title: Charge density and experimental electrostatic potentials of two penicillin derivatives.
abstract: Two penicillin derivatives, the active penamecillin and the inactive penamecillin-1beta-sulfoxide, were used to study the relationship between their charge density and their activity. Single crystals of both compounds were measured at the synchrotron beamline F1 at the HASYLAB/DESY, at 100 K and up to resolutions of around 0.4 A. Experimental charge densities were obtained by using the Hansen-Coppens multipole formalism. The cleavage of the amide bond in the beta-lactam ring is of paramount importance in the mechanism of action of penicillins. Topological analysis of this bond in terms of Bader's AIM theory showed that its strength is equal in both compounds; therefore a direct influence of bond strength on the activity can be ruled out. However, the two derivatives differ significantly in their experimental electrostatic potentials. These differences are discussed and provide further insight into the chemistry and activity of penicillins.
authors.affiliation: Institut für Chemie/Kristallographie, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Wagner
authors.forename: Ralf
authors.initials: R
authors.lastname: Flaig
authors.forename: Birger
authors.initials: B
authors.lastname: Dittrich
authors.forename: Horst
authors.initials: H
authors.lastname: Schmidt
authors.forename: Tibor
authors.initials: T
authors.lastname: Koritsánszky
authors.forename: Peter
authors.initials: P
authors.lastname: Luger
mesh_terms: D008958:Models, Molecular; D010400:Penicillin G / Q000031:analogs & derivatives* / Q000097:blood*; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013454:Sulfoxides / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D013454:Sulfoxides; C016646:penamecillin; D010400:Penicillin G