Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 2;147(13):11327-11335.
doi: 10.1021/jacs.5c00274. Epub 2025 Mar 19.

Imine-Based Transient Supramolecular Polymers

Gabriele Melchiorre  1 , Lucia Visieri  2 , Matteo Valentini  1 , Roberta Cacciapaglia  1 , Alessandro Casnati  2 , Laura Baldini  2 , José Augusto Berrocal  3 , Stefano Di Stefano  1
Affiliations

Imine-Based Transient Supramolecular Polymers

Gabriele Melchiorre et al. J Am Chem Soc. .

Abstract

Systems that change properties upon exposure to chemical stimuli offer the interesting prospect of (partially) mimicking the functions of living systems. Over the past decade, numerous supramolecular systems whose chemical composition and properties are regulated by the dissipation of chemical fuels have been reported. These systems are typically based on the transient transformation of a "dormant" species into an active, self-assembling supramolecular monomer. The process is powered by fuel consumption and terminates upon fuel depletion, restoring the initial dormant state. Previously reported out-of-equilibrium supramolecular polymerizations relied on the activation of the dormant species by adding or removing small structural units to enable supramolecular polymerization. Here, we present an approach that combines the reversibility of dynamic covalent chemistry and supramolecular chemistry to trigger transient supramolecular polymerizations by "recycling" the components of a dynamic combinatorial library (DCL). Treatment of an equilibrated DCL of aliphatic imines and aromatic amines with an activated carboxylic acid (ACA) generates a dissipative dynamic combinatorial library of aromatic imines and protonated aliphatic amines. The transient acidic conditions enable the creation of a supramolecular polymer held together by interactions between the protonated aliphatic amines and the crown ether moieties embedded in the scaffold of the aromatic imines. Thus, fuel dissipation reshuffles the chemical connectivity and enables the temporary transformation of a purely covalent (polymeric) system into a supramolecular polymer. We demonstrate the strategy using two different covalent dormant feedstocks consisting of a diimine macrocycle involving a calix[4]arene scaffold and a distribution of imine (cyclo)oligomers derived from an isophthalaldehyde skeleton.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) A transient supramolecular polymer obtained from a covalent cyclic monomer (CCM) by activation of one of the structural units present in the monomer. (B) A transient supramolecular polymer obtained from a covalent polymer (CP) by activation of one of the structural units present in the covalent feedstocks. (C) The equilibrium among N-aromatic (Ar-) and N-aliphatic (Alk-) imines and related amines is naturally shifted to the N-aliphatic imine side. (D) Transient protonation of the aliphatic amine by the ACA temporarily shifts the equilibrium in panel C toward the N-aromatic imine side. Such shift persists as long as the ACA is present.
Figure 2
Figure 2
(A) Partial 1H NMR spectra of CCM 1 before (trace a) and after (trace b) the addition of 4 (CDCl3/CD3OD 3:1). Trace b is related to a 200 mM 1 + 400 mM 4 solution warmed at 50 °C for 5 days. Prolonged warming and consequent change of medium composition are responsible for the downfield shift of the chloroform signal, which is marked with an asterisk. (B) Partial 1H NMR spectra of CP 2 before (trace a) and after (trace b) the addition of 4 (CDCl3/CD3OD 3:1). Trace b is related to a 100 mM CP 2 + 200 mM 4 solution warmed at 50 °C for 1 day. Species present in the mixture of trace b were identified by a combination of 1H NMR, ESI–MS, and APCI–MS spectra, see Supporting Information pages S18–S20 for details (complete NMR spectra are given in Figures S2, S8, S17, and S18 of the Supporting Information).
Figure 3
Figure 3
(A) Partial 1H NMR spectra (CDCl3/CD3OD 3:1) of 3 (trace a), 3·2H+ (trace b), 1:2 3·2H+ + 4 (trace c), and 1:2:2 CCM 1 + H+ + 4 (trace d) (see Figure S41 for complete spectra). The plot shows the dependence of DP in SP-α as a function of concentration, calculated from DOSY experiments (see Supporting Information, pages S33 and S34). (B) Partial 1H NMR spectra (CDCl3/CD3OD 3:1) of 5 (trace a), 5·2H+ (trace b), 1:2 5·2H+ + 4 (trace c), and 1:2:2 CP 2 + H+ + 4 (trace d) (see Figure S70 for complete spectra). The plot shows the dependence of DP in SP-β as a function of concentration calculated from DOSY experiments (see Supporting Information, pages S34 and S53–S54).
Figure 4
Figure 4
2D DOSY spectra (400 MHz, CDCl3/CD3OD 3:1) of CCM 1 and 4 mixed in a 1:2 molar ratio (200 mM 1 and 400 mM 4) before (A) and after (B) the addition of TFA (400 mM). The addition of TFA results in the formation of SP-α.
Figure 5
Figure 5
Behavior of a covalent or supramolecular polymer based on reversible interactions between monomers below and above the CC.
Figure 6
Figure 6
(A) 1H NMR spectra of the 1:2 mixtures of CCM 1 and 4 after addition of TFA (bottom trace) and TBA (top trace, the spectrum has been recorded immediately after the addition of TBA) and monitoring of CCM 1 and monomer 6 over the time (% data have been obtained from the relative integration of diagnostic imine signals). After 500 min, the temperature was raised to 50 °C (pink area) to allow reversion to the initial covalent material (the inset shows the initial phase of the reaction after addition of TBA at t = 0). (B) 1H NMR spectra of the 1:2 mixtures of CP 2 and 4 after addition of TFA (bottom trace) and TBA (top trace, the spectrum has been recorded immediately after the addition of TBA) and monitoring of CP 2 and 7 over the time (% data have been obtained from the relative integration of diagnostic imine signals). After 500 min, the temperature was raised to 50 °C (pink area) to allow reversion to the initial covalent material (the inset shows the initial phase of the reaction after addition of TBA at t = 0). The experimental error on % data for both (A,B) amounts to ca. 10%, the intrinsic error associated with the integration of NMR signals.
See this image and copyright information in PMC

