Cation exchange at the secondary building units of metal – organic frameworks

Cation exchange is an emerging synthetic route for modifying the secondary building units (SBUs) of metal–organic frameworks (MOFs). This technique has been used extensively to enhance the properties of nanocrystals and molecules, but the extent of its applications for MOFs is still expanding. To harness cation exchange as a rational tool, we need to elucidate its governing factors. Not nearly enough experimental observations exist for drawing these conclusions, so we provide a conceptual framework for approaching this task. We address which SBUs undergo exchange, why certain ions replace others, how the framework influences the process, the role of the solvent, and current applications. Using these guidelines, certain trends emerge from the available data and missing experiments become obvious. If future studies follow this framework, then a more comprehensive body of observations will furnish a deeper understanding of cation exchange and inspire future applications.


Introduction
Cation exchange is a powerful tool for designing new materials. Broadly defined, it is the partial or complete substitution of a metal ion at the site of another. This process offers an alternative, typically milder, route for accessing materials when conventional synthesis at high temperature fails. For decades, it has been employed to tailor the composition of zeolites and, more recently, nanocrystals. Metal-organic frameworks (MOFs) emerged decades ago, but cation exchange was only first demonstrated with them in 2007. 1 In these materials, the exchange occurs at the inorganic clusters, often called the metal nodes or secondary-building units (SBUs). Although these clusters are integral to the MOF structure, the metal ions can be replaced, sometimes entirely and in a matter of hours, without compromising the structure. The details of this fascinating transformation are unknown and the bounty of MOF structures that undergo metal ion substitution present a host of curiosities to be explained.
Geochemists have long known cation exchange as diadochy. 2 Minerals are rarely pure phases because minor amounts of foreign ions of similar charge and size often incorporate into the structure. The replacement of an ion for another at a particular crystalline lattice position is a diadochic transformation, and often requires high temperatures and pressures. For instance, the volcanic rocks known as the olivine series, (Mg 2+ , Fe 2+ )SiO 4 , differ by their relative composition of Mg 2+ or Fe 2+ , which result from diadochic transformations in magma. 3 Meanwhile, the substitution of Na + into porous leucite, KAlSi 2 O 6 , occurs at temperatures as low as 150 1C, illustrating the role of porosity in facilitating the exchange process. 4 V. M. Goldschmidt developed a set of rules to explain the mutual replacement of ions in magmatic minerals. 5 This contends that ions undergo diadochy if they possess similar charge and radii. Ions with greater charge or smaller radii are incorporated to a great degree because they form stronger, more ionic bonds. To account for the covalent components of these bonds, Ringwood's rule states that ions with similar electronegativity replace each other. 6 The ion with the lower value will be exchanged more because it will form bonds with greater ionic character. These trends are useful for assessing the cation exchange behavior of MOFs, though they derive from observations with minerals, which are typically densely packed structures.
Cation exchange is also employed with nanocrystals to finetune their band structures by inserting specific ions into welldefined environments. 7 Unlike in bulk CdSe, Cu 2 S, or similar extended materials, cation exchange in nanocrystals occurs at room temperature at sub-second rates due to enhanced surface area and low atomic counts. The small size of these particles also facilitates atomic reorganization and diminishes lattice strain. This technique enables the synthesis of metastable phases that are not achievable by conventional ''hot injection'' synthesis, such as Cu 2 S particles with turn-on plasmon resonance. 8 Cation exchange also enables complexity to be engineered into a nanocrystal device. For instance, templating CdSe on PbSe nanorods for fixed amounts of time generates CdSe-PbSe core-shell heterostructures so that electron and hole carriers are confined within the lower band-gap PbSe core, resulting in high quantum yield excitonic emission. 9 In solution, metallo-cluster compounds and mononuclear complexes are also known to substitute for other cations. For decades, transmetallation has been used to replace cations in mononuclear compounds featuring multidentate ligands. The mechanism of these exchanges often involves the transfer of a ligand to a new metal ion. 10 Cation substitution at a molecular cluster that left the anionic framework intact was first documented in 1982 for the adamantane-like cage compounds, [M 4Àn , M n 0 , (SC 6 H 5 )] 2À (M, M 0 = Fe 2+ , Co 2+ , Zn 2+ , Cd 2+ ). 