Zinc(II) Coordination Complexes as Membrane‐Active Fluorescent Probes and Antibiotics

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 µg/mL), but it is highly active against the Gram-positive bacteria Staphylococcus aureus (MIC of 1 µg/mL). 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 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.

Chemically triggered release of 5-aminolevulinic acid from liposomes

“…33 Unencapsulated CF was removed by either overnight dialysis (12–14,000 MWCO tubing) against TES buffer (5 mM TES, 145 mM NaCl, pH 7.4) or gel filtration through PD-10 columns packed with Sephadex ™ G-25M. From the stock solution of CF liposomes, samples (10 μM total phospholipid) were assayed for release of CF (λ ex = 492 nm, λ em = 517 nm) upon addition of chemical trigger (10 μM) at 60 seconds and Triton X-100 (20 % v/v, 20 μL) at 180 seconds in different media at 37 °C.…”

Imaging and therapeutic applications of zinc(ii)-dipicolylamine molecular probes for anionic biomembranes

“…114 Studies of other ZnDPA probe designs have consistently demonstrated high affinity for the anionic surfaces of bacteria. 115 …”

Long-Wavelength Probes and Labels Based on Cyanines and Squaraines

“…An interesting imaging probe 1d that can selectively target bacteria was recently reported by Smith et al [31] also based on a heptamethine chromophore. The probe is composed of a bacterial affinity group, which is a synthetic zinc (II) coordination complex that targets the anionic surfaces of bacterial cells and a near infrared dye.…”