Integrating replication-based selection strategies in dynamic covalent systems

In the past 15 years, the chemistry of reversible covalent bond formation (dynamic covalent chemistry (DCC)) has been exploited to engineer networks of interconverting compounds known as dynamic combinatorial libraries (DCLs). Classically, the distribution of library components is governed by their relative free energies, and so, processes that manipulate the free energy landscape of the DCL can influence the distribution of library members. Within the same time frame, the design and implementation of molecules capable of copying themselves--so-called replicators--has emerged from the field of template-directed synthesis. Harnessing the nonlinear kinetics inherent in replicator behavior offers an attractive strategy for amplification of a target structure within a DCL and, hence, engendering high levels of selectivity within that library. The instructional nature of replicating templates also renders the combination of replication and DCC a potential vehicle for developing complex reaction networks; a prerequisite for the development of the emerging field of systems chemistry. This Concept article explores the role of kinetically and thermodynamically controlled processes within different DCC frameworks. The effects of embedding a replicating system within these DCC frameworks is explored and the consequences of the different topologies of the reaction network for amplification and selectivity within DCLs is highlighted.     

A dynamic tricopper double helicate

The reaction between 8-aminoquinoline, 1,10-phenantholine-2,9-dicarbaldehyde, and copper(I) tetrafluoroborate gave a quantitative yield of a tricopper double helicate. The presence of dynamic covalent imine (C=N) bonds allowed this assembly to participate in two reactions not previously known in helicate chemistry: 1) It could be prepared through subcomponent substitution from a dicopper double helicate that contained aniline residues. An electron-poor aniline was quantitatively displaced; a more electron-rich aniline competed effectively with the aminoquinoline, setting up an equilibrium between dicopper and tricopper helicates that could be displaced towards the tricopper through the addition of further copper(I). 2) Both dicopper and tricopper helicates could be prepared simultaneously from a mixture of phenanthroline dialdehyde, aniline, and aminoquinoline, which contained all possible imine condensation products in equilibrium. Following the addition of copper(I), thermodynamic equilibration on both covalent and coordinative levels eliminated all partially-formed and mixed imine ligands from the mixture, leaving the helicates as exclusive products.     

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.     

An iminoboronate construction set for subcomponent self-assembly

Recently we have demonstrated a series of systems in which complex structures were created from simple amine and aldehyde subcomponents by copper(I)-templated imine bond formation. We describe herein the extension of this "subcomponent self-assembly" concept to the generation of structures based upon the iminoboronate ester motif. Equimolar amounts of diol, amine, and 2-formylphenylboronic acid reacted by reversible B-O and C=N bond formation to generate iminoboronate esters, as has recently been reported by James et al. (Org. Lett. 2006, 8, 609-612). The extent of ester formation was shown to depend upon a number of factors. The exploration of these factors allowed rules and predictions to be formulated governing the self-assembly process. These rules allowed the construction of more complex structures containing multiple boron atoms, including a trigonal cage containing six boron centers, as well as pointing the way to the construction of yet more intricate architectures. The lability of the B-O and C=N bonds also allowed different diol and amine subcomponents to be substituted within these structures. Selection rules were also determined for these substitution reactions, allowing the products to be predicted based upon the electronic properties of the diols and diamines employed. These results thus demonstrate the generality of the subcomponent self-assembly methodology through its application to a new dynamic covalent system.     

Dynamic covalent polymers

This Highlight presents an overview of the rapidly growing field of dynamic covalent polymers. This class of polymers combines intrinsic reversibility with the robustness of covalent bonds, thus enabling formation of mechanically stable, polymer‐based materials that are responsive to external stimuli. It will be discussed how the inherent dynamic nature of the dynamic covalent bonds on the molecular level can be translated to the macroscopic level of the polymer, giving access to a range of applications, such as stimuli‐responsive or self‐healing materials. A primary distinction will be made based on the type of dynamic covalent bond employed, while a secondary distinction will be based on the consideration whether the dynamic covalent bond is used in the main chain of the polymer or whether it is used to allow side chain modification of the polymer. Emphasis will be on the chemistry of the dynamic covalent bonds present in the polymer, in particular in relation to how the specific (dynamic) features of the bond impart functionality to the polymer material, and to the conditions under which this dynamic behavior is manifested. © 2016 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3551–3577.     