11 Metal exchange in these compounds was believed to involve free ions exiting the cage before the inserting species associated. However, mechanistic studies of the simpler case of Co 2+ incorporating into [M 4 (SPh) 10 ] 2À (M = Zn or Fe) revealed a process that was quite complex. 12 Few other reports have attempted to understand cation exchange in molecules, though metallothioneins are thought to mediate detoxification of trace metals through some version of metal ion substitution. 13 This article outlines the available observations of cation exchange at MOF SBUs so that general trends and future studies can be sketched. We organize data around questions that need to be answered to endow this technique with predictive capabilities. All known examples of metal ion substitution at MOF SBUs and relevant details are listed in Table 1 with pictorial representations of the SBUs in Table 2. We also note that we confined our discussion to substitution that occurs at SBUs and not in the pores or when metal ions are part of the ligands, in the so-called metalloligands. More general reviews of cation exchange in MOFs have been published elsewhere. 14,15 Cation exchange has already yielded some surprising results and new materials that have not been accessible otherwise, but the extent of its use for designing new MOFs in a systematic and predictive manner depends on understanding its mechanism. This tutorial review is intended to provide a blueprint towards this goal.

Which SBUs undergo cation exchange?
If we can predict which MOFs are susceptible to cation exchange, it will become a rational tool for synthesizing new materials with intended properties. After elucidating the factors that make an SBU exchangeable, specific materials could be selected for cation exchange from among the thousands of reported MOFs, and their exact compositions could be designed beforehand. These factors are yet unknown, but surveying the reported examples of cation exchange in MOFs reveals several common features among their SBUs.
A foremost observation is that the exchangeable metal ions in an SBU are often capable of higher coordination numbers than  16,17 Similarly, the tetrahedral Zn 2+ sites in ZIF-8 (Zn-(MeIm)) and ZIF-71 (Zn-(Cl 2 Im)) can be replaced by Mn 2+ ions, 18 while the four-coordinate Zn 2+ sites in MFU-4l (ZnZn 4 Cl 4 (BTDD 6 )) can be replaced by Co 2+ ions. 19 Table 2 The known examples of MOF SBUs that undergo cation exchange. Black, green, red, blue, and grey spheres denote metal, chloride, oxygen, nitrogen, and carbon atoms, respectively In several examples, the exchangeable metal ions contain open sites when fully evacuated, but become partially solvated when immersed in solution. The family of MOFs known as MM-BTT, M 3 [(M 4 Cl) 3 BTT 8 ] 2 , begin with a two-coordinate C s -symmetric Mn 2+ site and five-coordinate Mn 2+ site with C 4v symmetry. 20 When in methanol, the latter gains a solvent ligand to become six-coordinate, while the former becomes fully solvated in the cavities of the structure. Either the fully solvated or both Mn 2+ sites exchange for Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , or Zn 2+ . 1 An isostructural material known as Cd 3 [(Cd 4 Cl) 3 BTT 8 ] 2 contains Cd 2+ that demonstrates similar coordinative changes upon solvation and replaces for Co 2+ or Ni 2+ . 21 Not all structures can be desolvated as MM-BTT, but the metal sites in many other SBUs typically feature bound solvent molecules. x = 2, y = 0, z = 8.5, n = 8; x = 2, y = 1, z = 7, n = 8) contains a cobalt site with a bound solvent molecule and all three Co 2+ sites exchange to form an entirely new structure. 28 In another case of partial solvation, the exchangeable di-zinc sites in NTU-101-Zn 29 [Zn 2 (TADYDI)(DMF) 3 ] n and {[Zn 2 (BDCPPI)(DMF) 3 ]Á7DMFÁ5H 2 O} n contain a Zn 2+ ion held to the framework by only three bonds, with its remaining coordination sphere filled by three solvent molecules. 30 2+ ion is present in the asymmetric unit. 33 Consistent with the generally small degree of exchange for more highly coordinated ions, Cd 2+ centers in this structure exchange with Cu 2+ , Co 2+ , Ni 2+ , and Zn 2+ , but only to a small degree. Finally, the MOFs known as UiO-66 34 (Zr 6 O 4 (OH) 4 (BDC) 12 ) and MIL-53(Al)-Br 34 (Al(OH)(BDC-Br)) also contain SBUs with metals bound to the framework in high coordination and do not exchange for other ions completely. Given that Zr 4+ and Al 3+ form some of the strongest metal-oxygen bonds among the metals incorporated into MOFs, it is remarkable that they undergo any extent of cation exchange.
