H-bonding schemes of di- and tri-p-benzamides assessed by a combination of electron diffraction, X-ray powder diffraction and solid-state NMR

Tuning the solubility of hepta(p-benzamide)s via the monomer sequence

“…In this case, insolubility is a result of directional hydrogen bond formation between the individual amide groups, as has been shown for smaller oligomers via x-ray crystal structure analysis. 14,15 We were interested in exploring the aggregation behavior of heterosequences situated structurally in between the two insoluble extremes described above. 4-Amino-2-(hexyloxy)benzoic acid (3) was prepared as shown in Scheme 1.…”

“…13 Oligo(p-benzamide)s (OPBA) are particularly rigid aromatic amides which suffer from poor solubility due to their linearly aligned hydrogen bond donors and acceptors. 14,15 In order to solubilize these oligomers, we previously conjugated them with polyethylene glycol chains, resulting in supramolecular rod-coil block copolymers, which self-assemble into rod-like micelles in nonpolar solvents. 15,16,17,18 The most common strategy to improve solubility in rigid rod-like molecules is the attachment of flexible side chains to the stiff oligomer/polymer backbone.…”

Ab-initio crystal structure analysis and refinement approaches of oligo p-benzamides based on electron diffraction data

“…However, even the shortest members of the series turned out to be poorly crystalline. Their structures, solved by a combination of zonal electron diffraction data and X-ray powder diffraction, were reported recently (Gorelik et al, 2010). All recrystallization attempts for the next homologtetra-p-benzamide -did not improve the crystallinity.…”

Heterosynthon mediated tailored synthesis of pharmaceutical complexes: a solid-state NMR approach

“…specified by O/H, N/H or O/O distances, respectively, by X-ray analysis, 40 neutron 41 and even electron diffraction. 42 Additional structural insights may be obtained from double-quantum 1 H MAS NMR where homonuclear 1 H-1 H dipolar couplings correlate protons of different chemical entities thereby providing both precise information on proton-proton proximities as well as distances 43 (which in principle can be very fruitful for unambiguous identification of pharmaceutical salts) on length scales of up to 3.5 A 44 and proton positions in arrays of multiple hydrogen bonds. 45 Moreover, the combination of solid-state NMR spectroscopy with density functional theory (DFT) 46 computations not only corroborates chemical shift assignments but in some cases also provides an approach to ''NMR crystallography'', 47 which allowed for both polymorph screening, 48 e.g.…”