Synthesis of Imidazolium Oligomers with Planar and Stereo Cores and Their Antimicrobial Applications

Abstract

A series of imidazolium oligomers with novel planar and stereo core structures were designed and synthesized. These compounds have symmetric structures with different cores, tails, and linkers. These new imidazolium oligomers demonstrated a desirable set of bioactivities against four types of clinically relevant microbes including E. coli, S. aureus, P. aeruginosa, and C. albicans. The planar oligomers with three di-imidazolium arms and n-octyl tails showed good antimicrobial activity and biocompatibility. Oligomers with ortho-xylylene linkers exhibited higher antimicrobial activity and higher hemolytic ability than those oligomers with para-xylylene linkers. These results shed light on the structure-property relationships of synthetic polymeric antimicrobial agents.

Selective Catalytic Isomerization of β‐Pinene Oxide to Perillyl Alcohol Enhanced by Protic Tetraimidazolium Nitrate

“…imidazole (6.816 g, 0.1 mol), KOH (6.732 g, 0.12 mol) were stirred in methanol (100 ml) at 50°C for 1 h. After removing methanol, dibromomethane (8.592 g, 0.05 mol) and tetrabutyl ammonium bromide (0.1 g) were slowly added and stirred in acetonitrile (100 ml) at 80°C for 6 h. The reaction mixture was filtered to remove potassium bromide, the filtrate was cyclically steamed to remove the solvent, The crude product was recrystallized with acetone at a yield of 31.3 %. Synthesis of pentaerythrityl tetraimdazole: [31,32] Imidazole (6.816 g, 0.1 mol) was dissolved in toluene(12 ml) and dimethyl sulfoxide (12 ml), 50 % sodium hydroxide(16 g) was slowly added dropwise and stirred at room temperature for 30 min, then heated to 110°C until the generated water was removed. Pentaerythrityl tetrabromide (7.672 g, 0.02 mol) was added slowly, then the reaction mixture was heated to 110°C for 4 h, then filtered to remove sodium bromide.…”

Structural design of microbicidal cationic oligomers and their synergistic interaction with azoles against Candida albicans

“…All bacteria and fungus were frozen at −80 °C, and were grown overnight at 37 °C in Mueller Hinton Broth (MHB, BD Singapore) prior to experiments. Fungus was grown overnight at 22 °C in Yeast Mold Broth (YMB, BD Singapore) 27,58 . Subsamples of these cultures were grown for a further 3 h and diluted to give an optical density (O.D.)…”

“…All molecular dynamics simulations were performed using the GROMACS 4.5.3 suite of programs 27,47 . The amber03 force field was used to describe the drug and oligomer molecules.…”

“…Despite the excellent in vitro and in vivo antimicrobial activities, there is concern for the clinical application of synthetic polymers about the heterogeneity (a mixture of polymers with different chain lengths) and toxicity related to high molecular weight component. Instead, synthetic oligomers with defined chain length and molecular structure could be a better representation of AMPs 22–27 . The structure parameters of oligomers, such as balanced amphiphilicity, charge density and structural flexibility, could be tailored to achieve optimum antimicrobial functionality and biocompatibility.…”

Rational Design of Gram-Specific Antimicrobial Imidazolium Tetramers To Combat MRSA

“…Recently, our group has developed a series of polycationic imidazolium compounds which have emerged as a potential new class of antimicrobials. − The compounds can be conveniently synthesized and their structures can be easily altered to meet specific properties. In this paper, we report that changing the linkers and end groups of the tetrameric imidazolium oligomers could result in compounds with varied potency of antimicrobial properties besides exhibiting high biocompatibility.…”