Metallic–Organic Cages (MOCs) with Heterometallic Character: Flexibility-Enhancing MOFs

Abstract

The dichotomy between metal–organic frameworks (MOFs) and metal–organic cages (MOCs) opens up the research spectrum of two fields which, despite having similarities, both have their advantages and disadvantages. Due to the fact that they have cavities inside, they also have applicability in the porosity sector. Bloch and coworkers within this evolution from MOFs to MOCs manage to describe a MOC with a structure of Cu₂ paddlewheel Cu₄L₄ (L = bis(pyrazolyl)methane) with high precision thanks to crystallographic analyses of X-ray diffraction and also SEM-EDX. Then, also at the same level of concreteness, they were able to find the self-assembly of Pd(II)Cl₂ moieties on the available nitrogen donor atoms leading to a [Cu₄(L(PdCl₂))₄] structure. Here, calculations of the DFT density functional allow us to reach an unusual precision given the magnitude and structural complexity, explaining how a pyrazole ring of each bis(pyprazolyl)methane ligand must rotate from an anti to a syn conformation, and a truncation of the MOC structure allows us to elucidate, in the absence of the MOC constraint and its packing in the crystal, that the rotation is almost barrierless, as well as also explain the relative stability of the different conformations, with the anti being the most stable conformation. Characterization calculations with Mayer bond orders (MBO) and noncovalent interaction (NCI) plots discern what is important in the interaction of this type of cage with PdCl₂ moieties, also CuCl₂ by analogy, as well as simple molecules of water, since the complex is stable in this solvent. However, the L ligand is proved to not have the ability to stabilize an H₂O molecule.

1. Introduction

The evolution of the petrochemical industry during the 19th century, combined with the fact that the oil industry began to exploit the goodness of catalysis in processes such as the catalytic (hydro)cracking in the 1929s [1,2], led to the explosion of the polymer research field. Consequently, a new bunch of materials, including acrylonitrile and vinyl chlorides [3,4], and then followed by polymeric films and synthetic fibers including cellophane, nylon, rayon and polyester [5,6], have become essential in our everyday life. Despite the multiple advantages of polymers, there was a demand for new materials capable of enjoying macromolecular properties, such as polymers with more order and a clear structure, but at the same time also with storage capacity and even catalytic activity. This role could then be played by metal–organic frameworks (MOFs) [7,8], but with a fairly common drawback which is the lack of flexibility [9,10]. Since the 2000s, the simple change of infinite units of the frameworks could be changed to units with the metal–organic cages (MOC)s. They can also be called nanocapsules if they are meant to be a simple selective wrapper [11]. MOCs, among other properties, some still to be explored, present in the solid state the ability to modulate porosity [12,13], and in both the solid state and in the liquid state, to interact perfectly in highly selective host–guest systems [14,15,16]. These properties are not sterile, since they derive a wide range of applications from being reactive in simple systems, transporters [17,18,19], storage [20,21] or gas separators [22,23,24], or even being proactive in the field of sensors [25,26] or catalysis [27,28,29]. MOCs have also guided materials science towards new materials [30,31] and composites [32], from quasi-two-dimensional membranes [33,34] to three-dimensional networks or gels [35,36,37,38,39].

The MOCs synthesized so far, not by will but for simplicity, are composed of a single metal [40], and are designated as homometallic. To increase the scope of applications [41,42], once the range of ligands has been updated and expanded [43,44,45,46,47], two major strategies of work have been opened in MOCs that can be combined: increasing the complexity of the ligands [48,49] and/or adding different metal units to the original, that is, evolving to heterometallic MOCs [50,51], in analogy with bimetallic MOFs [52]. Despite the advantages of heterometallic MOCs, they still suffer from being materials that are practically only used for basic research since their synthesis is not trivial [53], and only small amounts are producible, often leading to homometallic MOCs, but this is being remedied by a battery of new solutions based on the assembly of already consolidated units [54,55,56,57,58,59,60,61], with special emphasis on the electron-donating capacity of the agents [62,63].

