Role of Metal-Organic Framework Topology on Thermodynamics of Polyoxometalate Encapsulation.

Polyoxometalates (POMs) are discrete anionic clusters whose rich redox properties, strong BroÌ·nsted acidity, and high availability of active sites make them potent catalysts for oxidation reactions. Metal-organic frameworks (MOFs) have emerged as tunable, porous platforms to immobilize POMs, thus increasing their solution stability and catalytic activity. While POM@MOF composite materials have been widely used for a variety of applications, little is known about the thermodynamics of the encapsulation process. Here, we utilize an up-and-coming technique in the field of heterogeneous materials, isothermal titration calorimetry (ITC), to obtain full thermodynamic profiles (ΔH, ΔS, ΔG, and Ka) of POM binding. Six different 8-connected hexanuclear Zr-MOFs were investigated to determine the impact of MOF topology (csq, scu, and the) on POM encapsulation thermodynamics.

Biomimetic Mineralization of Large Enzymes Utilizing a Stable Zirconium-Based Metal-Organic Frameworks.

Enzymes are natural catalysts for a wide range of metabolic chemical transformations, including selective hydrolysis, oxidation, and phosphorylation. Herein, we demonstrate a strategy for the encapsulation of enzymes within a highly stable zirconium-based metal-organic framework. UiO-66-F4 was synthesized under mild conditions using an enzyme-compatible amino acid modulator, serine, at a modest temperature in an aqueous solution. Enzyme@UiO-66-F4 biocomposites were then formed by an in situ encapsulation route in which UiO-66-F4 grows around the enzymes and, consequently, provides protection for the enzymes. A range of enzymes, namely, lysozyme, horseradish peroxidase, and amano lipase, were successfully encapsulated within UiO-66-F4. We further demonstrate that the resulting biocomposites are stable under conditions that could denature many enzymes. Horseradish peroxidase encapsulated within UiO-66-F4 maintained its biological activity even after being treated with the proteolytic enzyme pepsin and heated at 60 °C. This strategy expands the toolbox of potential metal-organic frameworks with different topologies or functionalities that can be used as enzyme encapsulation hosts. We also demonstrate that this versatile process of in situ encapsulation of enzymes under mild conditions (i.e., submerged in water and at a modest temperature) can be generalized to encapsulate enzymes of various sizes within UiO-66-F4 while protecting them from harsh conditions (i.e., high temperatures, contact with denaturants or organic solvents).

Thermodynamic Insights into Phosphonate Binding in Metal-Azolate Frameworks.

Organophosphorus chemicals, including chemical warfare agents (CWAs) and insecticides, are acutely toxic materials that warrant capture and degradation. Metal-organic frameworks (MOFs) have emerged as a class of tunable, porous, crystalline materials capable of hydrolytically cleaving, and thus detoxifying, several organophosphorus nerve agents and their simulants. One such MOF is M-MFU-4l (M = metal), a bioinspired azolate framework whose metal node is composed of a variety of divalent first-row transition metals. While Cu-MFU-4l and Zn-MFU-4l are shown to rapidly degrade CWA simulants, Ni-MFU-4l and Co-MFU-4l display drastically lower activities. The lack of reactivity was hypothesized to arise from the strong binding of the phosphate product to the node, which deactivates the catalyst by preventing turnover. No such study has provided detailed insight into this mechanism. Here, we leverage isothermal titration calorimetry (ITC) to monitor the binding of an organophosphorus compound with the M-MFU-4l series to construct a complete thermodynamic profile (Ka, ΔH, ΔS, ΔG) of this interaction. This study further establishes ITC as a viable technique to probe small differences in thermodynamics that result in stark differences in material properties, which may allow for better design of first-row transition metal MOF catalysts for organophosphorus hydrolysis.

Investigating the mechanical stability of flexible metal-organic frameworks.

As we continue to develop metal-organic frameworks (MOFs) for potential industrial applications, it becomes increasingly imperative to understand their mechanical stability. Notably, amongst flexible MOFs, structure-property relationships regarding their compressibility under pressure remain unclear. In this work, we conducted in situ variable pressure powder X-ray diffraction (PXRD) measurements up to moderate pressures (<1 GPa) using a synchrotron source on two families of flexible MOFs: (i) NU-1400 and NU-1401, and (ii) MIL-88B, MIL-88B-(CH3)2, and MIL-88B-(CH3)4. In this project scope, we found a positive correlation between bulk moduli and degree of flexibility, where increased rigidity (e.g., smaller swelling or breathing amplitude) arising from steric hindrance was deleterious, and observed reversibility in the unit cell compression of these MOFs. This study serves as a primer for the community to begin to untangle the factors that engender flexible frameworks with mechanical resilience.

