Structure and thermodynamics of the hetero-association of aromatic molecules in aqueous solution determined by NMR spectroscopy

A statistical-thermodynamical model of hetero-association, in which molecul es form indefinite aggregates for both self-association and hetero-associat ion, has been developed in this work to analyse the NMR parameters of compo nent molecules in mixed solutions. The NMR analysis has been used to invest igate the hetero-association of the phenanthridinium drug molecules, ethidi um bromide (EB) and propidium iodide (PI), and the method has been shown to be self-consistent by the same results being given for two independent set s of experiments having either PI or EB constant and the other varied. The magnitudes of the hetero-association parameters (equilibrium reaction const ants and thermodynamic parameters, entropy and free energy) for the phenant hridinium drugs, PI and EB, are found to be intermediate between those obse rved for self-association of these molecules, whereas the enthalpy of heter o-association of EB + PI is similar to that for self-association of these m olecules in solution. The most favourable structure of the PI + EB 1:1 hete ro-association complex has been determined from the calculated values of th e induced chemical shifts of the drug protons and it is found to be similar to that for PI determined in this work, and with EB determined previously. The results show that the size and charge of the side chains of EB [R = CH 2CH3] and PI [R = (CH2)(3)N+(CH2CH3)(2)CH3] significantly influence the the rmodynamics of molecular complexation but not the structures of the complex es, which are influenced more by the disposition of the phenyl group side c hains.