Tricarbonyl-Pyrazine-Molybdenum(0) Metal-Organic Frameworks for the Storage and Delivery of Biologically Active Carbon Monoxide

Abstract

Metal-organic frameworks (MOFs) have high potential as nanoplatforms for the storage and delivery of therapeutic gasotransmitters or gas-releasing molecules. The aim of the present study was to open an investigation into the viability of tricarbonyl-pyrazine-molybdenum(0) MOFs as carbon monoxide-releasing materials (CORMAs). A previous investigation found that the reaction of Mo(CO)₆ with excess pyrazine (pyz) in a sealed ampoule gave a mixture comprising a major triclinic phase with pyz-occupied hexagonal channels, formulated as fac-Mo(CO)₃(pyz)_3/2·1/2pyz (Mo-hex), and a minor dense cubic phase, formulated as fac-Mo(CO)₃(pyz)_3/2 (Mo-cub). In the present work, an open reflux method in toluene has been optimized for the large-scale synthesis of the pure Mo-cub phase. The crystalline solids Mo-hex and Mo-cub were characterized by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), FT-IR and FT-Raman spectroscopies, and ¹³C{¹H} cross-polarization (CP) magic-angle spinning (MAS) NMR spectroscopy. The release of CO from the MOFs was studied by the deoxy-myoglobin (deoxy-Mb)/carbonmonoxy-myoglobin (MbCO) UV-vis assay. Mo-hex and Mo-cub release CO upon contact with a physiological buffer in the dark, delivering 0.35 and 0.22 equiv (based on Mo), respectively, after 24 h, with half-lives of 3-4 h. Both materials display high photostability such that the CO-releasing kinetics is not affected by irradiation of the materials with UV light. These materials are attractive as potential CORMAs due to the slow release of a high CO payload. In the solid-state and under open air, Mo-cub underwent almost complete decarbonylation over a period of 4 days, corresponding to a theoretical CO release of 10 mmol per gram of material.

Keywords: CO-releasing materials; carbon monoxide; metal−organic frameworks; molybdenum; pyrazine.

Figure 1

Views of the crystal structures of (a) Mo-cub and (b) Mo-hex. Hydrogen atoms have been omitted for clarity. Mo, green; carbon, gray; nitrogen, blue; oxygen, red.

Figure 2

Representative SEM images at different magnifications for (a, b) Mo-hex and (c, d) Mo-cub.

Figure 3

TGA curves (under air) of pyz, Mo-hex, and Mo-cub. The inset shows the DTG profile for Mo-hex and Mo-cub between 70 and 150 °C.

Figure 4

Variable temperature PXRD study of (A) Mo-hex and (B) Mo-cub: (a) 25, (b) 40, (c) 65, (d) 150, (e) 320, and (f) 600 °C. Pattern (g) is a simulated pattern for α-MoO₃ calculated using the program Mercury. The asterisks mark reflections due to the platinum sample holder.

Figure 5

ATR FT-IR (A) and FT-Raman (B) spectra of (a) pyz, (b) Mo-hex, and (c) Mo-cub.

Figure 6

¹³C{¹H} CP MAS NMR spectra of (b) Mo-hex and (c) Mo-cub compared with (a) the solution ¹³C{¹H} NMR spectrum of pyrazine (CDCl₃).

Figure 7

Time courses of CO release (measured by the Mb assay) from Mo-cub and Mo-hex in the dark when suspended in 10 mM HEPES at 37 °C.