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

Abstract

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 (1) H 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.

Surface- and Guest-Promoted Product Selection from a Dynamic Covalent Library: A Scanning Tunneling Microscopic Study

“…In view of the reversible nature of the imine bond, Schiff base reaction was broadly applied in the realm of dynamic covalent chemistry (DCC). − DCC is a topic of increasing interest, and the establishment of combinatorial libraries under thermodynamic control helps redistribution of the initial products by changing the environmental conditions of a reaction. , In general, DCC is commonly performed in solution for the synthesis of, given enough time, the thermodynamically most stable product over the kinetically controlled ones. − Lately, surface-assisted Schiff base reaction was utilized to investigate the DCC confined on the HOPG surface by STM, which, specifically, included the transimination process and the redistribution of the imine products facilitated by the substrate, highlighting the particular significance of adsorption free energy in shifting the position of the chemical equilibrium in favor of the adsorbed products, thus altering the constituent of a dynamic covalent library. , Considering the template effect of guest species in the structural evolvement of supramolecular architectures on a surface, it is presumable to speculate that the guest molecule may, as well, influence the product distribution by coadsorption on the substrate.…”

Biomimetic Generation and Remodeling of Phospholipid Membranes by Dynamic Imine Chemistry

“…One of the most important reversible reactions in organic chemistry is the formation of imines from amines and aldehydes, leading to a dynamic system that can be tuned by the careful choice of both reaction partners, as well as other parameters such as temperature or pH. 9,10 Reversible imine formation is a cornerstone of several fields including organocatalysis, 11,12 supramolecular chemistry, 13,14 and DCC. 15,16 Despite the potential of this reaction to generate robust and biocompatible membranes under physiological conditions, there are limited examples of imine-based vesicles.…”

“…To meet these demands, we required a reversible transformation whose product stability could be readily tuned. One of the most important reversible reactions in organic chemistry is the formation of imines from amines and aldehydes, leading to a dynamic system that can be tuned by the careful choice of both reaction partners, as well as other parameters such as temperature or pH. , Reversible imine formation is a cornerstone of several fields including organocatalysis, , supramolecular chemistry, , and DCC. , Despite the potential of this reaction to generate robust and biocompatible membranes under physiological conditions, there are limited examples of imine-based vesicles. Moreover, their composing amphiphiles lack resemblance of natural phospholipids. , Herein we demonstrate that a natural amine-containing lysophospholipid, lysosphingomyelin, reacts chemoselectively with long-chain aldehydes to form imines, driving the de novo generation of dynamic biomimetic phospholipid liposomes (Figure B).…”

Ligand Mediated Metal Cations Exchanges within Metallo‐Dynameric Solid Films

“…[14] For this specific scaffolds, most of the reported work was focused on the ligand exchange, while replacement of the coordinated metal ions, despite its simplicity, is still rare, although the change of chelating metal did significantly alter the property of whole dynamers. [12,15] By extending the concept to solid metallo-dynameric films, herein, we envisioned the possibility of in situ metal exchanges within the scaffold of bis(pyridine-2,6-diimine) on the interfaces of solid films and solution, leading to smart membranes for adaptive capture of a variety of metal cations (Figure 1).…”