The irreversible migration of benzylpenicillin into human erythrocytes : honors thesis [(HONRS 499)]

Benzylpenicillin (14C) was incubated with whole human blood. It was shown that 88.5% of th epenicillin could be washed away or dialyzed away. The distribution of the bound penicillin was 5.2% to the plasma and 6.3% to the erythrocyte. The plasma was separated into its component protein fractiosn by gel electrophoresis. This separation indicated that 100% of the plasma associated penicillin was irreversibly bound to the albumen. The penicillin associated with the erythrocyte was not bound to the cell membrane or the intracellular proteins. Isolation and characterization of the penicillin moiety trapped in the erythrocyte was performed via IR spectroscopy and it was found that this trapped material was benzylpenicilloic acid. The rationale for this observed migration is that the monovalent anion, benzylpeicillin enters the erythrocyte and is enzymaticaly hydrolyzed to the divalent anion benzylpenicilloic acid. This change in charge traps the molecule in the erythrocyte, as the transport mechanism which brought the antibiotic into the cell will now allow it to migrate out of the cell in a divalent form. The subject of this thesis will be to compare the migration patterns of the penicillin derivatives: phenoxymethylpenicillin, 2, 6 – dimethoxy – phenylpenicillin, and alpha-aminobenzylpenicillin, into human erythrocytes to that of benzylpenicillin. Evidence will also be presented elucidating the mechanism of hydrolysis from benzylpenicillin to benzylpenicilloic acid.Honors CollegeThesis (B.?.