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

Abstract

A statistical-thermodynamical model of hetero-association, in which molecules form indefinite aggregates for both self-association and hetero-association, has been developed in this work to analyse the NMR parameters of component molecules in mixed solutions. The NMR analysis has been used to investigate the hetero-association of the phenanthridinium drug molecules, ethidium 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 sets of experiments having either PI or EB constant and the other varied. The magnitudes of the hetero-association parameters (equilibrium reaction constants and thermodynamic parameters, entropy and free energy) for the phenanthridinium drugs, PI and EB, are found to be intermediate between those observed for self-association of these molecules, whereas the enthalpy of hetero-association of EB + PI is similar to that for self-association of these molecules in solution. The most favourable structure of the PI + EB 1:1 hetero-association complex has been determined from the calculated values of the 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 = CH2CH3] and PI [R = (CH2)3N+(CH2CH3)2CH3] significantly influence the thermodynamics of molecular complexation but not the structures of the complexes, which are influenced more by the disposition of the phenyl group side chains.