Computed electrostatic potentials and average local ionization energies on the molecular surfaces of some tetracyclines

The electrostatic potentials and average local ionization energies computed on the molecular surfaces of four tetracyclines have been investigated with the objective of identifying common features as well as subtle differences that may be related to their biological activities. The four are the parent molecule tetracycline, chlortetracycline, oxytetracycline, and doxycyline. The calculations were carried out at the HF/STO-3G*//STO-3G* level. Our electrostatic potential results show that each molecule has a large negative region that extends along its lower portion, consistent with its ability to complex Ca-2 divided by and Mg2+ ions. Although the surface electrostatic potentials of the four tetracyclines show many similarities, our statistical measure of local polarity allows us to label doxycycline as the one with the lowest degree of local polarity, consistent with its longer half-life in vivo. The regions in the tetracyclines with the most reactive electrons are the amide nitrogen lone pairs and certain carbons of the outermost rings. (C) 2001 John Wiley & Sons, Inc. Int J Quantum Chem 82: 160-169, 2001.