Dynamic Diselenide Bonds: Exchange Reaction Induced by Visible Light without Catalysis

Dynamic covalent bonds are extensively employed in dynamic combinatorial chemistry. The metathesis reaction of disulfide bonds is widely used, but requires catalysis or irradiation with ultraviolet (UV) light. It was found that diselenide bonds are dynamic covalent bonds and undergo dynamic exchange reactions under mild conditions for diselenide metathesis. This reaction is induced by irradiation with visible light and stops in the dark. The exchange is assumed to proceed through a radical mechanism, and experiments with 2,2,6,6‐tetramethylpiperidin‐1‐yloxyl (TEMPO) support this assumption. Furthermore, the reaction can be conducted in different solvents, including protic solvents. Diselenide metathesis can also be used to synthesize diselenide‐containing asymmetric block copolymers. This work thus entails the use of diselenide bonds as dynamic covalent bonds, the development of a dynamic exchange reaction under mild conditions, and an extension of selenium‐related dynamic chemistry.     

Sampling protein conformations and pathways

Protein flexibility and rigidity can be analyzed using constraint theory, which views proteins as 3D networks of constraints involving covalent bonds and also including hydrophobic interactions and hydrogen bonds. This article describes an algorithm, ROCK (Rigidity Optimized Conformational Kinetics), which generates new conformations for these complex networks with many interlocked rings while maintaining the constraints. These new conformations are tracked for the flexible regions of a protein, while leaving the rigid regions undisturbed. An application to HIV protease demonstrates how large the flap motion can be. The algorithm is also used to generate conformational pathways between two distinct protein conformations. As an example, directed trajectories between the closed and the occluded conformations of the protein dihydrofolate reductase are determined.     

The hydrogen bond in the solid state

The hydrogen bond is the most important of all directional intermolecular interactions. It is operative in determining molecular conformation, molecular aggregation, and the function of a vast number of chemical systems ranging from inorganic to biological. Research into hydrogen bonds experienced a stagnant period in the 1980s, but re-opened around 1990, and has been in rapid development since then. In terms of modern concepts, the hydrogen bond is understood as a very broad phenomenon, and it is accepted that there are open borders to other effects. There are dozens of different types of X-H.A hydrogen bonds that occur commonly in the condensed phases, and in addition there are innumerable less common ones. Dissociation energies span more than two orders of magnitude (about 0.2-40 kcal mol(-1)). Within this range, the nature of the interaction is not constant, but its electrostatic, covalent, and dispersion contributions vary in their relative weights. The hydrogen bond has broad transition regions that merge continuously with the covalent bond, the van der Waals interaction, the ionic interaction, and also the cation-pi interaction. All hydrogen bonds can be considered as incipient proton transfer reactions, and for strong hydrogen bonds, this reaction can be in a very advanced state. In this review, a coherent survey is given on all these matters.     

Mechanism of immunoglobulin G4 Fab-arm exchange

Immunoglobulin G (IgG) antibodies are symmetrical molecules that may be regarded as covalent dimers of 2 half-molecules, each consisting of a light chain and a heavy chain. Human IgG4 is an unusually dynamic antibody, with half-molecule exchange ("Fab-arm exchange") resulting in asymmetrical, bispecific antibodies with two different antigen binding sites, which contributes to its anti-inflammatory activity. The mechanism of this process is unknown. To elucidate the elementary steps of this intermolecular antibody rearrangement, we developed a quantitative real-time FRET assay to monitor the kinetics of this process. We found that an intrinsic barrier is the relatively slow dissociation of the CH3 domains that noncovalently connect the heavy chains, which becomes rate determining in case disulfide bonds between the heavy chains are reduced or absent. Under redox conditions that mimic the previously estimated in vivo reaction rate, i.e., 1 mM of reduced glutathione, the overall rate is ca. 20 times lower because only a fraction of noncovalent isomers is present (with intra- rather than interheavy chain disulfide bonds), formed in a relatively fast pre-equilibrium from covalent isomers. Interestingly, Fab arms stabilize the covalent isomer: the amount of noncovalent isomers is ca. 3 times higher for Fc fragments of IgG4 (lacking Fab domains) compared to intact IgG4, and the observed rate of exchange is 3 times higher accordingly. Thus, kinetic data obtained from a sensitive and quantitative real-time FRET assay as described here yield accurate data about interdomain interactions such as those between Fab and/or Fc domains. The results imply that in vivo, the reaction is under control of local redox conditions.     

