To further investigate the nature of the missing linker defects at atomic level, in situ FTIR spectroscopy in presence of acetonitrile-d3 (CD3CN) vapors was performed. The acidity of pristine UiO-66(Zr) is mostly assigned to its intrinsic Brønsted acid sites (four μ3-OH), while, upon high temperature activation, additional Lewis acid sites associated to the defects (missing linker) are present. When introducing CD3CN aliquots to 10 torr equilibrium pressure, three vibrational bands could be observed at 2306, 2301, and 2276 cm -1 , associated with the chemisorption of CD3CN on different Lewis and Brønsted acid sites (Figure ). The ν(CN) bands at 2306 and 2301 cm -1 mostly dominate the spectra in the first three doses, indicating a strong interaction between the Lewis acid sites (Zr 4+ ) of the MOF and CD3CN. Interestingly, these Zr-CD3CN bands showed a slight blue shift, from 2296 cm -1 to 2306 and 2301 cm -1 , in comparison to the constant peak position of the physisorbed CD3CN (2261 cm -1 ) in other reported works. This clearly indicates a higher acidic strength of the sites, likely promoted by the large concentration of defects. Their concentration could be calculated by integrating the corresponding bands vs. the molar amount of CD3CN introduced. The obtained value of 1.19 mmol/g corresponded to a much larger number of Lewis acid sites than commonly reported defective UiO-66, e.g. typically around 300 µmol/g 42 , which further demonstrates that our ultra-small UiO-66 nanoparticles exhibit a much higher degree of defects, being therefore particularly interesting for Lewis acid based catalysis. Several hypotheses can be proposed to understand the formation of HD-US-UiO-66. First, the pre-formed Zr6 acetate oxoclusters establish the pH of the solution near 4 which favors ligand deprotonation of the carboxylic groups of the ligand and thus leads to a faster nucleation upon substitution of the terminal acetates from the oxoclusters in the presence of the dicarboxylate moieties. Then, the dilution upon addition of ethanol impairs the effective collision rate, and once combined with the high modulator content, might limit the crystal growth as well as Ostwald ripening. However, upon downsizing, the reaction kinetics becomes faster, from 3h for the largest particles to less than 1h for the 4-6 nm particles. Thus, other parameters are likely in play. For instance, the solubility of the ligand is limited at RT in ethanol and therefore, the proportion of ligand that is solubilized increases with the ethanol dilution, which favors a faster kinetics for the smallest particles. To validate this hypothesis, considering the much better solubility of BDC in DMF, we replaced 50% of EtOH by DMF whilst keeping all other synthetic parameters constant. The resulting nanoparticles were found to be only ca. 8 nm instead of 40 nm in comparison with the use of EtOH (Figure ), which corroborates the influence of the linker solubility on the kinetics. Such a bottleneck was observed previously by some of us when increasing the size of the dicarboxylic acid organic spacer over the crystallization under solvothermal conditions of UiO-66(Zr) and its extended analogues. 44 To gain further understanding about the formation mechanism of the HD-US-UiO-66, in situ timedependent dynamic light scattering experiments (TD-DLS) were conducted. Figure showed the evolution of particle size as a function of crystallization time of HD-US-UiO-66. The fast size increase process in the first 15 min was attributed to the formation of MOF nuclei. The MOF's growth was observed in the range between 15 min and 130 min and reached saturation after 130 min with a hydrodynamic size at ca. 18 nm. The clear slope revealed that the crystallization of HD-US-UiO-66 follows a growth-dominated process, in good agreement with the role of linker dissolution. The very low polydispersity index (Pdi) (Figure ) implied a homogeneous nucleation followed by crystal growth of UiO-66 in solution. To confirm the growth kinetics of HD-US-UiO-66, an ex situ HRTEM/STEM study was carried out after 0, 1, 120, and 180 min. Figure shows that only Zr6 oxoclusters (ca. 0.6 nm) were observed before the introduction of BDC. Larger nanoparticles (around 1.3 nm) very quickly formed as soon as the ligand was added (1 min), which indicates the very fast nucleation of UiO-66 nanoparticles in solution, in agreement with the stage (i) in Figure . The TEM images at 120 and 180 min demonstrated the growth of the small MOF nuclei and the saturation of nanoparticles growth. These results are fully consistent with TD-DLS, confirming the ligand dissolution acts as the bottleneck in controlling the MOF growth. Notably, the in-situ TD-DLS not only shed light on the crystallization process but also strongly highlighted the excellent colloidal stability of the HD-US-UiO-66. This effect, correlated to the highly positive charge evaluated by Zeta potential analysis, was observed whatever the nanocrystal size (Figures ) and is a strong asset for their solution processability in a view of applications such as ultrathin film fabrication, drug delivery, sensing and electronics, among others. One very appealing feature of MOFs is their ligand functionalization to achieve desired properties. Thus, we extended the new synthetic strategy to produce other functional HD-US-UiO-66-X derivatives, including X = NH2, NO2, (OH)2, Br, as well as replacing Zr6 by Hf6 oxocluster and BDC-based planar linkers by fumarate. Remarkably, all these MOFs exhibited 2-3 unit-cell sizes and very similar connectivity (ca. 3.3-4 linkers per formula) as the pristine HD-US-UiO-66 (see detailed analysis in SI).