Quaternary triphenylphosphonium compounds (TPP + ) have been widely recognized as an important antimicrobial because of their fast antimicrobial speed and broad antimicrobial spectrum. However, small-molecule TPP + compounds have the defects of toxicity, which is the key factor that limits their practical applications. Here, two mono-and one bis-quaternary phosphonium tosylate compounds with different lengths of oligo(ethylene glycol) (OEG) chains and TPP + as the active moiety were synthesized. Bis-TPP + have a short OEG chain coupling two TPP + at both ends, while mono-TPP + attaches the OEG chain at one end in one molecule. In vitro antibacterial activities were evaluated against both Gram-positive as well as Gram-negative bacteria in terms of the inhibition zone (ZOI) and minimum inhibitory concentration (MIC). To investigate the antibacterial mechanism, βgalactosidase activity was monitored for measuring the degree of membrane permeability correlated to the abilities to disrupt the membranes of bacteria. Moreover, their structure−antibacterial activity and structure−cytotoxicity relationships were further analyzed. The results indicated that bis-TPP + synthesized can reach the sterilization rate 90% or more against Escherichia coli and Staphylococcus aureus at MICs of 3.1 and 1.5 mg/mL, respectively, and meanwhile, the cell proliferation can reach more than 80%. This paper represents an excellent approach for development of bis-TPP + bactericidal molecules that would achieve an optimal balance between antimicrobial activity and cytotoxicity.
A new class of PEGylation quaternary (triphenyl‐) phosphonium tosylate (PQPT) was synthesized with different length of polyethylene glycol chain; the procedure is chromatography‐free and practical for large scale synthesis. All PQPTs are soluble in water and showed good anti‐bacterial activity. Particularly, cytotoxicity study on NIH 3T3 cell lines indicated PQPT with PEG750 does not inhibit cell proliferation even at relatively high concentration of 6 mg/ml. The observed excellent binding ability of quaternary (triphenyl‐) phosphonium centre with drug Fluorouracil and the low cytotoxicity in healthy cell lines make PQPTs promising candidates as carriers for drug/gene delivery targeting cells’ mitochondria.
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