Partition coefficients and thermodynamics of transfer of novel drug-like spiro-derivatives in model biological solutions

Temperature dependences of partition coefficient for 11 drug-like spiro-derivatives of 1,3-thiazine in the system aqueous phosphate buffer/organic phase (hexane, octanol) have been determined over the temperature range (293.15 to 315.15) K by the isothermal saturation method. The effects of aliphatic chain substituent structure and introduction of oxygen, chlorine, bromine and fluorine atoms on the partitioning processes of the substances studied were examined. It has been established that among the substances investigated halogen derivatives possess the lowest partition coefficients in buffer/hexane system and the highest ones in buffer/octanol system. Regularities between the partition coefficients and the descriptors reflecting the capability of the solutes to undergo specific and nonspecific interactions with solvent molecules were revealed. The thermodynamic functions describing the partitioning process were calculated. It was found that differences in the partition coefficients depend on the enthalpies of transfer.