References

    1. Hartlieb M.; Mansfield E. D. H.; Perrier S. A guide to supramolecular polymerizations. Polym. Chem. 2020, 11, 1083–1110. 10.1039/C9PY01342C. - DOI
    2. García F.; Korevaar P. A.; Verlee A.; Meijer E. W.; Palmans A. R. A.; Sánchez L. The influence of π-conjugated moieties on the thermodynamics of cooperatively self-assembling tricarboxamides. Chem. Commun. 2013, 49, 8674–8676. 10.1039/c3cc43845g. - DOI - PubMed
    3. De Greef T. F. A.; Smulders M. M. J.; Wolffs M.; Schenning A. P. H. J.; Sijbesma R. P.; Meijer E. W. Supramolecular Polymerization. Chem. Rev. 2009, 109, 5687–5754. 10.1021/cr900181u. - DOI - PubMed
    4. de Greef T. F. A.; Meijer E. W. Supramolecular polymers. Nature 2008, 453, 171–173. 10.1038/453171a. - DOI - PubMed
    5. Brunsveld L.; Folmer B. J. B.; Meijer E. W.; Sijbesma R. P. Supramolecular Polymers. Chem. Rev. 2001, 101, 4071–4097. 10.1021/cr990125q. - DOI - PubMed
    1. Yanagisawa Y.; Nan Y.; Okuro K.; Aida T. Mechanically robust, readily repairable polymers via tailored noncovalent cross-linking. Science 2018, 359, 72–76. 10.1126/science.aam7588. - DOI - PubMed
    2. Nakahata M.; Mori S.; Takashima Y.; Yamaguchi H.; Harada A. Self-Healing Materials Formed by Cross-Linked Polyrotaxanes with Reversible Bonds. Chem. 2016, 1, 766–775. 10.1016/j.chempr.2016.09.013. - DOI
    3. Würthner F.; Saha-Möller C. R.; Fimmel B.; Ogi S.; Leowanawat P.; Schmidt D. Perylene Bisimide Dye Assemblies as Archetype Functional Supramolecular Materials. Chem. Rev. 2016, 116, 962–1052. 10.1021/acs.chemrev.5b00188. - DOI - PubMed
    4. Erbas-Cakmak S.; Leigh D. A.; McTernan C. T.; Nussbaumer A. L. Artificial Molecular Machines. Chem. Rev. 2015, 115, 10081–10206. 10.1021/acs.chemrev.5b00146. - DOI - PMC - PubMed
    5. Aida T.; Meijer E. W.; Stupp S. I. Functional Supramolecular Polymers. Science 2012, 335, 813–817. 10.1126/science.1205962. - DOI - PMC - PubMed
    1. Borsley S.; Leigh D. A.; Roberts B. M. W. Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction. Angew. Chem., Int. Ed. 2024, 63, e202400495 10.1002/anie.202400495. - DOI - PubMed
    2. Del Giudice D.; Spatola E.; Valentini M.; Ercolani G.; Di Stefano S. Dissipative Dynamic Libraries (DDLs) and Dissipative Dynamic Combinatorial Chemistry (DDCC). ChemSystemsChem 2022, 4, e202200023 10.1002/syst.202200023. - DOI
    3. Otto S. An Approach to the De Novo Synthesis of Life. Acc. Chem. Res. 2022, 55, 145–155. 10.1021/acs.accounts.1c00534. - DOI - PMC - PubMed
    4. Out-of-Equilibrium (Supra)molecular Systems and Materials; Giuseppone N., Walther A., Eds.; Wiley-VCH, 2021.
