How Metal-to-Linker Ratio and Concentration Govern the Nucleation Mechanism of MOF-5-inspired Crystals: Insights from Multiscale Modeling

Predicting whether a computationally designed metal organic framework can be synthesized remains difficult.While efforts developing predictive viability of synthesis metrics have focused on inherent thermodynamic stability, not much focus has been placed on kinetics, nucleation mechanisms, and how these are impacted by synthesis conditions.Using the well-known MOF-5 in DMF system as a case study, we combine Hamiltonian replica exchange, coarse-grained molecular dynamics, unsupervised clustering, minimum free energy path (MFEP) analysis, and microkinetic modeling to examine how metal-to-linker ratio and linker concentration reshape the pathway, energetics, and kinetics of nucleation.At 20 mM linker concentration, we find that excess metal clearly thermodynamically and kinetically favors the formation of a crystalline nucleus, whereas stoichiometric metal-to-linker ratio and excess linker favor large amorphous aggregates.At excess metal conditions, we find that increasing concentration from 20 mM to 160 mM maintains thermodynamic favorability for the ordered nucleus but accelerates the pathway toward it.Within the concentration range tested, as concentration increased, aggregation also became more pronounced, and the dominant barrier became associated with healing instead of growth steps.Additionally, the nucleus yield and formation rate increased monotonically with concentration, albeit with clearly diminishing gains between 80 mM and 160 mM (well below the linker solubility limit).These results offer a plausible mechanistic rationale for the empirical preference for excess metal during MOF-5 synthesis and suggest that the benefits of higher precursor concentration diminish well before the linker solubility limit is reached.