Zinc(II) coordination complexes as membrane-active fluorescent probes and antibiotics.
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.
DiVittorio
Kristy M
KM
Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556, USA.
Leevy
W Matthew
WM
O'Neil
Edward J
EJ
Johnson
James R
JR
Vakulenko
Sergei
S
Morris
Joshua D
JD
Rosek
Kristine D
KD
Serazin
Nathan
N
Hilkert
Sarah
S
Hurley
Scott
S
Marquez
Manuel
M
Smith
Bradley D
BD
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002413:Cations, Divalent; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D005456:Fluorescent Dyes / Q000737:chemistry*; D008856:Microscopy, Fluorescence / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry*; D010068:Oxacillin / Q000494:pharmacology; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D012996:Solutions / Q000737:chemistry; D013194:Staining and Labeling; D013211:Staphylococcus aureus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D002413:Cations, Divalent; D005456:Fluorescent Dyes; D009942:Organometallic Compounds; D010743:Phospholipids; D012996:Solutions; D014867:Water; D014640:Vancomycin; D015032:Zinc; D010068:Oxacillin