexes, pipetting aqueous polyhistidine-tagged protein through the membrane and subsequent rinsing and elution yield purified polyhistidine-tagged protein in 2 min. These applications demonstrate the potential for combining functional membranes and pipet tips for rapid sample purification and pretreatment.

Role of Structural Dynamics at the Receptor G Protein Interface for Signal Transduction.

GPCRs catalyze GDP/GTP exchange in the α-subunit of heterotrimeric G proteins (Gαßγ) through displacement of the Gα C-terminal α5 helix, which directly connects the interface of the active receptor (R*) to the nucleotide binding pocket of G. Hydrogen–deuterium exchange mass spectrometry and kinetic analysis of R* catalysed G protein activation have suggested that displacement of α5 starts from an intermediate GDP bound complex (R*•GGDP). To elucidate the structural basis of receptor-catalysed displacement of α5, we modelled the structure of R*•GGDP. A flexible docking protocol yielded an intermediate R*•GGDP complex, with a similar overall arrangement as in the X-ray structure of the nucleotide free complex (R*•Gempty), however with the α5 C-terminus (GαCT) forming different polar contacts with R*. Starting molecular dynamics simulations of GαCT bound to R* in the intermediate position, we observe a screw-like motion, which restores the specific interactions of α5 with R* in R*•Gempty. The observed rotation of α5 by 60° is in line with experimental data. Reformation of hydrogen bonds, water expulsion and formation of hydrophobic interactions are driving forces of the α5 displacement. We conclude that the identified interactions between R* and G protein define a structural framework in which the α5 displacement promotes direct transmission of the signal from R* to the GDP binding pocket.

Ultrasound response of aqueous poly(ionic liquid) solution

Ultrasound (US) effects on aqueous poly(ionic liquid) (PIL) solution were investigated using viscosity and FT-IR spectroscopy after exposure to US of 23, 43, and 96kHz frequencies at 50W. The viscosity of the poly(1-vinyl-3-butyl-imidazolium chloride) (PIL) aqueous solution decreased during exposure to US. It then increased gradually within about 10min as US stopped. The aqueous PIL behavior was then observed using FT-IR spectroscopy. The US exposure enhanced the FT-IR band intensity of the OH stretching. The band intensity returned to its original value after the US stopped. These results responded cyclically to the US on/off. Analysis of the FT-IR spectra revealed that US influenced the breakage and reformation of hydrogen bonds in the PIL and water. Two-dimensional correlation and deconvolution were used to analyze the change of components in the region of 3000–3700cm−1 for US exposure. Results of these analyses suggest that US exposure might break hydrogen bonds between PIL segments and water. In the absence of US, hydrogen bonds reformation was also observed between the PIL and water.

Seeing Molecules in Motion in Aqueous Solutions

Hydrogen bonds play critical roles in determining the structural, thermodynamic and dynamical behavior of water and aqueous solutions. In solutions of ions in water, the hydrogen bonded network can be perturbed significantly by the presence of ions. This perturbation, in turn, changes many of the equilibrium and dynamical properties of water in the solutions compared to those in pure water. The network of hydrogen bonds is dynamic in nature. It fluctuates at a very fast rate due to breaking and reformation of hydrogen bonds. In the present article, a brief review is made of some of the recent computer simulation studies to ‘see’ these hydrogen bonded molecules in motion in aqueous solutions. Connections of the simulation results are also made to some of the recent experimental studies on aqueous solutions using the method of time dependent infrared spectroscopy.

Effect of swift-ion irradiation on DNA molecules: A molecular dynamics study using the REAX force field

Modern REAX potentials allow to use molecular dynamics simulation to study bond breaking and reformation in biomolecules. We use this technique to simulate the effects of a swift-ion track on a B-DNA fragment in water. We monitor the number of single- and double-strand breaks as a function of the deposited energy. In addition we compare the results of direct DNA heating with the effect of hydrolysis which we model by heating only the water environment.

