Stable and Transient Self-Propagating Supramolecular Gelation

The ability to program sol-gel transition in time is key for living organisms to maintain their vital functions and to grow complex materials. Replicating this behavior with synthetic chemical networks is challenging, but highly rewarding for the design of intelligent biomimetic materials. Thanks to a combination of autocatalysis and supramolecular complexation, the iodate-hydroxymethanesulfinate-poly(vinyl alcohol) system features the emergence of self-propagating gelation fronts, stable or transient depending on the fine-tuning of the system.


Introduction
Developing autonomous chemical systems that could imitate the properties of living matter is a challenge at the meeting point of materials science and systems chemistry [1][2][3][4][5] . The timeprogramming of sol-gel transition has gained increasing attention in recent years, an interest being fueled both by its possible technological applications 6 and its relevance for understanding living systems' biology [7][8][9][10] .
For our research on materials programming by chemical clocks 11 we are exploring new ways to control gelation in time. Chemical clocks are reaction networks in which the desired product(s) can be observed only after an initial, usually tailorable, induction time 12 . Their usefulness for programming the autonomous generation of chemical stimuli, such as pH changes, in self-assembly systems has been clearly demonstrated 11,[13][14][15][16] . Previous reports on controlled gelation mostly focused on pH-driven systems, using enzymatic reactions (e.g. between urease and urea [17][18][19][20] , or glucose oxidase and glucose 21 ), slow acid generators (e.g. δgluconolactone 22,23 ), or pH-clocks 24 to trigger sol-gel transitions. We recently described an alternative approach to program gelation in time by means of supramolecular complex formation 25 . "Iodine clocks", such as the iodide-persulfatethiosulfate (IPT) system, generate iodine ‡ as a product after an initial lagtime. By adding poly(vinyl alcohol) (PVA) to the IPT system, we could control both the time of formation and the mechanical properties of the resulting PVA-iodine gel simply by adjusting the parameters of the iodine clock as well as by introducing competitive iodine-complexing agents. However, due to internal constrains, this system would not allow us to program the gel to be transient i.e. to autonomously dissolve.
We then turned our attention to the oxidation of hydroxymethanesulfinate (HMS) by iodate , a reaction which has been investigated in detail by the group of R. H. Simoyi. 26 Under certain conditions, the iodate-HMS system behaves as an iodine clock thanks to interconnected reactions. First, iodide is generated through the reduction of iodate with hydroxymethanesulfinic acid (Figure 1a, eq. 1), then iodine is formed thanks to the reaction between iodate and iodide 2 (Dushman reaction 27 , Figure 1a, eq. 2, " -generating 2 reaction"), but is quickly transformed back to iodide if hydroxymethanesulfinate is in excess (Figure 1a, eq. 3, " -2 consuming reaction"). The formaldehyde generated in these reactions seems to have no or negligible contribution to the overall mechanism. (corresponding to pH ≈ 3.4) is needed to initiate the formation of iodine and the induction time is shortened by increasing the initial . An earlier report 28 stated that the iodate-iodide reaction (eq. 2) becomes fast enough only below pH 4.5. Both acid and iodide have a strong catalytic effect on the whole reaction network, and their concentration builds up autocatalytically. The oxidation of iodine by hydroxymethanesulfinate (eq. 3) is very fast, thus the appearance of iodine is delayed until all HMS has reacted. This is a typical feature of substrate-depletive chemical clocks 12 , like the previously mentioned IPT system. However, thanks to autocatalysis, much more complex dynamics (such as selfpropagating and transient reaction fronts) can emerge in the iodate-HMS system. We are the first to describe these phenomena and their use to control sol-gel transition in time through the formation of supramolecular PVA-complexes.