Metal sites that are coordinately saturated by the framework and undergo complete cation exchange might do so because their weak field ligands dissociate readily. A ligand field analysis of Ni-MOF-5 indicates that the MOF-5 framework is a stronger ligand than halides, but is significantly weaker than coordinating solvents such as DMSO or DMF. Considering that in MOF-5 the ligand field is weak despite the presence of an O 2À in the coordination sphere, this study suggests that SBUs comprised of only carboxylates form weak bonds with late transition metal ions. For example, the metal sites in both Na 0. 25  Taken together, these observations begin to reveal the factors that enable cation exchange at certain SBUs. The pervasiveness of partially solvated SBUs among these examples and the coordination changes that MM-BTT undergoes upon solvation call into question whether the metal sites in MOF-5, ZIF-8, and MFU-4l are indeed unsaturated when surrounded by a solvent. If geometric flexibility and the ability of metal sites to interact with the solvent are requisites for cation exchange, then we can begin to sketch a mechanism for this process (see Scheme 1). Perhaps the metal ion does not readily leave the cluster as a dissociated cation. Instead, solvent molecules might associate step-wise to the exiting metal ion as it remains partially bound to the cluster. Furthermore, since cation exchange occurs in ''paddlewheel'' structures with either a solvent or 4,4 0 -bipyridine at the axial position of the metal site, the clusters must be flexible enough to accommodate the inserting metal ions or, alternatively, the carboxylates and 4,4 0 -bipyridine must readily dissociate without compromising the framework. Alternatively, we may construct a model where the MOF ligands dynamically dissociate from metal sites in the presence of coordinating solvents and thereby enable cation exchange. The ability of coordinatively saturated metal sites to exchange when surrounded by weak field carboxylates, but not bridging O 2À ligands, suggests that cation exchange might become a predictable tool by quantifying the interaction of the SBU with the metal ions. If future studies measured the ligand field strength of the exchangeable SBUs, then general trends might emerge and aid our understanding of the cation exchange process. This might be achieved by UV-vis spectroscopy, for instance, in a manner analogous to classic solution studies of homoleptic complexes. 43

Which ions exchange into SBUs?
To program physical properties into a SBU through cation exchange, we must be able to predict whether a particular cation will replace another and to what extent. By controlling the initial concentration of the inserting cation solution, the thermodynamic equilibria of the exchange processes could be controlled to furnish heterometallic SBUs for specific catalytic applications. Clusters with unusual magnetic and electronic properties could be assembled through judicious cation exchange that might be otherwise impossible through direct synthesis. Attaining this depth of understanding can be achieved by comparing how a wide variety of cations replace SBUs in a particular MOF structure. Unfortunately, few studies report the results of more than one exchange and almost none report unsuccessful attempts, which in the context of mechanistic investigations can be equally informative.
