To investigate the importance of electrostatic interactions, aqueous electrophoresis studies of the nanosheets were undertaken in the presence and absence of each peptide. Zeta potentials of the three nanosheet systems were determined in dilute PBS (1.37 mmol with respect to NaCl) at 20 ℃ to replicate phage display conditions as closely as possible while meeting instrumental requirements. ZIF-7 and Hf-BTB-NH2 nanosheets exhibited moderately negative zeta potentials of -30.1 mV and -36.9 mV, respectively. Thus the surface chemistry of the ZIF systems is dominated by the anionic imidazole ligands, rather than the zinc cations. The negative zeta potential for Hf-BTB-NH2 most likely indicates the presence of surface hydroxyl and phosphate groups, which would confer overall anionic charge. The weakly positive zeta potential observed for ZIF-7-NH2 is attributed to the presence of surface amine groups. Such a low zeta potential is often associated with an unstable colloidal suspension. However, no sedimentation was observed over the timescale of the experiment and the zeta potential data proved to be reproducible. Amino acid side-chain and N-terminus pKa values were used to calculate the isoelectric point of the binding peptide and to predict the overall charge under phage display (PD) conditions (see section 5.3 in the Supporting Information). All three peptides contain a free terminal amine, which should be protonated under PD conditions and hence contribute a +1 charge. The ZIF-7-NH2 sequence contained no ionizable Rgroups; both ZIF-7 and Hf-BTB-NH2 contained arginine, which confers an additional +1 charge. However, this results in charge balance in the case of Hf-BTB-NH2 owing to its ionizable aspartic acid residue. The change in zeta potential (ΔZP) was determined upon MON incubation with excess binding peptide (Figure ). A large ΔZP is observed for ZIF-7 (+56.2 mV) and Hf-BTB-NH2 (+40.0 mV) but a rather smaller difference is observed for ZIF-7-NH2 (+20.9 mV). Thus, electrostatic interactions seem to be important for the binding of cationic peptides to the anionic surfaces of ZIF-7 and Hf-BTB-NH2, but this effect is less significant for peptide binding to ZIF-7-NH2. As the guanidinium moiety within arginine is most likely charged under the experimental conditions, we infer that it contributes to the overall electrostatic interactions. The importance of arginine interactions with aromatic residues is well-documented in the biomolecular recognition literature. The hydrophobicity of the MON surfaces was investigated using contact angle measurements using DSA100 and compared to the proportion of hydrophobic/hydrophilic residues within the peptide sequences. Nanosheets were packed onto a glass slide, water drops were added using a micro-syringe and the contact angle was measured using a drop shape analyser image system (Figure ). Although there are some limitations to this approach owing to surface roughness effects, clear differences were observed between the two types of nanosheets. Hf-BTB-NH2 nanosheets were considerably more hydrophilic (contact angle = 25 °) compared to the ZIF-7 and ZIF-7-NH2 nanosheets (contact angles of 149 ° and 141 °, respectively). This correlates with the known properties of these MOF classes: the surface chemistry of Hf-BTB-NH2 systems is dominated by their Hf6(μ3-O)4(μ3-OH)4(HCO2)6 clusters, while the Zn 2+ ions of the ZIF systems are largely shielded by the relatively hydrophobic imidazole rings. This trend in hydrophobicity is mirrored by the consensus binding peptides. The ZIF-7 binding sequence, YNYRNLL, contains several hydrophobic tyrosine and leucine residues, while the ZIF-7-NH2 peptide sequence, NNWWAPA, contains multiple hydrophobic tryptophan and alanine residues. Benzimidazole derivatives are known enzyme inhibitors owing to π-π interactions between aromatic residues. The presence of aromatic Tyr and Trp residues suggest probable π-π interactions with the electron-rich aromatic benzimidazole ligands of ZIF-7. The two peptides for the ZIF MONs both contain two polar asparagine residues, which may confer stability in aqueous solution. In contrast, the Hf-BTB-NH2 sequence, FTVRDLS, contains a broader range of amino acids, with only three hydrophobic residues (phenylalanine, valine and leucine) alongside hydrophilic residues such as threonine and serine, as well as anionic aspartic acid and cationic arginine residues. This suggests that hydrophobic binding effects are most likely dominant for the ZIF-7-NH2 but are much less important for the more polar Hf-BTB-NH2 nanosheets.