Monotone Chemical Reaction Networks

We analyze certain chemical reaction networks and show that every solution converges to some steady state. The reaction kinetics are assumed to be monotone but otherwise arbitrary. When diffusion effects are taken into account, the conclusions remain unchanged. The main tools used in our analysis come from the theory of monotone dynamical systems. We review some of the features of this theory and provide a self-contained proof of a particular attractivity result which is used in proving our main result.     

Accelerated Self‐Replication under Non‐Equilibrium,Periodic Energy Delivery

Self‐replication is a remarkable phenomenon in nature that has fascinated scientists for decades. In a self‐replicating system, the original units are attracted to a template, which induce their binding. In equilibrium, the energy required to disassemble the newly assembled copy from the mother template is supplied by thermal energy. The possibility of optimizing self‐replication was explored by controlling the frequency at which energy is supplied to the system. A model system inspired by a class of light‐switchable colloids was considered where light is used to control the interactions. Conditions under which self‐replication can be significantly more effective under non‐equilibrium, cyclic energy delivery than under equilibrium constant energy conditions were identified. Optimal self‐replication does not require constant energy expenditure. Instead, the proper timing at which energy is delivered to the system is an essential controllable parameter to induce high replication rates.     

Accelerated Self‐Replication under Non‐Equilibrium,Periodic Energy Delivery

Self‐replication is a remarkable phenomenon in nature that has fascinated scientists for decades. In a self‐replicating system, the original units are attracted to a template, which induce their binding. In equilibrium, the energy required to disassemble the newly assembled copy from the mother template is supplied by thermal energy. The possibility of optimizing self‐replication was explored by controlling the frequency at which energy is supplied to the system. A model system inspired by a class of light‐switchable colloids was considered where light is used to control the interactions. Conditions under which self‐replication can be significantly more effective under non‐equilibrium, cyclic energy delivery than under equilibrium constant energy conditions were identified. Optimal self‐replication does not require constant energy expenditure. Instead, the proper timing at which energy is delivered to the system is an essential controllable parameter to induce high replication rates.     

Dehydrogenative N‐Incorporation: A Direct Approach to Quinoxaline N‐Oxides under Mild Conditions

An efficient method for the synthesis of quinoxaline N‐oxides proceeds by the dehydrogenative N‐incorporation of simple imines by C(sp²)? H and C(sp³)? H bond functionalization. The overall transformation involves the cleavage of three C? H bonds. The reaction is easily handled and proceeds under mild conditions. Simple and readily available tert‐butyl nitrite (TBN) was employed as the NO source.     

Hydroxylation of Aromatics with the Help of a Non‐Haem FeOOH: A Mechanistic Study under Single‐Turnover and Catalytic Conditions

Ferric–hydroperoxo complexes have been identified as intermediates in the catalytic cycle of biological oxidants, but their role as key oxidants is still a matter of debate. Among the numerous synthetic low‐spin Fe^III(OOH) complexes characterized to date, [(L₅²)Fe(OOH)]²⁺ is the only one that has been isolated in the solid state at low temperature, which has provided a unique opportunity for inspecting its oxidizing properties under single‐turnover conditions. In this report we show that [(L₅²)Fe(OOH)]²⁺ decays in the presence of aromatic substrates, such as anisole and benzene in acetonitrile, with first‐order kinetics. In addition, the phenol products are formed from the aromatic substrates with similar first‐order rate constants. Combining the kinetic data obtained at different temperatures and under different single‐turnover experimental conditions with experiments performed under catalytic conditions by using the substrate [1,3,5‐D₃]benzene, which showed normal kinetic isotope effects (KIE>1) and a notable hydride shift (NIH shift), has allowed us to clarify the role played by Fe^III(OOH) in aromatic oxidation. Several lines of experimental evidence in support of the previously postulated mechanism for the formation of two caged Fe^IV(O) and OH ^. species from the Fe^III(OOH) complex have been obtained for the first time. After homolytic O? O cleavage, a caged pair of oxidants [Fe^IVO+HO ^. ] is generated that act in unison to hydroxylate the aromatic ring: HO ^. attacks the ring to give a hydroxycyclohexadienyl radical, which is further oxidized by Fe^IVO to give a cationic intermediate that gives rise to a NIH shift upon ketonization before the final re‐aromatization step. Spin‐trapping experiments in the presence of 5,5‐dimethyl‐1‐pyrroline N‐oxide and GC‐MS analyses of the intermediate products further support the proposed mechanism.     