Reticular Chemistry in Its Chiral Form: Axially Chiral Zr(IV)-Spiro Metal-Organic Framework as a Case Study.

The interplay of primary organic ligands and inorganic secondary building units (SBUs) has led to a continual boom of reticular chemistry, particularly metal-organic frameworks (MOFs). Subtle variations of organic ligands can have a significant impact on the ultimate structural topology and consequently, the material's function. However, the role of ligand chirality in reticular chemistry has rarely been explored. In this work, we report the organic ligand chirality-controlled synthesis of two zirconium-based MOFs (Spiro-1 and Spiro-3) with distinct topological structures as well as a temperature-controlled formation of a kinetically stable phase (Spiro-4) based on the carboxylate-functionalized inherently axially chiral 1,1'-spirobiindane-7,7'-phosphoric acid ligand. Specifically, Spiro-1 is a homochiral framework comprising only enantiopure S-spiro ligands and has a unique 4,8-connected sjt topology with large 3D interconnected cavities, while Spiro-3 contains equal amounts of S- and R-spiro ligands, resulting in a racemic framework of 6,12-connected edge-transitive alb topology with narrow channels. Interestingly, the kinetic product Spiro-4 obtained with racemic spiro ligands is built of both hexa- and nona-nuclear zirconium clusters acting as 9- and 6-connected nodes, respectively, giving rise to a newly discovered azs net. Notably, the preinstalled highly hydrophilic phosphoric acid groups combined with large cavity, high porosity, and outstanding chemical stability endow Spiro-1 with remarkable water vapor sorption performance, whereas Spiro-3 and Spiro-4 show poor performances due to inappropriate pore systems and structural fragility upon the water adsorption/desorption process. This work highlights the important role of ligand chirality in manipulating the framework topology and function and would further enrich the development of reticular chemistry.

Silver nanoparticle interactions with glycated and non-glycated human serum albumin mediate toxicity.

Introduction: Biomolecules bind to and transform nanoparticles, mediating their fate in biological systems. Despite over a decade of research into the protein corona, the role of protein modifications in mediating their interaction with nanomaterials remains poorly understood. In this study, we evaluated how glycation of the most abundant blood protein, human serum albumin (HSA), influences the formation of the protein corona on 40 nm silver nanoparticles (AgNPs) and the toxicity of AgNPs to the HepG2 human liver cell line. Methods: The effects of glycation on AgNP-HSA interactions were quantified using circular dichroism spectroscopy to monitor protein structural changes, dynamic light scattering to assess AgNP colloidal stability, zeta potential measurements to measure AgNP surface charge, and UV-vis spectroscopy and capillary electrophoresis (CE) to evaluate protein binding affinity and kinetics. The effect of the protein corona and HSA glycation on the toxicity of AgNPs to HepG2 cells was measured using the WST cell viability assay and AgNP dissolution was measured using linear sweep stripping voltammetry. Results and Discussion: Results from UV-vis and CE analyses suggest that glycation of HSA had little impact on the formation of the AgNP protein corona with protein-AgNP association constants of ≈2x107 M-1 for both HSA and glycated HSA (gHSA). The formation of the protein corona itself (regardless of whether it was formed from HSA or glycated HSA) caused an approximate 2-fold decrease in cell viability compared to the no protein AgNP control. While the toxicity of AgNPs to cells is often attributed to dissolved Ag(I), dissolution studies showed that the protein coated AgNPs underwent less dissolution than the no protein control, suggesting that the protein corona facilitated a nanoparticle-specific mechanism of toxicity. Overall, this study highlights the importance of protein coronas in mediating AgNP interactions with HepG2 cells and the need for future work to discern how protein coronas and protein modifications (like glycation) may alter AgNP reactivity to cellular organisms.

Structure-Activity Relationship Insights for Organophosphonate Hydrolysis at Ti(IV) Active Sites in Metal-Organic Frameworks.

