Search for: All records

Three fluorescent 5’-(p-hydroxyphenyl)pyridylthiazoles (HPPT) with different chelating groups at the 4’ position were synthesized and evaluated for their ability to detect transition metal ions in acetonitrile and aqueous buffers, based on changes in fluorescence intensity and intramolecular charge transfer (ICT). Both 4’-O-picolyloxy-HPPT (Pic-HPPT) and 4’-O-(o-carboxypicolyl)-HPPT (CPic-HPPT) respond strongly to Zn(II), Cd(II), and Pb(II) in CH3CN with a bathochromic shift in emission up to 68 nm, whereas 4’-O-carboxymethyl-HPPT (CM-HPPT) is unresponsive. Only CPic-HPPT responds to d10 metal ions in aqueous phosphate buffered solution (PBS, pH 7.4), attributable to the added chelating power of the ortho-carboxylate. CPic-HPPT forms a 2:1 complex with Zn(II) and a 1:1 complex with Cd(II) and Pb(II) in CH3CN, whereas a 1:1 complex forms with Zn(II), Cd(II), and Hg(II) ions in PBS. X-ray structural analysis of 1:1 Pic-HPPT–metal ion complexes reveals a planar tridentate binding motif with Zn(II) but a nonplanar tridentate geometry with the larger Cd(II) ion. Fluorescence titration of CPic-HPPT in PBS with Zn(NO3)2 established sub-micromolar sensitivity with a limit of quantitation at 50 nM. These results show that CPic-HPPT has promise as a fluorescent probe for d10 metal ions in physiologically relevant media. 

Bacteria subjected to antiseptic or antibiotic stress often develop tolerance, a trait that can lead to permanent resistance. To determine whether photodynamic agents could be used to counter tolerance, we evaluated three non-iron hemin analogs (M-PpIX; M = Al, Ga, In) as targeted photosensitizers for antimicrobial photodynamic inactivation (aPDI) following exposure to sublethal H2O2. Al-PpIX is an active producer of ROS whereas Ga- and In-PpIX are more efficient at generating singlet oxygen. Al- and Ga-PpIX are highly potent aPDI agents against S. aureus and methicillin-resistant strains (MRSA) with antimicrobial activity (3-log reduction in colony-forming units) at nanomolar concentrations. The aPDI activities of Al- and Ga-PpIX against S. aureus were tested in the presence of 1 mM H2O2 added at different stages of growth. Bacteria exposed to H2O2 during log-phase growth were less susceptible to aPDI but bacteria treated with H2O2 in their postgrowth phase exhibited aPDI hypersensitivity, with no detectable colony growth after treatment with 15 nM Ga-PpIX.