Solid-state carbon-13 nuclear magnetic resonance investigations of bismuth citrate complexes and crystal structure of Na-2[Bi-2(cit)(2)]center dot 7H(2)O

The complex Na[Bi-2(cit)(2)]. 7H(2)O (H(4)cit = 3-carboxy-3-hydroxypentane-1,5-dioic acid) crystallized during reactions of the antiulcer drug ranitidine bismuth citrate with the tripeptide glutathione (gamma-L-Glu-L-Cys-Gly) at low pH. X-Ray analysis showed one [Bi(cit)](-) fragment per asymmetric unit with Bi3+ chelated to a terminal carboxylate group; citrate also binds, in tridentate mode, to the bismuth of an equivalent [Bi(cit)](-) unit (related to the first by a C-2 axis) via one oxygen donor from each of the remaining two carboxylate groups and the alkoxy group. Both ends of the resultant dimeric anion {Bi(mu-cit)(2)Bi}(2-) bind to adjacent dimers, related by n-glide plane symmetry, via double carboxylate bridges, to form a continuous polymeric anionic chain [{Bi(mu-cit)(2)Bi}(n)](2n-) running throughout the crystal. In this way each bismuth atom achieves six-co-ordination [Bi-O 2.210(10)-2.505(10) Angstrom] with a nido-pentagonal-bipyramidal geometry, the vacant axial site providing evidence for a stereochemically active lone pair and the second axial site being occupied by the alkoxy donor. The parallel polyanionic chains are linked by anion-cation interactions [Na ... O (cit) 2.37-2.50 Angstrom] and by bonds of largely ionic character (Bi ... O 3.003-3.095 Angstrom) to give the overall three-dimensional solid-state structure which incorporates seven water molecules per dianionic subunit. The solid-state cross-polarization magic angle spinning C-13 NMR spectrum of this complex is assigned with the aid of dipolar-dephasing and inversion-recovery cross-polarization experiments, and compared to those of ranitidine bismuth citrate and bismuth citrate Bi(Hcit). The IR and solid-state C-13 NMR data suggested that the alkoxy group is protonated in Bi(Hcit) but deprotonated in ranitidine bismuth citrate, and that the latter contains similar dimeric units to Na-2[Bi-2(cit)(2)]. 7H(2)O. The general modes of aggregration of dimeric [{Bi(mu-cit)(2)Bi}(n)](2n-) units and the relevance to antiulcer activity are discussed.