Sergiy Rogalsky

Antibacterial Activity of Imidazolium-Based Ionic Liquids Investigated by QSAR Modeling and Experimental Studies

Predictive QSAR models for the inhibitors of B. subtilis and Ps. aeruginosa among imidazolium‐based ionic liquids were developed using literary data. The regression QSAR models were created through Artificial Neural Network and k‐nearest neighbor procedures. The classification QSAR models were constructed using WEKA‐RF (random forest) method. The predictive ability of the models was tested by fivefold cross‐validation; giving q2 = 0.77–0.92 for regression models and accuracy 83–88% for classification models. Twenty synthesized samples of 1,3‐dialkylimidazolium ionic liquids with predictive value of activity level of antimicrobial potential were evaluated. For all asymmetric 1,3‐dialkylimidazolium ionic liquids, only compounds containing at least one radical with alkyl chain length of 12 carbon atoms showed high antibacterial activity. However, the activity of symmetric 1,3‐dialkylimidazolium salts was found to have opposite relationship with the length of aliphatic radical being maximum for compounds based on 1,3‐dioctylimidazolium cation. The obtained experimental results suggested that the application of classification QSAR models is more accurate for the prediction of activity of new imidazolium‐based ILs as potential antibacterials.

Erratum to: Structural, thermal and antibacterial properties of polyamide 11/polymeric biocide polyhexamethylene guanidine dodecylbenzenesulfonate composites

Antimicrobial polyamide 11 (PA-11) films containing low-cost, thermally stable and water resistant polymeric biocide polyhexamethylene guanidine dodecylbenzenesulfonate (PHMG-DBS) have been obtained by compression moulding. The structure of the modified PA-11 films containing from 3 to 10 wt% of PHMG-DBS was characterized using Raman and FTIR spectroscopy and atomic force microscopy (AFM). The surface properties were evaluated both by contact angle and contactless inductive method. The introduction of PHMG-DBS into PA-11 films was found to increase positive surface charge density to 5.5·10−11 C/cm2 for 10 wt% of PHMG-DBS. Antibacterial activity of PA-11/PHMG-DBS films against both Gram-positive (Escherichia coli) and Gram-negative (Bacillus subtilis) bacteria was demonstrated for films containing from 5 to 7 wt% of polymeric biocide. According to thermal investigations data, PA-11/PHMG-DBS composite has excellent thermal stability to at least 390 °C both in air and in argon atmosphere which indicates on its availability for the melt processing by common methods. It has also been found that polymeric biocide is highly resistant to leaching from PA-11 film.

Promising silicones modified with cationic biocides for the development of antimicrobial medical devices

We have tested silicones containing 2% or 5% of the cationic biocides polyhexamethylene guanidine dodecylbenzenesulfonate (PHMG-DBS), 1-octyl-3-methylimidazolium tetrafluoroborate (OMIM-BF4) or 1-dodecyl-3-methylimidazolium tetrafluoroborate (DMIM-BF4) against the major relevant bacterial and yeast species in health care-associated infections (HCAI). Study conducted according to the international standard ISO 22196 revealed that silicones containing 2% or 5% DMIM-BF4 or 5% PHMG-DBS presented the highest antimicrobial activity, leading to a logarithmic growth reduction of 3.03 to 6.46 and 3.65 to 4.85 depending on the bacterial or fungal species. Heat-pretreated silicones containing 2% DMIM-BF4 kept a high activity, with at least a 3-log reduction in bacterial growth, except against P. aeruginosa where there was only a 1.1-log reduction. After 33days, the release ratio of cationic biocide from silicone films containing 5% of DMIM-BF4 was found to be 5.6% in pure water and 1.9% in physiological saline solution, respectively. No leaching of PHMG-DBS polymeric biocide was detected under the same conditions. These results demonstrate unambiguously that silicones containing 2% DMIM-BF4 or 5% PHMG-DBS present high antimicrobial activity, as well as high leaching resistance and therefore may be good candidates for the development of safer medical devices.

