Finally, domains in biogenic guanine are observed with similar thicknesses and shape, likely biologically controlled 2 . This is consistent with the regular thickness of xanthine domains observed in Figure and S5.1. However, domains of xanthine are otherwise less uniform in shape. Not all molecules with planar crystal structures have polytypes. For example, hydrogenbonding networks in adenine are different between polymorphic forms, made possible due to the diversity of stable hydrogen bonding interactions . As another example, both known crystal structures of caffeine are disordered, in which intra-layer molecular positions are not fixed and there are multiple sites of partial occupancy in the unit cell . Although these crystal structures are not known to display polytypism, they could still display evidence of planar disorder through disruption of stacking sequences or twinning. These systems are obvious candidates for further investigation using 3D-ED and 4D-STEM. Additional degrees of structural complexity may be included when considering that molecular configurations within layers may also alternate.