Since 2020, a series of works with paddlewheel-derived M_nL_n MOCs with M(II), including copper, rhodium and chromium [64,65,66], have led to multifunctional materials. More interestingly, the addition of N-donor ligands allowed the assembly of MOCs thanks to axial coordination sites on the surface of the cage [67,68,69]. Particularly, Bloch et al. have been able to combine Cu₄L₄ MOCs with bis(pyrazolyl)methane sites. The MOC resulting from the synthesis in Scheme 1 led to a subsequent assembly of simple metal halides [70,71].

Then, Bloch and coworkers obtained a crystallographic series that confirms the flexibility of the bis(pyrazolyl)methane site [70], observing MOC conformations as being either syn or anti, regardless. However, when the heterometallic system is obtained, the conformation is only in syn. Interestingly, the same research group previously achieved MOFs with the same organic ligand with the consequent increase in rigidity and low porosity [72,73,74,75]. Nevertheless, the post metalation of MOFs is relatively facile, while the same process on MOCs is a challenge synthetically speaking [76]. In view of the flexible character of the pyrazoles of Cu(II)-Pd(II) heterooctametallic cage-type complexes [77], and with the applicability as porous agents, density functional theory (DFT) calculations were performed with the aim of rationalizing the reversibility of the above structures.

2. Results

The calculations started from the crystallographic structure of the anti-MOC included in Scheme 1, checking what it means to have the axial positions of the copper atoms saturated with dimethylformamide (DMF) molecules, replaced by simple formaldehydes. However, the stabilizing effect, despite its multiplicative power, for each of the eight copper atoms in the cage, is compensated by the entropic cost, thus leaving a destabilization, but only of 2.5 kcal/mol. Thus, it is intriguing to understand the structural features of the current MOC, considering the rules of maximum site occupancy [78,79].

The Mayer bond orders (MBOs) [80] were calculated using the equation based on the atomic orbital overlap matrix and the α and β electron density matrices. It is a method to describe the interaction between two fragments, and by default also the strength of any bond [81]. Actually, the MBOs are fundamental here to screen how strong the Cu₂ linkers are, in particular the Cu-Cu bond [82], with a remarkable value of 0.426 with formaldehydes on each copper center, while nearly constantly removing the latter molecules, with a MBO of 0.412. This allows us to remark that the formaldehyde coordination is rather weak with a MBO of 0.178 [10,83].

The most important thing about binding solvent molecules to copper atoms is that it involves the saturation of the inside of the cage. Then, to study the bis(pyrazolyl)methane site, the crystallographic anti conformation anti-MOC (Scheme 2a), owing the four existing bis(pyrazolyl)methane sites of the cage in anti fashion, was taken into account, and the conversion to syn thermodynamically entailed a destabilization of 2.5, 3.2, 4.1 and 4.7 kcal/mol, respectively, transforming from one to four sites, leading finally to syn-MOC (Scheme 2b). It should be mentioned that the movement of the pyrazole ring forming the syn conformation was tackled so that the four different centers were arranged symmetrically, that is, with a pseudo symmetry of c4v between them, or a c2v typology. It should be mentioned that the second was less stable by 3.3 kcal/mol. The effect is robust, because by converting three of the four groups into syn instead of completeness, the less symmetrical conformation was also unfavored, but by only 0.8 kcal/mol. However, the initial anti structure always remains as the most stable, by at least 1.3 kcal/mol. Therefore, the small differences are almost unappreciable, and the motion dynamics of the cage will lead to one or the other indiscriminately, which explains that crystallographically when the cage uses bis(pyrazolyl)methane moiety as a bidentate ligand both the pseudo c2v conformations are formed like c4v [70].

