Templated Chromophore Assembly by Dynamic Covalent Bonds

Through the simultaneous use of three orthogonal dynamic covalent reactions, namely disulfide, boronate, and acyl hydrazone formation, we conceived a facile and versatile protocol to spatially organize tailored chromophores, which absorb in the blue, red, and yellow regions, on a preprogrammed α‐helix peptide. This approach allowed the assembly of the dyes in the desired ratio and spacing, as dictated by both the relative positioning and distribution of the recognition units on the peptide scaffold. Steady‐state UV/Vis absorption and emission studies suggest an energy transfer from the yellow and red donors to the blue acceptor. A molecular dynamics simulation supports the experimental findings that the helical structure is maintained after the assembly and the three dyes are confined in defined conformational spaces.     

Dynamic Helicates Self-Assembly from Homo- and Heterotopic Dynamic Covalent Ligand Strands

The understanding and the application of reversible covalent reactions and coordination chemistry together with the proper design of the molecular frameworks, allow to achieve not only well-defined output architectures but also different grades of complex behavior. In this work, the dynamic nature of the helical systems offers an additional level of complexity by combining self-sorting on two levels: 1) the build-up of the ligand strand constituents from their components through dynamic covalent chemistry; 2) the assembly of the helicates from the ligands and the metal cations through dynamic metallo-supramolecular chemistry. The information encoded in the ligands constituent molecule was read differently (and accurately at the same time) by metal cations that varied in the coordination algorithms. It enabled the selective formation of a specific type of helicates from a wide library of helicates formed by the possible combination of subcomponents. Ligands containing dynamic tridentate and/or bidentate binding motifs in the same strand were studied to explore the helicates self-assembly with appropriate metal cations.     

Dynamic Expression of DNA Complexation with Self‐assembled Biomolecular Clusters

We report herein the implementation of a dynamic covalent chemistry approach to the generation of multivalent clusters for DNA recognition. We show that biomolecular clusters can be expressed in situ by a programmed self‐assembly process using chemoselective ligations. The cationic clusters are shown, by fluorescence displacement assay, gel electrophoresis and isothermal titration calorimetry, to effectively complex DNA through multivalent interactions. The reversibility of the ligation was exploited to demonstrate that template effects occur, whereby DNA imposes component selection in order to favor the most active DNA‐binding clusters. Furthermore, we show that a chemical effector can be used to trigger DNA release through component exchange reactions.     

Helicate, macrocycle, or catenate: Dynamic topological control over subcomponent self-assembly

The aqueous reaction between equimolar amounts of 2-(2-(2-aminoethoxy)ethoxy)ethanamine, 1,10-phenanthroline-2,9-dialdehyde and copper(I) produced a dimeric helical macrocycle in quantitative yield. This ring could also be generated by the addition of two equivalents of the diamine to an acyclic helicate containing four mono-imine residues: A transimination occurred, the chelate effect being implicated as a driving force. In the case of a helicate containing mono-imines derived from anilines, the substitution of diamine for monoamine was reversible upon lowering the pH. The aliphatic diamine was protonated at a higher pH than the arylamine, which left the arylamine free for incorporation instead of the alkyl diamine. This reaction thus opened the possibility of switching between closed macrocyclic and open helicate topologies by changing the pH. An additional closed topology became accessible through the use of a diamine that incorporates two rigid phenylene spacer groups between a flexible chain and the imine-forming nitrogen atoms. The resulting catenate consists of a pair of topologically interlinked macrocycles. The presence of the phenylene groups appeared to dictate the topology of the final product, making the formation of a single macrocycle energetically disfavoured.     

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.     

Helicate extension as a route to molecular wires

We describe the preparation of a helicate containing four closely spaced, linearly arrayed copper(I) ions. This product may be prepared either directly by mixing copper(I) with a set of precursor amine and aldehyde subcomponents, or indirectly through the dimerization of a dicopper(I) helicate upon addition of 1,2-phenylenediamine. A notable feature of this helicate is that its length is not limited by the lengths of its precursor subcomponents: each of the two ligands wrapped around the four copper(I) centers contains one diamine, two dialdehyde, and two monoamine residues. This work thus paves the way for the preparation of longer oligo- and polymeric structures. DFT calculations and electrochemical measurements indicate a high degree of electronic delocalization among the metal ions forming the cores of the structures described herein, which may therefore be described as "molecular wires".     

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.     

