When less becomes more: dilution-induced supramolecular polymerization revived

Decreasing the concentration of a solution containing supramolecular polymers normally decreases the degree of aggregation and leads to shorter polymer chains. In our paper, we describe a counterintuitive increase in fiber length with dilution due to coupled equilibria between aggregates.

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Controlling the length of supramolecular polymers is inherently more complicated compared to classical, covalent polymers due to their dynamic nature. In supramolecular systems, the monomers are interacting not through covalent bonds, but through multiple weak, non-covalent interactions such as hydrogen bonding and π-π stacking. In order to decrease the chain-length one can 1) decrease the concentration, 2) add a sequestrator or 3) use a chain-capper to obtain shorter polymers. In our paper we show the use of manganese-centered porphyrin monomers (S- or R-Mn) as monotopic chain-cappers for the fibrous aggregates of chiral, zinc-centered porphyrins (S-Zn). In apolar solvents Zn-monomers form highly cooperative, helical H-aggregates and to a lesser extent isodesmic J-aggregates. The Mn-monomers bear a surplus charge that is balanced out by a chloride counterion, making the monomers essentially monotopic chain-cappers. Mixing the chain-capper with the S-Zn monomers results in a decrease in chain-length observable in the circular dichroism (CD) and absorbance spectra as well as static light scattering (SLS) measurements. 

The idea of using manganese centered porphyrins as chain-cappers was first proposed in our group more than 10 years ago, but it could not be realized at the time. In recent years, however, we have deepened our understanding of multi-component systems and investigated the fundamental principles of length control in supramolecular systems with combinations of experimental and computational studies. With this new knowledge we had a fresh look on the copolymerization of Mn- and Zn-porphyrins and conducted the initial spectroscopy and scattering experiments. Rather quickly we realized, that S-Mn monomers very efficiently reduce the length of supramolecular fibers of S-Zn and also cause the formation of J-aggregates when the H-aggregates become too short. 

To visualize the changes in aggregate length and morphology we conducted additional atomic force microscopy (AFM) experiments. In the images we observed the transition from long, one-dimensional fibers to short, disordered aggregates when adding the homochiral S-Mn chain-cappers to solutions of 25 µM S-Zn. Because the surface of the AFM substrates was quite crowded with deposited material, we diluted the solutions five-fold and imaged again to get clearer images of the fibers. To our surprise we observed the reformation of long fibers on all samples at the lower concentration. After the first confusion we realized that this is a rare example of dilution-induced supramolecular polymerization which was only once before reported using S-Zn monomers and pyridine as a sequestrator. We then repeated the spectroscopy and scattering experiments at lower concentrations of 5 µM S-Zn and could confirm the reformation of H-aggregates from the depolymerized mixtures. This intriguing effect arises from the coupled equilibria between the different aggregate types and species. When decreasing the concentration, the interaction between chain-capper and monomer becomes less favorable than the S-Zn monomer-monomers interactions and polymerization is induced again. 

Chiral porphyrin monomers are also known to be narcissistic in their self-assembly behavior, meaning that they do not copolymerize with monomers that are their mirror image because it is energetically unfavorable for them. Making use of these enantioselective interactions, we showed that heterochiral R-Mn monomers do not act as chain-cappers for helical H-aggregates of S-Zn, but only interact with the achiral J-aggregates. Similar to nature, we used chiral recognition of monomers to discriminate between the aggregation pathways that lead to the capping of either helical H-aggregates (pathway 1) or non-helical J-aggregates (pathway 2). 

Enantioselective chain-capping of porphyrin monomers. Only Mn-monomers of same chirality can act as chain-cappers while monomers of opposite chirality do not.

Finally, to help us paint a molecular picture, we asked our collaborators from the Pavan Lab for help to create all-atom and coarse-grained molecular models to describe our system. With their simulations we could obtain insights on the dynamic behavior, the mechanism of monomer exchange and interactions between the monomers. It was found that exchanging a Mn-monomers happens approximately 1000 times faster (or more probable) than exchanging a Zn-Monomer from the tip of a Zn-fiber. This means that there is an abundance of free Mn-monomers in solution, which will act as chain-cappers when they interact with the supramolecular fibers. Furthermore, the GC-MD simulations show the formation of chain-capped species starting from both free monomers or from preformed Zn-fibers with free Mn-monomers. 

With the combination of experiments and simulations, we have shed light on the complex interplay of aggregation pathways and equilibria in the co-assembly of Zn- and Mn-based porphyrin monomers. We reported on an intriguing example of dilution-induced supramolecular polymerization and could exploit enantioselective interactions between monomers as an additional handle to gain control over the length of supramolecular polymers. 

If you want to find out more you can read our paper under https://doi.org/10.1038/s41467-021-27831-2 or also check out this animation on dilution-induced supramolecular polymerization of porphyrin aggregates https://www.youtube.com/watch?v=G25mMDCFMwo (credit: ICMS Animation Studio). 

Elisabeth Weyandt

PhD, TU Eindhoven