Results and Discussion
We started our investigation of the iodate-HMS-PVA system by triggering the reaction with a drop of acid (50 mM sodium bisulfate ). The addition of methyl yellow (MY) and 4 bromocresol green (BG) allowed to visualize changes in pH during the reaction course 29 . Full experimental details are available in the ESI. As shown in Figure 1b- (Figure 1a, eq. 2) develops as a selfpropagating circular front ("ring"). However, a stable PVA-2 supramolecular gel forms only when iodate is in excess (Figure  1b, Movie S1). If HMSNa is in excess, the gel is either transient (Figure 1c, Movie S2) or does not even form (Figure 1d and Movie S3, the outer ring is light brown because of uncomplexed iodine). In these two latter cases, the -generating ring is 2 followed by an -consuming one (eq. 3). In the case shown in 2 Figure 1d, the decomposition of iodine is so fast that the complex with PVA cannot form.
While the -producing reaction is activated by acid, the - consuming reaction produces acid. This behavior is confirmed by the color change from light green (pH ≈ 10) to pink (pH < 2) that accompanies the -consuming reaction front § . We   Figure  S3.
It is noteworthy that the iodate-hydroxymethanesulfinate reaction has some elements of similarity with another autocatalytic iodine clock, the iodate-sulfite-thiosulfate (IST) system 31,32 . Both are autocatalytic in acid and iodide, and can generate complex nonlinear phenomena such as reactiondiffusion acid and iodine fronts, instabilities and patterns. However, in the IST system the iodine front follows the acid one, while in the iodate-HMS system the behavior is exactly the opposite.
As mentioned before, a certain pH value is needed for the iodate-HMS reaction to occur at an appreciable rate, and in the experiments described so far this was achieved by the direct addition of acid. However, our main interest is to program chemical systems to perform their tasks autonomously, without external control. We already showed that slow acid generators such as cyclic esters can be used to control the dynamics of clock reactions 14,15,33,34 . Here we demonstrate the same approach for programming autonomous sol-gel transitions in the iodate-HMS-PVA system with δ-gluconolactone (GL). The gradual hydrolysis of GL yields gluconic acid ( ), which lowers = 3.86 the pH allowing reactions (1) and (2)  Once started, the gel formation is very fast (Figure 2a, Figure  S2). We further investigated this behavior by means of rheology. As can be seen from Figure 2b, the storage modulus suddenly increases when the iodine clock strikes, and quickly ' reaches its maximum value. How sudden this sol-gel transition is can be best appreciated by comparing it with the one observed for the IPT-PVA system 25 (Figure S4). In both systems the storage modulus increased of about four orders of ′ magnitude after the iodine clock struck, but in the iodate-HMS-PVA system this change happened much faster compared to the IPT-PVA one.
Using bisulfate the same rheological behavior was observed (Figure 2c) but the lagtimes were consistently shorter ( Figure  S5), from ~9 min to ~3 min for 3 mM and 5 mM bisulfate, respectively, and the resulting gels were less stiff, with values ′ about one order of magnitude lower. More importantly, bisulfate allowed the development of autonomously transient sol-gel transition, which was not possible with GL. With 10 mM bisulfate in a mixture of 100 mM iodate, 200 mM HMSNa and 5% PVA 130 kDa, islands of dark blue PVA-complex formed 2 over time and subsequently started to degrade (Figure 3). Due to its very fast and complex dynamics, we could not obtain proper rheological data for the transient gel system. indicated with an arrow. It is noteworthy that, while the gel formation is very fast, its dissolution is much slower and happens by gradual surface erosion § § . The snapshots were taken from Movie S7.

Conclusions
Our results shows that self-propagating supramolecular sol-gel transition can be achieved and programmed in time using an iodine clock, the iodate-HMS system, and that stable or transient PVA-gels can be obtained depending on the chosen 2 reaction conditions. We were able to program gelation in time and thus to quantify the almost instantaneous gel formation induced by the autocatalytic iodine buildup. Other complex phenomena displayed by the iodate-HMS system, such as the generation of chemical patterns, also deserve further investigation.
Our approach further demonstrates the power of chemical clocks for the programming of soft materials, and it will inform the design of future programmable and transient hydrogels.
The sharp pH change that accompanies the dissolution of the transient gel could be exploited for example to trigger the selfassembly of a different building block, or even another set of reactions. Thanks to its excitable behavior, the iodate-HMS system could be applied also for the development of transient chemomechanical actuators and for chemistry-based computing.

Conflicts of interest
There are no conflicts to declare.