Main-chain flexibility and hydrophobicity of ionenes strongly impact their antimicrobial activity: an extended study on drug resistance strains and Mycobacterium

The spread of antibiotic-resistant pathogens and the resurgence of tuberculosis disease are major motivations to search for novel antimicrobial agents. Some promising candidates in this respect are cationic polymers, also known as synthetic mimics of antimicrobial peptides (SMAMPs), which act through the membrane-lytic mechanism. Development of resistance toward SMAMPs is less likely than toward currently employed antibiotics; however, further studies are needed to better understand their structure–activity relationship. The main objective of this work is to understand the cross-influence of hydrophobicity, main-chain flexibility, and the topology of ionenes (polycations containing a cationic moiety within the main-chain) on activity. To fulfill this goal, a library of ionenes was developed and compared with previously investigated molecules. The obtained compounds display promising activity against the model microorganisms and drug-resistance clinical isolates, including Mycobacterium tuberculosis. The killing efficiency was also investigated, and results confirm a strong effect of hydrophobicity, revealing higher activity for molecules possessing the flexible linker within the polymer main-chain.

A high significance of the main chain flexibility and an unexpected effect of hydrophobicity on the biological activity in series of ionenes was observed. The most potent among the tested polycations showed high activity toward clinical bacterial isolates.     

Computational and Experimental Studies of Selected Types of Biomass Combustion in a Domestic Boiler

The paper analyzes the suitability of four types of biomass pellets as a fuel for heating purposes. Three types of waste biomass (sunflower husks, rapeseed cake, and corn straw) and one type of biomass grown for energy purposes (willow) were selected. After appropriate preparation, the selected starting materials were subjected to the pelletization process. Selected physical and chemical properties of the studied biomass pellets were determined. All four types of the analyzed pellets met the EN-ISO-17225-2:2014 standard in terms of bulk density, dimensions, as well as nitrogen and moisture content. The highest calorific value was pellets made of sunflower husk (17.27 MJ/m³) and willow (16.81 MJ/m³), while the calorific value of pellets made of corn straw and rapeseed cake did not exceed 16.5 MJ/m³ and did not meet the standard. In addition, the ash content for these two types of pellets was well above the standard. A 10 kW domestic biomass boiler was employed for burning the tested pellets. The consumption of analyzed fuels during boiler operation was determined. The concentration of CO, CO₂, and NO_x in exhaust gases was also examined. The obtained experimental results were compared with the numerical calculations with the use of ANSYS Chemkin-Pro using two mechanisms. The highest concentrations of CO₂ and CO were observed during the combustion of sunflower and willow husk pellets, which probably resulted from the highest carbon content and, thus, the highest calorific value when compared to cake and straw pellets. For all analyzed pellets, the value of NO and NO₂ concentration was similar and did not exceed 368 ppm and 18 ppm, respectively. The results closest to the experiment were obtained for calculations using the mechanism developed by Glarborg et al. The research carried out in the article shows that out of the four analyzed types of pellets, only sunflower and willow husk pellets can be burned in a domestic boiler adapted to burning wood pellets, which is a cheap alternative to wood pellets.     

Selected Physical and Spectroscopic Properties of TPS Moldings Enriched with Durum Wheat Bran

The impact of the amount of durum wheat bran additive used on the selected structural, mechanical, and spectroscopic properties of thermoplastic starch moldings was examined in this study. Bran was added to corn starch from 10 to 60% by weight in the blends. Four temperature settings were used for the high-pressure injection: 120, 140, 160, and 180 °C. The highest value of elongation at break (8.53%) was observed for moldings containing 60% bran. Moreover, for these moldings, the tensile strength and flexural strength were lower (appropriately 3.43 MPa and 27.14 MPa). The highest deformation at break (1.56%) were obtained for samples with 60% bran and injection molded at 180 °C. We saw that higher bran content (50 and 60%) and a higher injection molding temperature (160 °C and 180 °C) significantly changed the color of the samples. The most significant changes in the FTIR spectra were observed at 3292 and 1644 cm⁻¹ and in the region of 1460–1240 cm⁻¹. Moreover, notable changes were observed in the intensity ratio of bands at 1015 and 955 cm⁻¹. The changes observed correspond well with the amount of additive used and with the injection temperature applied; thus it may be considered as a marker of interactions affecting plasticization of the material obtained.     

