From the outset, there were two hypotheses to investigate around how diffusion is slowed by acetylation, (1) that acetyl groups directly interact with small molecule solutes, or (2) that the reduction in hydration results in slower diffusion. The diffusion measures in our two hypothetical cell walls clearly indicate that there is some merit to both hypotheses, as the diffusion went down with acetylation regardless of how much water was present (Fig. ). Ion interactions with cell wall biopolymers in Figs. and indicate that Na + ions react more readily with acetyl group than the hydroxyl group. This leads to an increased aggregation as the cell wall is further acetylated, and at supports the hypothesis that acetyl-ion interactions hinder ion diffusion. Fig. highlights that the carbonyl-like oxygen on the acetyl group with an accessible partial negative charge is the leading candidate for this interaction with cations. In isolation, this would strongly suggest that the first hypothesis is correct, and we certainly see that diffusion slows with increasing acetylation under all conditions. However the change in diffusion is just much greater when hydration was reduced. Comparing the diffusion for the "constant" and "expanded" systems, the diffusion decreased with increasing acetylation by 10x and 2x, respectively (Fig. ). Thus, while maximizing acetylation alone reduces diffusion by 2x, the reduction in the equilibrium moisture content from 30% to 19.4% (Table ) contributes an extra 5x diffusion deceleration. This 5x change had been noted previously for a similar change in moisture content through simulation. The multiplicative effect of acetylation beyond what moisture content reduction alone would do is likely influenced by the increased hemicellulose-lignin interactions facilitated by the additional bulk of the acetyl groups. Compared with prior unacetylated studies, 11 there are ≈1.12× more ion interactions with hemicellulose and ≈1.55× more ion interactions with lignin in acetylated cell walls.Thus, the hydration mechanism in our view should be considered the primary mechanism by which diffusion and uptake is slowed by wood acetylation.