Mechanistic insights into band broadening in MOF-based liquid chromatography: Role of sub-nanopore diffusion and packing heterogeneity.

Metal-organic frameworks (MOFs) have emerged as a promising class of porous materials for liquid chromatography (LC) stationary phases, owing to their exceptional structural tunability. However, the fundamental understanding of separation efficiency in MOF-packed columns remains limited. In this study, we systematically investigated the contribution of intra-particle diffusion to chromatographic band broadening using a sub-nanoporous MOF, [Zn2(ndc)2(ted)]n (ndc = 1,4-naphthalenedicarboxylate, ted = triethylenediamine). A column packed with [Zn2(ndc)2(ted)]n particles was evaluated via peak parking experiments to determine the effective longitudinal diffusion coefficient (Deff), from which the intra-particle diffusion coefficient (Dpart) was derived via effective medium theory (EMT), employing a series of phenone-based analytes with varying molecular sizes. The MOF column exhibited relatively high plate height and significantly low optimal velocity compared to a conventional reversed-phase (RP) LC column. Analysis using peak parking and EMT revealed Dpart/Dm ≤ 0.02 (Dm: bulk molecular diffusion coefficient), markedly lower than typical values observed in RPLC, highlighting severe diffusion constraints. A clear trend of decreasing Dpart/Dm with increasing analyte molecular size was observed, indicative of a size-selective diffusion mechanism within sub-nanometer pores. Despite the substantial intra-particle mass transfer resistance, the dominant contribution to band broadening was attributed to eddy dispersion, underscoring the pronounced impact of packing heterogeneity stemming from the broad particle size distribution and non-spherical morphology of the MOF crystals. These findings offer valuable insights into the underlying mechanisms of efficiency loss in MOF-based LC and inform the design of improved stationary phase architectures and packing strategies.