    5. Pappas C. G. A sound approach to self-assembly. Nat. Chem. 2020, 12, 784–785. 10.1038/s41557-020-0526-0. - DOI - PubMed
    6. Walther A. Viewpoint: From Responsive to Adaptive and Interactive Materials and Materials Systems: A Roadmap. Adv. Mater. 2020, 32, 1905111. 10.1002/adma.201905111. - DOI - PMC - PubMed
    7. Ragazzon G.; Prins L. J. Energy consumption in chemical fuel-driven self-assembly. Nat. Nanotechnol. 2018, 13, 882–889. 10.1038/s41565-018-0250-8. - DOI - PubMed
    1. Olivieri E.; Gasch B.; Quintard G.; Naubron J.-V.; Quintard A. Dissipative Acid-Fueled Reprogrammable Supramolecular Materials. ACS Appl. Mater. Interfaces 2022, 14, 24720–24728. 10.1021/acsami.2c01608. - DOI - PubMed
    2. Mishra A.; Dhiman S.; George S. J. ATP-Driven Synthetic Supramolecular Assemblies: From ATP as a Template to Fuel. Angew. Chem., Int. Ed. 2021, 60, 2740–2756. 10.1002/anie.202006614. - DOI - PubMed
    3. Singh N.; Lainer B.; Formon G. J. M.; De Piccoli S.; Hermans T. M. Re-programming Hydrogel Properties Using a Fuel-Driven Reaction Cycle. J. Am. Chem. Soc. 2020, 142, 4083–4087. 10.1021/jacs.9b11503. - DOI - PubMed
    4. Bal S.; Das K.; Ahmed S.; Das D. Chemically Fueled Dissipative Self-Assembly that Exploits Cooperative Catalysis. Angew. Chem., Int. Ed. 2019, 58, 244–247. 10.1002/anie.201811749. - DOI - PubMed
    5. Rieß B.; Boekhoven J. Applications of Dissipative Supramolecular Materials with a Tunable Lifetime. ChemNanoMat 2018, 4, 710–719. 10.1002/cnma.201800169. - DOI
    6. De S.; Klajn R. Dissipative Self-Assembly Driven by the Consumption of Chemical Fuels. Adv. Mater. 2018, 30, 1706750. 10.1002/adma.201706750. - DOI - PubMed
    7. Tena-Solsona M.; Rieß B.; Grötsch R. K.; Löhrer F. C.; Wanzke C.; Käsdorf B.; Bausch A. R.; Müller-Buschbaum P.; Lieleg O.; Boekhoven J. Non-equilibrium dissipative supramolecular materials with a tunable lifetime. Nat. Commun. 2017, 8, 15895. 10.1038/ncomms15895. - DOI - PMC - PubMed
    8. van Rossum S. A. P.; Tena-Solsona M.; van Esch J. H.; Eelkema R.; Boekhoven J. Dissipative out-of-equilibrium assembly of man-made supramolecular materials. Chem. Soc. Rev. 2017, 46, 5519–5535. 10.1039/C7CS00246G. - DOI - PubMed
    9. Maiti S.; Fortunati I.; Ferrante C.; Scrimin P.; Prins L. J. Dissipative self-assembly of vesicular nanoreactors. Nat. Chem. 2016, 8, 725–731. 10.1038/nchem.2511. - DOI - PubMed
    1. Reisler E.; Egelman E. H. Actin Structure and Function: What We Still Do Not Understand. J. Biol. Chem. 2007, 282, 36133–36137. 10.1074/jbc.R700030200. - DOI - PubMed

LinkOut - more resources