Synthesis of Metal-Organic Cages via Orthogonal Bond Cleavage in 3D Metal-Organic Frameworks.

Herein we address the question of whether a supramolecular finite metal-organic structure such as a cage or metal-organic polyhedron (MOP) can be synthesized via controlled cleavage of a three-dimensional (3D) metal-organic structure. To demonstrate this, we report the synthesis of a Cu(II)-based cuboctahedral MOP through orthogonal olefinic bond cleavage of the cavities of a 3D, Cu(II)-based, metal-organic framework (MOF). Additionally, we demonstrate that controlling the ozonolysis conditions used for the cleavage enables Clip-off Chemistry synthesis of two cuboctahedral MOPs that differ by their external functionalization: one in which all 24 external groups represent a mixture of aldehydes, carboxylic acids, acetals and esters, and one in which all are aldehydes.

Isolation of the Secondary Building Unit of a 3D Metal-Organic Framework through Clip-Off Chemistry, and Its Reuse To Synthesize New Frameworks by Dynamic Covalent Chemistry.

Herein, we present a novel methodology for synthesizing metal clusters or secondary building units (SBUs) that are subsequently employed to construct innovative metal-organic frameworks (MOFs) via dynamic covalent chemistry. Our approach entails extraction of SBUs from preformed MOFs through complete disassembly by clip-off chemistry. The initial MOF precursor is designed to incorporate the desired SBU, connected exclusively by cleavable linkers (in this study, with olefinic bonds). Cleavage of all the organic linkers (in this study, via ozonolysis under reductive conditions) liberates the SBUs functionalized with aldehyde groups. Once synthesized, these SBUs can be further reacted with amines in dynamic covalent chemistry to build new, rationally designed MOFs.

Modulation of the Dynamics of a Two-Dimensional Interweaving Metal-Organic Framework through Induced Hydrogen Bonding.

Inducing, understanding, and controlling the flexibility in metal-organic frameworks (MOFs) are of utmost interest due to the potential applications of dynamic materials in gas-related technologies. Herein, we report the synthesis of two isostructural two-dimensional (2D) interweaving zinc(II) MOFs, TMU-27 [Zn(bpipa)(bdc)] and TMU-27-NH2 [Zn(bpipa)(NH2-bdc)], based on N,N'-bis-4-pyridyl-isophthalamide (bpipa) and 1,4-benzenedicarboxylate (bdc) or 2-amino-1,4-benzenedicarboxylate (NH2-bdc), respectively. These frameworks differ only by the substitution at the meta-position of their respective bdc groups: an H atom in TMU-27 vs an NH2 group in TMU-27-NH2. This difference strongly influences their respective responses to external stimuli, since we observed that the structure of TMU-27 changed due to desolvation and adsorption, whereas TMU-27-NH2 remained rigid. Using single-crystal X-ray diffraction and CO2-sorption measurements, we discovered that upon CO2 sorption, TMU-27 undergoes a transition from a closed-pore phase to an open-pore phase. In contrast, we attributed the rigidification in TMU-27-NH2 to intermolecular hydrogen bonding between interweaving layers, namely, between the H atoms from the bdc-amino groups and the O atoms from the bpipa-amide groups within these layers. Additionally, by using scanning electron microscopy to monitor the CO2 adsorption and desorption in TMU-27, we were able to establish a correlation between the crystal size of this MOF and its transformation pressure.

Isoreticular Contraction of Metal-Organic Frameworks Induced by Cleavage of Covalent Bonds.

Isoreticular chemistry, in which the organic or inorganic moieties of reticular materials can be replaced without destroying their underlying nets, is a key concept for synthesizing new porous molecular materials and for tuning or functionalization of their pores. Here, we report that the rational cleavage of covalent bonds in a metal-organic framework (MOF) can trigger their isoreticular contraction, without the need for any additional organic linkers. We began by synthesizing two novel MOFs based on the MIL-142 family, (In)BCN-20B and (Sc)BCN-20C, which include cleavable as well as noncleavable organic linkers. Next, we selectively and quantitatively broke their cleavable linkers, demonstrating that various dynamic chemical and structural processes occur within these structures to drive the formation of isoreticular contracted MOFs. Thus, the contraction involves breaking of a covalent bond, subsequent breaking of a coordination bond, and finally, formation of a new coordination bond supported by structural behavior. Remarkably, given that the single-crystal character of the parent MOF is retained throughout the entire transformation, we were able to monitor the contraction by single-crystal X-ray diffraction.

Retrosynthetic Analysis Applied to Clip-off Chemistry: Synthesis of Four Rh(II)-Based Complexes as Proof-of-Concept.