Catalytic Asymmetric Synthesis of 3‐Indolyl Methanamines Using Unprotected Indoles and N‐Boc Imines under Basic Conditions

A chiral imidazolidine‐containing NCN/Pd‐OTf catalyst ( C4 ) promoted the nucleophilic addition of unprotected indoles to N‐Boc imines. Using sulfinyl amines as the N‐Boc imine precursors, the combined use of C4 with K₂CO₃ activated the NH indoles to give chiral 3‐indolyl methanamines with up to 98 % ee. Compared with conventional acid‐catalyzed Friedel–Crafts reactions, this reaction proceeds under mildly basic conditions and is advantageous for the use of acid‐sensitive substrates.     

Imidazole‐Aided Native Chemical Ligation: Imidazole as a One‐Pot Desulfurization‐Amenable Non‐Thiol‐Type Alternative to 4‐Mercaptophenylacetic Acid

Various bioactive proteins have been synthesized by native chemical ligation (NCL) and its combination with subsequent desulfurization (e.g., conversion from Cys to Ala). In NCL, excess 4‐mercaptophenylacetic acid (MPAA) is generally added to facilitate the reaction. However, co‐elution of MPAA with the ligation product during preparative high‐performance liquid chromatography sometimes reduces its usefulness. In addition, contamination of MPAA disturbs subsequent desulfurization. Here, we report for the first time that imidazole can be adopted as an alternative to MPAA in NCL using a peptide‐alkylthioester. The efficiency of the imidazole‐aided NCL (Im‐NCL) is similar to that of traditional MPAA‐aided NCL. As model cases, we successfully synthesized adiponectin(19‐107) and [Ser(PO₃H₂)⁶⁵]‐ubiquitin using Im‐NCL with a one‐pot desulfurization.     

Determination of Nitrophenols in Water Using Dynamic Liquid‐Liquid‐Liquid Microextraction under Non‐Equilibrium Consideration

To pursue optimum condition in liquid‐liquid‐liquid microextraction (LLLME), extraction parameters dominating extraction efficiency were investigated by theoretical considerations. The theoretical considerations discussed equilibrium model for equilibrium LLLME and non‐equilibrium model for dynamic LLLME. A method described here is a dynamic LLLME technique combined with high‐performance liquid‐chromatography ultraviolet absorbance detection (HPLC/UV) to determine traces of nitrophenols in water. Analytical parameters such as organic phase, acceptor phase volume, sample agitation, extraction time, acceptor phase NaOH concentration, donor phase HCl concentration, salt addition, and absorption wavelength were identified as variable settings. Relative standard deviation (RSD, 1.8‐4.4%), coefficient of estimation (R², 0.9994‐0.9999), and detection limit (0.032‐0.065 ng mL^?1) were achieved under the variable settings. The proposed method was successfully applied to the analysis of a lake water sample, and the relative recoveries of nitrophenols from spiked water sample were up to 92.5%. The variable settings of LLLME close to optimization was responsible for an acceptable extraction efficiency.     

Intermolecular and Regioselective Access to Polysubstituted Benzo‐ and Dihydrobenzo[c]azepine Derivatives: Modulating the Reactivity of Group 6 Non‐Heteroatom‐Stabilized Alkynyl Carbene Complexes

We highlight the versatility of non‐heteroatom‐stabilized tungsten–carbene complexes 3 synthesized in situ, which have been used in a modular approach to access 2‐benzazepinium isolable intermediates 5 . By employing very mild conditions, benzazepinium derivatives 5 have been obtained in high yield from simple compounds, such as acetylides 2 , Fischer‐type alkoxycarbenes 1 , and phenylimines 4 . The process, involving a formal [4+3] heterocycloaddition, occurs in a totally regioselective manner, which differs from the approach previously observed in similar procedures for other carbene analogues. This work, which involves three components, reveals a control of the reactivity of non‐heteroatom‐stabilized carbene complexes 3 ([4+3] vs. [2+2]‐heterocycloaddition reactions) depending on the acetylide substitution pattern. The influence of the substitution pattern in the behavior of the complexes has been computationally analyzed and rationalized. Finally, elaboration of the 2‐benzazepinium intermediates allows access to 3H‐benzo[c]azepines 6 and 3H‐1,2‐dihydrobenzo[c]azepines 7 – 9 with high control of the substitution of the nine positions of the heterocycle.     

