The NMR-derived solution structure of trans-3,4',5-trihydroxystilbene (resveratrol) was compared with two recent literature crystal x-ray structures, resveratrol in complex with human transthyretin (TTR-RES) from 1DVS.pdb and resveratrol bound to chalcone synthase (CHS-RES) from 1CGZ.pdb. 1H and 13C NMR spectra of resveratrol were acquired in DMSO-d6. Assignments were obtained from an analysis of DQF-COSY, TOCSY, DEPT, HMQC/HSQC, HMBC and INADEQUATE NMR spectra. Past 1H and 13C NMR literature assignments are corrected. The dihedral angle 2-1-1'-2' provides an indication of the relative spatial orientation of the two phenolic rings. Values of 1.62, - 54.10 and 12.6 +/- 1.1 degrees were found for the 1DVS.pdb, 1CGZ.pdb and NMR resveratrol structures, respectively. The 1DVS.pdb resveratrol structure is 'flat' with the two phenolic rings along the same plane. The 1CGZ.pdb structure has these two rings almost orthogonal to each other, and the NMR structure has these two rings much closer to being along the same plane. The angles 1-alpha--alpha' and 1'-alpha'--alpha are along the same trace and of similar magnitude for the 1CGZ.pdb and NMR resveratrol structures. For the 1DVS.pdb resveratrol structure, these angles are about 7-10 degrees greater, with alpha and alpha' being 180 degrees out-of-phase from the other two structures. The alpha rings did not overlap, with the NMR result representing a 'median model' of the two x-ray structures.

The NMR-derived structure of estrogen (17b-estradiol, E2), the drug of choice for postmenopausal women, was compared with a recent literature crystal x-ray structure of Fab-bound E2.1 H and 13 C NMR spectra of E2 were acquired in DMSO-d 6 . Assignments were obtained from an analysis of DQF-COSY, TOCSY, HETCOR, HMQC and HMBC 2D NMR spectra. The 1 H and 13 C NMR assignments are the first reported for E2 in DMSO-d 6 . Two solution structures, S1 and S2, were obtained with molecular modeling using NOE constraints. S1 overlaps with the crystal structure for all rings. S2 shows prominent differences in the C-ring (C9-C11-C12-C13) segment, which deviates from a chair conformation, and excellent overlap in the A-, B-and D-rings of E2. The C-ring in S2 adopts a boat conformation as opposed to a chair conformation in the x-ray and S1 structures. The S2 structure is about 6• more twisted than the bound x-ray and S1 models. The S1, S2 and x-ray structures had ring bowing values of 10.1 ± 0.3, 11 ± 1 and 10.37• , respectively. Of the 100 solution conformers generated, 83 had S1 conformation and 17 had S2 conformation, with average internal energies of 112 ± 2 and 141 ± 2 kcal mol −1 , respectively. The 100 S1-and S2-derived conformers showed a r.m.s.d. of 0.72Å for all atoms. The x-ray, S1 and S2 C18 -O17 distances were 2.93, 2.92 ± 0.01 and 2.93 ± 0.01Å, respectively, and the O3 -O17 distances were 11.06, 11.18 ± 0.12, and 10.89 ± 0.05Å, respectively.

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