Zinc(II) coordination complexes as membrane-active fluorescent probes and antibiotics |
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Authors: | DiVittorio Kristy M Leevy W Matthew O'Neil Edward J Johnson James R Vakulenko Sergei Morris Joshua D Rosek Kristine D Serazin Nathan Hilkert Sarah Hurley Scott Marquez Manuel Smith Bradley D |
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Affiliation: | Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, USA. |
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Abstract: | Molecular probes with zinc(II)-(2,2'-dipicolylamine) coordination complexes associate with oxyanions in aqueous solution and target biomembranes that contain anionic phospholipids. This study examines a new series of coordination complexes with 2,6-bis(zinc(II)-dipicolylamine)phenoxide as the molecular recognition unit. Two lipophilic analogues are observed to partition into the membranes of zwitterionic and anionic vesicles and induce the transport of phospholipids and hydrophilic anions (carboxyfluorescein). These lipophilic zinc complexes are moderately toxic to mammalian cells. A more hydrophilic analogue does not exhibit mammalian cell toxicity (LD(50) >50 microg mL(-1)), but it is highly active against the Gram-positive bacteria Staphylococcus aureus (MIC of 1 microg mL(-1)). Furthermore, it is active against clinically important S. aureus strains that are resistant to various antibiotics, including vancomycin and oxacillin. The antibiotic action is attributed to its ability to depolarize the bacterial cell membrane. The intense bacterial staining that was exhibited by a fluorescent conjugate suggests that this family of zinc coordination complexes can be used as molecular probes for the detection and imaging of bacteria. |
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Keywords: | antibiotics fluorescent probes membranes phospholipids zinc |
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