Redetermined crystal structure of N-(β-carboxyethyl)-α-isoleucine

Redetermination of the crystal structure of N-(β-carboxyethyl)-α-isoleucine, C9H18N2O3, reported earlier by Nehls et al. [Acta Cryst. (2013), E69, o172–o173], was undertaken in which the ionization state assigned to the molecule as unionized has been modified as zwitterionic in the present work. Single-crystal X-ray intensity data obtained from freshly grown crystals and freely refining the amino H atoms provide enhanced refinement and structural parameters, particularly the hydrogen-bonding scheme. N—H⋯O hydrogen bonds dominate the intermolecular interactions along with a C—H⋯O hydrogen bond. The intermolecular interaction pattern is a three-dimensional network. The structure was refined as a two-component perfect inversion twin.


S1. Introduction
Amino acids in their free form exist as 'zwitterions′ in their crystals with a deprotonated carboxyl group (COO-) and a protonated NH 3 + group (NH 2 + in proline). Any deviation from this general preferences of amino acids is worth careful considerations. The motivation for the present work is the unionized state reported by Nehls et al., 2013, for the title compound in contrast to the usually preferred 'zwitterionic′ state. In this context, redetermination of the crystal structure of the title compouned was undertaken.

S2.2. Refinement
Coordinates were refined for amino H atoms; other H atoms were positioned with idealized geometry, with fixed C-H = 0.98 (methyl), 0.99 (methylene) or 1.00 Å (methine). U iso (H) values were set at 1.2U eq of the carrier atom or at 1.5U eq for methyl and amino groups. The absolute configuration could not be determined by anomalous-dispersion effects in the X-ray diffraction measurements of the crystal, but assigned as L-based on an unchanged chiral centre in the synthetic procedure. The absoulte structure was refined as a perfect inversion twin. Nehls et al., (2013) seem to have presumed an unionized state for the title compound with an undissociated carboxyl (COOH) and a deprotonated amino (NH) group. A scrutiny of the work by Nehls et al. revealed that all the H-atoms, including the donor group H atoms were assigned an idealized geometry and refined as riding on their respective non-H atoms to which they are attached. Redetermination of the crystal structure carried out by measuring X-ray intensity data from freshly grown crystals and freely refining the amino-H atoms clearly indicate that the title compound indeed exist as a zwitterion. The correct assignment of the ionized state provided enhanced refinement and structural parameters. Thus, the present redtermination demonstrates the importance of freely refining donor group hydrogens. The S,S (equivalently L-) absolute configuration is deduced from the synthetic pathway as the starting material involved L-isoleucine. The absoulte structure was refined as a perfect inversion twin in order that the Flack x (Flack, 1983;Flack & Bernardinelli, 2000;Parsons et al., 2013) and Hooft y parameters (Spek, 2009) showed good agreement.

S3. Results and discussion
The correct assignment of the ionization state to the title compound as 'zwitterion′ presents an acceptable description of the intermolecular interaction patterns with all the amino-H atoms participating in them. The carboxylate O1 atom of the amino acid derivative participates in a strong head-to-tail N-H···O hydrogen bond characteristic of amino acids, in addition to a C-H···O hydrogen-bond as acceptor. This has consequently resulted in the lengthening of the C6- hydrogen-bonds within themselves leading to C 3 2 (8) chains linking screw related molecules along the shortest a-axis. The respective amino and carboxylate group N and O atoms form characteristic head-to-tail hydrogen-bonds leading to a layers parallel to the ab-plane. The intermolecular interaction pattern is a three-dimensional network dominated by N-H···O hydrogen bonds, in addition to a C-H···O hydrogen-bond involving the α-carbon atom (C2) as donor and the carboxylate O1 as acceptor.

Figure 1
Thermal ellipsoid plot of the title compound, showing the atom numbering scheme.

Figure 2
The characteristic head-to-tail N-H···O hydrogen bonds involving the carboxylate and the amino groups. Non pariticipating N-carboxyethl group atoms have been omitted for clarity.  Carbamoyl group N2 and O3 forming N-H···O hydrogen-bonds within themselves leading to C32(8) chains linking screw related molecules along the a axis.