Pathway Dependence in Redox‐Driven Metal–Organic Gels

Abstract Pathway dependence is common in self‐assembly. Herein, the importance of pathway dependence for redox‐driven gels is shown by constructing a FeII/FeIII redox‐based metal–organic gel system is shown. In situ oxidation of the FeII ions at different rates results in conversion of a FeII gel into a FeIII organic gel, which controls the material properties, such as gel stiffness, gel strength, and an unusual swelling behaviour, is described. The rate of formation of FeIII ions determines the extent of intermolecular interactions and so whether gelation or precipitation occurs.

Supramolecular low molecular weighth ydrogels (LMWGs) formed by the self-assembly of small organic molecules induced by non-covalentinteractions are fascinating smartm aterials, which have multifunctional applications. [1] Of the different kinds of supramolecular gels, metal-organic gels have received significanti nterest in recent years because of their widespread applications, particularly in optoelectronics, pharmaceuticals and catalysis. [2] Metal-organic gels are as pecial class of supramolecular gels that incorporate am etallic elementi nto the ligand during self-assembly.C onceptually,m etal-organic gels are synthesized based on strongm etal-ligand interactions, in which the organic ligand may compose of as ingle component or can be derived from the reactionb etween multiplef unctional groups. Incorporation of metal ions into the organic frameworks often dramatically changes the optical and chemical properties of the ligand and thereforec an be used as a powerful strategyt om odify the materialp roperties. [2a,b, 3] One interesting property of supramolecular gels is their responsiveness towards variouss timuli including heat, pH, irradiation, chemical entities, and redox reactions. [3b, 4] Redox responses make the gel systems desirable for biomimicry,a sw ell as for numerousp ossible applications. [4f, 5] However,m ost of the redox-fuelled gels found in the literature are polymerici n nature and are usually developed from the intermolecular di-sulfidee xchange reaction-based molecular systems. [4f, 5c-e,g] Therefore, designinga nd constructiono fn ew supramolecular low molecular weight redox-based gels is highly desirable; these are expected to have very different underlying properties. [6] Ak ey issue for many supramolecular gels is that the properties significantly depend on the preparative pathway. [7] Because of such effect, even thought he compositiono ft he final materials remains same, the material properties can vary depending on the self-assembly kinetics. [7a] Gelsf ormed at ah igh rate are often kinetically trapped, which means that they can be hard to reproduce and control. To avoid this kinetic trapping during the gelation process, the environmental conditions need to be well controlled to achieve homogeneous and reproducible gels.
Herein, we designed an ew redox-responsivem etal-organic hydrogels ystem and discuss thep athway dependence of these redox-based gels ( Figure 1). Unlike otherr edox systems, instead of using sulfide/disulfide-basedl igands, [4f, 5c,d,g] herein, we utilize dynamic imine bond formation between an aldehyde (1)a nd an amine (2)a st he key chemical reaction to synthesize the ligand (3). To make the organic framework redox responsive, we incorporatedF e II ions into the gel medium. In situ oxidation of the Fe II ions by an oxidisinga gent resultsi n formation of aF e III -organic gel. The final properties of the Fe III gel significantly depend upon the rate of oxidation of Fe II .A lthoughaslow rate of oxidation gives Fe III gels with high stiffness, av ery fast oxidation drives the system towards precipitation. Precipitation also occurred on direct treatmento ft he mixture of the aldehyde (1)a nd amine (2)w ith Fe III .H ence, we showed that we can prepareF e III metallogels,w hich cannotb e preparedd irectly by controlling the reactionp athway.I ns ome   cases, we also find that the materials exhibit ah ighly unusual swelling, whichi sv ery uncommon for such supramolecular gels.
To prepare the gel, we employed dynamic imine bond formation [8] reactionb etween 4-(dimethylamino)benzaldehyde (1) and N,N-dimethyl-p-phenylenediamine (2)i nD MSO/H 2 O( 25:75 v/v). When am ixture of equimolar amounto f1 and 2 (0.134 m)i nD MSO is dilutedw ith water,abrown self-supporting gelw as rapidly formed (Figure 2a). The gelation process was followed by rheology. By time sweep rheology, initially the storagem odulus (G')w as considerably higher than the loss modulus (G''), indicating that gelation was very quick ando ccurred before the measurement could be begun ( Figure 2a). The gel continued to evolve with time and G' and G'' reach a plateau after approximately 14 hours (Figures 2b and S1 in the Supporting Information). The gel exhibits ah igh stiffness ( % 2 10 5 Pa), but starts to collapse at al ow strain of approximately 0.2 %( the criticalstrain;Figures2ca nd S1).
