Perturbation of enzyme structure by nano-metal organic frameworks: A question mark on their safety-by-design?

Abstract

Our study investigates the interactions between nanoscale Metal-Organic Frameworks (nMOFs), specifically ZIF-8 and CuIm, and key enzymes: Acetylcholine Esterase (AChE), α-amylase. Using circular dichroism (CD) spectroscopy, we observed significant alterations in the secondary structures of these enzymes upon interaction with nMOFs. AChE showed a reduction in α-helix content from 20.1 % to a significantly lower value when exposed to 160 µg/mL of nMOFs, with a corresponding increase in β-sheet and other structural components. Enzymatic activity assays revealed that CuIm nMOFs decreased AChE activity by 67.08 % at the highest concentration tested (160 µg/mL). ZIF-8 also affected AChE activity significantly at this concentration. Similarly, α-amylase exhibited structural changes, with increasing concentrations of nMOFs leading to a near-total loss of secondary structure at 80 and 160 µg/mL. These structural changes were accompanied by a marked decrease in enzymatic activity, particularly with CuIm nMOFs showing the most substantial inhibitory effects. Our findings highlight the profound impact of nMOFs on enzyme structures and functions, emphasising the need for comprehensive assessments of nMOFs' potential toxicity and understanding the aspects of their safety-by-design.