A series of (E)‐5‐(arylideneamino)‐1‐tert‐butyl‐1H‐pyrrole‐3‐carbonitriles and their reduction products to secondary amines: syntheses and X‐ray structural studies

An efficent access to a series of N‐(pyrrol‐2‐yl)amines, namely (E)‐1‐tert‐butyl‐5‐[(4‐chlorobenzylidene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₆ClN₃, (7a), (E)‐1‐tert‐butyl‐5‐[(2,4‐dichlorobenzylidene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₅Cl₂N₃, (7b), (E)‐1‐tert‐butyl‐5‐[(pyridin‐4‐ylmethylene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₅H₁₆N₄, (7c), 1‐tert‐butyl‐5‐[(4‐chlorobenzyl)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₈ClN₃, (8a), and 1‐tert‐butyl‐5‐[(2,4‐dichlorobenzyl)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₇Cl₂N₃, (8b), by a two‐step synthesis sequence (solvent‐free condensation and reduction) starting from 5‐amino‐1‐tert‐butyl‐1H‐pyrrole‐3‐carbonitrile is described. The syntheses proceed via isolated N‐(pyrrol‐2‐yl)imines, which are also key synthetic intermediates of other valuable compounds. The crystal structures of the reduced compounds showed a reduction in the symmetry compared with the corresponding precursors, viz. Pbcm to P from compound (7a) to (8a) and P2₁/c to P from compound (7b) to (8b), probably due to a severe change in the molecular conformations, resulting in the loss of planarity observed in the nonreduced compounds. In all of the crystals, the supramolecular assembly is controlled mainly by strong (N,C)—H…N hydrogen bonds. However, in the case of (7a)–(7c), C—H…Cl interactions are strong enough to help in the three‐dimensional architecture, as observed in Hirshfeld surface maps.     

Self‐Organized Stationary Patterns in Networks of Bistable Chemical Reactions

Experiments with networks of discrete reactive bistable electrochemical elements organized in regular and nonregular tree networks are presented to confirm an alternative to the Turing mechanism for the formation of self‐organized stationary patterns. The results show that the pattern formation can be described by the identification of domains that can be activated individually or in combinations. The method also enabled the localization of chemical reactions to network substructures and the identification of critical sites whose activation results in complete activation of the system. Although the experiments were performed with a specific nickel electrodissolution system, they reproduced all the salient dynamic behavior of a general network model with a single nonlinearity parameter. Thus, the considered pattern‐formation mechanism is very robust, and similar behavior can be expected in other natural or engineered networked systems that exhibit, at least locally, a treelike structure.     

Total Chemical Synthesis and Biological Activities of Glycosylated and Non‐Glycosylated Forms of the Chemokines CCL1 and Ser‐CCL1

CCL1 is a naturally glycosylated chemokine protein that is secreted by activated T‐cells and acts as a chemoattractant for monocytes. 1 Originally, CCL1 was identified as a 73 amino acid protein having one N‐glycosylation site, 1 and a variant 74 residue non‐glycosylated form, Ser‐CCL1, has also been described. 2 There are no systematic studies of the effect of glycosylation on the biological activities of either CCL1 or Ser‐CCL1. Here we report the total chemical syntheses of both N‐glycosylated and non‐glycosylated forms of (Ser‐)CCL1, by convergent native chemical ligation. We used an N‐glycan isolated from hen egg yolk together with the Nbz linker for Fmoc chemistry solid phase synthesis of the glycopeptide‐^αthioester building block. 3 Chemotaxis assays of these glycoproteins and the corresponding non‐glycosylated proteins were carried out. The results were correlated with the chemical structures of the (glyco)protein molecules. To the best of our knowledge, these are the first investigations of the effect of glycosylation on the chemotactic activity of the chemokine (Ser‐)CCL1 using homogeneous N‐glycosylated protein molecules of defined covalent structure.     

