title: 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 beta-adrenoreceptor blocking agents with unilamellar dimyristoylphosphatidylcholine (DMPC) liposomes has been studied by proton nuclear magnetic resonance (1H-NMR) in the presence of praseodymium cation (Pr3+) at 30 degrees 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 (approximately 3%). The difference in chemical shift of the external and internal peaks (delta Hz) 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+.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
authors.forename: G V
authors.initials: GV
authors.lastname: Betageri
authors.forename: Y
authors.initials: Y
authors.lastname: Theriault
authors.forename: J A
authors.initials: JA
authors.lastname: Rogers
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology*; D002412:Cations; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011221:Praseodymium / Q000378:metabolism / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D013010:Sonication; D013329:Structure-Activity Relationship
chemical_list: D000319:Adrenergic beta-Antagonists; D002412:Cations; D008051:Lipid Bilayers; D008081:Liposomes; D011433:Propranolol; D011221:Praseodymium; D004134:Dimyristoylphosphatidylcholine