Vacuum Assisted Graphene Oxide Membranes for Polymer Electrolyte Membrane Fuel Cells

Undisputedly hydrogen is the preferred and prominent fuel for polymer electrolyte membrane fuel cells (PEMFCs) because of its high electro reactivity for the anodic reaction, the lack of onsite green-house gas emissions (pure water is the only product) and higher cell efficiency. The presence of various oxygenated functional groups can facilitate the proton transportation through reformation of hydrogen bonds and makes graphene oxide (GO) itself as a good candidate as a proton exchange membrane in low temperature fuel cells. Besides ionic conductivity, GO can act as a physical barrier separating the fuels such as hydrogen and oxidant and prevents their cross-overs. In the recent times, significant attention has been shifted towards employing pristine/Virgin GO membranes as such in low temperature polymer electrolyte fuel cells. A number of preparation methods have been proposed to synthesise free-standing GO films in the recent past. However, the influence of method on the membrane properties and applications in fuel cells needs to be addressed and requires further exploration.In this work, graphene oxide membranes of different thickness will be prepared using two different methods: vacuum evaporation and hydrosol evaporation. The influence of the method of preparation, thickness, will be studied in relation to the membrane properties including proton conductivity, ion exchange capacity, and water uptake, swelling behavior, thermal stability and fuel cell performance. A comparative study made with the conventional membrane electrode assembly (Pt/C-Nafion-Pt/C) will be discussed in detail.

Controllable Scission and Seamless Stitching of Metal-Organic Clusters by STM Manipulation.

Scanning tunneling microscopy (STM) manipulation techniques have proven to be a powerful method for advanced nanofabrication of artificial molecular architectures on surfaces. With increasing complexity of the studied systems, STM manipulations are then extended to more complicated structural motifs. Previously, the dissociation and construction of various motifs have been achieved, but only in a single direction. In this report, the controllable scission and seamless stitching of metal-organic clusters have been successfully achieved through STM manipulations. The system presented here includes two sorts of hierarchical interactions where coordination bonds hold the metal-organic elementary motifs while hydrogen bonds among elementary motifs are directly involved in bond breakage and re-formation. The key to making this reversible switching successful is the hydrogen bonding, which is comparatively facile to be broken for controllable scission, and, on the other hand, the directional characteristic of hydrogen bonding makes precise stitching feasible.

Motion of proximal histidine and structural allosteric transition in soluble guanylate cyclase

We investigated the changes of heme coordination in purified soluble guanylate cyclase (sGC) by time-resolved spectroscopy in a time range encompassing 11 orders of magnitude (from 1 ps to 0.2 s). After dissociation, NO either recombines geminately to the 4-coordinate (4c) heme (τG1 = 7.5 ps; 97 ± 1% of the population) or exits the heme pocket (3 ± 1%). The proximal His rebinds to the 4c heme with a 70-ps time constant. Then, NO is distributed in two approximately equal populations (1.5%). One geminately rebinds to the 5c heme (τG2 = 6.5 ns), whereas the other diffuses out to the solution, from where it rebinds bimolecularly (τ = 50 μs with [NO] = 200 μM) forming a 6c heme with a diffusion-limited rate constant of 2 × 10(8) M(-1)⋅s(-1). In both cases, the rebinding of NO induces the cleavage of the Fe-His bond that can be observed as an individual reaction step. Saliently, the time constant of bond cleavage differs depending on whether NO binds geminately or from solution (τ5C1 = 0.66 μs and τ5C2 = 10 ms, respectively). Because the same event occurs with rates separated by four orders of magnitude, this measurement implies that sGC is in different structural states in both cases, having different strain exerted on the Fe-His bond. We show here that this structural allosteric transition takes place in the range 1-50 μs. In this context, the detection of NO binding to the proximal side of sGC heme is discussed.

Structures of water molecules in carbon nanotubes under electric fields.

