pH-Responsive Dipeptide-Based Dynamic Covalent Chemistry Systems Whose Products and Self-Assemblies Depend on the Structure of Isomeric Aromatic Dialdehydes

Abstract

Facile control over preparation of organic building blocks and self-assembled aggregations to construct the desired materials remains challenges. This article reports selective dynamic covalent bonds formation and the corresponding self-assembly behaviors by using a dipeptide, glycylglycine (GlyGly), reacting with isomeric aromatic dialdehydes o-phthalaldehyde (OPA), p-phthalaldehyde (PPA), and m-phthalaldehyde (MPA) to demonstrate diversified aggregation forms caused by structure topology variations. Under alkaline condition, the aldehyde groups of phthalaldehydes can be connected with the amino groups of GlyGly by imine bonds as the dynamic chemical bonds. Owing to the fact that formation and dissociation of the imine bonds were reversibly pH-responsive, the reactions and aggregates assembled by their products were also reversibly controlled by changing pH. Three products, including two-armed product (OPGG, in which two GlyGly molecules were connected with one OPA molecule), single-armed product (PPG, in which only one GlyGly molecule was connected with a PPA molecule), and a mixture product (MPGG and MPG), as well as their different self-assembly behaviors, were obtained from OPA/GlyGly, PPA/GlyGly, and MPA/GlyGly systems, respectively, at the same condition of pH 8.6 in 90% methanol aqueous solution. However, for OPA/GlyGly system, another different type of product with benzopyrrole structure (OPG) was obtained by nucleophilic substitution via mixing OPA and GlyGly in water, which generated organic nanoparticles. Based on the results above, we conjectured the differences in dynamic covalent bond formation and supramolecular assembly clearly were influenced by the structure topologies of phthalaldehydes (OPA, PPA, and MPA). The experimental phenomenon verified the hypothesis as well, which may guide us to realize facile construction of selective reaction products and intelligent reversibly responsive materials with diverse morphologies and functions.

Dynamic covalent polymers for biomedical applications

“…Dynamic covalent polymers have thus been shown to demonstrate many unique properties, such as self-healing ability, recyclability, stimuli-responsiveness, shape memory behavior, degradability, etc., which will be discussed in the following sections. [51][52][53][54][55][56][57]…”

Oxidation-Induced Breakage of the Imine Bond and Aggregate Transition in a Se-Containing Dynamic Covalent Surfactant

“…Compared to traditional pH stimulus, oxidation cannot destroy all imine bonds but can virtually disrupt vesicles because of an increase in the polarity of the micellar microenvironment resulting from the oxidation of Se atoms. Furthermore, with the breakage and reformation of imine bonds, the surfactant can be reversibly switched between asymmetric and symmetric structures accompanied by a transition in microstructures from spherical micelles to vesicles, other than surface active and nonsurface active. − ,, In addition, pH stimulus can hardly release the loaded hydrophobic drug, but oxidation can release the drug without precisely controlling the concentration of the surfactant under cmc . Comprehending the mechanism of oxidation-induced breakage of imine bonds and disruption of vesicles is very important for the designation of redox-responsive imine-based carriers that can unload cargoes on the site with locally high reactive oxygen species.…”

“…Over the past decade, dynamic covalent chemistry has gained considerable attention because of its reversible and dynamic nature. , Among various dynamic covalent bonds, imine bonds are particularly interesting and have been used to construct micelles, , vesicles, − gels, , and nanoparticles . Minkenberg et al developed the first dynamic covalent surfactant based on imine formation that can be triggered by pH and temperature.…”

“…Obviously, surfactants and aggregates based on imine bonds are very sensitive to pH and temperature. In addition, imine formation in surfactants is also adjusted by changing the molecular structures of aldehydes or amines . Naturally, a concern may be raised as follows: are imine bonds also affected by other factors such as polarity or steric hindrance?…”

Polymerization, Stimuli-induced Depolymerization, and Precipitation-driven Macrocyclization in a Nitroaldol Reaction System

“…2,4,[18][19][20][21][22][23] These materials are characterized by their adaptive properties, able to predictably respond to various stimuli, and can give rise to emergent properties. 4,11,[24][25][26][27] A variety of dynamic covalent reactions have been applied to dynamer formation, such as imine formation (incl. hydrazones, oximes, etc.…”