To study thermodynamically and above all kinetically how the transition from anti to syn with respect to the two pyrazole groups of the bis(pyrazolyl)methane moiety occurs, the system was truncated (see Figure 1), simply taking the organic bis(pyrazolyl)methane moiety. Thus, the anti-bis(pyrazolyl)methane (anti-O) structure was brought to the syn conformation, reaching the isomer of syn-O, 0.5 kcal/mol less stable. Structurally, the N-C-N-N dihedral angle evolves from 85.1° to −121.7°. Due to the interconversion between conformations the reaction path must go through TS1, i.e., a transition state located 2.2 kcal/mol above anti-O, with a dihedral angle of −103.7°, in perfect agreement with similar rotations [84]. If the pyrazole ring would rotate in the reverse direction, there is more steric hindrance due to the methyl located alpha to the nitrogen atom, but simply this TS2 requires an additional kinetic cost of 2.4 kcal/mol and the dihedral angle is −168.4° instead of 1.5° for TS1. In addition, the movement of the rotation of one of the pyrazole rings is of a small dimension that, in the conformation of the MOC, would also be feasible with all certainty, although a little more constrained. It is of such a small dimension that quantum mechanics makes its calculation difficult, and this is evident with an imaginary frequency of 17.0 and 24.2 cm⁻¹ for TS1 and TS2, respectively, but only TS1 would be feasible since the rotation in the case of the TS2 would be prevented by the cage itself. On the other hand, syn-O fails to have c2v symmetry, and in fact, instead of being an intermediate, it is a transition state, which requires only a barrier of 2.0 kcal/mol, with a dihedral angle of −80.9°. It actually corresponds to the transition state that binds the two enantiomers of the syn conformation.

To understand how the bis(pyrazolyl)methane sites are orientated, we computed the noncovalent interactions (NCI) plots using the NCIPLOT package of Contreras-García and coworkers [85,86]. NCI diagrams allow a qualitative analytical study of the strength of noncovalent interactions between different fragments. Since in Figure 2a the interaction among sites is null, missing interactions between aromatic rings [87], we centered our analysis on the truncated structures. Knowing the low covalent character presented by the interaction between all the N atoms of the pyrazolyl moieties, the hydrogen atoms of the methylene bridge, or methyl substituents, the NCI plots in Figure 2 not only qualitatively evaluate the strength of the noncovalent interactions, but they are able to conclude the preference for the anti conformation of the bis(pyrazolyl)methane sites, since more favorable interactions are included when the nitrogen atoms of both pyrazole rings are placed farther from each other [10]. This is thanks to N···H interactions, corresponding to the closest H atom of the methyl group, while for the syn conformation these interactions do not exist. The current study, where a single cage misses the observed intermolecular hydrogen bonding between the two methylene bridge hydrogens and the nitrogen atoms of the adjacent cage molecules that were observed in the extended crystal packing, with expected H-bonds of around 2.4 Å, is thus of remarkable importance compared to the homologous intramolecular H-bonds which are placed at slightly less than 2.6 Å.

Since paddlewheels are often related to water [88,89], and to address the importance of the crystal of the MOC with a water molecule achieved by Bloch and coworkers [70], DFT calculations unveiled the nonexistence of a strong interaction with a water molecule, and such a structure could be defined simply as an adduct, with a remarkable H-bond placed at 1.891 Å. From the thermodynamic point of view, the coordination of a water molecule was found to be unfavorable by 5.6 and 7.5 kcal/mol, respectively, owing or not to axial ligands on the copper acetate centers, respectively, and for the truncated anti-O again unfavored by 5.6 kcal/mol. Thus, this leads to the conclusion that the packing of the crystal helped to sequester a water molecule close to two pyrazolic N-donor atoms from two cages.