Carbon nanotubes (CNTs) are promising for water transport through membranes and for use as nano-pumps. The development of CNT-based nanofluidic devices, however, requires a better understanding of the properties of water molecules in CNTs because they can be very different from those in the bulk. Using all-atom molecular dynamics simulations, we investigate the effect of axial electric fields on the structure of water molecules in CNTs having diameters ranging from (7,7) to (10,10). The water dipole moments were aligned parallel to the electric field, which increases the density of water inside the CNTs and forms ordered ice-like structures. The electric field induces the transition from liquid to ice nanotubes in a wide range of CNT diameters. Moreover, we found an increase in the lifetime of hydrogen bonds for water structures in the CNTs. Fast librational motion breaks some hydrogen bonds, but the molecular pairs do not separate and the hydrogen bonds reform. Thus, hydrogen bonds maintain the water structure in the CNTs, and the water molecules move collectively, decreasing the axial diffusion coefficient and permeation rate.

Hydrogen-bonding-supported self-healing antifogging thin films.

Inspired by the repair of DNA through efficient reformation of hydrogen bonds (H-bonds), herein we report a facile one-step approach to construction of self-healing antifogging thin films on the basis of partly cross-linked poly(vinyl alcohol)(PVA) and poly(acrylic acid)(PAA). By designing the molar ratio of hydroxyl groups to carboxyl groups, the cross-linked polymer thin films maintain abundant free hydroxyl groups to present excellent antifogging property, which is derived from the hydrophilicity and hygroscopicity of the thin films. The thin films showed smart intrinsic self-healing characteristics towards wounds caused by external forces, which is attributed to sufficient free hydroxyl groups at the scratched interfaces to reform H-bonds across the interfaces and a sufficient chain mobility that is indispensable for chain diffusion across the interfaces and hydroxyl groups association to form H-bonds. No synthetic surfaces reported so far possess all the unique characteristics of the polymer thin films: intrinsic self-healing, long-term antifogging, excellent mechanical property, high transmittance and large-scale feasibility.

Viscoelasticity using reactive constrained solid mixtures

This study presents a framework for viscoelasticity where the free energy density depends on the stored energy of intact strong and weak bonds, where weak bonds break and reform in response to loading. The stress is evaluated by differentiating the free energy density with respect to the deformation gradient, similar to the conventional approach for hyperelasticity. The breaking and reformation of weak bonds is treated as a reaction governed by the axiom of mass balance, where the constitutive relation for the mass supply governs the bond kinetics. The evolving mass contents of these weak bonds serve as observable state variables. Weak bonds reform in an energy-free and stress-free state, therefore their reference configuration is given by the current configuration at the time of their reformation. A principal advantage of this formulation is the availability of a strain energy density function that depends only on observable state variables, also allowing for a separation of the contributions of strong and weak bonds. The Clausius–Duhem inequality is satisfied by requiring that the net free energy from all breaking bonds must be decreasing at all times. In the limit of infinitesimal strains, linear stress–strain responses and first-order kinetics for breaking and reforming of weak bonds, the reactive framework reduces exactly to classical linear viscoelasticity. For large strains, the reactive and classical quasilinear viscoelasticity theories produce different equations, though responses to standard loading configurations behave similarly. This formulation complements existing tools for modeling the nonlinear viscoelastic response of biological soft tissues under large deformations.

Microscopic dynamics of water around unfolded structures of barstar at room temperature.

