Ml. Go et al., THERMODYNAMICS OF THE PARTITIONING OF 7-CHLORO-4-(4'-METHOXY)ANILINOQUINOLINE AND ITS CYCLIZED ANALOG IN OCTANOL-BUFFER AND LIPOSOME SYSTEMS, Chemical and Pharmaceutical Bulletin, 43(2), 1995, pp. 289-294
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.