We first evaluated the ability of each framework to catalyze the aldol reaction between 4nitrobenzaldeyde and acetone to yield products 2 and 3 (Scheme 1a). This reaction has been widely used to benchmark heterogenous bifunctional acid-base catalysts. Initial control experiments using the unfunctionalized Mg2dotpdc framework revealed highly variable background reactivity. We hypothesized that the coordinatively unsaturated magnesium sites in the framework may be acting as Lewis acid catalysts, with activity that is highly sensitive to the presence of trace water. Indeed, this background reaction was nearly completely quenched upon the addition of a small amount of water (2 vol%) in the solvent mixture (Table ). Given these results, we adopted 2 vol% water in acetone as our default solvent for all subsequent catalytic runs. We next compared the performance of each framework by monitoring substrate conversion after 5 h at 60 °C. The results, which are summarized in Table , show that 1-templated achieves the highest conversion under these conditions (82%), followed by 1-nontemplated with 41% conversion. Both frameworks outperform the monofunctionalized 1-COOH and 1-CH2NH2, which achieve only 11% and 25% conversion, respectively. These initial catalyst screenings provide strong evidence that not only is the presence of both acid and base critical to activity, but also their spatial distribution.