Clip-off Chemistry is a synthetic strategy that our group previously developed to obtain new molecules and materials through selective cleavage of bonds. Herein, we report recent work to expand Clip-off Chemistry by introducing into it a retrosynthetic analysis step that, based on virtual extension of the products through cleavable bonds, enables one to define the required precursor materials. As proof-of-concept, we have validated our new approach by synthesising and characterising four aldehyde-functionalised Rh(II)-based complexes: a homoleptic cluster; a cis-disubstituted paddlewheel cluster; a macrocycle; and a crown.

Multicomponent, Functionalized HKUST-1 Analogues Assembled via Reticulation of Prefabricated Metal-Organic Polyhedral Cavities.

Metal-organic frameworks (MOFs) assembled from multiple building blocks exhibit greater chemical complexity and superior functionality in practical applications. Herein, we report a new approach based on using prefabricated cavities to design isoreticular multicomponent MOFs from a known parent MOF. We demonstrate this concept with the formation of multicomponent HKUST-1 analogues, using a prefabricated cavity that comprises a cuboctahedral Rh(II) metal-organic polyhedron functionalized with 24 carboxylic acid groups. The cavities are reticulated in three dimensions via Cu(II)-paddlewheel clusters and (functionalized) 1,3,5-benzenetricarboxylate linkers to form three- and four-component HKUST-1 analogues.

Clip-off Chemistry: Synthesis by Programmed Disassembly of Reticular Materials.

Bond breaking is an essential process in chemical transformations and the ability of researchers to strategically dictate which bonds in a given system will be broken translates to greater synthetic control. Here, we report extending the concept of selective bond breaking to reticular materials in a new synthetic approach that we call Clip-off Chemistry. We show that bond-breaking in these structures can be controlled at the molecular level; is periodic, quantitative, and selective; is effective in reactions performed in either solid or liquid phases; and can occur in a single-crystal-to-single-crystal fashion involving the entire bulk precursor sample. We validate Clip-off Chemistry by synthesizing two topologically distinct 3D metal-organic frameworks (MOFs) from two reported 3D MOFs, and a metal-organic macrocycle from metal-organic polyhedra (MOP). Clip-off Chemistry opens the door to the programmed disassembly of reticular materials and thus to the design and synthesis of new molecules and materials.

Synthesis of Polycarboxylate Rhodium(II) Metal-Organic Polyhedra (MOPs) and their use as Building Blocks for Highly Connected Metal-Organic Frameworks (MOFs).

Use of preformed metal-organic polyhedra (MOPs) as supermolecular building blocks (SBBs) for the synthesis of metal-organic frameworks (MOFs) remains underexplored due to lack of robust functionalized MOPs. Herein we report the use of polycarboxylate cuboctahedral RhII -MOPs for constructing highly-connected MOFs. Cuboctahedral MOPs were functionalized with carboxylic acid groups on their 12 vertices or 24 edges through coordinative or covalent post-synthetic routes, respectively. We then used each isolated polycarboxylate RhII -MOP as 12-c cuboctahedral or 24-c rhombicuboctahedral SBBs that, upon linkage with metallic secondary building units (SBUs), afford bimetallic highly-connected MOFs. The assembly of a pre-synthesized 12-c SBB with a 4-c paddle-wheel SBU, and a 24-c SBB with a 3-c triangular CuII SBU gave rise to bimetallic MOFs having ftw (4,12)-c or rht (3,24)-c topologies, respectively.

Net-Clipping: An Approach to Deduce the Topology of Metal-Organic Frameworks Built with Zigzag Ligands.

Herein we propose a new approach for deducing the topology of metal-organic frameworks (MOFs) assembled from organic ligands of low symmetry, which we call net-clipping. It is based on the construction of nets by rational deconstruction of edge-transitive nets comprising higher-connected molecular building blocks (MBBs). We have applied net-clipping to predict the topologies of MOFs containing zigzag ligands. To this end, we derived 2-connected (2-c) zigzag ligands from 4-c square-like MBBs by first splitting the 4-c nodes into two 3-c nodes and then clipping their two diagonally connecting groups. We demonstrate that, when this approach is applied to the 17 edge-transitive nets containing square-like 4-c MBBs, net-clipping leads to generation of 10 nets with different underlying topologies. Moreover, we report that literature and experimental research corroborate successful implementation of our approach. As proof-of-concept, we employed net-clipping to form three new MOFs built with zigzag ligands, each of which exhibits the deduced topology.

Phase Transfer of Rhodium(II)-Based Metal-Organic Polyhedra Bearing Coordinatively Bound Cargo Enables Molecular Separation.

