Crystal structures of anhydrous and hydrated ceftibuten

Area of Science:

• Crystallography and Structural Chemistry
• Medicinal Chemistry
• Pharmaceutical Sciences

Background:

• Ceftibuten is a third-generation cephalosporin antibiotic known for its broad-spectrum activity and stability against extended-spectrum β-lactamases.
• The compound can exist in various hydration states, which may influence its solid-state properties and efficacy.
• Understanding the crystal structure is crucial for characterizing the drug's physical and chemical behavior.

Purpose of the Study:

• To determine and compare the crystal structures of anhydrous and hydrated ceftibuten.
• To investigate the role of water molecules in the crystal lattice and their effect on the molecular structure.
• To analyze the hydrogen bonding patterns and intermolecular interactions in both forms.

Main Methods:

• Single-crystal X-ray diffraction was employed to determine the crystal structures of anhydrous (I) and hydrated (II) ceftibuten.
• Analysis of crystallographic data to identify molecular conformation, zwitterionic forms, and hydrogen bonding networks.
• Comparison of structural features between the anhydrous and hydrated forms.

Main Results:

• Both anhydrous and hydrated ceftibuten crystallize as zwitterions, with proton transfer from the carboxylate group to the thiazole nitrogen.
• The β-lactam ring in the anhydrous form is nearly planar, while it is slightly buckled in the hydrated form.
• Extensive O-H⋯O and N-H⋯O hydrogen bonds form 3D networks in both structures; the hydrated form also exhibits water-water hydrogen bonding and incorporates water into a void space.

Conclusions:

• The hydration state significantly influences the crystal packing and conformation of the β-lactam ring in ceftibuten.
• The identified hydrogen bonding networks and zwitterionic nature are key features of ceftibuten's solid-state structure.
• The void space in the anhydrous structure highlights the potential for water molecule incorporation.