Postsynthetic modification of zirconium metal-organic frameworks

Metal-organic frameworks (MOFs) have been in the spotlight for a number of years due to their chemical and topological versatility. As MOF research has progressed, highly functionalised materials have become desirable for specific applications, and in many cases the limitations of direct synthesis have been realised. This has resulted in the search for alternative synthetic routes, with postsynthetic modification (PSM), a term used to collectively describe the functionalisation of pre-synthesised MOFs whilst maintaining their desired characteristics, becoming a topic of interest. Advances in the scope of reactions performed are reported regularly; however reactions requiring harsh conditions can result in degradation of the framework. Zirconium-based MOFs present high chemical, thermal and mechanical stabilities, offering wider opportunities for the scope of reaction conditions that can be tolerated, which has seen a number of successful examples reported. This microreview discusses pertinent examples of PSM resulting in enhanced properties for specific applications, alongside fundamental transformations, which are categorised broadly into covalent modifications, surface transformations, metalations, linker and metal exchange, and cluster modifications

Image-guided therapy using maghemite-MOF nanovectors

Advances in nanotechnology offer the possibility of tailored delivery of therapeutics with real-time imaging of disease. In this issue of Chem, Steunou and co-workers amalgamate the powerful MRI properties of ultra-small paramagnetic iron oxides with the excellent drug-delivery capabilities of metal-organic frameworks to produce theranostic nanoparticulate devices for cancer treatment and imaging

Crystallographic investigation into the self-assembly, guest binding, and flexibility of urea functionalised metal-organic frameworks

Introduction of hydrogen bond functionality into metal-organic frameworks can enhance guest binding and activation, but a combination of linker flexibility and interligand hydrogen bonding often results in the generation of unwanted structures where the functionality is masked. Herein, we describe the self-assembly of three materials, where Cd2+, Ca2+, and Zn2+ are linked by N,Nʹ-bis(4-carboxyphenyl)urea, and examine the effect of the urea units on structure formation, the generation of unusual secondary building units, structural flexibility, and guest binding. The flexibility of the Zn MOF is probed through single-crystal to single-crystal transformations upon exchange of DMF guests for CS2, showing that the lability of the [Zn4O(RCO2)6] cluster towards solvation enables the urea linkers to adopt distorted conformations as the MOF breathes, even facilitating rotation from the trans/trans to the trans/cis conformation without compromising the overall topology. The results have significant implications in the mechanistic understanding of the hydrolytic stability of MOFs, and in preparing heterogeneous organocatalysts

The surface chemistry of metal-organic frameworks and their applications

Modifying the outer surfaces of metal-organic frameworks (MOFs) has received considerably less attention than functionalization of the bulk, despite the range of physical and chemical properties that can be tuned by controlling MOF surface chemistry. In this Frontier article, we summarise developments over the last five years in both functionalizing and visualizing the outer surfaces of MOFs, with particular focus on their application as surface-modified nanoparticles for drug delivery and in the enhanced self-assembly of hybrid materials

Modulated self-assembly of metal-organic frameworks

Exercising fine control over the synthesis of metal-organic frameworks (MOFs) is key to ensuring reproducibility of physical properties such as crystallinity, particle size, morphology, porosity, defectivity, and surface chemistry. The principle of modulated self-assembly – incorporation of modulator molecules into synthetic mixtures – has emerged as the primary means to this end. This perspective article will detail the development of modulated synthesis, focusing primarily on coordination modulation, from a technique initially intended to cap the growth of MOF crystals to one that is now used regularly to enhance crystallinity, control particle size, induce defectivity and select specific phases. The various mechanistic driving forces will be discussed, as well as the influence of modulation on physical properties and how this can facilitate potential applications. Modulation is also increasingly being used to exert kinetic control over self-assembly; examples of phase selection and the development of new protocols to induce this will be provided. Finally, the application of modulated self-assembly to alternative materials will be discussed, and future perspectives on the area given

