The binding of drugs by macmmolecules is of interest because of its physioiogical, pharmacological, or pharmaceutical significance. Phenol and its related derivatives are used as model compounds of drugs. In this connection, for example, the interaction of polyvinylpyrd i d o n e with phenolic coeolutes has been investigated. 'l In a previous article the binding of acid a m dyea carrying phenolic hydmxyl p u p s such as orange I, orange 11, chrome violet, Chydroxyazobenzene4'-sulfonate, and 2.rl-dihydroxyazobenzenea'-sdfonate by polyethylenimine (PEI) was studied. The results show that the extent of binding of chrome violet and 2,4dihydroxyauobenzene4'-sulfonate, which involve two hydroxyl groups in their StNCtUre, is extraordimwily large compared with the other dyes. It was further shown that there is an effect of added metal ions on the complex formation between the dyes and PEI.4In thia article the combination of phenola and OH-aubstituted benzoic acids with PEI was examined by equilibrium dialyeia and spectmscopic methods. The effects of the number and position of phenolic hydroxyl groups on the small molecules upon the extent of binding were investigated to gain an inaight into the nature of the forces governing afiinity between two binding entities.The phenolic consolutes used in this experiment were phenol, resorcinoi, benmic acid, & hydroxybemic acid (salicylic acid), 3 -h y b x y b e m i c acid, Chydroxybenzoic acid, 2.3dihy-droxybemic acid, 2,edihydroxybenzoic acid, and 2,5dihydroxybenzoic acid, which were purs e d by vacuum distillation or repeated recrys-tion from water. PEI, a commercially available polyethylenimine of average molecular weight 40,00060,000, was furnished from Tokyo Kaeai Co. The extent of binding of each of the coeolutes studied was measured by an equilibrium dialysis technique in 0.1MTrbacetata bufYer, pH 7.0, at 25CSThe ability of PEI to bind phenol and reeorcinol is shown in Figure 1, in which the extent of binding is expressed in terms of a common unit of weight: 1P g of PEI.As is evident in Figure 1, resorcinol, which has two OH p u p s in ita structure, exhibits the greater extent of binding for PEI compared with phenol. Phenol haa the value of pK, of 9.99 (2~5'0.~ Also the values of pKI and pK* of resorcinol are 9.15 and 11.3 (W, respectively.6 Accordingly, at pH 7.0, in which the binding experimenta were carried out, both compounds are unionized in bulk aque6us solution. Thus, these cosolutea are likely to be bound to PEI in the undissociated state. The results of binding observed indicate that the binding is subject to dramatic OH group dependence. The second hydroxyl group present in resorcinol plays a dominant role in the enhancement of the binding for PEI. Both hydroxyl groups of reeorcinol are apparently capable of interacting simultaneousIy with the polymer. Figure 2 shows the extent of binding of benzoic acid and OH-substituted benzoic acids by PEI. These benmic acids behake similarly to phenols. Evidently the binding aEnity of PEI for these small molecules increase...
