Adaptation and Optical Signal Generation in a Constitutional Dynamic Network

Self‐sorting dynamic library : The effector‐induced modulation of the shape and constitution of the members of a constitutional dynamic network (see scheme) allows for the regulation of the interconnected constituents and for the control of an emergent function, here the generation of an optical output which originates from a charge‐transfer interaction.

     

Organocatalysis of CN/CN and CC/CN Exchange in Dynamic Covalent Chemistry

The reversibly formed C?N bond plays a very important role in dynamic covalent chemistry and the C?N/C?N exchange of components between different imine constituents to create dynamic covalent libraries has been extensively used. To facilitate diversity generation, we have investigated an organocatalyzed approach, using L ‐proline as catalyst, to accelerate the formation of dynamic libraries of [n×n] imine components. The organocatalysis methodology has also been extended, under somewhat modified conditions, to reversible C?C/C?N exchange processes between Knoevenagel derivatives of barbituric acid and imines, allowing for the generation of increased diversity.     

Dynamic Covalent Chemistry: A Facile Room‐Temperature,Reversible, Diels–Alder Reaction between Anthracene Derivatives and N‐Phenyltriazolinedione

A series of readily accessible, dynamic Diels–Alder reactions that are reversible at room temperature have been developed between anthracene derivatives as dienes and N‐phenyl‐1,2,4‐triazoline‐3,5‐dione as the dienophile. The adducts formed undergo reversible component exchange to form dynamic libraries of equilibrating cycloadducts. Furthermore, reversible adduct formation allows temperature‐dependent modulation of the fluorescent properties of anthracene components; a feature of potential interest for the design of optodynamic polymeric materials by careful selection and manipulation of these simple dienes and dienophiles.     

Organocatalyzed and Uncatalyzed CC/CC and CC/CN Exchange Processes between Knoevenagel and Imine Compounds in Dynamic Covalent Chemistry

Molecular diversity generation through reversible component exchange has acquired great importance in the last decade with the development of dynamic covalent chemistry. We explore here the recombination of components linked by C?C and C?N bonds through reversible double‐bond formation, and cleavage in C?C/C?C and C?C/C?N exchange processes. The reversibility of the Knoevenagel reaction has been explored, and C?C/C?C C/C exchanges have been achieved among different benzylidenes, under organocatalysis by secondary amines such as L ‐proline. The substituents of these benzylidenes were shown to play a very important role in the kinetics of the exchange reactions. L ‐Proline is also used to catalyze the reversible C?C/C?C exchange between Knoevenagel derivatives of barbituric acid and malononitrile. Finally, the interconversion between Knoevenagel derivatives of dimethylbarbituric acid and imines (C?C/C?N exchange) has been studied and was found to occur rapidly in the absence of catalyst. The results of this study pave the way for the extension of dynamic combinatorial chemistry based on C?C/C?C and C?C/C?N exchange systems.     

Metal Cation-Driven Dynamic Covalent Formation of Imine and Hydrazone Ligands Displaying Synergistic Co-catalysis and Auxiliary Amine Effects

Optimizing C=N bond formation and C/N component exchange has major significance in Dynamic Covalent Chemistry (DCC). Imine and hydrazone generation from their aldehyde, amine and hydrazine components showed large accelerations in presence of AgOTf or Zn(OTf)₂, up to 10⁴ for the Zn(II)-(p-anisidine)imine complex. Zn(OTf)₂ and auxiliary p-anisidine together accelerated 630 times the formation of the Zn(II)-hydrazone complex, revealing a strong synergistic effect, traced to very fast initial formation of the reactive Zn(II)-imine complex presenting a C=N bond metallo-activated towards reaction with the hydrazine component. Reactions involving more entities showed kinetically faster and thermodynamically simpler outputs due to dynamic competition within a mixture of higher complexity. Catalytic amounts of metal salts and auxiliary amine gave similar marked rate accelerations and turnover, indicating true catalysis. The synergistic effect achieved by combining metallo- and organo-catalysis points to a powerful co-catalysis strategy of bond-formation in DCC through interconnected chemical transformations.     

Synthesis of a Two‐Dimensional Covalent Organic Monolayer through Dynamic Imine Chemistry at the Air/Water Interface

A two‐dimensional covalent organic monolayer was synthesized from simple aromatic triamine and dialdehyde building blocks by dynamic imine chemistry at the air/water interface (Langmuir–Blodgett method). The obtained monolayer was characterized by optical microscopy, scanning electron microscopy, and atomic force microscopy, which unambiguously confirmed the formation of a large (millimeter range), unimolecularly thin aromatic polyimine sheet. The imine‐linked chemical structure of the obtained monolayer was characterized by tip‐enhanced Raman spectroscopy, and the peak assignment was supported by spectra simulated by density functional theory. Given the modular nature and broad substrate scope of imine formation, the work reported herein opens up many new possibilities for the synthesis of customizable 2D polymers and systematic studies of their structure–property relationships.     

