An atomic resolution description of folic acid using solid state NMR measurements

The chemical shift anisotropy tensor and site-specific spin-lattice relaxation time of folic acid were determined by a (13)C 2DPASS CP-MAS NMR experiment and Torchia CP experiment respectively. The molecular correlation time at various carbon nuclei sites of folic acid was evaluated by assuming that the (13)C spin-lattice relaxation mechanism is mainly governed by chemical shift anisotropy interaction and hetero-nuclear dipole–dipole coupling. CSA parameters are larger for the carbon nuclei residing at the heteroaromatic ring and aromatic ring, and those attached to double-bonded electronegative oxygen atoms. It is comparatively low for C9, C19, C21, and C22. The molecular correlation time is of the order of 10(−4)/10(−5) s for C9, C19, C21 and C22 carbon nuclei, whereas it is of the order of 10(−3) s for the rest of the carbon nuclei sites. Spin lattice relaxation time varies from 416 s to 816 s. For C23 and C14, the value is 816 s, and it is 416 s for C7 nuclei. The correlation between structure and dynamics on an atomic scale of such an important drug as folic acid can be visualized by these types of extensive spectroscopic measurements, which will help to develop an advanced drug for DNA replication.