Enhancing anticancer cytotoxicity through bimodal drug delivery from ultrasmall Zr MOF nanoparticles

Dual delivery of dichloroacetate and 5-fluorouracil from Zr MOFs into cancer cells is found to enhance in vitro cytotoxicity. Tuning particle size and, more significantly, surface chemistry, further improves cytotoxicity by promoting caveolae-mediated endocytosis and cytosolic cargo delivery

Synthetic considerations in the self-assembly of coordination polymers of pyridine-functionalised hybrid Mn-Anderson polyoxometalates

The incorporation of polyoxometalates (POMs) as structural units into ordered porous constructs such as metal-organic frameworks (MOFs) is desirable for a range of applications where intrinsic properties inherited from both the MOF and POM are utilised, including catalysis and magnetic data storage. The controlled self-assembly of targeted MOF topologies containing POM units is hampered by the wide range of oxo and hydroxo units on the peripheries of POMs that can act as coordinating groups towards linking metal cations leading to a diverse range of structures, but incorporation of organic donor units into hybrid POMs offers an alternative methodology to programmably synthesise POM/MOF conjugates. Herein, we report six coordination polymers obtained serendipitously wherein Zn2+ and Cu2+ link pyridine-appended Mn-Anderson clusters into two- and three-dimensional network solids with complex connectivities and topologies. Careful inspection of their solid-state structures has allowed us to identify common structure-directing features across these coordination polymers, including a square motif where two Zn2+ cations bridge two POMs. By correlating certain structural motifs with synthetic conditions we have formulated a series of design considerations for the self-assembly of coordination polymers of hybrid POMs, encompassing the selection of reaction conditions, co-ligands and linking metal cations. We anticipate that these synthetic guidelines will inform the future assembly of hybrid POMs into functional MOF materials

Application of zirconium MOFs in drug delivery and biomedicine

Nanoparticulate metal-organic frameworks (MOFs) have the requisite high storage capacities, tailorable structures, ease of functionalisation, and excellent biocompatibilities for application as nanoscale drug delivery devices (DDSs). Zirconium MOFs in particular combine optimal stability towards hydrolysis and postsynthetic modification with low toxicity, and so are particularly suited for biological applications. This review covers the use of Zr MOFs as DDSs with focus on the different physical properties that makes them attractive for use. The various methods for modifying the surfaces of Zr MOFs are described with pertinent examples of the resulting enhancements in aqueous stability, colloidal dispersion, and stimuli-responsive drug release. The in vitro and in vivo application of Zr MOFs for photodynamic therapy and drug delivery are discussed with respect to the structural features of the MOFs and their surface functionality, and perspectives on their future applications and analogous hafnium MOFs are given

Uncovering the structural diversity of Y(III) naphthalene-2,6-dicarboxylate MOFs through coordination modulation

Metal-organic frameworks (MOFs) – network structures built from metal ions and clusters and connecting organic ligands – are typically synthesized by solvothermal self-assembly. For transition metal based MOFs, structural predictability is facilitated by control over coordination geometries and linker connectivity under the principles of isoreticular synthesis. For rare earth MOFs, coordination behaviour is dominated by steric and electronic factors, leading to unpredictable structures and poor control over self-assembly. Herein we show that coordination modulation – the addition of competing ligands into MOF syntheses – offers programmable access to six different Y(III) MOFs all connected by the same naphthalene-2,6-dicarboxylate ligand, despite controlled synthesis of multiple phases from the same metal-ligand combination often being challenging for rare earth MOFs. Four of the materials are isolable in bulk phase purity, three are amenable to rapid microwave synthesis, and the fluorescence sensing ability of one example towards metal cations is reported. The results show that a huge variety of structurally versatile MOFs can potentially be prepared from simple systems, and that coordination modulation is a powerful tool for systematic control of phase behaviour in rare earth MOFs

