Relative energies reported in Table are not consistent in sign with B3LYP-based heterogeneous PCM calculations reported previously by We have not attempted to mimic their computational paradigm exactly; for example, calculations in Ref. 107 omit diffuse functions and any dispersion correction. Experiments suggest that π-π interactions near the active sites of Cucontaining metalloenzymes have a significant impact on pK a values, 126 suggesting dispersion effects may be important. Another difference, relative to the calculations reported in Ref. 107, is that the latter employ a unitedatom cavity construction with no explicit atomic spheres for the hydrogen atoms. Although this seems like an odd choice for pK a calculations, we have performed calculations at the B3LYP+D3(BJ)/6-31+G* level using the same cavity construction, for comparison. Results in Table S11 demonstrate that the relative energies are rather erratic in sign and magnitude.