60th Annual Report on Research 2015

Metal-Organic Frameworks: MOFs are known as porous coordination polymers and become an emerging type of porous materials, which are formed by the self-assembling of metallic centers and bridging organic linkers. The metal ions or clusters reacted with ligands to form secondary building units. ^[2] MOFs, as an important family of compounds have diversified applications in gas storage, ^[3] separation, ^[4] catalysis, ^[5] drug delivery, ^[6] and molecular sensing. ^[7] MOFs are characterized by their tunable pore sizes, topologies, and functionality and their inherent flexibility ^[8] arising from their inorganic−organic hybrid nature, leading to their classification as soft porous crystals. Such flexibility is not generally observed in more classic carbon- or oxide-based porous materials. ^[9] Framework flexibility usually occurs as a guest-induced transformation between two or more structures that occurs upon desolvation and/or guest readsorption. ^[10] The design and synthesis of organic linkers are pivotal to MOFs with required structures and properties. ^[11]

MOFs synthesis: The linear ditopic-carboxylate ligands were used to product MOFs. The carboxylate units are important due to their preference to stabilize MOFs through secondary building units. ^[12] Thus, carboxylate-containing units with aromatic backbones could be used as linkers to construct porous MOFs.  The structures, topologies, pore/cage sizes and porosities can be functionalized. ^[11] Use of m-benzenedicarboxylate unit, Cu₃(BTC)₂ holding  the highest methane adsorption has been synthesized. ^[13] It was found that Zr-based MOFs confer superior stability compared to common Zn/Cu based MOFs. ^[14] Therefore, the terphenyl-4,4-dicarboxylic acid with two carboxylates was used as the primary building. Totally, eight formulations of MOFs were prepared by solvothermal chemistry under moderate conditions. Specifically, a mixture of inorganic ionic compounds (ZrCl₄) and ligands (Table 2 from Zhou’s group), solvent and benzoic acid were placed in a capped glass bottle.  This solution was ultrasonically dissolved and heated at 100 °C for 2 days. The final product was cooled down to ambient condition.

Table 2: The ligands with different bridging angles, leading to diverse architectures of MOFs.

Gas Adsorption: Solvent-exchanged MOFs were obtained by soaking the samples in acetone /Dichloromethane (DCM) for 3 days, refreshing every 5 h. The completely desolvated MOFs would be afforded by heating the solvent-exchanged bulk at 393 K under a vacuum overnight. The samples were further activated by using the degassing port in the surface area analyzer for 10 h at 393 K to measure the gas uptake. Low-pressure methane (CH₄) sorption experiments were recorded on a Quantachrome IQ2 system under different conditions. The Micrometrics ASAP 2020 Physisorption Surface Area and Pore Analyzer was used to determine methane adsorption isotherms at 195K. The ASAP 2020 measures pressure and then computes volume adsorbed as a result of pressure changes.

Materials Safety Evaluation: It is also important to ensure the MOFs and gas-absorbed MOFs will not cause health concerns due to their incidental release into the environment.  In this study, we conducted the degree of apoptosis (cell death) in retinal pigment epithelium (RPE) cells. ^[15] The cytotoxicity bioassay was based on total fluorescence yield of 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF FM DA, as measure of NO), which was a ratio between treated and untreated cells in PBS (pH 7.4) solution. The NO was measure at 10 minute time point versus control RPE (120´10³ cells/well) whole cells [WC] with the following treatments: 0.5 mL (1mg/mL of MOFs). Other control agents were also added for comparison. These were: 25 mL (10 mg/mL of sodium cyanide) [CN]; 25 mL (1 mg/mL of 7-Ethyl-10-hydroxy-camptothecin)[SN-38], 5 mL (100 mg/mL  of rotenone) [Rot]; and 5 mL (100 mg/mL of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone) [FCCP].

Gas adsorption of CH₄: Low pressure CH₄ uptake was measured using micrometrics ASAP 2020 instrument at 195K. The methane uptake of Zr-WX2 is shown in Fig. 2. It is estimated that the isoreticular MOFs in the WX series will show higher uptake and higher surface area with the presence of the extended side aliphatic chains (further study will be carried out).

                                Fig. 2: The CH₄ adsorption isotherm: A: CH₄ (courtesy for Dr. Zhou) B: adsorption of Zr-WX2.

Toxicity study: Measured NO from cells treated with the MOFs and other agents whose mode of inhibition or stimulation in NO generation was compared. Results indicated that some MOFs were not toxic to RPE cells, whereas others exhibited toxicity (Fig. 3). The bioassay using NO as a diagnostic molecule is a broad responsive bioassay to examine the toxicity of MOFs. The results demonstrate that tuned MOFs were not harmful to human health, but protective agent against oxidative stress through release of NO.

Fig. 3: Toxicity study of MOFs (two slected), A: Fluorescence of DAF FM DA, as measure of NO, B: Fluorescence of tetramethylrhodamine ethyl ester as measure of mitochondrial membrane potential; C: Fluorescence of singlet oxygen sensor green; and D: Proposed mechanism for increased RPE cell death induced by MOFs.

Conclusion:

Eight formulations of MOFs were synthesized and methane gas uptake was measured. The MOFs are estimated to show improved volumetric and gravimetric capacities. The ligands consisted mainly of four dicarboxylic acids with an aromatic backbone. The biochemical processes through which MOFs exhibits toxicity was evaluated and shown to be consistent with that mitochondrial oxidative stress and associated cellular dysfunction.