Bis(oxotremorine) fumarate bis(fumaric acid)

In the title molecular salt, 2C12H19N2O+·C4H2O4 2−·2C4H4O4, the components are held together by N—H⋯O and O—H⋯O hydrogen bonds, forming chains along [001].


Structure description
Oxotremorine is a selective agonist of the muscarinic acetylcholine receptor, which reproduces many of the symptoms observed in Parkinson's disease. This property has made it an invaluable tool in studying potential pharmaceuticals for Parkinson's (Ringdahl & Jenden, 1983). A salt of oxotremorine that is commonly used in biological studies is produced by treating oxotremorine free base with fumaric acid. The resulting salt is reported as the sesquifumarate, indicating that the compound possesses an empirical formula with a 1:1.5 ratio of cation to fumarate dianion. However, the structure reported here shows that in the solid-state, the compound consists of two monocationic, protonated oxotremorines, one doubly deprotonated dianionic fumarate, and two fully protonated fumaric acid molecules. One half of these ions and molecules are present in the asymmetric unit (Fig. 1).
The only compound found by searching on 'sesquifumarate' in the Cambridge Structural Database (CSD, version 5.43, update of March 2022;Groom et al., 2016) is that of the anti-arrhythmic agent tedisamil, which also exists as the bis(cation) bis(fumaric acid) fumarate and not the technical sesquifumarate (Jones et al., 2004: CSD refcode EYOYUM). There are seven other bis(cation) bis(fumaric acid) fumarate salts (Haynes et al., 2006 Mohamed et al., 2009: FUTNIS;Fang et al., 2022: CCDC 2092690), and one bis(cation) bis(fumarate) fumaric acid salt (Collin et al., 1987: FEMKIR) found in a search of the CSD. Although all of these structures incorporate three equivalents of fumaric acid into their structures relative to two cations, none is a formal sesquifumarate. The only such example in the CSD is that of Ã-cobalt(III) tris(ethylenediamine), which shows all three fumaric acid molecules to be fully deprotonated and in a 3:2 ratio with the tricationic cobalt complex ions (Liebig & Ruschewitz, 2012: PEJGAO). In general, there is a lack of precision when characterizing salts of fumaric acid, and diffraction studies are invaluable in distinguishing the different forms.
In the structure of the title compound, the pyrrolidinium N-H of oxotremorine has bifurcated hydrogen bonds to two O atoms of a symmetry-generated fumarate dianion. One fumaric acid O-H hydrogen bonds to the carbonyl oxygen of the oxopyrrolidine of oxotremorine. The other fumaric acid O-H hydrogen bonds to one of the fumarate dianion oxygen atoms (Table 1). These hydrogen bonds connect two oxotre-morine cations, two fumaric acid molecules and two fumarate dianions into rings that have graph-set notation R 6 6 (40) (Etter et al., 1990) (Fig. 2). The fumarate ions connect these rings together into infinite one-dimensional chains along [001]. The crystal packing of the title compound is shown in Fig. 3.

Figure 2
The hydrogen-bonding network forms chains along [001], which consist of R 6 6 (40) rings that are joined together by the fumarate dianions. The ring structure is shown above. Hydrogen atoms not involved in hydrogen bonds, and the second component of the disordered fumarate dianion are omitted for clarity.

Figure 3
The crystal packing of the title compound viewed along the b axis. Hydrogen bonds are shown as dashed lines. Hydrogen atoms not involved in hydrogen bonds, and the second component of the disordered fumarate dianion are omitted for clarity.

Figure 1
The molecular structure of the title compound showing the atomic labeling. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds are shown as dashed lines. The asymmetric unit contains one half of a fumarate dianion, which is disordered over two positions. The other half of the inversion-generated fumarate dianion is shown. Symmetry code: (i) 2 À x, 1 À y, Àz.
respectively. The C-O distances of the fumarate molecules are delocalized with values of 1.270 (3) and 1.243 (2) Å . The C-O distances in the fumaric acid molecules are localized, with the carbonyl distances being 1.209 (2) and 1.203 (2) Å and the carbon-hydroxyl distances being 1.310 (2) and 1.316 (18) Å . The C-O distances and the location of the hydrogen atoms from the difference-Fourier map make the assignment of fumarate and fumaric acid clear.

Synthesis and crystallization
Single crystals suitable for X-ray diffraction studies were grown by dissolving 15 mg of oxotremorine sesquifumarate purchased from Sigma-Aldrich in 5 ml of water. Solvent was allowed to evaporate at ambient temperature and pressure and crystals formed after 12 h.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The fumarate dianion is disordered over two positions (C17, C18, O6, O7 and C17A, C18A, O6A, O7A), which were modeled using a SAME restraint, as well as EADP instructions. The two components showed a 0.855 (4) to 0.145 (4) occupancy ratio.  where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max < 0.001 Δρ max = 0.18 e Å −3 Δρ min = −0.15 e Å −3 Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

data-2
IUCrData (2022). 7, x220364 Refinement. Hydrogen atoms H2, H3 and H4 were found from a difference-Fourier map and were refined isotropically, using DFIX restraints with O-H distances of 0.90 (1) Å. Isotropic displacement parameters were set to 1.2 U eq of the parent nitrogen atom and 1.5 U eq of the parent oxygen atom. All other hydrogen atoms were placed in calculated positions with C-H = 0.93 Å (sp 2 ) or 0.97 Å (sp 3 ). Isotropic displacement parameters were set to 1.2 U eq of the parent carbon atom.