Organophosphorus nerve agents are among the most toxic chemicals known and remain threats to humans due to their continued use despite international bans. Metal-organic frameworks (MOFs) have emerged as a class of heterogeneous catalysts with tunable structures that are capable of rapidly detoxifying these chemicals via hydrolysis at Lewis acidic active sites on the metal nodes. To date, the majority of studies in this field have focused on zirconium-based MOFs (Zr-MOFs) that contain hexanuclear Zr(IV) clusters, despite the large toolbox of Lewis acidic transition metal ions that are available to construct MOFs with similar catalytic properties. In particular, very few reports have disclosed the use of a Ti-based MOF (Ti-MOF) as a catalyst for this transformation even though Ti(IV) is a stronger Lewis acid than Zr(IV). In this work, we explored five Ti-MOFs (Ti-MFU-4l, NU-1012-NDC, MIL-125, Ti-MIL-101, MIL-177(LT), and MIL-177(HT)) that each contains Ti(IV) ions in unique coordination environments, including monometallic, bimetallic, octanuclear, triangular clusters, and extended chains, as catalysts to explore how both different node structures and different linkers (e.g., azolate and carboxylate) influence the binding and subsequent hydrolysis of an organophosphorus nerve agent simulant at Ti(IV)-based active sites in basic aqueous solutions. Experimental and theoretical studies confirm that Ti-MFU-4l, which contains monometallic Ti(IV)-OH species, exhibits the best catalytic performance among this series with a half-life of roughly 2 min. This places Ti-MFU-4l as one of the best nerve agent hydrolysis catalysts of any MOF reported to date.

Silver Nanoparticle Surface Chemistry Determines Interactions with Human Serum Albumin and Cytotoxic Responses in Human Liver Cells.

Engineered nanomaterials (ENMs) are synthesized with a diversity of surface chemistries that mediate biochemical interactions and physiological response to the particles. In this work, silver engineered nanomaterials (AgENMs) are used to evaluate the role of surface charge in protein interactions and cellular cytotoxicity. The most abundant protein in blood, human serum albumin (HSA), was interacted with 40 nm AgENMs with a range of surface-charged coatings: positively charged branched polyethyleneimine (bPEI), negatively charged citrate (CIT), and circumneutral poly(ethylene glycol) (PEG). HSA adsorption to AgENMs was monitored by UV-vis spectroscopy and dynamic light scattering, while changes to the protein structure were evaluated with circular dichroism spectroscopy. Binding affinity for citrate-coated AgENMs and HSA is largest among the three AgENM coatings; yet, HSA lost the most secondary structure upon interaction with bPEI-coated AgENMs compared to the other two coatings. HSA increased AgENM oxidative dissolution across all particle types, with the greatest dissolution for citrate-coated AgENMs. Results indicate that surface coating is an important consideration in transformation of both the particle and protein upon interaction. To connect results to cellular outcomes, we also performed cytotoxicity experiments with HepG2 cells across all three AgENM types with and without HSA. Results show that bPEI-coated AgENMs cause the greatest loss of cell viability, both with and without inclusion of HSA with the AgENMs. Thus, surface coatings on AgENMs alter both biophysical interactions with proteins and particle cytotoxicity. Within this study set, positively charged bPEI-coated AgENMs cause the greatest disruption to HSA structure and cell viability.

Tröger's Base Chemistry in Solution and in Zr(IV)-Based Metal-Organic Frameworks.

Tröger's base (TB) and its derivatives have been studied extensively due to their unique concave shape stemming from the endomethylene strap. However, the strap-clipped TB chemistry has been largely overlooked in metal-organic framework (MOF) solids, leading to a gap in our knowledge within this field. In this work, we report the in situ strap elimination of a carboxylate-carrying TB in the presence of formic acid, both in solution and in Zr(IV)-based MOFs. In the solution system, the methanodiazocine nucleus can be exclusively transformed into an N,N'-diformyl-decorated phenhomazine derivative, regardless of the solvent used (DMF, DMA, or DEF), as unambiguously uncovered by single crystal X-ray crystallography. In contrast, while in the MOF synthetic system, the degree of derivatization reaction can be effectively controlled to give either the secondary diamine or formyl-decorated diamine, depending on the solvent used (DMF or DEF), resulting in the formation of two Zr-MOFs with 8-connected bcu (NU-1900) and 12-connected fcu (NU-407) topologies, respectively. The derivatization mechanism is proposed to be topology-guided and dependent on the local acid concentration during the MOF formation processes. Moreover, we discovered a novel post-synthetically water-induced in situ linker formylation process in NU-1900 through sequential formic acid elimination, migration, and condensation processes, affording an isostructural framework with the same linker as in NU-407, which further corroborates our proposed mechanism. Additionally, the highly defective NU-1900 with abundant accessible Zr sites was demonstrated to be an outstanding catalyst for the detoxification of a nerve agent simulant with a half-life of less than 1 min.

Sulfated Zirconium Metal-Organic Frameworks as Well-Defined Supports for Enhancing Organometallic Catalysis.

