NMR Study of the Interaction of Beta-Blockers with Sonicated Dimyristoylphosphatidylcholine Liposomes in the Presence of Praseodymium Cation

Abstract

The interaction of a series of β-adrenoreceptor blocking agents with unilamellar dimyristoylphosphatidylcholine (DMPC) liposomes has been studied by proton nuclear magnetic resonance (¹H-NMR) in the presence of praseodymium cation (Pr^{3 +}) at 30°C. Addition of Pr³⁺ increased the splitting of the trimethylammonium group signals arising from the phospholipid molecules located at the internal and external surfaces of the bilayers. Adding Pr³⁺ caused a considerable downfield shift of the external peak but only a slight upfield shift of the internal peak (∼3%). The difference in chemical shift of the external and internal peaks (δHz) increased linearly as a function of Pr³⁺ concentration up to 10 mM. The addition of beta-blockers reversed the effect of Pr³⁺, and propranolol exerted the most pronounced effect, causing complete reversal of the splitting at a concentration of 5 mM. Much higher concentrations of other beta-blockers were required to displace Pr³⁺. A linear correlation between Pr³⁺ displacement (P) and logarithm of the apparent partition coefficient (K′_m) in DMPC liposomes was obtained for hydrophobic beta-blockers, but hydrophilic beta-blockers did not fit this correlation. It appears that beta-blockers that have ortho or meta substitution require penetration of the liposome bilayers before significant polar group interaction can occur. On the other hand, beta-blockers that have para substitution and low K′_m values are able to interact with the polar surfaces of the liposomes without penetration to cause displacement of Pr³⁺

Key Words:

• ¹H-NMR
• beta-blockers
• praseodymium
• liposome interactions