Open versus Interpenetrated: Switchable Supramolecular Trajectories in Mechanosynthesis of a Halogen-Bonded Borromean Network

Abstract

•Three-component halogen-bonded ionic co-crystals•Solvent-free mechanosynthesis of Borromean-type network via ball milling•Polymorph selection through ball milling of multi-component co-crystals•Real-time in situ monitoring of the complex supramolecular reaction trajectories Complex topologies in co-crystals are attracting the attention of the scientific community due to their often unique properties. However, the design, preparation, and control over the self-assembly process of these systems remain a challenging task. Here, we demonstrate a facile, solvent-free strategy to control the supramolecular trajectory of the self-assembly of a three-component crystalline adduct via mechanosynthesis; i.e., ball milling. Through modification of milling conditions, e.g., by choosing the number and size of milling balls, it is possible to switch topological selectivity between a non-interpenetrated and Borromean-type entanglement. These results pave the way for the controlled solvent-free synthesis of novel materials with complex topologies and unexplored functionalities. Precise control over topologically intricate molecular architectures remains an open challenge for chemists due to their inherent structural complexity. We report a simple solvent-free strategy to selectively prepare two multi-component supramolecular crystalline systems based on the halogen bond, endowed with either an unknot topology or a Borromean-type entanglement. Real-time in situ monitoring of the solvent-free mechanochemical synthesis of these three-component halogen-bonded ionic co-crystals reveals that the choice of milling conditions leads to a switch in the supramolecular reaction trajectory, resulting in the selective formation of an open halogen-bonded network or a halogen-bonded Borromean-type assembly. Precise control over topologically intricate molecular architectures remains an open challenge for chemists due to their inherent structural complexity. We report a simple solvent-free strategy to selectively prepare two multi-component supramolecular crystalline systems based on the halogen bond, endowed with either an unknot topology or a Borromean-type entanglement. Real-time in situ monitoring of the solvent-free mechanochemical synthesis of these three-component halogen-bonded ionic co-crystals reveals that the choice of milling conditions leads to a switch in the supramolecular reaction trajectory, resulting in the selective formation of an open halogen-bonded network or a halogen-bonded Borromean-type assembly. Mechanochemistry by ball milling has emerged as a versatile, unique, and general approach to conduct chemical and materials syntheses in the absence of solvents. 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Sci. 2017; 8: 1801-1810Crossref PubMed Google Scholar (1) formed between potassium iodide (KI), 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane (crypt-222), and 1,8-diiodohexadecafluorooctane (DIPFO) in a respective 1:1:1.5 molar ratio, we demonstrate how minor changes in mechanochemical conditions can lead to selective formation of topologically different supramolecular architectures.26Kim T. Singh N. Oh J. Kim E.H. Jung J. Kim H. Chi K.W. Selective synthesis of molecular Borromean rings: engineering of supramolecular topology via coordination-driven self-assembly.J. Am. Chem. Soc. 2016; 138: 8368-8371Crossref PubMed Scopus (81) Google Scholar Previously, some of us have shown that slow evaporation of an ethanol solution of KI, crypt-222, and DIPFO at room temperature yields 1, based on a triply interwoven BR-topology net of halogen-bonded anionic frameworks, with complex K+⊂crypt-222 counterions (Figure 1). Each of the interwoven anionic frameworks exhibits a hexagonal (6,3) honeycomb (hcb) topology, based on DIPFO molecules as bidentate telechelic halogen-bond donors and I- ions as tridentate halogen-bond acceptors. By screening different crystallization conditions in the attempt to find new polymorphs of 1 with different structural topologies, we discovered that slow evaporation of a saturated MeOH solution afforded a previously unreported crystalline phase (2), as indicated by powder X-ray diffraction (PXRD), see Section S6. Single-crystal X-ray structural analysis revealed that 2 is a polymorph of 1, based on non-interpenetrated halogen-bonded (6,3) rectangular nets, as shown in Figure 1 and Section S4. The two polymorphs also possess different crystalline habits with 1 crystallizing in hexagonal plate-like crystals25Kumar V. Pilati T. Terraneo G. Meyer F. Metrangolo P. Resnati G. Halogen bonded Borromean networks by design: topology invariance and metric tuning in a library of multi-component systems.Chem. Sci. 2017; 8: 1801-1810Crossref PubMed Google Scholar and 2 forming needle-like crystals with preferential growth direction along the a axis, as confirmed by BFDH (Bravais, Friedel, Donnay, and Harker) crystal morphology predictions (see Figures S7 and S8). An investigation by differential scanning calorimetry (DSC) and hot-stage polarized optical microscopy (POM) strongly suggested that 2 is a kinetic polymorph, metastable to 1 (Figure 2, Experimental Procedures). Specifically, heating