PARTITION BEHAVIOR OF TROPANE ALKALOIDS BETWEEN ORGANIC-SOLVENTS AND WATER

The partition behavior of tropane alkaloids (TrA) between organic solvent and water was studied under various conditions. The apparent partition 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 phase is based on the neutral form of TrA. From the pH dependency of the partition 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 homatropine. It was considered that the presence of the epoxide ring in scopolamine 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 portion 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 was measured in the presence of various kinds of anions (halides and alkyl sulfonates, C5-C-8) at about pH 2, where almost all TrA are present as a protonated form. The relations between the log P' and the logarithmic concentration of anions is linear at low concentrations of anions as expected from the ion-pair partition equation. The ion-pair partition coefficient P(i) and the ion-pair formation constant K(i) for each 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 product P(i).K(i) between anions and/or TrAs were discussed in detail.