New promising antifouling agent based on polymeric biocide polyhexamethylene guanidine molybdate

A new polymeric biocide polyhexamethylene guanidine (PHMG) molybdate has been synthesized. The obtained cationic polymer has limited water solubility of 0.015 g/100 mL and is insoluble in paint solvents. The results of acute toxicity studies indicate moderate toxicity of PHMG molybdate, which has a median lethal dose at 48 h of 0.7 mg/L for Daphnia magna and at 96 h of 17 mg/L for Danio rerio (zebrafish) freshwater model organisms. Commercial ship paint was then modified by the addition of a low concentration of polymeric biocide 5% (w/w). The painted steel panels were kept in Dnipro River water for the evaluation of the dynamics of fouling biomass. After 129-d exposure, Bryozoa dominated in biofouling of tested substrates, forming 86% (649 g/m2 ) of the total biomass on control panel surfaces. However, considerably lower Bryozoa fouling biomass (15 g/m2 ) was detected for coatings containing PHMG molybdate. Dreissenidae mollusks were found to form 88% (2182 g/m2 ) of the fouling biomass on the control substrates after 228 d of exposure, whereas coatings containing PHMG molybdate showed a much lower biomass value of 23.6 g/m2 . The leaching rate of PHMG molybdate in water was found to be similar to rates for conventional booster biocides ranging from 5.7 μg/cm2 /d at the initial stage to 2.2 μg/cm2 /d at steady state. Environ Toxicol Chem 2017;36:2543-2551.

Imidazolium Ionic Liquids as Potential Anti-Candida Inhibitors: QSAR Modeling and Experimental Studies

Quantitative structure-activity relationships (QSAR) of imidazolium ionic liquids (ILs) as inhibitors of C. albicans collection strains (IOA-109, KCTC 1940, ATCC 10231) have been studied. Predictive QSAR models were built using different descriptor sets for a set of 88 ionic liquids with known minimum inhibitory concentrations (MIC) against C. albicans. We applied the state-of-the-art QSAR methodologies such as WEKA Random Forest (RF) as a binary classifier, Associative Neural Networks (ASNN) and k-Nearest Neighbors (k-NN) to build continuum non-linear regression models. The obtained models were validated using a 5-fold cross-validation approach and resulted in the prediction accuracies of 80% ± 5.0 for the classification models and q2 = 0.73-0.87 for the non-linear regression models. Biological testing of newly synthesized 1,3-dialkylimidazolium ionic liquids with predicted activity was performed by disco-diffusion method against C. albicans ATCC 10231 M885 strain and clinical isolates C. albicans, C. krusei and C. glabrata strains. The high percentage of coincidence between the QSAR predictions and the experimental results confirmed the high predictive power of the developed QSAR models within the applicability domain of new imidazolium ionic liquids.

Antimicrobial polycarbonates for biomedical applications

BackgroundPolycarbonate (PC) is one of the most widely used engi-neering polymers due to its unusual combination of opti-cal clarity, heat resistance,high impact strength anddimensional stability over wide thermal range [1]. Lowwater absorption, ease of sterilization and biocompatibilityof PC have led to its use in a wide range of medical equip-ment, including critical medical devices [2]. The preven-tion of biofilm formation on the internal medical devicesis of great importance since it can initiate a degradationprocess of the material, as well as cause infections andhealth related problems [3]. In order to obtain antimicro-bial properties, polymers are usually compounded withorganic or inorganic biocides [4,5]. However, the use oforganic biocides as additives for PC is significantly limiteddue to their insufficient thermal stability in the tempera-ture range used for PC processing (300 – 320 °C).The aimof research was to develop novel low toxic biocides forPC having sufficient thermal stability for the joint meltprocessing with PC resin.Materials and methodsTwo kinds of potential antimicrobial additives for PC havebeen synthesized: imidazolium and guanidinium ionenes,as well as imidazolium based ionic liquids. PC films con-taining from 1 to 10 wt% of biocides were prepared by sol-vent casting or by compression molding methods. Thethermal stability of novel biocides as well as modified PCwas investigated by using thermogravimetric analysis(TGA). Antimicrobial testing of PC composites were per-formed using a model bacteriaPseudomonas fluorescensSBW25 with a help of classical microbiological methodsfor bacterial suspension as well as a live-dead assay forbiofilms [6].ResultsAccording to TGA data, the thermal stability of PC sam-ples containing biocidal additives was found to be in therange of 350-425