Rikkyo University

*) Nippon Soda Co.
A comprehensive chemical company led by President Eiji Aga that celebrated its 100th anniversary in 2020. Under a new slogan—"Brilliance Through Chemistry"—the company manufactures and markets high value-added chemical products such as agricultural chemicals, pharmaceutical additives, and electronic materials.

*1)
Thiabendazole (TBZ): A type of fungicide. Its main applications are as an additive for the preservation of foods such as citrus fruits and bananas, wood preservative, and industrial antibacterial/antifungal agent (paint, refrigerator door packing, antibacterial clothing, etc.).

*2)
Metal-organic framework (MOF): A general term for coordination polymers composed of organic ligands and metal ions. Also known as porous coordination polymer.

Products used in daily life should be safe, healthy, and provide reliability and comfort. In particular, there is a great deal of interest in preventing bacterial and microbial contamination. Consumers are increasingly demanding antibacterial/antifungal properties in products such as building materials, cooking utensils, home appliances, office supplies, clothing, and toys. These agents are mostly classified as inorganic (metal ions, photocatalysts such as titanium oxide) or organic compounds. Inorganic types are characterized by their high thermal stability and a broad antibacterial spectrum, while organic types have a high effectiveness per unit volume. However, physiological durability is difficult to achieve with inorganic metal ion systems, while organic types have issues with heat sensitivity and narrow antibacterial spectrums.
In this study, the research group focused on the fact that MOFs are composed of both metal ions and organic ligands. By combining bioactive metal ions and organic ligands, their goal was to develop a bioactive material with the characteristics of both metal ion and organic types.

Many MOF organic ligands use a carboxyl group (RCOO^–) or a nitrogen heterocycle as the coordination site. In the present study, zinc chloride and TBZ were combined to synthesize TBZ-MOF-1, which forms 2D horizontal network structures, and TBZ-MOF-2, which forms 1D linear structures when BDC is added as an auxiliary ligand (Figure 2). Their structures were described using single crystal X-ray structural analysis.

Thermal analysis testing conducted on these MOF (Figure 3) showed that weight loss due to sublimation occurred at 230 ºC with TBZ alone. TBZ-MOF-1 and TBZ-MOF-2, however, exhibited strong heat resistance with no weight loss or thermal decomposition until at least 400ºC. This value is higher than that of existing organometallic complexes containing TBZ, indicating that it is an extremely stable substance.

The water solubility of TBZ and MOF was investigated using the elution concentration of TBZ as the evaluation criterion. The elution concentration of TBZ alone was 20.4 ppm, while for TBZ-MOF-1 it was 0.9 ppm and TBZ-MOF-2 it was 13.7 ppm, indicating better controlled-release than TBZ alone. This shows that better bioactive durability than TBZ can be expected.

Minimum inhibitory concentration (MIC)^*3 tests were also conducted to evaluate antibacterial and antifungal activity (Table 1). Individual components of the MOF and their physiological activity were assessed with bacteria (Escherichia coli, Staphylococcus aureus subsp. aureus) and fungi (Aspergillus niger, Trichoderma virens), which showed that while TBZ alone was only antifungal and zinc alone was only antibacterial, both TBZ-MOF-1 and TBZ-MOF-2 exhibited strong antibacterial and antifungal properties.

*3)
The minimum inhibitory concentration (MIC) is the minimum level at which an antimicrobial material can inhibit the growth of a microorganism. It is calculated in drug susceptibility tests and is an important indicator for selecting antimicrobial materials.

The bioactive material developed in this study can be synthesized by a simple method using existing and readily available bioactive materials. It has a broader antimicrobial spectrum than the raw materials alone, and both controlled-release and heat-resistant properties, which indicates it could be a useful high-performance antibacterial/antifungal material.

In this study, the research group showed that with a metal-organic framework, it is possible to achieve both high levels physiological activity along with durability and stability, which has been difficult to achieve in a single agent. They plan to pursue further research that can contribute to society through collaboration between industry and academia.