The transfer of nanoparticles between immiscible phases can be driven by externally triggered changes in their surface composition. Interestingly, phase transfers can enhance the processing of nanoparticles and enable their use as vehicles for transporting molecular cargo. Herein we report extension of such phase transfers to encompass porous metal-organic polyhedra (MOPs). We report that a hydroxyl-functionalized, cuboctahedral Rh(II)-based MOP can be transferred between immiscible phases by pH changes or by cation-exchange reactions. We demonstrate use of this MOP to transport coordinatively bound cargo between immiscible layers, including into solvents in which the cargo is insoluble. As proof-of-concept that our phase-transfer approach could be used in chemical separation, we employed Rh(II)-based MOPs to separate a challenging mixture of structurally similar cyclic aliphatic (tetrahydrothiophene) and aromatic (thiophene) compounds. We anticipate that transport of coordinatively bound molecules will open new avenues for molecular separation based on the relative coordination affinity that the molecules have for the Rh(II) sites of MOP.

Postsynthetic Covalent and Coordination Functionalization of Rhodium(II)-Based Metal-Organic Polyhedra.

Metal-organic polyhedra (MOP) are ultrasmall (typically 1-4 nm) porous coordination cages made from the self-assembly of metal ions and organic linkers and are amenable to the chemical functionalization of its periphery; however, it has been challenging to implement postsynthetic functionalization due to their chemical instability. Herein, we report the use of coordination chemistries and covalent chemistries to postsynthetically functionalize the external surface of ≈2.5 nm stable Rh(II)-based cuboctahedra through their Rh-Rh paddlewheel units or organic linkers, respectively. We demonstrate that 12 N-donor ligands, including amino acids, can be coordinated on the periphery of Rh-MOPs. We used this reactivity to introduce new functionalities (e.g., chirality) to the MOPs and to tune their hydrophilic/hydrophobic characteristics, which allowed us to modulate their solubility in diverse solvents such as dichloromethane and water. We also demonstrate that all 24 organic linkers can be postsynthetically functionalized with esters via covalent chemistry. In addition, we anticipate that these two types of postsynthetic reactions can be combined to yield doubly functionalized Rh-MOPs, in which a total of 36 new functional molecules can be incorporated on their surfaces. Likewise, these chemistries could be synergistically combined to enable covalent functionalization of MOPs through new linkages such as ethers. We believe that both reported postsynthetic pathways can potentially be used to engineer Rh-MOPs as scaffolds for applications in delivery, sorption, and catalysis.

MXCuBE2: the dawn of MXCuBE Collaboration.

MXCuBE2 is the second-generation evolution of the MXCuBE beamline control software, initially developed and used at ESRF - the European Synchrotron. MXCuBE2 extends, in an intuitive graphical user interface (GUI), the functionalities and data collection methods available to users while keeping all previously available features and allowing for the straightforward incorporation of ongoing and future developments. MXCuBE2 introduces an extended abstraction layer that allows easy interfacing of any kind of macromolecular crystallography (MX) hardware component, whether this is a diffractometer, sample changer, detector or optical element. MXCuBE2 also works in strong synergy with the ISPyB Laboratory Information Management System, accessing the list of samples available for a particular experimental session and associating, either from instructions contained in ISPyB or from user input via the MXCuBE2 GUI, different data collection types to them. The development of MXCuBE2 forms the core of a fruitful collaboration which brings together several European synchrotrons and a software development factory and, as such, defines a new paradigm for the development of beamline control platforms for the European MX user community.

Zigzag Ligands for Transversal Design in Reticular Chemistry: Unveiling New Structural Opportunities for Metal-Organic Frameworks.

Herein we describe the topological influence of zigzag ligands in the assembly of Zr(IV) metal-organic frameworks (MOFs). Through a transversal design strategy using reticular chemistry, we were able to synthesize a family of isoreticular Zr(IV)-based MOFs exhibiting the bcu-rather than the fcu-topology. Our findings underscore the value of the transversal parameter in organic ligands for dictating MOF architectures.

Single-Crystal-to-Single-Crystal Postsynthetic Modification of a Metal-Organic Framework via Ozonolysis.

We describe solid-gas phase, single-crystal-to-single-crystal, postsynthetic modifications of a metal-organic framework (MOF). Using ozone, we quantitatively transformed the olefin groups of a UiO-66-type MOF into 1,2,4-trioxolane rings, which we then selectively converted into either aldehydes or carboxylic acids.

Purification of Uranium-based Endohedral Metallofullerenes (EMFs) by Selective Supramolecular Encapsulation and Release.

Supramolecular nanocapsule 1⋅(BArF)8 is able to sequentially and selectively entrap recently discovered U2 @C80 and unprecedented Sc2 CU@C80 , simply by soaking crystals of 1⋅(BArF)8 in a toluene solution of arc-produced soot. These species, selectively and stepwise absorbed by 1⋅(BArF)8 , are easily released, obtaining highly pure fractions of U2 @C80 and Sc2 CU@C80 in one step. Sc2 CU@C80 represents the first example of a mixed metal actinide-based endohedral metallofullerene (EMF). Remarkably, the host-guest studies revealed that 1⋅(BArF)8 is able to discriminate EMFs with the same carbon cage but with different encapsulated cluster and computational studies provide support for these observations.

