As anticipated, the use of HD-US-UiO-66-NH2 led to ca. 3 times higher reactivity compared to conventional UiO-66-NH2 particles (ca. 200 nm) reported previously (Figure ). Such an enhancement might be due to the significantly expanded external surface area and/or the large defect content. Thus, we have compared the performance of HD-US-UiO-66-NH2 and MI-US-UiO-66-NH2 nanoMOFs with the previous study. Noteworthy, although MI-US-UiO-66-NH2 showed better reactivity compared to the previous study, it performed worse (ca. 2 times) than HD-US-UiO-66-NH2, despite their very similar particle size. This suggests that maximizing the amount of missing linker defects is critical to enhance the reactivity of UiO-66 derivatives towards peptide bond hydrolysis, in combination with decreasing the particle size. Notably, the reactivity here is comparable to benchmarks materials such as "superactive" MOF-808 (35 nm), which exhibited a GG hydrolysis rate of 2.69 x10 -4 s -1 . 47 The recyclability of HD-US-UiO-66-NH2 nanoMOF was tested over five subsequent reaction cycles (Figure ), with the slight loss of reactivity being only recorded after the 4 th cycle, where the reactivity dropped to 80% of the reactivity observed in cycle 1. This is however still an excellent recyclability, especially when compared to benchmark materials, such as MIP-201 and MOF-808, which suffered from lower recyclability (55% and 80% activity reduction after up to 5 cycles, respectively, Figure ), and highlights the water stability of these ultra-small highly defective nanoMOFs, The specificity of the catalyst was further studied, as GG may be hydrolyzed to G, or may undergo cyclisation (amide bond formation), forming cyclic GG (cGG) (Figure ). By using HD-UiO-66-NH2 nanoMOFs of two different sizes (4 nm vs 200 nm), the influence on particle size and external vs internal surface area on the reaction specificity was examined. The 200 nm UiO-66-NH2 is labeled as HD-200-UiO-66-NH2, and was fully characterized prior to catalytic reaction (Figure -38). Interestingly, the HD-US-UiO-66-NH2 was found to be more selective, consistently giving a greater proportion of hydrolysis product G, rather than cGG, regardless of the starting concentration of GG substrate (Figure ). The HD-200-UiO-66-NH2 produced considerably more cGG (40 -50% of product), likely due to the increased internal surface area compared to HD-US-UiO-66-NH2, which promotes amide bond condensation in the absence of water in the more hydrophobic pores, rather than hydrolysis reaction at the water exposed external surface of the nanoMOF.