title: The kinetics of ampicillin complexation by γ-cyclodextrins. A single molecule approach.
abstract: Efficient measuring of binding thermodynamics of interactions between cyclodextrins (CDs) and antibiotics remains a challenge in the fields of physical chemistry and pharmaceutics. Here we report on a single-molecule investigation of pH- and voltage-dependent reversible interactions between ampicillin and γ-CDs, through monitoring of ionic current signatures across an α-hemolysin (α-HL) protein entrapping a γ-CD molecule. Our data reveal that electric and electro-osmotic driving forces alter the reversible reaction rates of ampicillin interaction with γ-CDs, as well as free energy changes accompanying the interaction. We found that close to neutral pH values facilitate more unstable γ-CD-ampicillin complexes, as well as a decreased affinity of the γ-CD-ampicillin reversible interaction, as compared to acidic pH. We posit that a pH-dependent partial electric charge on the ampicillin molecule and anionic selectivity of the α-HL·γCD complex account for the antibiotic and γ-CD intracavity manifestations. This approach may provide unique alternatives for the characterization of CD-guest interactions, useful for pharmaceutical formulations and tunable drug delivery systems.
authors.affiliation: Department of Physics, Laboratory of Molecular Biophysics and Medical Physics, Alexandru I. Cuza University, Boulevard Carol I, No. 11, Iasi 700506, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Asandei
authors.forename: Loredana
authors.initials: L
authors.lastname: Mereuta
authors.forename: Tudor
authors.initials: T
authors.lastname: Luchian
mesh_terms: D000667:Ampicillin / Q000737:chemistry*; D006460:Hemolysin Proteins / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013816:Thermodynamics; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D006460:Hemolysin Proteins; D047408:gamma-Cyclodextrins; D000667:Ampicillin