PPh3‐Catalyzed Reactions of Alkyl Propiolates with N‐Tosylimines: A Facile Synthesis of Alkyl 2‐[aryl(tosylimino)methyl]acrylate and an Insight into the Reaction Mechanism

A new PPh₃‐catalyzed synthesis of alkyl 2‐[aryl(tosylimino)methyl]acrylates from propiolate and N‐tosylimine has been developed. Deuterium‐labelling experiments show that the reaction mechanism involves several hydrogen‐transfer processes, which are not the turnover‐limiting step and strongly rely on the nature of the reaction media. The stable phosphonium–enamine zwitterion, which was proven to play an important role in the catalytic cycle, has been isolated and characterised by X‐ray analysis.     

Three‐Arm Branched Microporous Organic Nanotube Networks

Here, a novel method is demonstrated for the preparation of three‐arm branched microporous organic nanotube networks (TAB‐MONNs) based on molecular templating of three‐arm branched core–shell bottlebrush copolymers and Friedel–Crafts alkylation reaction. The unique three‐arm branched bottlebrush copolymers are synthesized by a combination of atom transfer radical polymerization, reversible addition‐fragmentation chain transfer polymerization, and ring‐opening polymerization techniques. In this approach, the length and diameter of branched tube units can be well‐controlled by rational molecular design. Moreover, the as‐prepared TAB‐MONNs possess a high surface area and exhibit a superior adsorption capacity for Rhodamine 6G (R6G) and p‐cresol.

     

Screening of Three Transition Metal‐Mediated Reactions Compatible with DNA‐Encoded Chemical Libraries

The construction of DNA‐encoded chemical libraries (DECLs) crucially relies on the availability of chemical reactions, which are DNA‐compatible and which exhibit high conversion rates for a large number of diverse substrates. In this work, we present our optimization and validation procedures for three copper and palladium‐catalyzed reactions (Suzuki cross‐coupling, Sonogashira cross‐coupling, and copper(I)‐catalyzed alkyne‐azide cycloaddition (CuAAC)), which have been successfully used by our group for the construction of large encoded libraries.     

No‐Barrier Theory: Calculating Rates of Chemical Reactions from Equilibrium Constants and Distortion Energies

No‐barrier theory is a new approach to the calculation of rate constants for reactions in solution, from the corresponding equilibrium constants. It requires relatively small molecular orbital theory calculations, and has been very successful. It is in the spirit of Marcus theory, but does not require an “intrinsic barrier”. The approach is explained, with an examination of the way in which the ideas on which it is based were “in the air”.     

Bottom‐Up On‐Surface Synthesis of Two‐Dimensional Graphene Nanoribbon Networks and Their Thermoelectric Properties

Graphene, the one‐atom‐thick two‐dimensional (2D) carbon material, has attracted tremendous interest in both academia and industry due to its outstanding electrical, mechanical, and thermal properties. For electronic applications, the challenging task is to make it as a semiconductor. The bottom‐up synthesis of semiconducting one‐dimensional (1D) nanometer‐wide graphene strips, namely, graphene nanoribbons (GNRs), has attracted much attention owing to its promising electronic, optical, and magnetic properties. In this regard, we report the fabrication of cove‐type 2D GNR networks (GNNs) via the interconnection of 1D self‐assembled GNRs on the surface of Au(111). The cove‐type 2D GNRs networks (GNNs) were fabricated from the GNR, 5‐CGNR‐1‐1 , synthesized using the precursor of DBSP . Annealing of high‐density self‐assembled GNRs on the surface of Au(111) through two‐zone chemical vapour deposition (2Z CVD) successfully generated a 2D interconnected structure with high yield via the fusion and ladder coupling reactions of GNR chains. In order to validate the later fusion reaction, we have also synthesized the GNR, 7‐AGNR‐1‐1 , using the precursor of DBBA . The GNNs, which consist of hybridized metallic‐like and semiconducting GNRs, are a new class of carbon‐based materials. Further, we applied this material for thermoelectric (TE) applications and found a very low cross‐plane thermal conductivity of 0.11 Wm^?1 K^?1, which is one of the lowest value among the carbon‐based materials as well as inorganic semiconductors, while maintaining the cross‐plane electrical conductivity of 188 S m^?1.