Understanding heterogeneous catalysts is a challenging pursuit due to surface site nonuniformity and aperiodicity in traditionally used materials. One example is sulfated metal oxides, which function as highly active catalysts and as supports for organometallic complexes. These applications are due to traits such as acidity, ability to act as a weakly coordinating ligand, and aptitude for promoting transformations via radical cation intermediates. Research is ongoing about the structural features of sulfated metal oxides that imbue the aforementioned properties, such as sulfate geometry and coordination. To better understand these materials, metal-organic frameworks (MOFs) have been targeted as structurally defined analogues. Composed of inorganic nodes and organic linkers, MOFs possess features such as high porosity and crystallinity, which make them attractive for mechanistic studies of heterogeneous catalysts. In this work, Zr6-based MOF NU-1000 is sulfated and characterized using techniques such as single crystal X-ray diffraction in addition to diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The dynamic nature of the sulfate binding motif is found to transition from monodentate, to bidentate, to tridentate depending on the degree of hydration, as supported by density functional theory (DFT) calculations. Heightened Brønsted acidity compared to the parent MOF was observed upon sulfation and probed through trimethylphosphine oxide physisorption, ammonia sorption, in situ ammonia DRIFTS, and DFT studies. With the support structure benchmarked, an organoiridium complex was chemisorbed onto the sulfated MOF node, and the efficacy of this supported catalyst was demonstrated for stoichiometric and catalytic activation of benzene-d6 and toluene with structure-activity relationships derived.

Exchange of coordinated carboxylates with azolates as a route to obtain a microporous zinc-azolate framework.

Metal-organic frameworks (MOFs) containing open metal sites are advantageous for wide applications. Here, carboxylate linkers are replaced with triazolate coordination in pre-formed Zn-MOF-74 via solvent-assisted linker exchange (SALE) to prepare the novel NU-250, within the known hexagonal channel-based MAF-X25 series that has not previously been synthesized de novo.

Environmental dimensions of the protein corona.

The adsorption of biomolecules to the surface of engineered nanomaterials, known as corona formation, defines their biological identity by altering their surface properties and transforming the physical, chemical and biological characteristics of the particles. In the first decade since the term protein corona was coined, studies have focused primarily on biomedical applications and human toxicity. The relevance of the environmental dimensions of the protein corona is still emerging. Often referred to as the eco-corona, a biomolecular coating forms upon nanomaterials as they enter the environment and may include proteins, as well as a diverse array of other biomolecules such as metabolites from cellular activity and/or natural organic matter. Proteins remain central in studies of eco-coronas because of the ease of monitoring and structurally characterizing proteins, as well as their crucial role in receptor engagement and signalling. The proteins within the eco-corona are optimal targets to establish the biophysicochemical principles of corona formation and transformation, as well as downstream impacts on nanomaterial uptake, distribution and impacts on the environment. Moreover, proteins appear to impart a biological identity, leading to cellular or organismal recognition of nanomaterials, a unique characteristic compared with natural organic matter. We contrast insights into protein corona formation from clinical samples with those in environmentally relevant systems. Principles specific to the environment are also explored to gain insights into the dynamics of interaction with or replacement by other biomolecules, including changes during trophic transfer and ecotoxicity. With many challenges remaining, we also highlight key opportunities for method development and impactful systems on which to focus the next phase of eco-corona studies. By interrogating these environmental dimensions of the protein corona, we offer a perspective on how mechanistic insights into protein coronas in the environment can lead to more sustainable, environmentally safe nanomaterials, as well as enhancing the efficacy of nanomaterials used in remediation and in the agri-food sector.

Low-Dose Silver Nanoparticle Surface Chemistry and Temporal Effects on Gene Expression in Human Liver Cells.

Silver nanoparticles (AgNPs) are widely incorporated into consumer and biomedical products for their antimicrobial and plasmonic properties with limited risk assessment of low-dose cumulative exposure in humans. To evaluate cellular responses to low-dose AgNP exposures across time, human liver cells (HepG2) are exposed to AgNPs with three different surface charges (1.2 µg mL-1 ) and complete gene expression is monitored across a 24 h period. Time and AgNP surface chemistry mediate gene expression. In addition, since cells are fed, time has marked effects on gene expression that should be considered. Surface chemistry of AgNPs alters gene transcription in a time-dependent manner, with the most dramatic effects in cationic AgNPs. Universal to all surface coatings, AgNP-treated cells responded by inactivating proliferation and enabling cell cycle checkpoints. Further analysis of these universal features of AgNP cellular response, as well as more detailed analysis of specific AgNP treatments, time points, or specific genes, is facilitated with an accompanying application. Taken together, these results provide a foundation for understanding hepatic response to low-dose AgNPs for future risk assessment.