Gelation-driven component selection in the generation of constitutional dynamic hydrogels based on guanine-quartet formation

Abstract

The guanosine hydrazide 1 yields a stable supramolecular hydrogel based on the formation of a guanine quartet (G-quartet) in presence of metal cations. The effect of various parameters (concentration, nature of metal ion, and temperature) on the properties of this gel has been studied. Proton NMR spectroscopy is shown to allow a molecular characterization of the gelation process. Hydrazide 1 and its assemblies can be reversibly decorated by acylhydrazone formation with various aldehydes, resulting in formation of highly viscous dynamic hydrogels. When a mixture of aldehydes is used, the dynamic system selects the aldehyde that leads to the most stable gel. Mixing hydrazides 1, 9 and aldehydes 6, 8 in 1:1:1:1 ratio generated a constitutional dynamic library containing the four acylhydrazone derivatives A, B, C, and D. The library constitution displayed preferential formation of the acylhydrazone B that yields the strongest gel. Thus, gelation redirects the acylhydrazone distribution in the dynamic library as guanosine hydrazide 1 scavenges preferentially aldehyde 8, under the pressure of gelation because of the collective interactions in the assemblies of G-quartets B, despite the strong preference of the competing hydrazide 9 for 8. Gel formation and component selection are thermoreversible. The process amounts to gelation-driven selforganization with component selection and amplification in constitutional dynamic hydrogels based on G-quartet formation and reversible covalent connections. The observed self-organization and component selection occur by means of a multilevel selfassembly involving three dynamic processes, two of supramolecular and one of reversible covalent nature. They extend constitutional dynamic chemistry to phase-organization and phasetransition events.dynamic combinatorial chemistry ͉ component selection ͉ supramolecular chemistry S upramolecular entities present the ability to reversibly modify their constitution through exchange and rearrangement of their molecular components because of the lability of the noncovalent interactions that hold them together (1, 2). Similar features may be imported into molecular species if reversible covalent bonds are introduced into their structure, allowing cleavage and formation of interatomic connections with fragment exchange under specific conditions. Thus, entities, capable of reversible modification of their constitution, define a constitutional dynamic chemistry on both the supramolecular and the molecular levels (3). Because the constitutional changes may be expected to respond to external factors, constitutional dynamic chemistry is the basis for the design and development of adaptive chemical systems. It generates constitutional dynamic libraries (CDLs) whose constituents are in dynamic equilibrium, such that they can exchange their components and express all of the entities that are potentially accessible through recombination by means of reversible covalent bonds and noncovalent interactions. The CDL may then adapt to (internal or) external phy...

Co‐existence of Distinct Supramolecular Assemblies in Solution and in the Solid State

“…G‐derivatives that respond to external stimuli such as light, concentration, specific reagents, cation and anion binding are of considerable interest for designing switchable assemblies 9a, 14d, 25. To probe interconversion between quartet and ribbon‐like assemblies, powdered samples of GaceC10⋅K⋅Pic 8:1 were suspended in known quantities of CHCl 3 and the dissolution process was monitored through a combined solution‐state/solid‐state NMR approach (Figure 6).…”

Research Highlights

“…On submicron diamond, where cells were less well spread, filopodial clumping was noted around larger diamond grains, which the authors attributed to differential protein adsorption. Filopodia can respond to topographic features as small as 10 nm high [2], and it seems likely that physical guidance could also have contributed to the filopodial polarization. After 21 days of culture, osteoblasts on both diamond surfaces had higher levels of collagen and alkaline phosphatase (markers of osteo blast activity) than controls, with the nanocrys talline surface inducing deposition of most extracellular calcium.…”

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“…This paper is part of a steadily grow ing body of work on fabricating nanoscale features into metals (e.g., [2]). This is clearly important if we want to translate this techno logy from the laboratory to the clinic.…”

Supramolecular Self-organization of Potential Hydrogelators on Attracting Surfaces

“…Equally is the finding with many other hydrogelators described in literature. In some cases, the addition of buffers like sodium carbonate [4,5] and others [6] is required. Jørgensen et al report about hydrogelators which necessitate adding of ethanol or dimethylformamide [7].…”