Smart macrocyclic molecules: induced fit and ultrafast self-sorting inclusion behavior through dynamic covalent chemistry

A family of macrocycles with oligo(ethylene glycol) chains, 4O, 5O, and 6O, was developed to construct a series of new incorporated macrocycles through dynamic covalent chemistry. These flexible macrocycles exhibited excellent "self-sorting" abilities with diamine compounds, which depended on the "induced-fit" rule. For instance, the host macrocycles underwent conformational modulation to accommodate the diamine guests, affording [1+1] intramolecular addition compounds regardless of the flexibility of the diamine. These macrocycles folded themselves to fit various diamines with different chain length through modulation of the flexible polyether chain, and afforded intramolecular condensation products. However, if the chain of the diamine was too long and rigid, oligomers or polymers were obtained from the mixture of the macromolecule and the diamine. All results demonstrated that inclusion compounds involving conformationally suitable aromatic diamines were thermodynamically favorable candidates in the mixture due to the restriction of the macrocycle size. Furthermore, kinetic and thermodynamic studies of self-sorting behaviors of both mixed 4O-5O and 4O-6O systems were investigated in detail. Finally, theoretical calculations were also employed to further understand such self-sorting behavior, and indicated that the large enthalpy change of H(2)NArArNH(2)@4O is the driving force for the sorting behavior. Our system may provide a model to further understand the principle of biomolecules with high specificity due only to their conformational self-adjusting ability.     

The dynamic chemistry of molecular borromean rings and Solomon knots

The dynamic solution equilibria between molecular Borromean rings (BRs) and Solomon knots (SKs), assembled from transition metal‐templated macrocycles, consisting of exo‐bidentate bipyridyl and endo‐tridentate diiminopyridyl ligands, have been examined with respect to the choice of the metal template and reaction conditions employed in the synthesis of the metalated BRs, otherwise known as Borromeates. Three new Borromeates, their syntheses templated by Cu^II, Co^II, and Mn^II, have been characterized extensively (two by X‐ray crystallography) to the extent that the metal centers in the assemblies have been shown to be distanced sufficiently from each other not to communicate. The solid‐state structure of the Co^II–Borromeate reveals that six MeOH molecules, arranged in a [O? H???O] hydrogen bonded, chair‐like conformation, are located within its oxophilic central cavity. When a mixture of Cu^II and Zn^II is used as the source of templation, there exists a dynamic equilibrium, in MeOH at room temperature, between a mixed‐metal BR and a SK, from which the latter has been fractionally crystallized. By employing appropriate synthetic protocols with Zn^II or Cd^II as the template, significant amounts of SKs are formed alongside BRs. Modified crystallization conditions resulted in the isolation of both an all‐zinc BR and an all‐zinc SK, crystals of which can be separated manually, leading to the full characterization of the all‐zinc SK by ¹H NMR spectroscopy and X‐ray crystallography. This doubly interlocked [2]catenate has been identified retrospectively in recorded spectra, where it was attributed previously to a Borromeate with a Zn^II cation coordinated to the oxophilic interior walls of the ensemble. Interestingly, these Zn^II‐templated assemblies do not interconvert in MeOH at room temperature, indicating the significant influence of both the metal template and solvent on the solution equilibria. It would also appear that d¹⁰ metal ions favor SK formation—no evidence of Cu^II‐, Co^II‐, or Mn^II‐templated SKs has been found, yet a 1:0.9 ratio of BR:SK has been identified by ¹H NMR spectroscopy when Cd^II is used as the template.     

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".     

Self-assembly vesicles made from a cyclodextrin supramolecular complex

Self-assembly vesicles have been made from a cyclodextrin (CD) supramolecular complex, which is cooperatively formed with natural beta-CD, 1-naphthylammonium chloride (NA), and sodium bis(2-ethyl-1-hexyl)sulfosuccinate (AOT) by weak noncovalent interactions. In the complex structure, a NA molecule is included inside a beta-CD molecule while it is coupled with an AOT molecule on one side. The supramolecular structure and morphology of the vesicles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. The mechanism of vesicle formation and transition is discussed along with the data obtained from induced circular dichroism (ICD) and UV/visible spectroscopy, polarized optical microscopy (POM), and (1)H NMR spectroscopy. Both the fabrication and the transition of vesicles are controlled by the inclusion equilibria and the cooperative binding of noncovalent interactions, which include the "key-lock" principle, electrostatic interactions, pi-pi stacking, and amphiphilic hydrophobic association.     

Ribbons, vesicles, and baskets: supramolecular assembly of a coil-plate-coil emeraldicene derivative

Concentration matters: the self-assembly of title compound 1 evolves from well-defined ribbons to vesicles to baskets, upon simply decreasing the concentration of 1 in tetrahydrofuran. Electron microscopy revealed a unique self-assembled structure: baskets are formed by curved and self-wrapped nanometer-thin ribbons. The self-assembly of π-conjugated molecule 1 enables to construct nano/micro structures with desired optoelectronic properties.     

Interplay of Interactions Governing the Dynamic Conversions of Acyclic and Macrocyclic Helicates

Systemic change : A system of transformations between helical structures was observed to be governed by interactions mediated by the electronic effects of substituents, entropic effects, the conformational preferences of organic building blocks, and the coordinative preferences of the metal ion. All of these effects were important, but all must be considered together to allow the prediction of the product observed (see scheme).