Following the experimental crystallographic effort of Bloch and coworkers [70], where they were able to complexate PdCl₂ moieties on the syn-MOC and then obtain crystals of the combination, the truncated syn-MOC structure with metal centers in all four sites was consequently optimized. In particular, the PdCl₂ unit was chosen for the simplicity (see Scheme 2c) and also then for the comparative effect of the copper counterpart. Formulating the direct equation for the formation of the heterometallic complex is highly complex since it is made from the monomer PdCl₂ (or CuCl₂ in the case of copper, which would obviously not be heterometallic, but the two metal centers are of different natures anyway). However, it is a thermodynamically favored process by almost 50 kcal/mol, and it should be mentioned that for palladium this process is 23.2 kcal/mol more stable than for copper. Going further by analyzing the energy decomposition, the fragment that undergoes the most deformational change is the organic one with 4.6 kcal/mol (5.1 kcal/mol for copper), while the metallic part undergoes negligible deformation of 0.9 kcal/mol. In fact, it explains that to force a structure of an organic ligand almost with c2v symmetry, as it was explained above, implies a destabilization, but this was then widely surpassed by the formation of the squared planar center around the metal. Structurally, to validate more consistently the comparison between metals [90], the results of MBOs for the metal-N bonds reinforce the stronger character of the Pd-N bonds (0.486) compared to the Cu-N bonds (0.441) [91,92].

3. Computational Details

Density functional theory (DFT) calculations were performed with the Gaussian16 package [93]. Without symmetry constraints, the geometry optimizations were carried out via the spin-restricted Kohn–Sham (RKS) formalism and employing the M06L GGA functional of Zhao and Truhlar [94]. The double-zeta polarization basis set Def2-SVP keyword was used for all atoms [95,96]. Frequency calculations were carried out to confirm the nature of the stationary points. The reported Gibbs energies in the current work contain electronic energies obtained at the M06L/Def2-TZVP level of theory corrected with zero-point energies, thermal corrections and entropy effects evaluated at 298.15 K, achieved at the M06L/Def2SVP level plus a solvation contribution evaluated by the SMD continuum solvation model, a variation of the IEFPCM of Truhlar and co-workers [97], based on the quantum mechanical charge density of the solute interacting with a continuum description of the solvent (dimethylformamide).

4. Conclusions

MOCs represent a very promising class of metal-organic materials (MOFs) in terms of host-host binding ability related to their well-defined cavities and engineered pores. Discrete MOCs can also be thought of as infinite cage-based frameworks that use each MOC unit as supramolecular building blocks. And among the advantages, we have the relative solubility and stability of MOCs. Despite the complexity of the MOC structure, containing hundreds of atoms, DFT calculations, without losing the robustness of the results, have allowed us to understand the flexibility of a recently synthesized structure of Cu₄L₄ MOC, functionalized with non-coordinating bis(pyrazolyl)methane sites. The heterometallic character was achieved with the inclusion of palladium metal halides (and also by comparison with copper), demonstrating that thermodynamics favor the process, and the kinetics of rotation of a pyrazole to have syn conformations of the two N-donor atoms in each bis(pyrazolyl)methane center is entirely feasible. On the other hand, it is confirmed that the interaction of a molecule outside the cage is not of strong nature and is due to a simple misfortune of the packing of the crystals. The porosity of the systems paves the way for ongoing calculations to understand if the porosity of the system allows molecules to be stabilized, not outside the cage [98], but inside it and selectively [23].

In the discussion of the results above, the truncation of the bis(pyrazolyl)methane site allows us to understand how one of the pyrazole rings rotates, but it must be understood that the cage imposes a constraint that undoubtedly makes movement a little difficult, and in an MOF it might reach the point of not being possible. Indeed, this is an experimental example where the calculations find the reason for the need to have a cage, and not in a framework format. It is a decisive step towards the achievement of new structures [99] and not a step back from MOFs, but it paves the way to widening the applicability of the structures that have already been generated in the field of MOFs. In short, this study has allowed us to understand that the flexibility of pyrazoles is the driving force of the selectivity of the coordinating capacity in metal assembly.