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Charge Density and Experimental Electrostatic Potentials of Two Penicillin Derivatives
Author(s) -
Wagner Armin,
Flaig Ralf,
Dittrich Birger,
Schmidt Horst,
Koritsánszky Tibor,
Luger Peter
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200305627
Subject(s) - chemistry , computational chemistry , charge density , density functional theory , amide , electrostatics , hydrogen bond , crystallography , stereochemistry , molecule , organic chemistry , physics , quantum mechanics
Two penicillin derivatives, the active penamecillin and the inactive penamecillin‐1β‐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 Å. Experimental charge densities were obtained by using the Hansen–Coppens multipole formalism. The cleavage of the amide bond in the β‐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.