Tuning the pKa of the antihistaminic drug chlorpheniramine maleate by supramolecular interactions with water-soluble polymers

The interaction of the pharmacologically important chlorpheniramine maleate (CPM) with polyanions containing sulfonate groups such as poly(sodium 4-styrenesulfonate) (PSS), poly(sodium vinylsulfonate) (PVS), and the more hydrophobic poly(sodium 2-(N-acrylamido)-2-methyl-propanesulfonate) (PAMPS) has been studied by H-1 NMR. It was found that the pK(a) of the low-molecular weight molecule (LMWM) may be modified by its interaction with the polyanions, changing from 3 to 5, due to electric charge compensation. Interestingly, the interaction of CPM with PSS produces changes in CPM resonances, such as a general broadening and upfield shifts of the signals, and NOE effects between the LMWM and the water-soluble polymer (WSP) that indicate the presence of pi-pi interactions. (c) 2006 Elsevier Ltd. All rights reserved.