To characterize the chemical component responsible for gelation, 1 HNMR spectroscopy and high-resolution mass spectroscopy( HRMS) of the gel state werep erformed ( Figure 2d). By 1 HNMR spectroscopy,t he appearance of an ew peak at 8.39 ppm clearly demonstrated the imine bond formation between the aldehyde and amine. Integration of the 1 HNMR spectra showed around2 6% conversion to the imine 3 after 16 hours.T his presumably represents the position of the equilibrium of the reaction under these conditions, because imines are susceptible to hydrolysed in water. [8,9] The imine bond formation was furtherc onfirmed by recording the HRMS of the gel ( Figure S2 in the Supporting Information). The appearance of the mass at 268.1792s hows the formation of compound 3 [expected mass = 268.1814 for the formula (M+ +H) + ]i nt he gel state. Moreover,b yF TIR spectroscopy,t he stretchings ignal for the aldehyde carbonyl of 1 appeared at 1656 cm À1 ,w hilst in the gel state it remained almost unaffected ( Figure S3 in the Supporting Information). However,abroad peak appeared at 1680 cm À1 for the C=N bond, again confirming the formation of the imine 3 in the gel state.
We incorporated Fe II ions (as sulfate salt) into the gel mediumt oc onvert this supramolecular gel into ar edox responsivem etal-organic gel. [2c, 5a,f, 10] We used 0.134 m of Fe II to preparet he Fe II gel (1 molare quivalent with respectt ot he aldehyde). Addition of aqueous solution of Fe II to the mixture of 1 and 2 not only modified the gelationk inetics, but also changed the final mechanical properties of the gels. Time sweep rheologyi ndicated that the initial values of both G' and G'' were significantly lower compared to the case when Fe II was absent (Figures 2b and S1). With time, both G' and G'' stated to increase rapidly. After approximately 2hours, G' and G'' started to decrease and becamea lmost constanta fter approximately 13 hours ( Figure S1 in the Supporting Information). The presence of Fe II resultedi na round approximately six times decrease in both G' and G'' of the gel (Figures 2c and S1). However,n os ignificant change in gel strength (critical strain)w as observed ( Figure 2c). Surprisingly, when we tried to make ac ontrolg el with preformed imine 3,n og el formation was noticed either in absence or presence of Fe II ( Figure S4 in the Supporting Information). Compound 3 is poorly soluble in DMSO.U pon addition of H 2 Ot oasuspensiono f3 in DMSO,a yellow and orange yellow precipitate was formed in absence and presence of Fe II respectively.H ence, in situ formationo f3 is necessary for gelationt oo ccur.
The presence of Fe II also changed the visual appearance of the gel (Figure 2a). The colouro ft he gel changed from brown to reddish brown in presence of Fe II .U V/Vis and emission spectroscopy measurements of 1 and 2 were conducted under differentc onditions to highlight the aggregation properties (Figures S5 and S6 in the Supporting Information). By UV/Vis analysis, 1 and 2 exhibited absorption at 353 and 305 nm, respectively.I nc omparison, the gel state obtained from the mixture of 1 and 2 showedastrong absorption at 338 nm with two shoulder peaks at 310 and 434 nm. Time-dependent emission experiments showed that as the reaction proceeds, the strong emission of the aldehyde at 410 nm started to decrease, and a new band appeared at 468 nm. In presence of Fe II ,t he absorption peak at 310 nm becamem ore intense, whereas the shouldering at 434 nm remained unaffected. By fluorescence, the emission of the gel at 468 nm blueshifted by 8nmi np resence of Fe II along with the generation of an ew band at 550 nm. These data suggest existence of different intermolecular interactions in the gel matrices formed in absence and presence of Fe II .T oc onfirmt his, the 1 HNMR spectrum of the Fe II gel was superimposed with that obtained in absence of Fe II (Figure 2d). Comparison of the data shows that the signal for the imine protonH a of 3 moved to the downfield region by 0.2 ppm due to the interaction with Fe II .M oreover,d ue to metal coordination,t he aromatic protons H b-c also showed approximately 0.2 ppm downfield shift. Interestingly,w hilet he signals for aromatic protons, as well as the carbonyl ÀCH of 1, exhibitedn os hift in 1 HNMR upon interaction with Fe II ,t he aromatic protons of 2 becameb road ands hifted downfield by 0.2 ppm. These results indicate that Fe II not only binds with the imine bond of 3,b ut also interacts with the amine functionality of 2.B yH RMS, no evidenceo ff ormation of 3-Fe II complex was found ( Figure S7 in the Supporting Information). This indicates that although the interaction of the imine bond with Fe II ion is subtle, it causes significant change at the macroscopic level.
