Centerband‐Only Detection of Exchange NMR with Natural‐Abundance Correction Reveals an Expanded Unit Cell in Phenylalanine Crystals

Abstract The NMR pulse sequence CODEX (centerband‐only detection of exchange) is a widely used method to report on the number of magnetically inequivalent spins that exchange magnetization via spin diffusion. For crystals, this rules out certain symmetries, and the rate of equilibration is sensitive to distances. Here we show that for 13C CODEX, consideration of natural abundance spins is necessary for crystals of high complexity, demonstrated here with the amino acid phenylalanine. The NMR data rule out the C2 space group that was originally reported for phenylalanine, and are only consistent with a larger unit cell containing eight magnetically inequivalent molecules. Such an expanded cell was recently described based on single crystal data. The large unit cell dictates the use of long spin diffusion times of more than 200 seconds, in order to equilibrate over the entire unit cell volume of 1622 Å3.

NMR crystallography with CODEX: hundreds of seconds of spin diffusion are used to detect the eight molecules in a large unit cell. Encoded chemical shift anisotropy reveals information hidden in the isotropic spectrum. Accuracy requires correction for natural‐abundance spins in the single‐site carbon‐13‐labelled sample. image