Most examples of cation exchange at SBUs involve Cu 2+ replacing Zn 2+ or Cd 2+ . The Zn 2+ ions in porph@MOM-11-Zn, PCN-921, NTU-101-Zn, and PMOF-2 are known to undergo a high degree of substitution for Cu 2+ , with no reported attempts to exchange with other ions. 22,23,29,36 Similarly, the Cd 2+ ions in {[Cd 2 (BTX) 2 (BDC) 2 ]H 2 O} n and [Cd(BTX) 2 Cl 2 ] n can be totally replaced by Cu 2+ , but their exchange with other ions is unknown. 39 In the isostructural variants of {[M 2 (BDCPPI)(DMF) 3 ]Á7DMFÁ5H 2 O} n (M = Cd 2+ or Zn 2+ ) both Cd 2+ and Zn 2+ are fully replaced by Cu 2+ . 30 The Zn 2+ ions in Zn-HKUST-1 22 and Zn 2+ or Cd 2+ ion in {[M(BP) 2 (FcphSO 3 )]Á(CH 3 OH) 4 } n (M = Zn 2+ or Cd 2+ ) both exchange for Cu 2+ , 40,41 though not to completion. These reports do not always test whether the cation exchange is reversible, but the reversibility of a process lends insight into the relative thermodynamic stability of the exchanged variants. We do know, however, that reversible Zn 2+ exchange into NTU-101-Cu 29 or Cu-PMOF-2 22 is impossible, while Zn 2+ can partially replace Cu 2+ in the framework of porph@MOM-11-Cu, but not at the porphyrin metalloligand. 36 When information is available for Cu 2+ as well as other transition metals exchanging in the same host structure, Cu 2+ typically inserts to the greatest extent and is the least reversible. In {[Zn 2 (BDCPPI)(DMF) 3 ]Á7DMFÁ5H 2 O} n , 97% of the Zn 2+ sites are exchangeable for Cu 2+ , but none can be replaced by Ni 2+ , Co 2+ , or Cd 2+ . 30 31 In a related system, Pb 2+ replaces 75% of the Zn 2+ sites of [Zn(4,4 0 -BP) 2 -(FcphSO 3 ) 2 ] n , whereas Cu 2+ replaces just 50%. 40 Although little rigorous work has been done to interrogate the kinetics of cation exchange in MOFs, the present studies indicate that the rate of substitution into a particular SBU depends on the identity of the metal ions. For MOF-5, Ni 2+ requires up to a year to replace 25% of the original Zn 2+ sites, whereas Cr 2+ and Fe 2+ reach that extent in a week. Furthermore, the exchange with Mn 2+ is so rapid at room temperature that the process destroys the crystals and only proceeds in a controlled fashion when conducted at À35 1C. 17 Though the resulting materials are isostructural, Cu 2+ fully exchanges Zn 6 (BTB) 4 (BP) 3 in 2 days, Co 6 (BTB) 4 (BP) 3 in 1 day, and Ni 6 (BTB) 4 (BP) 3 in 15 days. 38 Pb 2+ replaces Cd 2+ in 7 days for Cd 1.5 8 ]Á6H 2 O, yet Co 2+ , Ni 2+ , and Cu 2+ require 12 days to replace Mn 2+ in a similar structure. 25 The dominance of Cu 2+ among these examples and the preference for Cd 2+ and Pb 2+ over Cu 2+ might be explained by differences in electronegativity. Calculations suggest that Pb 2+ has the lowest electronegativity among the cations that undergo exchange, followed by Mn 2+ and Cd 2+ . Cu 2+ , on the other hand, has the highest electronegativity. 46 Perhaps Pb 2+ , Mn 2+ , and Cd 2+ ions form labile ionic bonds, allowing them to perform cation exchange faster. This kinetic argument might explain why Pb 2+ and Cd 2+ exchange more sites than Cu 2+ in {[Zn(OOCClH 3 C 6 Fc) 2 (H 2 O) 3 ]-(H 2 O)} n (ref. 31) and why Mn 2+ replaces more sites than Cu 2+ in porph@MOM-10-Cd. 32 If these experiments were allowed to go on longer, Cu 2+ might have been exchanged completely. The high electronegativity of Cu 2+ would enable it to form bonds that are more covalent and thermodynamically stable. A greater thermodynamic driving force would be consistent with the irreversibility and high degree of substitution of Cu 2+ exchanges. This trend in electronegativity is also consistent with cation preference following the Irving-Williams series, 47 since labile Mn 2+ species and thermodynamically stable Cu 2+ bonds constitute either end of the series.

(H 3 O) 3 [(Cd 4 O) 3 (HMTT)
Even with the general trends exposed above, we cannot yet predict whether a particular cation will replace another and to what extent. In the absence of more experimental and empirical evidence, quantum chemical calculations could prove useful in predicting which cations form more thermodynamically stable complexes in a given SBU. With the computed energy values, thermodynamic equilibria could be manipulated to engineer SBUs with certain mixed-metal compositions. The mechanism of cation exchange, on the other hand, will need to be studied on a case-bycase basis. With a more detailed understanding of how the process depends on the identity of the cation, one might control the kinetics and harness cation exchange as a synthetic tool.