Modification of Phenolic Oximes for Copper Extraction

The thesis deals with the modification of salicylaldoxime-based reagents used in hydrometallurgical extraction, addressing rational ligand design to tune copper(II) extractant strengths and also the development of reagents which are capable of transporting transition metal salts. Chapter 1 reviews current solvent extractant technology for metal recovery, including the limited knowledge of the effect of substituents on extractive efficacy. Advances in leaching technology have led to systems wherein increases in process efficiency could be obtained using reagents which can transport both a transition metal cation and its attendant anion(s), and the potential advantages of metal salt extractants are discussed. The problems encountered when trying to extract hydrophilic anions selectively into organic media are also considered. Chapter 2 discusses techniques used in industry to tune reagent properties, many of which depend on the importance of H-bonding in non-polar solvents. Synthesis of a series of 5-alkyl-3-X-2-hydroxybenzaldehyde oximes (X = a range of substituents) is described and copper extraction experiments are reported. 3-Substitution is found to alter reagent strength by two orders of magnitude, with 3-bromo-5-tert-butyl-2- hydroxybenzaldehyde oxime the strongest extractant. An analysis of X-ray structures of several ligands and copper(II) complexes is given in an attempt to establish whether trends in the solid state structures can account for variations in extractant strength. A more detailed analysis of the hydrogen bonding in salicylaldoximato copper(II) complexes and ligand dimers is carried out in Chapter 3, with the aim of defining how substituent effects could be used to design reagents with appropriate extractive behaviour. 3-X-2-Hydroxybenzaldehyde oximes with no 5-alkyl substituent are synthesised and subjected to a detailed study by X-ray crystallography and computational techniques, which, alongside evidence provided by CID-MS experiments, suggest that the dominant substituent effect in determining extractant strength is the ability to “buttress” the pseudomacrocyclic hydrogen bonding motif involving the oximic hydrogen and phenolic oxygen. Ligands with 3-substituents capable of accepting H-bonds were found to be stronger extractants than those which could not, and the steric hindrance afforded by bulky substituents made 3,5-di-tert-butyl-2-hydroxybenzaldehyde oxime the weakest extractant. Ligand acidity is also noted to have a significant effect on reagent strength, with electronwithdrawing substituents lowering the pKa of the phenolic proton and increasing extractive efficacy. Chapter 4 focuses on metal salt extraction, and the development of selective, robust and hydrolytically stable reagents. Six novel extractants, based on a salicylaldoxime scaffold with a pendant dialkylaminomethyl arm, are described. Only 5-tert-butyl-3- dihexylaminomethyl-2-hydroxybenzaldehyde oxime and 3-tert-butyl-5- dihexylaminomethyl-2-hydroxybenzaldehyde oxime have sufficient solubility to be effective reagents. The former extracts CuCl2 and ZnCl2 in a highly efficient manner, with one mole of metal salt extracted per mole of ligand, twice the expected capacity. X-ray structure determination of complexes of the related ligand 5-tertbutyl- 2-hydroxy-3-piperidin-1-ylmethylbenzaldehyde oxime defines the binding mode, with the chloride anions bound to the inner sphere of the metal cations. Loading and stripping experiments show it to be an extractant with potential commercial application. Cation and anion selectivity of the two extractants defined above is the focus of Chapter 5, which begins with an overview of techniques and attempts to attenuate the Hofmeister bias, the main factor in the selective extraction of hydrophilic anions into organic media. pH loading profiles show the 3- dihexylaminomethyl isomer to be an effective CuCl2 and CuSO4 extractant, but the cation extractive efficacy of the 5-isomer is hampered by the 3-tert-butyl group. Both ligands are found to be selective for Cl- > SO4 2-, following the Hofmeister bias. Further information on anion binding is provided by solid state structures of copper salt complexes, showing that in all cases the copper(II) cation interacts in some way with the anion. Cation extraction is affected significantly by the anion present, with FeIII selectively extracted against CuII in the presence of SO4 2- which is consistent with cation-anion interactions having great influence on the overall stability of the ligand-metal salt assembly