Interactions of a non-fluorescent fluoroquinolone with biological membrane models: A multi-technique approach

Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance

“…Table 2. Values for the partition constants (K p ± SD) of metalloantibiotics in different membrane mimetic systems of prokaryotic and eukaryotic cells, obtained by fluorescence and UV-vis spectroscopies and molecular dynamics (MD) simulations, from [38,71,75,77,87]. Speciation under physiological conditions (pH 7.4; concentrations in the same range of those used in the partition studies).…”

“…Speciation under physiological conditions (pH 7.4; concentrations in the same range of those used in the partition studies). Fluorescence TR E. coli total lipid extract 4.87 ± 0.08 [71] Fluorescence ST E. coli total lipid extract 5.24 ± 0.01 [71] Fluorescence TR Based on differences of the chemistry of free FQs and metalloantibiotics (neutral/ zwitterionic vs. cationic forms, prevalent under physiological conditions, respectively), and taking into account the negative charge characteristic of bacterial membranes (mean zeta potential of the E. coli total extract liposomes: −36.8 mV [71]), distinct interactions and potential alternative influx routes in bacteria are expected. Analysing K p values, metalloantibiotics strongly interact with bacterial model systems, showing greater constants compared to FQs [38,71,75,77,87], with no exception.…”

“…Nevertheless, liposomes became excellence model systems to mimic membranes, due to their amphiphilic character (absent in octanol/water systems), anisotropic nature (versus the isotropic nature of octanol) and structural similarity with biological membranes [ 67 , 68 ]. Generally, the partition constants are determined by spectroscopic techniques as nuclear magnetic resonance (NMR) [ 69 , 70 , 71 ], derivative spectrophotometry [ 71 , 72 , 73 , 74 ], and fluorescence spectroscopy [ 74 , 75 , 76 , 77 ], the last one being the most sensitive [ 78 ]. Additionally, values determined by computational approaches have been recently reported [ 38 , 79 , 80 , 81 ].…”

“…Based on differences of the chemistry of free FQs and metalloantibiotics (neutral/zwitterionic vs. cationic forms, prevalent under physiological conditions, respectively), and taking into account the negative charge characteristic of bacterial membranes (mean zeta potential of the E. coli total extract liposomes: −36.8 mV [ 71 ]), distinct interactions and potential alternative influx routes in bacteria are expected. Analysing values, metalloantibiotics strongly interact with bacterial model systems, showing greater constants compared to FQs [ 38 , 71 , 75 , 77 , 87 ], with no exception. Analysing the values obtained by fluorescence and UV-vis spectroscopies, it is possible to conclude that metalloantibiotics with higher percentage of di-cationic form ([Cu(HFQ)phen] 2+ ) exhibit higher partition constants: Cucpxphen > Cumxfxphen ≈ Cuspxphen ≈ Cuerxphen > Culvxphen.…”

“…These insights predict an influx route strongly dependent on hydrophobic interactions [ 30 , 38 , 71 , 75 , 77 , 87 ], contrarily to what is commonly observed for free FQs (with exception of spx [ 39 , 71 ]), whose translocation occurs through porins and/or by a combination of hydrophobic and hydrophilic routes, via porin/lipid interface [ 30 , 39 , 51 , 88 , 89 , 90 ]. The distinct translocation routes proposed for free FQs and metalloantibiotics were also corroborated by the changes observed in the emission spectra of the compounds in the presence of increasing amounts of liposomes.…”