Zwitterionic 4-piperidinecarboxylic acid monohydrate Gerzon Delgado, a Asiloe  J. Mora a * and Ali Bahsas b a Laboratorio de Cristalografõ Âa, Facultad de Ciencias, Departamento de Quõ Âmica, Universidad de Los Andes, Me Ârida 5101, Venezuela, and b Laboratorio de Resonancia Magne Âtica Nuclear, Facultad de Ciencias, Departamento de Quõ Âmica, Universidad de Los Andes, Me Ârida 5101, Venezuela Correspondence e-mail: asiloe@ciens.ula.ve Received 23 November 2000 Accepted 14 May 2001 The title compound, 4-piperidiniocarboxylate (isonipecotic acid), crystallizes as a zwitterion and incorporates one water molecule, i.e. C 6 H 11 NO 2 H 2 O. The piperidine ring adopts a chair conformation and the -carboxylate group is oriented in the equatorial position. The combination of the interactions between the -amino and -carboxylate groups and the water molecules builds a three-dimensional assembly of hydrogen bonds. Comment Compounds with both amino and carboxylic acid groups in their molecular structure, such as -amino acids, can exist as zwitterions in the crystalline state as well as in aqueous solu- tions. In a zwitterion, both charged groups, COO  and NH 3 + (or NH 2 + or NH + ), interact with each other and with the aqueous solvent by means of electrostatic, polarization and hydrogen-bonding interactions. These interactions affect their structural conformation, functionality and biological activity (Price et al. , 1998). In the solid state, zwitterions often cocrystallize with solvent molecules. The role played by the solvent molecules is diverse (Go È rbitz & Hersleth, 2000); they might be directly involved in the formation of hydrogen bonds with themselves and with the zwitterion, or they could just ®ll void space. Proline, for example, crystallizes forming in®nite chains of dimers linked by head-to-tail hydrogen bonds; water molecules act as bridges among chains, stabilizing the three-dimensional structure (Padmanabhan et al., 1995; Janczak & Luger, 1997). Other examples of amino acids with lateral chains strictly hydrophobic, which pack in a similar way to proline, have been reported in the recent literature (Dalhus & Go È rbitz, 1999a,b). In the gaseous phase, the amino acid exists in its neutral form, however, in the presence of solvent molecules, generally water, the amino acid rapidly ionizes forming the zwitterion (Jensen & Gordon, 1995; Tajkhorshid et al., 1998). The solvation effects in the zwitterion formation have been the subject of much interest and theoretical studies using different approaches have appeared in the recent literature, particularly concerning the simplest -amino acids, e.g. glycine and alanine (Jensen & Gordon, 1995; Tajkhorshid et al., 1998). From a theoretical point of view, it is interesting to study the structural isomers 2-piperidinecarboxylic acid, (I) (pipecolic acid or homoproline), 3-piperidinecarboxylic acid, (II) (nipe- cotic acid), and 4-piperidinecarboxylic acid, (III) (isonipecotic acid). These compounds have a piperidinium ring, which enables the charge separation between the amino and carboxylic acid groups, and offer additional degrees of freedom due to the possibility of different conformers, keeping in mind the simplicity of the molecule to avoid costly computational calculations. Preliminary theoretical calcula- tions (Cuervo et al. , 2000) at the ab initio and density- functional-theory levels have shown that in the absence of water the three isomers exist as the favourable neutral form, with isomer (III) being the least stable by about 20 kcal mol 1 . As water is introduced, the zwitterion becomes the stable form and, for instance, zwitterion (I) is stabilized when two water molecules are added in its vicinity. The crystalline structure of (I), a potent amino acid antagonist, has been reported (Bhattacharjee & Chacko, 1979). In the solid state, this compound is a zwitterion and crystallizes with four water molecules. Compound (II) is also a zwitterion, but it is not a hydrate (Brehm et al., 1976). Very little is known of 4-piperidinecarboxylic acid, (III). Our study shows this compound is zwitterionic and crystallizes in the space group Pna2 1 , incorporating one water molecule as crystallization solvent. Fig. 1 shows the molecular diagram and labelling scheme of (III)H 2 O. The existence of the zwitter- ionic form of (III)H 2 O is con®rmed by the presence of two H atoms bonded to the N1 atom, as was depicted in the differ- ence Fourier map where the two H atoms were located, and the almost symmetrical -carboxylate group, with C1ÐO1 and C1ÐO2 distances being equal within 2 (see Table 1). The Acta Cryst. (2001). C57, 965±967 # 2001 International Union of Crystallography  Printed in Great Britain ± all rights reserved 965 organic compounds Acta Crystallographica Section C Crystal Structure Communications ISSN 0108-2701 Figure 1 ORTEPIII (Burnett & Johnson, 1996; Farrugia, 1997) drawing of (III)H 2 O showing the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as spheres of arbitrary radii.