Can protonated beta-blockers interact with biomembranes stronger than neutral isolipophilic compounds? A chromatographic study on three different phospholipid stationary phases (IAM-HPLC).
The chromatographic capacity factors (k') of 10 beta-adrenoceptor antagonists ("beta-blockers") were measured on three different immobilized artificial membrane-phosphatidylcholine (IAM-PC) HPLC stationary phases, namely IAM-PC-MG, IAM-PC-DD2, and IAM-PC-DD. The two former phases are made of phosphatidylcholine as found in biomembranes and differ each other in end-capping of free propylamino residues whereas the latter is made of single-chain phosphatidylcholine analogues. On IAM-PC-DD2 we found that structurally unrelated neutral compounds give a single correlation between logk' values and the respective octanol/water partition coefficients (logP), as previously observed on IAM-PC-MG phase. This was not observed on the IAM-PC-DD phase. IAM chromatography was performed at a pH of the aqueous eluent (7.0) close to the physiological pH 7.4. Retention on all IAM phases showed a biphasic pattern, being proportional to logP(N) (lipophilicity of neutral forms) for more lipophilic congeners (logP(N)>1.90), and quite constant for the others. The comparison of beta-blocker retention with that of neutral compounds on IAM-PC-MG and IAM-PC-DD2 suggests that they can interact with phospholipids as strongly or more strongly than neutral isolipophilic compounds, despite their being more than 98% in their ionized form. Therefore, we hypothesize that electrostatic interactions play a pivotal role in the interactions between beta-blockers and membrane phospholipids.
Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, Via D. Montesano, 49 I-80131 Naples, Italy. fbarbato@unina.it
Francesco
F
Barbato
Giuseppina
G
di Martino
Lucia
L
Grumetto
Maria Immacolata
MI
La Rotonda
D000319:Adrenergic beta-Antagonists / Q000032:analysis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004058:Diffusion; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008567:Membranes, Artificial; D010713:Phosphatidylcholines / Q000737:chemistry*; D055672:Static Electricity; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D008567:Membranes, Artificial; D010713:Phosphatidylcholines