How does the framework influence the exchange?
To rationalize how cation exchange occurs at SBUs, one must remember that SBUs are embedded in the lattice of a MOF. Although they often resemble molecular clusters, they do not possess the degrees of freedom of molecules in solution. Thus, the lattice limits the geometrical distortions available to an SBU. We must also understand that the cation exchange process must occur in the MOF pores. The process is therefore likely influenced by diffusion and pore size effects. We do not know how these intrinsic features of MOFs impact cation exchange, but any mechanistic understanding must account for them. The scant observations already suggest the MOF lattice impacts the cation exchange and vice versa.
An important evidence for this co-dependency is that certain cation exchanges can compromise the structural integrity of a framework. For instance, after Cu 2+ replaces the Zn 2+ 42 the resulting crystals are known to crack. As mentioned above, especially fast exchanges into MOF-5, such as Mn 2+ , also cause deterioration of the crystals, which is evidenced both optically and especially through surface area measurements. For example, synthesizing Fe-MOF-5 using a solution of anhydrous FeCl 2 is rapid and leads to inferior quality powder, whereas the exchange from Fe(BF 4 ) 2 ÁxH 2 O is slow and gives a superior material. 17 Among the cations that substitute into MOF-5, Ni 2+ is the slowest and has the highest apparent surface area. Similarly, after Co 2+ replaces Cd 2+ in MMPF-5(Cd), the surface area decreases, possibly due to collapsed pores. 48 Observations suggest that the framework itself limits the extent of cation exchange. The replacement of Zn 2+ by Co 2+ in Zn 6 (BTB) 4 (BP) 3 occurs initially at the exterior of the crystals and replaces the interior sites after approximately a day. The authors contend that this time dependence is the result of the lattice being more flexible at the exterior, not of diffusion limitations in the framework pores. 38 When rationalizing why Cu 2+ exchanges 53% of the Zn 2+ sites in Zn-HKUST-1 but all sites in PMOF-2, the authors invoked a similar argument: the longer linkers in PMOF-2 endow the lattice with greater flexibility, even though its SBUs are the same as in Zn-HKUST-1. 22 Perhaps this reasoning might explain why the extent of cation exchange in Zn(4,4 0 -BP) 2 -(FcphSO 3 ) 2 is lower for a powder material than for single crystals. 40 Larger particles might better accommodate distortions and defects introduced by the exchange process than a small one. In perhaps the most surprising case of homogeneous exchange limited by a MOF lattice, the substitution of cations in the SBU of MOF-5 is almost universally capped at 25% (i.e. only one Zn 2+ ion in every Zn 4 O cluster). In fact, it may be surprising that the MOF-5 lattice, which has seemingly saturated pseudo-tetrahedral Zn 2+ ions, enables cation exchange at all. Attempting to substitute Ni 2+ into basic zinc acetate, a molecular analogue of the MOF-5 SBUs, is not possible with retention of the cluster geometry. 16 Perhaps the M-MOF-74 class of materials do not undergo cation exchange because any distortion to the [-M 2+ -O 2À -M 2+ -] N SBUs would require a large activation energy imposed by the lattice.
Predicting how a MOF framework influences the cation exchange process will become a general tool by first proceeding on a case-by-case basis. Still, knowing how a lattice inhibits or enables substitution at a SBU would allow us to design the composition of a material with greater precision.
What role does the solvent play in cation exchange?
Solvents differ along a wide variety of parameters that might be relevant to the mechanism of cation exchange at SBUs. The dielectric constant of solvent, HOMO level, molecular size, or ligand field strength might dictate how substitution occurs. When we develop a deeper understanding of this process, careful selection of the solvent might become a powerful handle for studying the rate and extent of cation exchange. Studies on the effect of employing different solvents are rarest for cation exchange in MOFs, but the available observations are still useful.
