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.