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Structure and function of propranolol: A β‐adrenergic blocking drug
Author(s) -
Phadke Ratna S.,
Kumar N. Vasanth,
Hosur R. V.,
Saran Anil,
Govil Girjesh
Publication year - 1981
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560200109
Subject(s) - chemistry , membrane , lipid bilayer , bilayer , spin label , moiety , crystallography , hydrogen bond , phospholipid , membrane fluidity , phase transition , stereochemistry , organic chemistry , molecule , biochemistry , physics , quantum mechanics
In our earlier studies using quantum chemical methods we had proposed that propranolol has an extended structure. These results were confirmed using proton NMR . We have now carried out extensive magnetic resonance and model building studies to examine the interaction of this drug with model membranes. The effect of propranolol on organization of lipid bilayers has been studied using ESR spin labeling technique. Spin label Tempo and spin labeled stearic acid (5 SASL ) have been used to monitor changes in the fluidity of model membranes. Presence of the drug is found to fluidize the lipids. In case of 0.2 M dipalmitoyl phosphatidyl choline (DPPC), presence of drug (0.1 M ) is found to decrease the gel‐liquid crystalline phase transition temperature by about 10°C. The order parameter measured from the spectrum of 5 SASL shows a 4% decrease on incorporation of the drug in membranes. 13 C spin lattice relaxation time ( T 1 ) measurements have been carried out for different nuclear sites of the drug. The aromatic moiety shows a high degree of molecular rigidity when the drug is bound to the lipid bilayers. The oxypropanolamine group is however relatively flexible. It appears from these studies that the aromatic group binds strongly to the hydrophobic regions of the lipid bilayer, while the oxypropanolamine moiety remains relatively free and lies in the hydrophilic region. The 13 C chemical shifts indicate the involvement of the β‐hydroxyl group in hydrogen bonding with the lipids. The NH 2 +group may be involved in electrostatic interactions with the negatively charged phosphate group of the lipid bilayers.