Net-clipping as a top-down approach for the prediction of topologies of MOFs built from reduced-symmetry linkers.

Reticular materials constructed from regular molecular building blocks (MBBs) have been widely explored in the past three decades. Recently, there has been increasing interest in the assembly of novel, intricate materials using less-symmetric ligands; however, current methods for predicting structure are not amenable to this increased complexity. To address this gap, we propose herein a generalised version of the net-clipping approach for anticipating the topology of metal-organic frameworks (MOFs) assembled from organic linkers and different polygonal and polyhedral MBBs. It relies on the generation of less-symmetric nets with less-connected linkers, via the rational deconstruction of more-symmetric and more-connected linkers in edge-transitive nets. We applied our top-down strategy to edge-transitive nets containing 4-c tetrahedral, 6-c hexagonal, 8-c cubic or 12-c hexagonal prism linkers, envisaging the formation of 102 derived and 46 clipped nets. Among these, we report 33 new derived nets (icn7-icn39) and 6 new clipped nets (icn1-icn6). Importantly, the feasibility of using net-clipping to anticipate clipped nets is supported by literature examples and new experimental additions. Finally, we suggest and illustrate that net-clipping can be extended to less-regular, non-edge transitive nets as well as to covalent-organic frameworks (COFs), thus opening new avenues for the rational design of new reticular materials exhibiting unprecedented topologies.

Stepwise assembly of heterometallic, heteroleptic "triblock Janus-type" metal-organic polyhedra.

Increasing the chemical complexity of metal-organic cages (MOCs) or polyhedra (MOPs) demands control over the simultaneous organization of diverse organic linkers and metal ions into discrete caged structures. Herein, we show that a pre-assembled complex of the archetypical cuboctahedral MOP can be used as a template to replicate such caged structure, one having a "triblock Janus-type" configuration that is both heterometallic and heteroleptic.

A mesoporous Zr-based metal-organic framework driven by the assembly of an octatopic linker.

Metal-organic frameworks (MOFs) based on high-connected nets are generally very attractive due to their combined robustness and porosity. Here, we describe the synthesis of BCN-348, a new high-connected Zr-MOF built from an 8-connected (8-c) cubic Zr-oxocluster and an 8-c organic linker. BCN-348 contains a minimal edge-transitive 3,4,8-c eps net, and combines mesoporosity with thermal and hydrolytic stability. Encouraging results from preliminary studies on its use as a catalyst for hydrolysis of a nerve-agent simulant suggest its potential as an agent for detoxification of chemical weapons and other pernicious compounds.

Structural and biochemical evidence that ATP inhibits the cancer biomarker human aldehyde dehydrogenase 1A3.

Human aldehyde dehydrogenase (ALDH) participates in the oxidative stress response and retinoid metabolism, being involved in several diseases, including cancer, diabetes and obesity. The ALDH1A3 isoform has recently elicited wide interest because of its potential use as a cancer stem cell biomarker and drug target. We report high-resolution three-dimensional ALDH1A3 structures for the apo-enzyme, the NAD+ complex and a binary complex with ATP. Each subunit of the ALDH1A3-ATP complex contains one ATP molecule bound to the adenosine-binding pocket of the cofactor-binding site. The ATP complex also shows a molecule, putatively identified as a polyethylene glycol aldehyde, covalently bound to the active-site cysteine. This mimics the thioacyl-enzyme catalytic intermediate, which is trapped in a dead enzyme lacking an active cofactor. At physiological concentrations, ATP inhibits the dehydrogenase activity of ALDH1A3 and other isoforms, with a Ki value of 0.48 mM for ALDH1A3, showing a mixed inhibition type against NAD+. ATP also inhibits esterase activity in a concentration-dependent manner. The current ALDH1A3 structures at higher resolution will facilitate the rational design of potent and selective inhibitors. ATP binding to ALDH1A3 enables activity modulation by the energy status of the cell and metabolic reprogramming, which may be relevant in several disease conditions.

Synthesis of the two isomers of heteroleptic Rh12L6L'6 metal-organic polyhedra by screening of complementary linkers.

We have synthesised and characterised the two possible isomers of heteroleptic trigonal antiprismatic M12L6L'6 MOPs by screening reactions of rhodium acetate with different pairs of complementary dicarboxylate linkers. The resulting 12 new MOPs (eight of isomer A + four of isomer B) are microporous in the solid state, exhibiting Brunauer-Emmett-Teller (BET) surface areas as high as 770 m2 g-1.