The presence of Fe II ions makes the gel medium redox responsive. [2c, 5a,f, 10] Practicalu ses of Fe II /Fe III redoxs ystems involving LMWGs are limited in the literature. For example, recently, Das et al. reported ar eusable transienth ydrogel system based on Fe II /Fe III redox conversiona nd explored those transient aggregatesi nm imicking peroxidasea ctivity. [5a] Panja and Ghosh utilized aF e II metallogelf or visual recognition of H 2 O 2 from other reactive oxygen species (ROS) by performing Fenton reaction inside the gel medium. [11] Inspired by their work, we attempted to convert our Fe II gel into aF e III gel through an in situ oxidation of the Fe II ions by different oxidizing agents.
Prior to this, we investigated the role of dissolved oxygen on our Fe II gel. For this purpose, instead of deionized water, we used degassed, deionized water to preparet he gel. Rheological studies showedt hat the rheological moduli, as well as viscosity,follow similartrends as in the case with normalw ater. Interestingly,f inal values of both G' and G'' of the gel formed with normalw ater are considerably lower than the gel formed with degassed water (FigureS8i nt he Supporting Information). However,n os ignificantc hange in the gel strength (the critical strain) wasobserved. These results point out that the dissolved oxygen has as ubtle effect on the stabilityo fF e II ions and presumably oxidise some Fe II ions into Fe III ions inside the gel medium, resultingi nt he decrease in stiffness of the material (by % 3times).H owever,n os ignificant change in the absorption and emission spectra of the gels were noticed ( Figure S9).
Next, we used NaNO 2 (0.067 m)a sa ni ns itu oxidizing agent and monitored the self-assembly kinetics by time sweep rheology.B ecause the NaNO 2 is am ildo xidant, it causess low conversion of Fe II ions into Fe III .B yt ime sweep rheology,a tt he early stages, as light increasei nt he rate of increase of both G' and G'' was noticed( Figure3a). Interestingly,a fter reaching the maxima, the rheological moduli startedt od ecreasee arlier than the case with no oxidizing agent before the values become almost constanta fter approximately 12 hours. Viscosity data recordedo ver time follows as imilart rend as that of rheology ( Figure S10 in the Supporting Information). Instead of NaNO 2 ,w hen same concentrationo fH 2 O 2 (0.067 m)w as used, which is as tronger oxidant, the self-assembly kinetics behave differently (Figures 3b and S10 in the Supporting Information). In this case, the variation of the rheological moduli was straightforward, in which G' and G'' increasea st he aggregation proceeds and finally reached the plateau after approximately three hours. However,i nb oth cases, formation of Fe III resultedi nasignificant decrease in the stiffness of the final gels, whereas the extent of reductioni nt he values of G' depends on the rate of oxidation of Fe II (Figures 3c, S 11,S 12, and Ta ble S1 in the Supporting Information). While as low oxidation of Fe II by NaNO 2 causes approximately four times reduction in G',f ast oxidation involving H 2 O 2 resulted in at enfoldd ecrease in the stiffness of the gel compared to the pristine Fe II gel. However,i rrespectiveo fr ate of oxidation of Fe II ,t he final Fe III gels showeda pproximately four times increasei ns trength of the materials.