{[Zn 2 (BDCPPI)(DMF) 3 ]Á7DMFÁ5H 2 O} n is the only exchangeable material to be tested against several solvents. Though perhaps expected because of intra-pore diffusion limitations, the results suggest that the size of the solvation sphere impacts the rate of substitution. While the exchange is fast in methanol, it is slow in acetone and does not occur in larger solvents such as DMF or 1-pentanol. 30 However, solvents appear to play a mechanistic role aside from shuttling solvated cations through pores. Given that most SBUs feature coordinatively unsaturated metal sites or solvent ligands, it is significant that all exchanges involve coordinating solvents. Most use methanol, DMF, or H 2 O -all of which are strongly donating ligands with relatively high ligand field strengths. The Cu 2+ substitution into Zn-HKUST-1 occurs more slowly in DMF than in the stronger field ligand methanol. 22 Perhaps the Co 2+ exchange into MMPF-5(Cd) does not go to completion because the weak field solvent, DMSO, is used. 48 Based on the ligand field analysis of Ni-MOF-5, 16 the lattice is a far weaker ligand than solvents used for cation exchange. If solvents act as ligands during the exchange mechanism, then they might associate with SBUs and weaken the bonds between the exiting metal ion and the framework. They might also stabilize reactive intermediates or dictate the rate at which the inserting metal ion desolvates and subsequently enters the SBU.
Systematic studies will be needed to elucidate how solvents influence the mechanistic details. Future reports should attempt their synthesis procedures with multiple solvents and plot the extent of exchange versus relevant solvent parameters. Finding a single parameter that correlates well with exchange rate would shed light on the crucial steps of the exchange process. For an example, if substitution rate in a particular MOF correlates with the dielectric constant, then perhaps the role of the solvent is to stabilize an intermediate with a large dipole moment. Each system will need to be studied individually, but with many thorough solvent investigations we could learn about the cation exchange mechanism in general.

Applications
As a research direction, cation exchange at MOF SBUs is still in its infancy, but the exchange process already has applications that are impossible to achieve through conventional synthetic routes. Most of the materials covered in this review can only be made through cation exchange. Isolating Ni-MOF-5 is possible by solvothermal synthesis, but all other variants in the  only by cation exchange, the partially exchanged Co 2+ derivative exhibited an unprecedented initial enthalpy of adsorption, DH, of 10.5 kJ mol À1 . Calculations suggest that ZnZn-BTT should exhibit the largest enthalpy of adsorption. Although only a partially substituted Zn analogue has been reported, the all-Zn material may be accessible through cation exchange. 51 Soaking POST-65(Mn) in a solution of Fe 2+ , Co 2+ , Ni 2+ , or Cu 2+ leads to isostructural analogues with enhanced H 2 uptake when measured in mol mol À1 . Most variants show greater DH than the initial 5.21 kJ mol À1 of POST-65(Mn), with POST-65(Fe) displaying a DH of 6.60 kJ mol À1 . Each variant also displays distinct magnetic properties, with the Co 2+ , Ni 2+ , and Cu 2+ materials showing antiferromagnetic coupling while the Fe 2+ version exhibits ferromagnetic coupling. 26 The Zn 2+ -variants of HKUST-1 and PMOF-2 do not show appreciable gas uptake since they are not stable to complete desolvation. The Cu 2+ analogue of HKUST-1 is, on the other hand, stable to desolvation, and greater amounts of Cu 2+ substitution into the Zn 2+ parent material lead to significant N 2 uptake indicative of greater porosity and stability. 22 Similarly, the ability of M 6 (BTB) 4 (BP) 3 (M = Co 2+ , Ni 2+ , or Zn 2+ ) to adsorb N 2 can be tailored by altering the ratio of any two of these cations in the structure. 38 Finally, while NTU-101-Zn exhibits a BET surface area of just 37 m 2 g À1 , the Cu 2+ variant adsorbs significant amounts of H 2 , CO 2 , and N 2 to give a BET value of 2017 m 2 g À1 . 29 The most exciting potential application of cation exchange lies in the area of small molecule reactivity and catalysis, yet catalysis at SBUs altered through cation exchange is only just emerging. Even in these examples, most reports focus on simply demonstrating reactivity or catalysis; it is unfortunately not yet common practice to show how the new SBUs compare with the state-of-the-art (heterogeneous) catalysts for a given transformation. For instance, after replacing the Cd 2+ ions in porph@MOM-10-Cd with Mn 2+ or Cu 2+ , the MOFs are capable of catalysing the oxidation of trans-stilbene to stilbene oxide and benzaldehyde in the presence of tert-butyl hydroperoxide. 32 Here, the conversion and turnover number compare well to molecular Mn 3+ TMPyP under similar conditions. The Cu 2+ , Zn 2+ , and Co 2+ variants of the helical framework known as Cu 8 (BIM) 16 catalyse the self-coupling of 2,6-di-tert-butylphenol under ambient conditions to afford 3,3 0 ,5,5 0 -tetra-tert-butyl-4,4 0 -diphenoquinone. 44 After replacing the four exterior Zn 2+ sites in the SBU of MFU-4l with Co 2+ , Co-MFU-4l becomes catalytically active in oxidizing CO to CO 2 .