Electronegativities of elements in covalent crystals

A new electronegativity table of elements in covalent crystals with different bonding electrons and the most common coordination numbers is suggested on the basis of covalent potentials of atoms in crystals. For a given element, the electronegativity increases with increasing number of bonding electrons and decreases with increasing coordination number. Particularly, the ionicity of a covalent bond in different environments can be well-reflected by current electronegativity values; that is, the ionicity of chemical bonds increases as the coordination number of the bonded atoms increases. We show that this electronegativity scale can be successfully applied to predict the hardness of covalent and polar covalent crystals, which will be very useful for studying various chemical and physical properties of covalent materials.     

Live Monitoring of Strain-Promoted Azide Alkyne Cycloadditions in Complex Reaction Environments by Inline ATR-IR Spectroscopy

The strain-promoted azide alkyne cycloaddition (SPAAC) is a powerful tool for forming covalent bonds between molecules even under physiological conditions, and therefore found broad application in fields ranging from biological chemistry and biomedical research to materials sciences. For many applications, knowledge about reaction kinetics of these ligations is of utmost importance. Kinetics are commonly assessed and studied by NMR measurements. However, these experiments are limited in terms of temperature and restricted to deuterated solvents. By using an inline ATR-IR probe we show that the cycloaddition of azides and alkynes can be monitored in aqueous and even complex biological fluids enabling the investigation of reaction kinetics in various solvents and even human blood plasma under controlled conditions in low reaction volumes.     

Natural polyelectron population analysis

A method to perform a polyelectron population analysis of correlated molecular orbital wave functions on the basis of natural atomic orbitals (NAO s), as given by Weinhold, is presented. The method allows calculations of the probabilities of finding various types of electronic events occuring in some target AO positions, including the contributions of ionic and covalent resonance structures. This method is general and neither the theory nor the developed algorithm limit the number of electrons and holes that can be considered. Thus, the analyzed MO wave function can be a usual CI or a MCSCF one, and apart from Weinhold's NAO s. any other type of orthogonal AO s can be used as analyzers, provided that these AO s are linear combinations of the SCF-AO s. Numerical applications are given for ethylene, formaldehyde, butadiene, and acroleine, by adopting various AO basis-set levels (STO ?4G , 4–31G , and 6–31G ) and by analyzing correlated wave functions (CISD ). Improvements in the polyelectron populations when increasing the quality of AO basis sets and the corresponding valence NAO s are revealed by several examples. Furthermore, it is shown that the electroegativity of oxygen in acroleine only has an effect on contributions of ionic and covalent resonance structures, but not on delocalization of the double bonds. 1993 John Wiley & Sons, Inc.     

Physical aspects of network polymerization from calorimetry and dielectric spectroscopy of a triepoxide reacting with different monoamines

Calorimetry and dielectric relaxation spectroscopy were used to study the evolution of molecular dynamics during the isothermal polymerization of two stoichiometric mixtures of a molecule with three epoxide groups with (i) aniline and (ii) 3-chloroaniline, whose dipole moments as well as the degrees of steric hindrance to chemical reactions differ. The heat evolved on polymerization was used to calculate the number of covalent bonds formed at any instant during the polymerization reaction. The approach of the DC conductivity towards a singularity as the reaction progressed agrees with the Flory-Stockmayer theory of connectivity at gelation and not the percolation theory. It is demonstrated that a plot of DC conductivity against the extent of reaction does not have the same shape as the plot against the time of reaction. The permittivity and loss spectra obtained for structural states containing a fixed number of covalent bonds could be described by equations analogous, but not equivalent to, or the same as, the equations used for describing the dielectric properties measured for a fixed frequency during the growth of a macromolecule's network structure. For a fixed temperature, the relaxation time of the structure formed increased as the exponential of the extent of reaction (raised to the power > 1) increased. Comparative parameter-fits to the spectra showed that the DC conductivity and interfacial polarization alter the shape of the dielectric spectra such as to make misleadingly alternative parameter fits possible. The decrease of the equilibrium dielectric permittivity on polymerization is attributed to a decrease in the dipolar orientational correlation as well as the net dipole moment on increase in the number of covalent bonds. The configurational entropy decreased with increase in the number of covalent bonds formed in a manner that differs from the decrease on cooling, and a formalism relating the two effects is given. As the network structure grew isothermally, a second, high-frequency relaxation process came into evidence. This relaxation is attributed to the availability and growth of local regions of low density and high density in the network structure of the macromolecule. A number of issues of a fundamental nature that have risen since our earliest report on this subject have been elaborated and analytically clarified. © 1997 John Wiley & Sons, Inc.     