We further increased ther ate of oxidation of Fe II by increasing the concentrationo ft he oxidizing agents.S imilar trends in G',G '',a nd viscosity were monitored when we increasedt he initial concentration of NaNO 2 from 0.067 m to 0.134 m (Figures 3a and S10i nt he Supporting Information). The final values of G' and G'' of the gels concomitantly decreases with an increase in the initial concentrationo fN aNO 2 (Figures 3c,S 11,a nd Ta ble S1 in the SupportingI nformation). Notably, when we increased the concentration of H 2 O 2 (0.134 m), instead of ag el, precipitation occurred ( Figure S12). These resultss uggestt hat the formation of Fe III gel depends significantly on the rate of oxidation of Fe II .I nterestingly,d irect treatment of the mixture of 1 and 2 with Fe III (0.134 m)p roduced precipitation (Figure S12). Correlation of theser esultsi ndicates ac omplex mechanism for the formation of Fe III gels via oxidation processes, in which two phenomena are occurring simultaneously by the formation of the imine 3 and the conversion of Fe II to Fe III . As low conversion to Fe III allows formation of continuous net- work structures involving 3,w hereas fast oxidation drives the system towards kinetically trapped states, in whicht he intermolecular interactions involving Fe III were strong enought o produce precipitation. [12] The visual appearance of the gels also depends on the initial reactionc onditions. Oxidation of Fe II either by NaNO 2 or H 2 O 2 turned the reddish brownF e II gels into deep brown Fe III gels ( Figure S12 in the Supporting Information). However,t hese gels behaved differently by spectroscopy.I nf luorescence, the emission of all Fe III gels was quenched at 550 nm ( Figure S13). In UV/Vis data, all the Fe III gels showeda bsorption in the region 330-360 nm (Figure 3d). Interestingly,t he absorption intensity in this region increased as the formation of Fe III was faster.W hen the rate of oxidation of Fe II was significantly high, particularly with H 2 O 2 ,adistinct peak at 550 nm appeared. A similar spectrala ppearance was also observed for the sol obtained from direct treatment of Fe III with 1 and 2.T hese results suggest that when the rate of oxidation of Fe II is extremely high, almosta ll the Fe II is converted to Fe III very rapidly and the binding interactions follow the similar pattern as in the case with Fe III alone. To get more insight, FTIR studies were conducted with the metallogels prepared under different conditions ( Figure S14 in the Supporting Information). FTIR studies showedt hat irrespective of rate of oxidation, for the Fe III gels (as well as sols), C=Nb ond formation occurs as in all cases with appearance of ab road peak at 1680 cm À1 .T ou nderstand the interactions with Fe III ,w ea ttempted to collect 1 HNMR spectra of the Fe III -containing gels and sols obtained under different conditions. First, we recordedt he 1 HNMR spectrum of 1 and 2 in presenceo fN aNO 2 and H 2 O 2 separately to investigate if oxidation leads to any chemical changes in the systems. From FiguresS15-S17 in the Supporting Information, it is evident that no chemical changes occurto1 and 2 in presence of the oxidizing agents. Similarly,t he presence of NaNO 2 does not alter the compositiono ft he gelf ormed from 1 and 2 (Figure S18). We were unable to record the 1 HNMR spectra of the gels obtained from mixture of Fe II with 1 and 2 in the presence of NaNO 2 .H owever,H RMS experiments showed formation of 3 both in absence and presence of Fe II involving NaNO 2 (Figure S19). For the systems formed from 1 and 2 involving H 2 O 2 , the aromatic protons of 2 became broad both in absence and presence of Fe II ( Figure S20 in the Supporting Information). A similar spectrala ppearance was observed in the sol obtained from direct treatment of the mixture of 1 and 2 with Fe III (Figure S21). Correlation of the results from Figures S16 and S20 shows that H 2 O 2 readily reacts with Fe II (as the peak at 10.48 ppm corresponds to H 2 O 2 disappeared in presence of Fe II )b ut causesn oc hemical changes to 3.H RMSa nalysis also confirms the formation of compound 3 in all cases ( Figures  S22, S23). Furthermore, analysiso f 1 HNMR spectra showedt he presenceo fc hemical analytes (oxidizing agents, metal ions) have no significant effect on conversion of 3 (the percentage