Structure elucidation of cyameluric acid by combining solid-state NMR spectroscopy, molecular modeling and direct-space methods

We present the structure solution for solvent-free cyameluric acid which has first been synthesized more than 150 years ago. By densely intertwining the complementary methods solid-state NMR spectroscopy, molecular modeling as well as direct-space methods for the analysis of the X-ray powder diffraction data we succeeded where conventional powder diffraction analysis alone failed. In a first step, the correct tautomer was identified by combining solid-state NMR and ab initio calculations. The quantum-chemically optimized molecule was further employed in direct-space methods for the crystal structure solution. After a subsequent Rietveld refinement the positions of the hydrogen atoms in the crystal were determined by comparing experimental and calculated NMR chemical shift parameters. In this context, the sensitivity of the anisotropy δ aniso and the asymmetry parameter η of the carbonyl 13 C towards the hydrogen bonding environment proved to be very valuable. Cyameluric acid crystallizes in space group P 2 1 2 1 2 1 ( Z = 4, a = 6.4701(5) Å, b = 9.9340(6) Å, c = 12.0985(7) Å) with one complete molecule in the asymmetric unit. It consists of the symmetric trioxo tautomer which is arranged in a three-dimensional hydrogen bond network where all three NH groups interact with carbonyl groups.