Mixed metal-organic framework mixed-matrix membranes : insights into simultaneous moisture-triggered and catalytic delivery of nitric oxide using cryo-scanning electron microscopy

Funding: This work was supported by the European Research Council grant ADOR (Advanced Grant 787073). The authors acknowledge the EPSRC Light Element Analysis Facility Grant (EP/T019298/1) and the EPSRC Strategic Equipment Resource Grant (EP/R023751/1).The fundamental chemical and structural diversity of metal–organic frameworks (MOFs) is vast, but there is a lack of industrial adoption of these extremely versatile compounds. To bridge the gap between basic research and industry, MOF powders must be formulated into more application-relevant shapes and/or composites. Successful incorporation of varying ratios of two different MOFs, CPO-27-Ni and CuBTTri, in a thin polymer film represents an important step toward the development of mixed MOF mixed-matrix membranes. To gain insight into the distribution of the two different MOFs in the polymer, we report their investigation by Cryo-scanning electron microscopy (Cryo-SEM) tomography, which minimizes surface charging and electron beam-induced damage. Because the MOFs are based on two different metal ions, Ni and Cu, the elemental maps of the MOF composite cross sections clearly identify the size and location of each MOF in the reconstructed 3D model. The tomography run was about six times faster than conventional focused ion beam (FIB)-SEM and the first insights to image segmentation combined with machine learning could be achieved. To verify that the MOF composites combined the benefits of rapid moisture-triggered release of nitric oxide (NO) from CPO-27-Ni with the continuous catalytic generation of NO from CuBTTri, we characterized their ability to deliver NO individually and simultaneously. These MOF composites show great promise to achieve optimal dual NO delivery in real-world medical applications.Publisher PDFPeer reviewe

Antibacterial efficacy from NO-releasing MOF–polymer films

Authors gratefully thank the following funding sources for financial support: Scottish Enterprise (POC13), EPSRC (EP/K005499/1 and Capital for Great Technologies grant EP/L017008/1), European Social Fund Studentship and the University of St Andrews School of Chemistry.The formulation and antibacterial efficacy of nitric oxide (NO)-releasing MOF–polyurethane films are reported for the first time. Uniform standalone films were successfully prepared containing 1, 5, 10, and 15 wt% CPO-27 (Ni). The MOF within each film was successfully activated and loaded with NO. Adsorption and release profiles are reported for the films and show that while the polymer influences the quantity of NO adsorbed and stored by the MOF and the time scale of release; the proportion of stored NO that is released is dependent on wt% loading of MOF in the film. In a cytotoxicity assay, the formulations exhibited very low toxicity (<20% cell death), and this toxicity was attributed to the NO rather than the MOF. Antibacterial data against E. coli and S. aureus indicated that bactericidal efficacy can be achieved in 5 hours from 1 wt% films, and within 1 hour for films containing at least 5 wt% MOF.Publisher PDFPeer reviewe

Nonstoichiometric layered LixMnyO2 intercalation electrodes: a multiple dopant strategy

Layered LixMnyO2 materials with the O3 (alpha-NaFeO2) structure have been synthesised by a low temperature ion exchange route from the corresponding sodium compounds. Previous studies have concentrated upon the undoped and singly doped families of O3 layered lithium manganese oxides. This is the first report of multiply doped analogues. The effects on electrochemical performance (ability to store reversibly large quantities of lithium and hence charge) and crystal chemistry of partially substituting some of the Mn ions with two dopants have been investigated. A range of structural (X-ray and neutron diffraction) and electrochemical (galvanostatic cycling and a. c. impedance) techniques as well as chemical analyses were utilised. The new materials, LixMny-2zMzM'O-z(2) (M, M' = Li, Cu, Mg, Ni, Zn, Al and Co), offer high capacities in excess of 200 mA h g(-1) at a rate of 50 mA g(-1) (C/4) with the highest values being for the z = 0.025 series. The main advantage of the multiply doped materials over the previously reported undoped and singly doped O3 layered lithium manganese oxides is their far superior rate capability. All the compounds in this study irreversibly transform to spinel-like materials on extended cycling. This is not, however, detrimental to their electrochemical performance and is analogous to the behaviour of other lightly doped O3 layered lithium manganese oxides.</p

Water based scale-up of CPO-27 synthesis for nitric oxide delivery

The authors thank Scottish Enterprise for funding for the scale up work (POC13). We gratefully acknowledge the EPSRC (EP/K025112/1) and the Royal society for the Brian Mercer Award for Innovation (MI120033).The applicability of water-based reflux and room temperature synthesis processes for the production of CPO-27 MOFs, suitable for NO delivery applications, is investigated. NO adsorption, storage and release performance of products obtained under reflux conditions are comparable to those of equivalent samples synthesised from traditional solvothermal methods at small scale. Products obtained from room temperature processes show lower NO release capability, although the quantities that are released are still more than adequate for biomedical applications. Results also reveal differences for the first time in NO uptake, storage and release depending on whether Zn, Ni or Mg is employed. The results indicate that while the crystallinity of CPO-27 (Zn) and CPO-27 (Mg) is not affected by moving to lower temperature methods, the crystallinity of CPO-27 (Ni) is reduced. Particle morphology and size is also affected. The low temperature processes are successfully demonstrated at 20L and 100L scale and the main problems encountered during scale-up are outlined. The 100L scale is in itself an appropriate production scale for some niche biomedical products. Indeed, results indicate that this synthesis approach is suitable for commercial production of MOFs for this application field. We also confirm that BET surface area from nitrogen adsorption at 77 K is not a good indicator for successful adsorption of NO.Publisher PDFPeer reviewe