Oxazoline scaffold in synthesis of benzosiloxaboroles and related ring-expanded heterocycles: diverse reactivity,structural peculiarities and antimicrobial activity

Two isomeric benzosiloxaborole derivatives 3a and 5a bearing fluorine and 4,4-dimethyl-2-oxazolin-2-yl substituents attached to the aromatic rings were obtained. Both compounds were prone to hydrolytic cleavage of the oxazoline ring after initial protonation or methylation of the nitrogen atom. The derivative 3c featuring N-methylammoniumalkyl ester functionality was successfully subjected to N-sulfonylation and N-acylation reactions to give respective derivatives which demonstrates its potential for modular synthesis of structurally extended benzosiloxaboroles. Compound 5c bearing N-ammoniumalkyl ester underwent conversion to a unique macrocyclic dimer due to siloxaborole ring opening. Furthermore, an unexpected 4-electron reduction of the oxazoline ring occurred during an attempted synthesis of 5a. The reaction gave rise to an unprecedented 7-membered heterocyclic system 4a comprising a relatively stable B–O–B–O–Si linkage and stabilized by an intramolecular N–B coordination. It could be cleaved to derivative 4c bearing BOH and SiMe₂OH groups which acts as a pseudo-diol as demonstrated by formation of an adduct with Tavaborole. Apart from the multinuclear NMR spectroscopy characterization, crystal structures of the obtained products were determined in many cases by X-ray diffraction. Investigation of biological activity of the obtained compounds revealed that derivatives 3e and 3f with pendant N-methyl arylsulfonamide groups exhibit high activity against Gram-positive cocci such as methicillin-sensitive Staphylococcus aureus ATCC 6538P, methicillin-resistant S. aureus (MRSA) ATCC 43300 as well as the MRSA clinical strains, with MIC values in the range of 3.12–6.25 mg L⁻¹. These two compounds also showed activity against Enterococcus faecalis ATCC 29212 and Enterococcus faecium ATCC 6057 (with MICs of 25–50 mg L⁻¹). The results of the antimicrobial activity and cytotoxicity studies indicate that 3e and 3f can be considered as potential antibacterial agents, especially against S. aureus MRSA.

Transformations of oxazoline–benzosiloxaborole conjugates gave rise to novel boracyclic systems as well as functionalized derivatives featuring antibacterial activity.     

Synthesis and Structure–Activity Relationship of 2,6-Disubstituted Thiosemicarbazone Derivatives of Pyridine as Potential Antituberculosis Agents

In this study, six new 2,6-disubstituted thiosemicarbazone derivatives of pyridine were synthesized (4–9), and their tuberculostatic activity was evaluated. All of them showed two- to eightfold higher activity (minimum inhibitory concentration (MIC) 0.5–4 µg/mL) against the resistant strain compared with the reference drug. Compounds 5 and 7, which contained the most basic substituents—pyrrolidine and piperidine—in their structure, strongly inhibited the growth of the standard strain (MIC 2 µg/mL). Furthermore, the same derivatives exhibited activity comparable to that of the reference drugs against some types of Gram-positive bacteria (MIC 0.49 µg/mL) and showed no cytotoxicity (IC50 > 50 µg/mL) in HaCaT cells. The zwitterionic structure of each compound was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion analyses showed that all compounds are good drug candidates. Thus, compounds 5 and 7 were identified as leading structures for further research on antituberculosis drugs with extended effects.