Kinetic and thermodynamic aspects of in vitro interphase transfer of tetracyclines I: influence of hydroxyl group substitution.
The influence of hydroxyl group substitution on the kinetic and thermodynamic aspects of the interphase transfer of three tetracycline derivatives was studied in a two-phase in vitro system composed of an aqueous pH 5.5 buffer and 1-octanol. Data are reported on the kinetic and thermodynamic parameters of activation, the net thermodynamic parameters for interphase transfer, and the contribution of hydroxyl group substituents to the energy changes associated with partitioning. For each derivative, deltaH, deltaS, T deltaS, and deltaF were positive with enthalpy dominating the entropic energy contribution. Introduction of a hydroxyl group at C-5 on the tetracycline nucleus promoted partitioning through an entropy-dominated decrease in the "apparent" free energy of partitioning, whereas shifting the hydroxyl group to C-6beta retarded partitioning due to an enthalpy-dominated gain in the apparent free energy.
D004058:Diffusion; D004318:Doxycycline; D007700:Kinetics; D010118:Oxytetracycline; D013329:Structure-Activity Relationship; D013752:Tetracycline; D013754:Tetracyclines; D013816:Thermodynamics
D013754:Tetracyclines; D013752:Tetracycline; D004318:Doxycycline; D010118:Oxytetracycline