Multirate delivery of multiple therapeutic agents from metal-organic frameworks

REM is a Royal Society Industry Fellow and thanks the Royal Society for the provision of the Brian Mercer Award for Innovation, and thanks Scottish Enterprise for support. REM also thanks the British Heart Foundation for a New Horizons Award (NH/11/8/29253). REM and TD thank the EPSRC for funding (EP/K025112/1 and EP/K005499/1).The highly porous nature of metal-organic frameworks (MOFs) offers great potential for the delivery of therapeutic agents. Here, we show that highly porous metal-organic frameworks can be used to deliver multiple therapeutic agents—a biologically active gas, an antibiotic drug molecule, and an active metal ion—simultaneously but at different rates. The possibilities offered by delivery of multiple agents with different mechanisms of action and, in particular, variable timescales may allow new therapy approaches. Here, we show that the loaded MOFs are highly active against various strains of bacteria.Publisher PDFPeer reviewe

Multifaceted study of the interactions between CPO-27-Ni and polyurethane and their impact on nitric oxide release performance

S.M.V. would like to thank the EPSRC for funding opportunities under grant agreement EP/K005499/1. S.M.V. and D.N.M. would further like to acknowledge the EPSRC Capital for Great Technologies grant (EP/L017008/1) and the EPSRC Strategic Equipment Resource grant (EP/R023751) for funding and supporting electron microscopy facilities at the University of St Andrews. M.J.D. and S.J.W. would like to acknowledge the ProDIA project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 685727.A multifaceted study involving focused ion beam scanning electron microscopy techniques, mechanical analysis, water adsorption measurements, and molecular simulations is employed to rationalize the nitric oxide release performance of polyurethane films containing 5, 10, 20, and 40 wt % of the metal-organic framework (MOF) CPO-27-Ni. The polymer and the MOF are first demonstrated to exhibit excellent compatibility. This is reflected in the even distribution and encapsulation of large wt % MOF loadings throughout the full thickness of the films and by the rather minimal influence of the MOF on the mechanical properties of the polymer at low wt %. The NO release efficiency of the MOF is attenuated by the polymer and found to depend on wt % of MOF loading. The formation of a fully connected network of MOF agglomerates within the films at higher wt % is proposed to contribute to a more complex guest transport in these formulations, resulting in a reduction of NO release efficiency and film ductility. An optimum MOF loading of 10 wt % is identified for maximizing NO release without adversely impacting the polymer properties. Bactericidal efficacy of released NO from the films is demonstrated against Pseudomonas aeruginosa, with a >8 log10 reduction in cell density observed after a contact period of 24 h.Publisher PDFPeer reviewe

Preventing undesirable structure flexibility in pyromellitate metal organic frameworks

Removal of coordinated water molecules from the porous Zn‐pyromellitate metal organic framework Zn5(OH)2(PMA)2(H2O)4· x H2O (PMA = pyromellitic acid or 1,2,4,5‐benzene tetracarboxylic acid) should generate coordinatively unsaturated metal sites suitable for gas adsorption. However, reports of instability towards dehydration have restricted the study and utility of this MOF. Here we examine in more detail the nature of the structural transformation that occurs upon dehydration. This study reveals that a fully reversible crystalline‐crystalline transformation from a porous to a non‐porous homologue takes place, proceeding through a partially dehydrated intermediate. We show that doping the structure with Ni2+ ions at greater than 30 % prevents structural rearrangement, thereby maintaining porosity, and rendering the material effective for gas (nitric oxide) adsorption applications. These results indicate that doping can be an effective means to increase the utility of otherwise unserviceable structures

Antibacterial efficacy from NO-releasing MOF–polymer films

The formulation and antibacterial efficacy of nitric oxide (NO)-releasing MOF–polyurethane films are reported for the first time. Uniform standalone films were successfully prepared containing 1, 5, 10, and 15 wt% CPO-27 (Ni). The MOF within each film was successfully activated and loaded with NO. Adsorption and release profiles are reported for the films and show that while the polymer influences the quantity of NO adsorbed and stored by the MOF and the time scale of release; the proportion of stored NO that is released is dependent on wt% loading of MOF in the film. In a cytotoxicity assay, the formulations exhibited very low toxicity (&lt;20% cell death), and this toxicity was attributed to the NO rather than the MOF. Antibacterial data against E. coli and S. aureus indicated that bactericidal efficacy can be achieved in 5 hours from 1 wt% films, and within 1 hour for films containing at least 5 wt% MOF