of 2 led to a monotropic transition to form 1, mediated by a melt phase. The formation of the BR-topology phase 1 was additionally confirmed in POM studies by the appearance of hexagonal crystals typical of co-crystals based on Borromean network topologies (Figure 3A) and by PXRD analysis performed on the powders of 2, after heating above the transition temperature (ca. 120°C), as shown in Figure S13. Importantly, the BR-topology interpenetrated structure 1 could be readily discriminated from the non-interpenetrated 2 by infrared (IR) spectroscopy, with the most important differences arising in the νC-H stretching region of crypt-222 around 2,800–2,900 cm−1 and in the νC-F regions of DIPFO around 600–700 and 1,000–1,200 cm−1 (see Section S5).Figure 3Real-Time In Situ Monitoring of the Reaction of KI, DIPFO, and Crypt-222 by Milling with Two Stainless Steel Balls (1.38 g)Show full caption(A and B) 2D PXRD plot of the in situ monitoring (A) and its sequential Rietveld analysis (B) with KI (black), the intermediate (DIPFO)(crypt-222) (red), and the final open hcb-framework product 2 (blue). Selected Bragg peaks assigned to 3 are marked by blue arrows in (A). Intermediate 3 was not included in Rietveld analysis, as its structure is not known. The error bars represent the standard deviation for the weight fractions determined from least-squares refinement of scale factors (of the known crystalline phases present) using Rietveld analysis.View Large Image Figure ViewerDownload Hi-res image Download (PPT) (A and B) 2D PXRD plot of the in situ monitoring (A) and its sequential Rietveld analysis (B) with KI (black), the intermediate (DIPFO)(crypt-222) (red), and the final open hcb-framework product 2 (blue). Selected Bragg peaks assigned to 3 are marked by blue arrows in (A). Intermediate 3 was not included in Rietveld analysis, as its structure is not known. The error bars represent the standard deviation for the weight fractions determined from least-squares refinement of scale factors (of the known crystalline phases present) using Rietveld analysis. 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Since the crystal structure of DIPFO is unknown, calculations on formation energies were not performed. The calculations revealed that the non-interpenetrated phase 2 is 8.02 kJ mol−1 higher in energy than the Borromean structure 1. Intrigued by these results, we explored the reactivity of the three starting components via a solvent-free approach, namely mechanosynthesis, to explore the possible outputs of the self-assembly process. Milling of KI, crypt-222, and DIPFO in the 1:1:1.5 stoichiometric ratio did not yield the Borromean structure 1, but the non-interpenetrated network 2. Real-time in situ monitoring using synchrotron PXRD revealed that mechanochemical formation of 2 proceeds via two crystalline intermediates (Figure 3).30Halasz I. Kimber S.A.J. Beldon P.J. Belenguer A.M. Adams F. Honkimäki V. Nightingale R.C. Dinnebier R.E. Friščić T. In situ and real-time monitoring of mechanochemical milling reactions using synchrotron X-ray diffraction.Nat. 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We have not yet been able to establish the crystal structure of 3, which is characterized by Bragg reflections at 1.30°, 2.13°, 2.30°, and 2.35° 2θ, for the wavelength λ = 0.207 Å (see Supplemental Information). However, since 3 was also observed when milling DIPFO and crypt-222, it may be inferred that 3 is a possible polymorph of (DIPFO)(crypt-222). The diffraction signals of the final product 2 appear after ca. 45 min of milling, accompanied by the disappearance of Bragg reflections of reactant KI. The appearance of the binary (DIPFO)(crypt-222) co-crystal as an intermediate in the mechanochemical formation of 2 is surprising, as it suggests that in the first minute of ball milling, the C–I···N halogen bonding prevails over the other possible supramolecular motifs (e.g., K+ endo coordination by crypt-222 and the formation of C–I···I− halogen bonds), which drive the co-crystallization to form halogen-bonded BR networks in solution. Indeed, in situ monitoring of the mechanochemical reactions of binary mixtures of DIPFO and crypt-222, as well as of KI and crypt-222, reveal the rapid formation of the (DIPFO)(crypt-222) co-crystal in the first case and the formation of the crystalline [K+⊂(crypt-222)]I− cryptate, only after an induction time of ca. 40 min milling, in the second case (see Section S3). The herein observed reaction sequence, involving the preferential formation of (DIPFO)(crypt-222) binary co-crystal, followed by the reaction with KI to form a three-component system, is probably related to two concomitant kinetic effects. Ball milling is known to lead to mild frictional heating,33Boldyreva E. Mechanochemistry of inorganic and organic systems: what is similar, what is different?.Chem. Soc. Rev. 2013; 42: 7719-7738Crossref PubMed Scopus (369) Google Scholar,34Užarević K. Ferdelji N. Mrla T. Julien P.A. Halasz B. Friščić T. Halasz I. Enthalpy vs. friction: heat flow modelling of unexpected temperature profiles in mechanochemistry of metal–organic frameworks.Chem. Sci. 2018; 9: 2525-2532Crossref PubMed Google Scholar which can improve the reactivity of soft and low-melting molecular solids, such as crypt-222 (Tm = 68°C–71°C) and