Conformational Analysis of Tetracycline using Molecular Mechanical and Semiempirical MO-Calculations

  A combination of gas phase molecular dynamics and systematic conformational searches with semiempirical MO-theory has been used to identify and characterise the low energy conformations of tetracycline in its neutral non-polar and zwitterionic forms and as the deprotonated zwitteranion. The conformations found have been characterised by cluster- and principal components analyses as belonging to three main groups. These are very similar for the nonpolar and zwitterionic neutral forms of tetracycline, but very different for the anion. The likely consequences of the conformational flexibilty for metal ion complexation by tetracycline are discussed.