Induced fit phenomena in clathrate structures of cephalosporins

The antibiotics cephalexin, cephradine, cefaclor and cefadroxil form clathr ate type inclusion compounds with naphthalene derivatives that readily crys tallize from an aqueous solution. In these clathrates the antibiotic molecu les form the hosting lattice and the naphthalene derivatives are the guest molecules, whereby water serves as "cement". A list of potential guest mole cules was drawn up using the concept of molecular similarity. This list was extended by a series of compounds which are not supposed to fit. It was sh own that a large variety of naphthalene derivatives can be hosted in clathr ates with cephalexin, cephradine and cefaclor. Cefadroxil, however, is much more selective in accommodating guest molecules. Although cephalexin, ceph radine and cefaclor form the principal hosting lattice and govern the overa ll crystal structure of the clathrates, the guest molecules are capable of inducing deviations in the framework of the host molecules, i.e. induced fi t. Cefadroxil, however, lacks this adaptability due to the rigid three-dime nsional hydrogen bonded structure of its hosting framework, and an exact fi t of a guest molecule in the hosting framework of cefadroxil is thus requir ed, i.e. lock and key concept. All four antibiotics have a limited adaptabi lity by varying the number of water molecules in the clathrates. Certain gu est molecules replace water in order to obtain the required space for inclu sion, whereas other guest molecules cause incorporation of extra water, whi ch is apparently beneficial for the crystal packing. However, the adaptabil ity due to varying the water content cannot account for the remarkable flex ibility in accommodating guest molecules exhibited by cephalexin, cephradin e and cefaclor. The concept of induced fit is relevant for the understandin g and design of clathrate type structures.