Spectroscopic Investigation of Solid Poly-p-Methoxystyrene-Aerosil Composites Obtained by Triphenylmethylium-Halide-Aerosil Initiation

Abstract

The composites of poly-p-methoxystyrene and aerosil obtained by interfacial initiation with triphenylmethylium-halide-aerosil have been investigated by the BET method, UV/Vis spectroscopy, FTIR spectroscopy, thermogravimetry, and elementary analysis. In the case of triphen-ylmethylium-bromide-aerosil initiation, cationically active composites are obtained which have covalent Si-O-C bonds. The structures of the polymer-aerosil bonds are discussed in comparison with results obtained from model compounds.     

The importance of electronic exchange-correlation in non-self-consistent frozen density approximation

The effects of different treatments for the exchange-correlation energy on the accuracy of non-self-consistent frozen density approximation (FDA) are discussed. Local spin density approximation (LSDA) and non-local spin density approximation (NLSDA) are employed, respectively. Corresponding results obtained by using full-self-consistent density functional theory (DFT) are also given for the purpose of comparison. Explicit calculations for hydrogen bonds, covalent bonds and ionic bonds indicate that, comparing with LSDA, NLSDA can improve the accuracy of FDA as well as that of DFT. This improvement attributed to the refinements in the treatment for the electronic exchange-correlation energy may help to extend the application of FDA.     

σ‐Noninnocence: Masked Phenyl‐Cation Transfer at Formal NiIV

Reductive elimination is an elementary organometallic reaction step involving a formal oxidation state change of ?2 at a transition‐metal center. For a series of formal high‐valent Ni^IV complexes, aryl–CF₃ bond‐forming reductive elimination was reported to occur readily (Bour et al. J. Am. Chem. Soc. 2015 , 137, 8034–8037). We report a computational analysis of this reaction and find that, unexpectedly, the formal Ni^IV centers are better described as approaching a +II oxidation state, originating from highly covalent metal–ligand bonds, a phenomenon attributable to σ‐noninnocence. A direct consequence is that the elimination of aryl–CF₃ products occurs in an essentially redox‐neutral fashion, as opposed to a reductive elimination. This is supported by an electron flow analysis which shows that an anionic CF₃ group is transferred to an electrophilic aryl group. The uncovered role of σ‐noninnocence in metal–ligand bonding, and of an essentially redox‐neutral elimination as an elementary organometallic reaction step, may constitute concepts of broad relevance to organometallic chemistry.     

Controlling Covalent Connection and Disconnection with Light

The on‐going need for feature miniaturization and the growing complexity of structures for use in nanotechnology demand the precise and controlled formation of covalent bonds at the molecular level. Such control requires the use of external stimuli that offer outstanding spatial, temporal, as well as energetic resolution. Thus, photoaddressable switches are excellent candidates for creating a system that allows reversible photocontrol over covalent chemical connection and disconnection. Here we show that the formation of covalent bonds between two reagents and their scission in the resulting product can be controlled exclusively by illumination with differently colored light. A furyl‐substituted photoswitchable diarylethene was shown to undergo a reversible Diels–Alder reaction with maleimide to afford the corresponding Diels–Alder adduct. Our system is potentially applicable in any field already relying on the benefits of reversible Diels–Alder reactions.     

A Versatile Approach to Dynamic Amide Bond Formation with Imine Nucleophiles

Dynamic covalent chemistry has rapidly become an important approach to access supramolecular structures. While the products generated in these reactions are held together by covalent bonds, the reversible nature of the transformations can limit the utility of many these systems in creating robust materials. We describe herein a method to form stable and commonly employed amide bonds by exploiting the reversible coupling of imines and acyl chlorides. The reaction employs easily accessible reagents, is dynamic under ambient conditions, without catalysts, and can be trapped with simple hydrolysis. This offers an approach to create broad families of amide products under thermodynamic control, including the selective formation of amide macrocycles or polymers.     

Molecular Networks in Dynamic Multilevel Systems

Dynamic multilevel systems can be assembled from molecular building blocks through two or more reversible reactions that form covalent bonds. Molecular networks of dynamic multilevel systems can exhibit different connectivities between nodes. The design and creation of molecular networks in multilevel systems require control of the crossed reactivity of the functional groups (how to connect nodes) and the conditions of the reactions (when to connect nodes). In recent years, the combination of orthogonal and communicating reactions, which can be simultaneous or individually activated, has produced a variety of systems that have given rise to macrocycles and cages, as well as molecular motors and multicomponent architectures on surfaces. A given set of reactions can lead to systems with unique responsiveness, compositions, and functions as a result of the relative reactivities. In this Concept article, different molecular networks from synthetic systems that can be produced by combinations of different reaction types are discussed. Moreover, applications of this chemistry are highlighted, and future perspectives are envisioned.     

