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

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 subset of nano-Cu-BTC, 4) released NO at 1.81 mu mol center dot mg(-1) in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO subset of Cu-BTC was successfully determined to be [CuC6H2O5]center dot(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 subset of Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO subset of Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.

Automated summary

In this study, micro-sized and nano-sized Cu-BTC MOFs were prepared and their NO storage and release properties were found to be morphology dependent. Control of hydration degree and morphology improved the NO release characteristics significantly. The nano-sized NO-loaded Cu-BTC met the requirements for clinical usage and exhibited significant antibacterial activity.