We aimed to design metal-ɑ-helical framework-forming peptides (MAHFs), which would assemble by coordination of metal ions with ɑ-helical peptides, in tandem with the hydrophobic effect, which strongly favors self-assembly. We based the design on a previously established porous ɑ-helical peptide framework that uses the hydrophobic effect and π-stacking to generate a supramolecular, three-dimensional arrangement with internal porosity. These peptides use Aib residues to enforce ɑ-helicity and three Leu residues along the nonpolar face of the helix to promote assembly by the hydrophobic effect. On the opposite face, two π-stacking groups promote further assembly and outline the channel perimeter. To create MAHF peptides, we exchanged the π-stacking interactions for metal-coordination bonds. The N-and C-terminal bipyridyl residues were replaced with acetyl and -NH2 caps, respectively. Using a heptad wheel, metal-binding residues, Glu and His, were placed on the same face of the α-helix, at positions 4 and 7, respectively. Furthermore, to minimize intermolecular interactions, we mutated a Hbonding residue, Gln8, to Ala. The resulting peptide is called Circular dichroism (CD) spectroscopy verified that the secondary structure in solution is helical (Figure ). Combining MAHF-9 with cobalt(II) acetate and cooling from reflux formed large purple crystals (Co-MAHF-9) suitable for singlecrystal X-ray crystallography (SC-XRD). Analysis of SC-XRD data reveals that Co-MAHF-9 is a porous lattice upheld by both hydrophobic interactions and Co(II)-ligand bonds in a Co(peptide)2 stoichiometry (Figure ). The relative helical orientations across the channel are anti-parallel, while along the channel axis they are parallel. Each peptide bridges two Co centers (μ2-ligand) via Glu4 and His7, and each Co is coordinated by a 2His-2Glu ligand set. This ligand set generates a distorted, 4-coordinate tetrahedral geometry (τδ = 0.72). Indeed, this geometry is consistent with the purple color of the crystals of Co-MAHF-9. Co-MAHF-9 possesses microporous rhombic channels, with a width of ~8.3 Å, solvated by water molecules. Ala8 is packed against Leu2 and Leu10 of neighboring chains, suggesting that an Ala8 mutation could significantly perturb the inter-helix packing and further lead to changes in how Glu4 and His7 interact with Co(II). For example, helices may shift in proximity, rotate, twist, or flip relative orientations (parallel versus antiparallel) to accommodate changes in inter-helical packing. The following sections will investigate the mutation of residue 8 to the remaining 19 canonical amino acids and its effect on framework topology and metal coordination. Non-polar mutations. Mutation of Ala8 to the other non-polar amino acids is expected to alter helix-helix packing interactions through steric effects caused by the various shapes and sizes of sidechains.