Controllable Nitric Oxide Storage and Release in Cu-BTC: Crystallographic Insights and Bioactivity

Abstract

Crystalline metal–organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg−1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.

Effect of CuBTC Composition, Structure, and Morphology on the Catalytic and Antimicrobial Properties

“…The view of the calculated diffraction patterns of [Cu 3 (BTC) 2 ] with a = 26.2792(3) Å (Figure a,b), [Cu 3 (BTC) 2 (H 2 O w ) 3 ] with a = 26.315(3) Å (no. 943962 in CCDC database) or a = 26.3015(4) Å (Figure c,d), [Cu 3 (BTC) 2 (H 2 O w ) 3.42(12) ] × 3.54H 2 O (total composition is Cu 3 (C 9 H 3 O 6 ) 2 (H 2 O) 6.96 ) with a = 26.3103(11) Å (Figure e,f) together with the similar calculation data for [Cu 3 (BTC) 2 ], [Cu 3 (BTC) 2 (H 2 O w ) 3 ], and [Cu 3 (BTC) 2 (H 2 O w ) 3 ] × n H 2 O structures, and their analysis indicates a redistribution of the intensities of a number of reflections.…”

“…aeruginosa bacterium, and the S , mm 2 , value is the highest for CuBTC-5. Our samples demonstrate a much higher AMA compared to the same sample from ref with S = 47.8 mm 2 .…”

“…It follows from Table that the average sensitivity of the E. coli bacterium is the highest to the “as-synthesized” CuBTC-2 sample, but the S , mm 2 value is still less than that for the [Cu 3 (BTC) 2 (H 2 O w ) 3 ] sample with a = 26.3015(4) Å and high sensitivity ( S = 712.3 mm 2 ) …”

Applications of Nano/Micromotors for Treatment and Diagnosis in Biological Lumens

“…(B) The bladder is not constantly filled with urine. We suggest that future works could design a structure, such as nano-sized Cu-BTC (BTC: benzene-1,3,5-tricarboxylate) [ 67 ], that allows the micromotor to store a portion of urea when it is abundant. When the bladder is empty, the micromotor reuses the stored urea, allowing it to move during the bladder’s “dry season”.…”

Frontiers in Antimicrobial Biomaterials

“…The nitric oxide release was maintained as constant for 12 h, meeting the requirements for clinical applications. Most importantly, the authors verified the structures’ antibacterial potential by their significant elimination of six bacteria strains, highlighting the synergistic effects between the payload and carrier [ 18 ].…”