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

Fluoroquinolones (FQs) are antibiotics widely used in the clinical practice due to their large spectrum of action against Gram‑negative and some Gram-positive bacteria. Nevertheless, the misuse and overuse of these antibiotics has triggered the development of bacterial resistance mechanisms. One of the strategies to circumvent this problem is the complexation of FQs with transition metal ions, known as metalloantibiotics, which can promote different activity and enhanced pharmacological behaviour. Here, we discuss the stability of FQ metalloantibiotics and their possible translocation pathways. The main goal of the present review is to frame the present knowledge on the conjunction of biophysical and biological tools that can help to unravel the antibacterial action of FQ metalloantibiotics. An additional goal is to shed light on the studies that must be accomplished to ensure stability and viability of such metalloantibiotics. Potentiometric, spectroscopic, microscopic, microbiological, and computational techniques are surveyed. Stability and partition constants, interaction with membrane porins and elucidation of their role in the influx, determination of the antimicrobial activity against multidrug‑resistant (MDR) clinical isolates, elucidation of the mechanism of action, and toxicity assays are described for FQ metalloantibiotics.

1-ALKYL-3-METHYL-4-HYDROXYIMINO-2-PYRAZOLINE-5-ONES AS EXTRACTION REAGENTS

With nitrosation of the corresponding 1-R-3-methylpyrazole-5-one (R = C4H9, C5H11, C6H13, C7H15, C8H17, C6H5) in acidic aqueous methanolic medium at 0-5 °C a series of 1-alkyl-3-methyl-4-hydroxyimino-2-pyrazolin-5-ones with a yield of 72-85% were synthesized. The compounds are soluble in CHCl3, C2H4Cl2, C6H5CH3, i-C4H9OH, CCl4, C2H5OH, slightly soluble in C6H14, H2O. They can be recrystallized from a mixture of C6H14: C6H5CH3 = 5: 1 or isooctane. The structure of the compounds was confirmed by the data of ECR, IR, Raman spectroscopy and TLC data. The interphase distribution of oxyiminopyrazolones between chloroform and aqueous solutions was studied as a function of pH. In alkaline media, the reagents completely transferred into the aqueous phase. In acidic solutions, up to 1 mol/l HCl, the compounds are in the organic phase. The maximum values of the partition coefficient are observed for the reagents with the maximum length of the aliphatic radical. The effect of the length of aliphatic radical at the first position of the pyrazoline ring on their extraction properties were studied by example of extraction of nickel and copper (II) ions. The length of the radical does not affect the composition of the recoverable complexes of nickel and copper (II). In all cases the ratio is close to 1:2. Extraction proceeds through a cation-exchange mechanism. Replacement of the phenyl radical in the first position of the pyrazoline ring by an aliphatic resulted to the increase in partition constants of the reagents between chloroform and aqueous solutions. The range of pH values of the maximum extraction of elements was widened. The capacity of the extractant for metals also increased. At the same time, the pH50 extraction values remained practically unchanged. In the case of 0.05 mol/l solution of 1-phenyl-3-methyl-4-oxyimino-2-pyrazolin-5-one in chloroform, when the extract was saturated with the metal ion, precipitation of the complex was observed.For citation:Lesnov A.E., Pavlov P.T., Pustovik L.V., Sarana I.A. 1-Alkyl-3-methyl-4-hydroxyimino-2-pyrazoline-5-ones as extraction reagents. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 2017. V. 60. N 5. P. 30-36.

Studies on the separation of some transition metals using trialkylimidazole as selective extractant

The possibility of Cu(II) ion separation from an equimolar Cu-Cd-Zn tertiary mixture by solvent extraction was investigated. The process was based on the use of 1,2,4-trimethylimidazole (TMI) and 1- decyl-2,4-dimethylimidazole (DDMI) as extractant. Dichloromethane was used as the solvent in the extraction process. The dissociation constant of extractants were found potentiometrically. Extraction data were used for finding stability constants and partition constants for the complexes being formed in the aqueous solution. For TMI, separation coefficients for Cu(II) with regard to zinc and cadmium are 2.9 and 1.3, respectively. For DDMI separation coefficients for Cu(II) with regard to zinc and cadmium are 1.4 and 1.6, respectively. Sparingly soluble in water 1-decyl-2,4-dimethylimidazole is a more useful extractant.