Potassium clavulanate

The title salt, K+·C8H8NO5 − [systematic name: potassium (2R,5R,Z)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate], a widely used β-lactam antibiotic, is usually chemically unstable even in the solid state owing to its tendency to be hydrolysed. In the crystal structure, the potassium cations are arranged along the a axis, forming interactions to the carboxylate and hydroxy groups, resulting in one-dimensional ionic columns. These columns are arranged along the b axis, connected by O—H⋯O hydrogen bonds, forming a layer in the ab plane.

The title salt, K + ÁC 8 H 8 NO 5 À [systematic name: potassium (2R,5R,Z)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo-[3.2.0]heptane-2-carboxylate], a widely used -lactam antibiotic, is usually chemically unstable even in the solid state owing to its tendency to be hydrolysed. In the crystal structure, the potassium cations are arranged along the a axis, forming interactions to the carboxylate and hydroxy groups, resulting in one-dimensional ionic columns. These columns are arranged along the b axis, connected by O-HÁ Á ÁO hydrogen bonds, forming a layer in the ab plane.
Grateful thanks are given to the High Directorate of the Education Ministry of Indonesia for a research grant and PT Tempo Scan Pacific Indonesia for the supply of the material. KF was supported by a Grant-in-Aid for JSPS Fellows (Tokyo Institute of Technology G-COE Program: Education and the Research Centre for Emergence of New Molecular Chemistry).
with β-lactamase-sensitive penicillins, such as amoxicillin. In that situation, CA protects the β-lactam ring of the amoxicillin from hydrolysis and can maintain its activity against β-lactamase producing bacteria (Bird et al., 1982). The CA potassium salt is widely used as a drug in injectable and solid form, especially combined with amoxicillin sodium and amoxicillin trihydrate (Navarro, 2005).
In this context, an understanding of the structure of CA is important in order to establish its ability to form molecular interactions. Unfortunately, CA is chemically unstable as are the other β-lactam antibiotics, being very sensitive to pH, temperature, and humidity via the hydrolysis degradation mechanism; (Bersanetti et al., 2005;Hickey et al., 2007;Saudagar et al., 2008). The decomposition is also self-catalyzed (Brethauer et al. 2008;Haginaka et al. 1985) and there have been some difficulties in obtaining a single crystals of CA. Therefore, until now there has been no report of a crystal structure of CA. In this study, single crystals of potassium clavulanate were successfully obtained by a low-temperature crystallization process and the crystal structure was determined.
In the molecular structure of potassium clavulanate, Fig. 1, the C5-O2 and C5-O3 distances of 1.262 (5)Å and 1.256 (5) Å, respectively, indicate that the negative charge of the carboxylate group is delocalised. The potassium cation is surrounded by six oxygen atoms, three O2, one O3 and two O4, deriv ed from four different clavulanate anions. The selected bond lengths around the potassium cation are listed in Table 1. These interactions are infinitely linked along the a axis and lead to an ionic (hydrophilic) column structure. These columns are connected by intermolecular O-H···O hydrogen bonds formed between O4-hydroxyl groups and carboxylate-O2 atoms, and form a hydrophobic layer in the ab plane; Fig. 2. By contrast, the remaining hydrophobic groups (i.e. bicyclo groups) form a hydrophobic layer so that the crystal structure comprises alternating hydrophilic and hydrophilic regions.

Experimental
The single crystals of potassium clavulanate were grown at a low temperature in order to prevent decomposition. After the compound was dissolved into an 8:2 mixture of methanol/water, a few drops of 1-propanol were added to the solution and the solution was kept at 235 K for a few days. The crystal used in the analysis was immediately covered with inert oil in order to prevent the decomposition through contact with atmospheric water vapor.