The breaking of the native structure of a protein and its influences on the dynamic response of the surrounding solvent is an important issue in protein folding. In this work, we have carried out atomistic molecular dynamics simulations to unfold the protein barstar at two different temperatures (400 K and 450 K). The two unfolded forms obtained at such high temperatures are further studied at room temperature to explore the effects of nonuniform unfolding of the protein secondary structures along two different pathways on the microscopic dynamical properties of the surface water molecules. It is demonstrated that though the structural transition of the protein in general results in less restricted water motions around its segments, but there are evidences of formation of new conformational motifs upon unfolding with increasingly confined environment around them, thereby resulting in further restricted water mobility in their hydration layers. Moreover, it is noticed that the effects of nonuniform unfolding of the protein segments on the relaxation times of the protein-water (PW) and the water-water (WW) hydrogen bonds are correlated with hindered hydration water motions. However, the kinetics of breaking and reformation of such hydrogen bonds are found to be influenced differently at the interface. It is observed that while the effects of unfolding on the PW hydrogen bond kinetics seem to be minimum, but the kinetics involving the WW hydrogen bonds around the protein segments exhibit noticeably heterogeneous characteristics. We believe that this is an important observation, which can provide valuable insights on the origin of heterogeneous influence of unfolding of a protein on the microscopic properties of its hydration water.

Hydrogen bond dynamics in primary alcohols: a femtosecond infrared study.

Hydrogen-bonded liquids are excellent solvents, in part due to the highly dynamic character of the directional interaction associated with the hydrogen bond. Here we study the vibrational and reorientational dynamics of deuterated hydroxyl groups in various primary alcohols using polarization-resolved femtosecond infrared spectroscopy. We show that the relaxation of the OD stretch vibration is similar for ethanol and its higher homologues (∼0.9 ps), while it is appreciably faster for methanol (∼0.75 ps). The fast relaxation for methanol is attributed to strong coupling of the OD stretch vibration to the overtone of the CH3 rocking mode. Subsequent to excited state relaxation, the dissipation of the excess energy leads to structural relaxation of the alcohol liquid structure. We show that this relaxation of the H-bonded network depends on the alkyl chain length. We find that the anisotropy of the excitation decays by both thermal diffusion from excited OD groups to nonexcited molecules and reorientational motion. The reorientation is described well by a model employing two relaxation times that increase linearly with increasing alcohol size. The short reorientation time is assigned to the partial reorientation of molecules within the alcohol cluster, while the long reorientation times can be attributed to breaking and reforming of hydrogen bonds.

Hydrogen‐Bonding Effects for the C–ON Bond Homolysis and Reformation Reactions of Alkoxyamines

N‐(2‐methylpropyl)‐N‐(1‐diethylphosphono‐2,2‐dimethylpropyl)‐O‐(2‐carboxyprop‐2‐yl) hydroxylamine (BlocBuilder MA) is, among the commercially available alkoxyamines, one of the most efficient for nitroxide‐mediated polymerization (NMP). However, recent results have shown that it does not perform well for the NMP of isoprene. The occurrence of intramolecular hydrogen bonding (IHB) between the carboxylic function and the diethoxyphosphoryl group has been proposed as the reason for its low efficiency. In this article, the presence of this IHB is confirmed using IR, 31P NMR, 31P‐1H HOESY, and DFT calculation results. The solvent effect on this IHB and consequently on kd values is also investigated. However, combining kinetic analysis and rate measurements in various solvents, the influence of this IHB on the CON bond homolysis and reformation in alkoxyamine is shown to be very weak. image

Oxidation Reactivity of a Structurally and Spectroscopically Well-defined Mononuclear Peroxocarbonato–Iron(III) Complex

Abstract A mononuclear peroxocarbonato–iron(III) complex [Fe(6Me-pic)2(O2C(O)O)]− (1-O2C(O)O) with bidentate ligands (6Me-pic), prepared by the reaction of a carbonato–iron(III) complex [Fe(6Me-pic)2(CO3)]− (1-CO3) with H2O2, was fully characterized. 1-O2C(O)O showed reversible O–O bond cleavage and reformation of the peroxo group under CO2 at 25 °C. 1-O2C(O)O is capable of not only oxidizing the C=C bond of cyclooctene but also the C–H bond of toluene. As for cyclooctene, epoxidation is favorable under CO2 in the presence of H2O, while cis-dihydroxylation precedes under N2, indicating that the oxidation reactivity of 1-O2C(O)O toward cyclooctene can be tuned by changing the concentration of CO2 and H2O.