Kinetics of Antimicrobial Drug Ion Transfer at a Water/Oil Interface Studied by Nanopipet Voltammetry

Abstract

Effective delivery and accumulation of antimicrobial agents into the microbial organism is essential for the treatment of bacterial infections. Transports of hydrophilic drug molecules, however, encounter a robust barrier of hydrophobic double membrane cell envelope, thus, leading to drug-resistance in Gram-negative bacteria. Accordingly, a deeper understanding about a transit of charged molecules through a bacterial membrane is needed to remediate the antibacterial resistance. Herein, we apply a steady-state voltammetry using nanopipet-supported interfaces between two immiscible electrolyte solutions (ITIES) to quantitatively study transport-kinetics of antimicrobial drug ions (quinolones and sulfonamides) at a water/oil interface. Importantly, ITIES can mimic a cellular membrane system, thus, being employed as insightful surrogates for the kinetic study of drug entry through bacterial cytoplasmic membranes. This approach enables us to voltammetrically and amperometrically detect redox-inactive drug ions as pristine under physiological conditions. Considerably slow kinetics of drug-ion transports are successfully measured by nanopipet voltammetry and theoretically analyzed. This analysis reveals that the drug-ion transport is ∼3 orders of magnitude slower than tetrabutylammonium ion transport. In addition, the extreme hydrophilicity of drug ions in comparison to ClO4 – is quantitatively assessed from half-wave potentials of obtained voltammograms. The high hydrophilicity exclusively attributed to localized negative charges on carboxylate or amide group of deprotonated quinolone or sulfonamide, respectively, may play a dominant role in sluggish kinetics due to the increase in energy barriers upon interfacial ion transfer. Notably, this study using nanopipet voltammetry provides physicochemical insights on the correlation between structural properties of pristine drug ions and their transfer kinetics at a water/oil interface in lieu of biological membranes.

Corynebacterium matruchotii fitness enhancement of adjacent streptococci by multiple mechanisms

“…With this submicrotip, an etched Ni/Cu electrode in the internal organic electrolyte exerts a bias across the submicroscale liquid/liquid interface against an electrode in the aqueous solution (Fig. S3A) to yield the amperometric tip current based on the selective interfacial transfer of a small probe ion (Puri and Kim, 2019). The coculture of C. matruchotii and S. mitis was immobilized over a poly L-lysine coated glass plate, and studied by scanning or approaching an 800 nm-diameter pipet tip over the bacteria (Fig.…”

“…Scanning electrochemical microscopy acquisition. Scanning parameters and nano-probe design are similar to methods described previously (Connell et al, 2014;Kim et al, 2014;Kim et al, 2016;Puri and Kim, 2019). A full description of SECM calibration, sample acquisition and metabolite quantification are provided in the Supplemental Materials.…”

“…To investigate lactate production and consumption in situ by bacteria as well as the topography of bacterial cells, a submicropipet-supported interface between two immiscible electrolyte solutions (ITIES) was employed (Figs 5, S3) (Puri and Kim, 2019). With this submicrotip, an etched Ni/Cu electrode in the internal organic electrolyte exerts a bias across the submicroscale liquid/liquid interface against an electrode in the aqueous solution (Fig.…”

Single-Entity Electrochemistry of Nanoemulsion: The Nanostructural Effect on Its Electrochemical Behavior

“…Pt UME (5 μm diameter) was fabricated by using a CO 2 -laser puller, microforge, and then a homemade polisher. Tapered nanopipets with an inner tip radius of ∼60 nm were obtained by pulling 10-cm-long quartz capillaries (outer/inner diameter ratio of 1.0/0.7; Sutter Instrument Co., Novato, CA) using a CO 2 -laser capillary puller (model P-2000, Sutter Instrument) . More detailed information about the fabrication of these electrodes is in the Supporting Information (SI).…”

Quantitative Analysis of Redox-Inactive Ions by AC Voltammetry at a Polarized Interface between Two Immiscible Electrolyte Solutions

“…Examples of redox-inactive ions quantitatively detected by their reversible ion transfer across the ITIES include drugs, such as cocaine, propranolol, − metoprolol, daunorubicin, topotecan, antimicrobial drug ions (quinolones and sulfonamides) and fluoroquinolone antibiotics, neurotransmitters and neuromodulators such as dopamine, − acetylcholine, − tryptamine, serotonin, and gamma-aminobutyric acid, pathogenic bacterial quorum sensing molecules such as 4-hydroxy-2-heptylquinoline (HHQ) and 2-heptyl-3,4-dihydroxyquinoline (pseudomonas quinolone signal, PQS), and heavy-metal-ions such as Pb­(II), , Cd­(II) ,− and Cr­(VI). , Comprehensive overviews of recent developments in this fast-evolving field can be found in reviews by Arrigan, − Dassie, Herzog, Lee, Shen, and their co-workers.…”