THERMODYNAMICS OF THE PARTITIONING OF 7-CHLORO-4-(4'-METHOXY)ANILINOQUINOLINE AND ITS CYCLIZED ANALOG IN OCTANOL-BUFFER AND LIPOSOME SYSTEMS

The thermodynamics of the partitioning of 7-chloro-4-(4'-methoxy)anili noquinoline (I) and its cyclized analogue, 3-chloro-8-methoxy-11H-indo lo[3,2-c]quinoline (II) have been determined in octanol-buffer and lip osome systems, Under the conditions of partitioning, the protonated fo rms of compounds I and IT were predominant, but partitioning involved only the non-ionized species, The van't Hoff plots for both compounds were linear in the octanol-buffer system from 11 degrees to 35 degrees C, The log P of compound I increased with temperature, and partitioni ng was entropically controlled, In contrast, the partitioning of compo und II decreased with temperature and was enthalpically driven. The va n't Hoff plots of compounds I and II in the dimyristoyl-L-alpha-phosph atidylcholine (DMPC) liposome-buffer were biphasic, A decrease in log P was observed from 13 degrees C to approximately the T-c of the phosp holipid, followed by a subsequent increase in log P as temperature inc reased to about 32 degrees C, In the case of compound I, partitioning was entropically controlled at temperatures below and above T-c. In co ntrast, the partitioning of compound II was enthalpically controlled b elow T-c but entropically driven above T-c. The thermodynamics of the partitioning of compounds I and II in octanol. and gel phase phospholi pid (below T-c) are similar, This may be attributed to their conformat ional differences, The planarity and rigidity of compound II allows it to interact well with the ordered matrices of octanol and phospholipi d with an expected loss of enthalpy, In contrast, the twisted conforma tion of compound I would have disrupted the ordered matrices of the oc tanol and phospholipid phases, resulting in an entropy gain upon parti tioning, This study shows that the molecular shape and conformational characteristics of solute molecules are important determinants in the partitioning process.