Xanthine powder was purchased from Sigma Aldrich and was deposited onto Quantifoil R1.2/1.3 grids as described in S1. TEM images of xanthine particles revealed a typically blocklike morphology (Figure .1). 3D-ED data were collected from micro-crystals using a Thermo Fisher Titan Krios G3i Transmission Electron Microscope operated at 300 kV and with a CETA-16M camera (further details in S2). Structure solution was successful using the ab initio dual space methods implemented in SHELXD . Initial solutions in the P21/c space group (Z = 8, Z' = 2) provided a structure in which all non-hydrogen atoms were found, giving the correct molecular connectivity for two crystallographically independent xanthine molecules. The structure was then kinematically refined using full-matrix least-squares in SHELXL . A difference Fourier synthesis (shown in Figure ) revealed the positions of all the hydrogen atoms, avoiding the need to place these in geometrically idealised positions (as is often the case for 3D-ED structures).