DIPFO (Tm = 73°C–77°C). On the other hand, the reactant KI is an ionic solid held together by strong electrostatic forces, whose mechanochemical reactivity is expected to be significantly lower in comparison. This may be explained by the fact that the organic components are likely softer and with lower lattice energies and, hence, are initially more mobile. Next, we explored the mechanochemical reaction of KI, DIPFO, and crypt-222 at a similar reaction set-up using only one stainless steel milling ball of 2.9-g weight instead of two 1.38-g milling balls. Such a change in the choice of milling media effectively introduced only a minor (12%) change in the ratio of milling media-to-sample weights, from 17 to 19. Monitoring of the reaction under these conditions again revealed the initial formation of the (DIPFO)(222-crypt) phase, but this time followed by the immediate, direct formation of the BR-topology target 1 after ca. 25-min milling (Figure 4). After 150 min, the reaction mixture exhibited only diffraction signals of 1. We further investigated milling of as-synthesized 2 in the presence of larger balls, attempting to convert 2 into the Borromean 1 framework, as observed by high-temperature experiments. However, no conversion of 2 into the Borromean 1 structure using mechanochemical activation was observed. Importantly, in an attempt to demonstrate that our results are general, we also obtained the interpenetrated Borromean framework product starting from yet another inorganic salt, i.e., NaI. In fact, milling of NaI, crypt-222, and DIPFO in a 1:1:1.5 stoichiometric ratio yielded a very clean transformation into the Borromean structure,25Kumar V. Pilati T. Terraneo G. Meyer F. Metrangolo P. Resnati G. Halogen bonded Borromean networks by design: topology invariance and metric tuning in a library of multi-component systems.Chem. Sci. 2017; 8: 1801-1810Crossref PubMed Google Scholar as demonstrated by PXRD (see Figure S14). We plan to adopt the same strategy to the obtainment of a full library of halogen-bonded three-component Borromean networks,25Kumar V. Pilati T. Terraneo G. Meyer F. Metrangolo P. Resnati G. Halogen bonded Borromean networks by design: topology invariance and metric tuning in a library of multi-component systems.Chem. Sci. 2017; 8: 1801-1810Crossref PubMed Google Scholar where varying milling conditions and following the reactions by in situ monitoring will allow for a deeper understanding of the mechanism behind the solid-state formation of such complex topologies. The observed difference in reactivity between milder and harsher milling conditions is striking: simple switching of milling media resulted in a change of the reaction mechanism, as well as in switching between an open network and an interpenetrated Borromean framework product. A subtle change from one to two milling balls, involving a minor change in the overall weight of milling media, resulted in a change of the supramolecular solid-state reaction trajectory from a multi-step reaction that yields an open halogen-bonded framework to one that forms a densely packed Borromean ring network. While the open framework 2 can readily be transformed into the interpenetrated Borromean structure 1 upon heating, this transformation has so far not been observed upon grinding, i.e., by mechanical activation. While it still remains unclear why milling with different choices of milling media leads to the formation of topologically different frameworks, in situ observation shows that mechanosynthesis of 1 proceeds via one, whereas the appearance of 2 involves at least two intermediates. We speculate that switching between 1 and 2 as a result of synthesis under different milling conditions might be due to a harsher environment producing a thermal effect that makes the pathway to the thermodynamically less stable 2 unlikely, possibly by preventing the formation of the second intermediate 3 or assisting in reducing the activation energy barrier for the direct formation of 1. In conclusion, this study represents a totally new strategy for creating complex multi-component supramolecular topologies and understanding their interconversion. Furthermore, our results highlight the sensitivity of the mechanochemical process to subtle changes in the milling conditions and the tremendous effect that these minor changes have on the reaction kinetics and trajectories. This evidences the paramount importance of the fundamental parameters of the mechanochemical process (e.g., milling media, jar volume and material, milling frequency, and milling time) in gaining control over solid-state reactivity and polymorph selection.35Julien P.A. Malvestiti I. Friščić T. The effect of milling frequency on a mechanochemical organic reaction monitored by in situ Raman spectroscopy.Beilstein J. Org. Chem. 2017; 13: 2160-2168Crossref PubMed Scopus (35) Google Scholar In the present study, the unprecedented control over the supramolecular synthetic pathway of a complex multi-component system is a striking example of the manifold possibilities of mechanochemistry in obtaining complex molecular topologies and in targeting specific crystalline forms. We expect that this simple, sustainable, and inexpensive processing will enable the discovery of new materials, phenomena, properties, and applications.