The influence of constitutional isomerism and change on molecular recognition processes

Three constitutionally isomeric bis(naphthylmethyl)ammonium ions, in which the two naphthyl groups are substituted 1) both at their 1-positions, 2) one at its 1-position and the other at its 2-position, and 3) both at their 2-positions, have been investigated separately in solution for their propensities to undergo spontaneous self-assembly with three different [24]crown-8 derivatives, namely, pyrido[24]crown-8 (P24C8), dipyrido[24]crown-8 (DP24C8) and dibenzo[24]crown-8 (DB24C8), in turn to form [2]pseudorotaxanes. The strengths of the 1:1 complexes depend on the composition of the secondary dialkylammonium ions and on the nature of the crown ether hosts; generally, as far as the guest cation is concerned, the 1/1- and 2/2-isomers form stronger complexes, as indicated by stability constant measurements, than the 1/2-isomer and, as far as the crown ethers are concerned, the more flexible P24C8 is a much more efficient host than either DP24C8 or DB24C8. The rates of formation of the [2]pseudorotaxanes are fast (i.e., taking no more than a few minutes) in solution with the exception of one case, that is, in which the crown ether host is DB24C8 and the guest cation is the 1/1-isomer, when it can take upwards of one month for the complexation-decomplexation equilibrium to be established at room temperature. In all cases, the equilibrium between complexed and uncomplexed species is slow on the NMR timescale, allowing the determination of stability constants to be made readily using the single-point method. X-ray crystallography and molecular modeling have been used to gain insight into ground and transition state interactions, respectively, in some of the [2]pseudorotaxanes. The relative stabilities of the three [2]pseudorotaxanes formed by each guest cation in the presence of the three crown ether hosts were also evaluated in solution by competition experiments that were monitored by (1)H NMR spectroscopy. By and large the results of the competition experiments could be predicted on the basis of the derived stability constants for the individual [2]pseudorotaxanes.     

Kinetic versus thermodynamic control during the formation of [2]rotaxanes by a dynamic template-directed clipping process

A template-directed dynamic clipping procedure has generated a library of nine [2]rotaxanes that have been formed from three dialkylammonium salts-acting as the dumbbell-shaped components-and three dynamic, imino bond-containing, [24]crown-8-like macrocycles-acting as the ring-shaped components-which are themselves assembled from three dialdehydes and one diamine. The rates of formation of these [2]rotaxanes differ dramatically, from minutes to days depending on the choice of dialkylammonium ion and dialdehyde, as do their thermodynamic stabilities. Generally, [2]rotaxanes formed by using 2,6-diformylpyridine as the dialdehyde component, or bis(3,5-bis(trifluoromethyl)benzyl)ammonium hexafluorophosphate as the dumbbell-shaped component, assembled the most rapidly. Those rotaxanes containing this particular electron-deficient dumbbell-shaped unit, or 2,5-diformylfuran units in the macroring, were the most stable thermodynamically. The relative thermodynamic stabilities of all nine of the [2]rotaxanes were determined by competition experiments that were monitored by (1)H NMR spectroscopy.     

Crystallization-controlled dynamic self-assembly and an on/off switch for equilibration using boronic ester formation

Macrocyclic boronic esters of different sizes can be prepared selectively from the same starting diboronic acid and 1,2-diol by means of an interesting dynamic self-assembly phenomena. More specifically, two kinds of macrocyclic boronic esters could be formed diastereoselectively and nearly quantitatively under neutral conditions by the addition of an appropriate guest molecule that acts as a template. Although a mixture of tetrol 1 and di(boronic acid) 2 in methanol gave only insoluble polymeric boronic esters, a soluble macrocyclic boronic ester, homo-[2+2], was obtained selectively in the presence of toluene as a guest molecule. Furthermore, when benzene was employed as a guest molecule, the selective formation of another macrocyclic boronic ester, hetero-[3+3], occurred. Interestingly, each of these macrocycles could be converted into the other in the presence of methanol and the appropriate guest molecule; however, under aprotic conditions, guest molecules encaged by the macrocyclic boronic ester could be exchanged without affecting its structure. Thus the presence or absence of a protic solvent could be used as a regulator to switch on or off the dynamic equilibrium of the system. In addition, investigation of the effect of reaction time, direct observation of the reaction mixture by NMR spectroscopy, and carrying out the reaction using optically active tetrol suggested that precipitation plays an essentially important role in the selective formation of the macrocyclic boronic esters. Thus, although both of [2+2] and [3+3] were present as solutes in the reaction mixture, the type of added guest molecule induced the selective precipitation of only one form of macrocyclic boronic ester, hence displacing the equilibrium of the system.