Depolymerization of supramolecular polymers by a covalent reaction; transforming an intercalator into a sequestrator

Abstract

Controlling the reciprocity between chemical reactivity and supramolecular structure is a topic of great interest in the emergence of molecular complexity. In this work, we investigate the effect of a covalent reaction as a trigger to depolymerize a supramolecular assembly. We focus on the impact of an in situ thiol-ene reaction on the (co)polymerization of three derivatives of benzene-1,3,5-tricarboxamide (BTA) monomers functionalized with cysteine, hexylcysteine, and alkyl side chains: Cys-BTA, HexCys-BTA, and a-BTA. Long supramolecular polymers of Cys-BTA can be depolymerized into short dimeric aggregates of HexCys-BTA via the in situ thiol-ene reaction. Analysis of the system by time-resolved spectroscopy and light scattering unravels the fast dynamicity of the structures and the mechanism of depolymerization. Moreover, by intercalating the reactive Cys-BTA monomer into an unreactive inert polymer, the in situ thiol-ene reaction transforms the intercalator into a sequestrator and induces the depolymerization of the unreactive polymer. This work shows that the implementation of reactivity into supramolecular assemblies enables temporal control of depolymerization processes, which can bring us one step closer to understanding the interplay between non-covalent and covalent chemistry.

Scheme 1. An overview of the structures of benzene-1,3,5-tricarboxamides Cys-BTA and HexCys-BTA and the transformation induced by the thiol–ene reaction. (A) The molecular structure of the helical stack formed by Cys-BTA derived from X-ray data and (B) the dimeric hydrogen-bonded structure formed by HexCys-BTA derived from DFT calculations.

Fig. 1. (A) IR spectra of Cys-BTA (blue), HexCys-BTA (orange), and 50 mol% Cys-BTA/HexCys-BTA (black) at 1 mM in MCH at 20 °C. (B) CD spectra of Cys-BTA (blue) and HexCys-BTA (orange) at 50 μM and 200 μM in MCH at 20 °C.

Fig. 2. (A) CD spectra of different ratios of HexCys-BTA and Cys-BTA (percentages are given in moles of HexCys-BTA mixed with Cys-BTA in solution) at a total concentration of 0.2 mM in MCH at 20 °C. (B) The IR spectra of different ratios of Cys-BTA/HexCys-BTA mixtures at 1 mM in MCH at 20 °C.

Scheme 2. Schematic overview of the supramolecular depolymerization of Cys-BTA polymers by thiol–ene reaction on the side chains of Cys-BTA. In solution, the monomer and polymer are in equilibrium and occurrence of the covalent thiol–ene reaction decreases the Cys-BTA monomer concentration and forms HexCys-BTA, which favours the formation of homo- and heterodimers.

Fig. 3. (A) CD spectra of Cys-BTA (blue), HexCys-BTA (orange) and the in situ formed HexCys-BTA (black) after 20 minutes exposure to UV light (λ = 365 nm, 70 mW cm⁻²) measured at 1 mM in MCH at 20 °C. (B) SLS data showing the change in particle size over UV irradiation time (λ = 365 nm, 70 mW cm⁻²) of the mixture of Cys-BTA with reactants (orange) and without reactants (blue) measured at 0.5 mM in MCH at 20 °C.

Fig. 4. The change in FT-IR spectra over time following the thiol–ene reaction in the Cys-BTA solution from the characteristic bands of polymers (blue) to the bands of dimers (orange). The spectra are taken at a concentration of 10 mM in MCH at 20 °C under UV light irradiation (λ = 365 nm, 70 mW cm⁻²). Each spectrum was taken at an interval of 30 seconds from the blue to the orange traces over the course of 20 minutes.

Fig. 5. (A) The normalized kinetics of the IR (ν = 2559 cm⁻¹, 10 mM in MCH, 70 mW cm⁻² or 2 mM in MCH, 7 mW cm⁻² for IR low light intensity), CD (at λ = 214 nm, 0.2 mM in MCH), and SLS data (0.5 mM in MCH) showing the change in signal intensities over time during UV irradiation at 20 °C. Fitting of the data is given in Fig. S16. (B) The normalized data of the change in CD intensity at λ = 214 nm during the thiol–ene reaction performed on pure Cys-BTA (blue) and on the 3/1 Cys-BTA/a-BTA mixture (75 mol% Cys-BTA, black) at 0.2 mM in MCH at 20 °C. The dotted lines are the fitted data to first order kinetics (see ESI†).