Two charge density studies on macrolide antibiotics ... ... 4Department of Chemistry, Aarhus...
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Two charge density studies on macrolide antibiotics: erythromycin and roxithromycin
J. Holstein1,3, B. Dittrich3, C. Paulmann2,5, W. Morgenroth3,4,5, P. Luger1
1Institut für Chemie / Kristallographie der Freien Universität Berlin, Fabeckstr. 36a, D-14195 Berlin, Germany
2Mineralogisch-Petrologisches Institut, Universität Hamburg, Grindelallee 48, D-20146 Hamburg, Germany
3Institut für Anorganische Chemie, Georg August Universität, Tammannstr. 4, D-37077 Göttingen, Germany
4Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark 5c/o DESY/HASYLAB, Notkestr. 85, 22607 Hamburg, Germany
Macrolide antibiotics are known to eliminate the protein synthesis in the bacterial ribosome by blocking the tunnel that channels the nascent peptides away form the peptidyl transferase center.  Due to this biological attribute the electronic properties of these compounds, especially of func- tional groups, which interact with nucleotids of the peptidyl transferase cavity are of interest. Two high resolution X-Ray experiments were executed: For roxithromycin 405336 Bragg reflections of have been collected at 100K (wavelength 0.56 Å) at beamline F1 up to a resolution of 1,25 Å−1 in sinθ/λ (d=0.40 Å) and were merged to 39480 unique refections. At the D3-beamline 177822 reflections (23653 unique) of erythromycin have been collected at 9K (wavelenght 0.5166 Å) up to a resolution of 0.91 Å−1 in sinθ/λ (d=0.55 Å). Their chemical structure is based on a 14-membered lactone cycle, substited by a desosamine and
Figure 1: ORTEP  representation of the molecular structure (50% probability) of ery- thromycin
Figure 2: Structure of roxithromycin
a clandinose sugar. The newly discovered modification of erythromycin is disordered. The ADP‘s are much larger, than expected for a 9 K measurement (figure 1). Therefore no charge density analysis should be performed. The dataset of roxithromycin was refined with the program package XD  using the aspherical atom multipole formalism according to the method of Hansen and Coppens  . To obtain first results based on the invariant atom formalism  the progam INVARIOMTOOL 
was used. The figures 3 and 4 were generated with the program Moliso . They show the electro- static potential mapped on an isosurface of the electron density on a level of 0.5 e·Å−3 and 0.0067 e·Å−3, calculated using the method of Su and Coppens . Figure 3 shows an extended negative region (red) which is accumulated around the oxygen atoms. The region around the dimethylamin group (figure 4) is positively charged.
Figure 3: electrostatic potential on an isosurface of the electron density on a level of 0.5 e·Å−3
Figure 4: electrostatic potential on an isosurface of the electron density on a level of 0.0067 e·Å−3 (van der Waals surface)
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