Highly covalent ferric-thiolate bonds exhibit surprisingly low mechanical stability

Depending on their nature, different chemical bonds show vastly different stability with covalent bonds being the most stable ones that rupture at forces above nanonewton. Studies have revealed that ferric-thiolate bonds are highly covalent and are conceived to be of high mechanical stability. Here, we used single molecule force spectroscopy techniques to directly determine the mechanical strength of such highly covalent ferric-thiolate bonds in rubredoxin. We observed that the ferric-thiolate bond ruptures at surprisingly low forces of ～200 pN, significantly lower than that of typical covalent bonds, such as C-Si, S-S, and Au-thiolate bonds, which typically ruptures at >1.5 nN. And the mechanical strength of Fe-thiolate bonds is observed to correlate with the covalency of the bonds. Our results indicated that highly covalent Fe-thiolate bonds are mechanically labile and display features that clearly distinguish themselves from typical covalent bonds. Our study not only opens new avenues to investigating this important class of chemical bonds, but may also shed new lights on our understanding of the chemical nature of these metal thiolate bonds.     

Entanglements in glass

Ground state and elementary excitations (tunnelling modes) in glass are obtained from an analysis of its symmetry, a local gauge invariance. The configuration of glass is represented as a discrete fiber bundle. The base space is a continuous random network, standard model of the structure of covalent glasses. The connection is determined naturally by the elasticity of the network. The bundle is non-trivial, the elastic connection is entangled in one of two ways. Sources of non-triviality are closed loops, threading through odd rings in the network. To restore gauge invariance, tunnelling must occur between the two possible configurations about an odd loop. Entanglement and elementary excitations are labelled by permutations of the covalent bonds incident on an atom.Work supported by the Herbette Foundation.     

Reversible microencapsulation of pybox-Ru chiral catalysts: scope and limitations

Chiral Pybox-Ru catalysts can be microencapsulated into linear polystyrene as a method to recover and recycle the valuable catalyst. These catalysts allow 60-68% yields to be achieved with enantioselectivities in the range 75-85% ee in the benchmark cyclopropanation reaction between styrene and ethyl diazoacetate. The catalyst is soluble in the reaction solvent and is re-encapsulated at the end of the reaction. The great advantage of this methodology is that the chiral ligand does not need to be modified, but the recycling is highly solvent dependent—in contrast with the catalysts immobilized through covalent bonds.     

Improving creep resistance while maintaining reversibility of covalent adaptive networks via constructing reversibly interlocked polymer networks

Thermoresponsive covalent adaptive networks (CANs) have attracted increasing research attention because of their temperature-dependent reversibility, which endows the materials with versatile smart functionalities including intrinsic self-healability not available for traditional thermosets. Nevertheless, the associated reduction in creep resistance of this type of CANs limits their practical application. Here in this work, we demonstrate that the reversibility and dimensional stability can be combined via interlocking the thermoresponsive network with an ultraviolet-responsive network. The two types of networks are, respectively, crosslinked by orthogonal reversible Diels-Alder (DA) bonds and coumarin. Owing to the interlocked architecture, the latter single network can be uniformly distributed in the former, restricting the chain movement and enhancing the creep resistance even when the former is decrosslinked at elevated temperature as a result of retro-DA reaction. Meanwhile, the ultraviolet-responsive network plays the role of a photo-reversible switch. Its decrosslinking on exposure to 254 nm ultraviolet (UV) light and recrosslinking under a UV irradiation of 350 nm lead to repeated releasing and reimposing of the restraints on the neighboring thermoresponsive network. By using this smart habit, the material can either be conditionally self-healed with moderate healing efficiency or completely self-healed depending on whether only DA bonds or both DA bonds and coumarin are triggered. More importantly, the conflicting properties, that is, creep resistance and reversibility of the CANs are thus united. The proposed strategy provides a facile way for overcoming the weaknesses of CANs while maintaining the advantage.     

Shape‐Persistent Organic Cage Compounds by Dynamic Covalent Bond Formation

One area of supramolecular chemistry involves the synthesis of discrete three‐dimensional molecules or supramolecular aggregates through the coordination of metals. This field also concerns the chemistry of supramolecular cage compounds constructed through the use of such coordination bonds. To date, there exists a broad variety of supramolecular cage compounds; however, analogous organic cage compounds formed with only covalent bonds are relatively rare. Recent progress in this field can be attributed to important advances, not least the application of dynamic covalent chemistry. This concept makes it possible to start from readily available precursors, and in general allows the synthesis of cage compounds in fewer steps and usually higher yields.