Strain‐Induced Reactivity in the Dynamic Covalent Chemistry of Macrocyclic Imines

The displacement of molecular structures from their thermodynamically most stable state by imposition of various types of electronic and conformational constraints generates highly strained entities that tend to release the accumulated strain energy by undergoing either structural changes or chemical reactions. The latter case amounts to strain‐induced reactivity (SIR) that may enforce specific chemical transformations. A particular case concerns dynamic covalent chemistry which may present SIR, whereby reversible reactions are activated by coupling to a high‐energy state. We herewith describe such a dynamic covalent chemical (DCC) system involving the reversible imine formation reaction. It is based on the formation of strained macrocyclic bis‐imine metal complexes in which the macrocyclic ligand is in a high energy form enforced by the coordination of the metal cation. Subsequent demetallation generates a highly strained free macrocycle that releases its accumulated strain energy by hydrolysis and reassembly into a resting state. Specifically, the metal‐templated condensation of a dialdehyde with a linear diamine leads to a bis‐imine [1+1]‐macrocyclic complex in which the macrocyclic ligand is in a coordination‐enforced strained conformation. Removal of the metal cation by a competing ligand yields a highly reactive [1+1]‐macrocycle, which then undergoes hydrolysis to transient non‐cyclic aminoaldehyde species, which then recondense to a strain‐free [2+2]‐macrocyclic resting state. The process can be monitored by ¹H NMR spectroscopy. Energy differences between different conformational states have been evaluated by Hartree–Fock (HF) computations. One may note that the stabilisation of high‐energy molecular forms by metal ion coordination followed by removal of the latter, offers a general procedure for producing out‐of‐equilibrium molecular states, the fate of which may then be examined, in particular when coupled to dynamic covalent chemical processes.     

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.     

Reversible Adaptation to Photoinduced Shape Switching by Oligomer–Macrocycle Interconversion with Component Selection in a Three‐State Constitutional Dynamic System

Light irradiation of the molecular photoswitch 1 ‐E causes isomerization into the 1 ‐Z configuration stabilized by an internal hydrogen bond. 1 ‐E bears aldehyde groups allowing for dynamic covalent reaction with linear diamines. On photoinduced E/Z shape switching of 1 in presence of diamines, the system undergoes interconversion between two states, a non‐cyclic oligomeric one and a macrocyclic one, corresponding respectively to the E and Z configurations of 1 . With a mixture of linear α,ω‐diamines, 1 ‐E yields non‐selective dynamic oligomers by random incorporation of diamine components. Photoswitching to the 1 ‐Z form leads to constitutional adaptation with preferential formation of the macrocycle incorporating the best suited diamine, H₂N(CH₂)₇NH₂. In presence of metal cations, the E form switches from its unbound W shape to its coordinated U shape and yields the macrocycle resulting from the selective incorporation of the diamine H₂NCH₂CH₂OCH₂CH₂NH₂ that contains an additional O coordination site. Taken together, the results obtained describe constitutional adaptation in a triple state system: an oligomeric one and two different macrocyclic ones generated in response to two orthogonal agents, a physical stimulus, light, or a chemical effector, metal cations. These three states present, towards the incorporation of diamine components, respectively no selection, photoselection and metalloselection.     

Dynamic Covalent Synthesis of Donor–Acceptor Interlocked Architectures in Solution and at the Solution:Surface Interface

Despite advances in the range of mechanically interlocked architectures that can be synthesized and operated as supramolecular machines, motors and sensors in solution, in many cases their synthesis is laborious and expensive requiring long multistep pathways with extensive purification at each stage. Dynamic covalent chemistry has been shown to overcome problems with traditional kinetically controlled synthetic approaches that often afford low yields of interlocked architectures due to irreversible formation of non‐interlocked by‐products. Herein, we describe the use of reversible disulfide exchange reactions as a means to assemble catenanes and rotaxanes in organic solutions. Moreover, the application of this thermodynamic approach to assemble interlocked architectures at the solution:surface interface, specifically polymer resins, is discussed.     

Triple Self‐Sorting in Constitutional Dynamic Networks: Parallel Generation of Imine‐Based CuI,FeII, and ZnII Complexes

Three imine‐based metal complexes, having no overlap in terms of their compositions, have been simultaneously generated from the self‐sorting of a constitutional dynamic library (CDL) containing three amines, three aldehydes, and three metal salts. The hierarchical ordering of the stability of the three metal complexes assembled and the leveraging of the antagonistic and agonistic relationships existing between the constituents within the constitutional dynamic network corresponding to the CDL were pivotal in achieving the sorting. Examination of the process by NMR spectroscopy showed that the self‐sorting of the Fe^II and Zn^II complexes depended on an interplay between the thermodynamic driving forces and a kinetic trap involved in their assembly. These results also exemplify the concept of “simplexity”—the fact that the output of a self‐assembling system may be simplified by increasing its initial compositional complexity—as the two complexes could self‐sort only in the presence of the third pair of organic components, those of the Cu^I complex.     

Covalent and non‐covalent binding in the ion/ion charge inversion of peptide cations with benzene‐disulfonic acid anions

Protonated angiotensin II and protonated leucine enkephalin‐based peptides, which included YGGFL, YGGFLF, YGGFLH, YGGFLK and YGGFLR, were subjected to ion/ion reactions with the doubly deprotonated reagents 4‐formyl‐1,3‐benzenedisulfonic acid (FBDSA) and 1,3‐benzenedisulfonic acid (BDSA). The major product of the ion/ion reaction is a negatively charged complex of the peptide and reagent. Following dehydration of [M + FBDSA‐H]^? via collisional‐induced dissociation (CID), angiotensin II (DRVYIHPF) showed evidence for two product populations, one in which a covalent modification has taken place and one in which an electrostatic modification has occurred (i.e. no covalent bond formation). A series of studies with model systems confirmed that strong non‐covalent binding of the FBDSA reagent can occur with subsequent ion trap CID resulting in dehydration unrelated to the adduct. Ion trap CID of the dehydration product can result in cleavage of amide bonds in competition with loss of the FBDSA adduct. This scenario is most likely for electrostatically bound complexes in which the peptide contains both an arginine residue and one or more carboxyl groups. Otherwise, loss of the reagent species from the complex, either as an anion or as a neutral species, is the dominant process for electrostatically bound complexes. The results reported here shed new light on the nature of non‐covalent interactions in gas phase complexes of peptide ions that can be used in the rationale design of reagent ions for specific ion/ion reaction applications. Copyright © 2012 John Wiley & Sons, Ltd.