conversion of 3 varies between 20-26 %i na ll cases). The slight variations in conversion of 3 is probably due to the fact that during recording of the NMR spectra, as mall amount of hydrolysism ay occur. [8b, 9] Notably,i nt he mixture of 1 and 2, unlike Fe II ,n os hift of the imine proton H a (Figures S20, S21) was observed whether Fe III is used directly or generated in situ by oxidation of Fe II .H ence, formation of 3 occurred in all cases,a nd the interaction of 3 with Fe III is not the only the determining factor for the formation ag el or sol, but instead dependsu pon the assembly of the underlying structures,i n which the rate of formation of Fe III also determines how the Fe salt interacts with the fibres. SEM images of the gels (and sols) clearlyd emonstrate different aggregation depending upon the preparation pathways ( Figure S24 in the SupportingI nformation). [12,13] The resulting Fe III gels showedu nusuals welling behaviour depending on the rate of oxidationo fF e II (Figure 4a). The volumeo ft he Fe II gels increases on conversion to the Fe III ions by NaNO 2 and the degree of swelling is proportionalt ot he initial concentration of NaNO 2 (Figure 4b and c). When 0.067 m of NaNO 2 was used as oxidant, the resulting Fe III gel showed approximately 23 %i ncrease in volumec ompared to the pristine Fe II gel. An increasei nN aNO 2 concentration from 0.067 to 0.134 m caused af urther increase in volume of the gel ( % 38 %). Figure4cs hows the increasei ng el volumewith time under differentr ate of oxidation of Fe II .I nterestingly,w hen H 2 O 2 was used as oxidant, no such swellingw as noticed.
We highlight that swelling of such as upramolecular,l ow molecular weight gel is very unusual. Normally,s uch swelling is limited to cross-linked polymer gels. To determine the reason, polarising optical microscopic (POM)i mages of the gels were recorded, whichs howed the existence of spherical gas bubbles inside the gel medium obtained from NaNO 2 oxidation ( Figure 5). The gas bubbles are formed because of the generation of NO and NO 2 due to the redox reaction, [14] which create internal stressesr esulting swelling. [15] The density of the gas bubbles increases with as the increaseininitial NaNO 2 concentration,w hich governs the amount of volume increase in the Fe III gels. In comparison, no such gas bubbles were observed in the POM images of other metallogels. The ability of the gels towards swelling beforet he destruction was also verified ( Figure S25 in the Supporting Information). For this purpose, we increased the initial concentration of NaNO 2 further. Swelling of the gel occurred up to ac oncentration of 0.134 m of NaNO 2 .A bove this concentration of NaNO 2 ,t he volumeo f the gels increases, but some amount of the gel from the upper surfacew as destroyed and appeared as sol upon inversion of the vials. These observations suggest that the gel network is strong enough to allow swelling until ac ertain point, after which the internal stresses produced by the air bubbles becomes predominant andc auses deformation of the network structures at the upper surface althought he rest of gels remained intact.
In conclusion, we have shown that the pathway dependence is applicable to the redox-driven gels by utilizing aF e II /Fe III redox-based metal-organic gel system.T oe stablish this, we utilize dynamic imine bond formation between an aldehyde (1)a nd an amine (2)a st he key chemical reactiona nd incorporated Fe II ions into the gel mediumd uring the self-assembly process.S ignificantly,d irectp reparation of the Fe III -gel from the mixture of 1, 2 and Fe III ions is not feasible in our case. However,i ns itu oxidation of the Fe II ions by various oxidising agent resultsinc onversion to aFe III -organic gel, where the material properties like gel stiffness, gel strength,swelling etc. can be controlled just by controlling the rate of oxidationo ft he Fe II ions. We established that the rate of formation of Fe III ions actually determines the extent of intermoleculari nteractions whether to produce gels or precipitations. Hence, for the Fe IIImetallogels, which cannot be prepared directly,wec an achieve those gel states in an indirect way by employing ar edox reaction. We envisage that, our approach will open up opportunities to construct new functional redox gels.