PARTITION BEHAVIOR OF TROPANE ALKALOIDS BETWEEN ORGANIC-SOLVENTS AND WATER

The partition behavior of tropane alkaloids (TrA) between organic solv ent and water was studied under various conditions. The apparent parti tion coefficient, log P', increases with pH with a slope of +1 in the acidic to neutral pH range, then tends to approach to a constant value in the alkaline region. Thus the partition of TrA to the organic phas e is based on the neutral form of TrA. From the pH dependency of the p artition and pH titration of TrA, the intrinsic partition coefficients log P0 and pK(a) values for each TrA were estimated. Values of pK(a) and log P0 for scopolamine were smaller than those for atropine or hom atropine. It was considered that the presence of the epoxide ring in s copolamine molecule reduces the log P0 and pK(a) because of its polar and electro-inductive effect. It was also expected from the results of pH-dependent partition behavior that in the low pH region some portio n of TrA cations is transferred to the organic phase by forming an ion -pair complex with an anion, in the aqueous phase. The log P' of TrA w as measured in the presence of various kinds of anions (halides and al kyl sulfonates, C5-C-8) at about pH 2, where almost all TrA are presen t as a protonated form. The relations between the log P' and the logar ithmic concentration of anions is linear at low concentrations of anio ns as expected from the ion-pair partition equation. The ion-pair part ition coefficient P(i) and the ion-pair formation constant K(i) for ea ch ion-pair of TrA/anion were obtained separately from the reciprocal plot of 1/[X-]w versus 1/P'. The differences of P(i), K(i) and the pro duct P(i).K(i) between anions and/or TrAs were discussed in detail.