¹³C NMR Investigation of Solid-State Polymorphism in 10-Deacetyl Baccatin III

Abstract

To investigate the origins of solid-state NMR shift differences in polymorphs, carbon NMR chemical shift tensors are measured for two forms of solid 10-deacetyl baccatin III: a dimethyl sulfoxide (DMSO) solvate and an unsolvated form. A comparison of ab initio computed tensors that includes and omits the DMSO molecules demonstrates that lattice interactions cannot fully account for the shift differences in the two forms. Instead, conformational differences in the cyclohexenyl, benzoyl, and acetyl moieties are postulated to create the differences observed. X-ray analysis of six baccatin III analogues supports the suggested changes in the cyclohexenyl and benzoyl systems. The close statistical match of the (13)C chemical shifts of both polymorphic forms with those calculated using the X-ray geometry of 10-deacetyl baccatin III supports the contention that the B, C, and D rings are fairly rigid. Therefore, the observed tensor differences appear to arise primarily from conformational variations in ring substituents and the cyclohexenyl ring.

Calculations of chemical shieldings: Theory and applications

“…Another important aspect to consider when using chemical shieldings for structural determinations is that in many cases there are no simple relationships between structural parameters and chemical shieldings. For instance the ␦ 11 principal component of the 13 C 4 chemical shielding tensor in verbenol (see Scheme A) has been found to by highly dependent of the torsional angle of the OH group attached to this carbon (67).…”

Molecular structure of actein: 13C CPMAS NMR, IR, X-ray diffraction studies and theoretical DFT–GIAO calculations

“…In principle, the slope of such plots should be unity. Using different plots for fitting data for sp3 and sp2 carbons, yielded a difference of 4.7 ppm in the shielding for TMS [32]. Constraining the slope to be unity, results in computed vs. experimental differences which are larger but arguably more realistic [33].…”

Measurement of the principal values of the chemical-shift tensors of overlapping protonated and unprotonated carbons with the 2D-SUPER technique and dipolar dephasing (DD-SUPER)

“…Accurate measurement of the principal values of 13 C and 15 N chemical-shift tensors, d 11 , d 22 , and d 33 , is a challenging, but important, task for gaining insight into the electronic structure and geometry of pharmaceutically significant organic solids [1][2][3][4][5][6][7]. In principle, the principal values of single dilute nuclear spins (e.g., 13 C or 15 N) can be measured directly from the line shape of a powder pattern obtained with high-power proton decoupling.…”