Cation exchange builds a fundamentally new platform for reactivity studies because the resultant metal clusters of SBUs are often unusual coordination motifs that are difficult or impossible to achieve as solution-phase molecules. For example, no molecule is known to stabilize Ni 2+ or Co 2+ in the twocoordinate environment conferred by MM-BTT. The metal species in the (Cl)M-MOF-5 family are without a precedent in both materials and molecules because of the unusual alloxygen, dianionic, and tripodal ligand field in the MOF-5 SBU. These sites are some of the few examples of divalent metal ions in three-fold symmetric tetradentate environments. A ligand field analysis of Ni-MOF-5 indicates that MOF-5 is by far the strongest ligand to stabilize Ni 2+ in a pseudo-tetrahedral geometry, which is remarkable because ligand fields of similar strength coerce Ni 2+ to assume a square planar configuration. Preliminary studies demonstrate that these unusual species perform small molecule activation without compromising the integrity of the lattice. The Fe 2+ centers in Fe-MOF-5 react with NO to generate an unusual ferric nitrosyl, which is the only example of electron transfer to NO in a MOF and the only example of a ferric nitrosyl in an all-oxygen environment.
Viewing the cation exchanged SBUs as molecular entities will be a useful perspective for conceiving new applications in reactivity and catalysis. Reimagining SBUs as coordination pockets for various transition metal ions constructs an entirely new platform for coordination and redox chemistry. SBUs will act as superior catalysts only by treating them as an unusual ligand environment. This viewpoint inspired the use of open coordination and open shell metal ions to enhance H 2 uptake. Novel porous magnets might result from installing particular metal ions into desirable molecular entities. Only a few reports have investigated the applications of cation exchange, but the ability to insert reactive metal ions into specific geometries should enable chemistry that is otherwise impossible to achieve.

Outlook
Being able to substitute specific metal ions into predefined environments is a level of control uncommon to solid state synthetic chemistry. Cation exchange into the SBUs of MOFs is already unlocking materials with unprecedented properties that cannot be achieved otherwise. However, harnessing this process as a predictive synthetic tool will require understanding its mechanistic details. The available experimental observations are insufficient to draw meaningful conclusions about how the process transpires in even a particular material. Future studies, including those we proposed here, will uncover trends that will make this technique predictive. We recommend that if a MOF appears active for cation exchange, then the substitution should be attempted for a variety of metal species and solvents to tease out trends. The rate and extent of exchange under these different conditions could be compared against various chemical properties of the metal ions and solvents to find parameters that are most relevant to the mechanism. Future studies should also report exchange conditions that did not work along with those that did. Such detailed, seemingly obscure, observations might prove critical in uncovering a deeper understanding of cation exchange.
Discovering how SBUs undergo cation exchange will teach us about MOF chemistry and dynamics in general. For example, if coordinating solvents enable the exchange process by binding to metal sites in SBUs, perhaps this will reveal that MOFs dynamically interact with solvents and are not as rigid as commonly assumed or as portrayed by X-ray crystal structures. Elucidating these sorts of fundamentals about MOFs will have profound consequences for any of their applications. Understanding how the lattice flexibility or the symmetry of the SBU