A novel bimacrocyclic polyamine-based fluorescent probe for sensitive detection of Hg2+ and glutathione in human serum.

Detection of glutathione in human serum is of great importance for clinical diagnosis of various diseases, such as AIDS, diabetes mellitus, Alzheimer disease and cancer. In this work, a new water-soluble bismacrocyclic polyamine-derived compound, namely L, which contains two molecules of 4-nitro-1,2,3-benzoxa-diazole as the fluorophores, was designed and prepared. The experiments of selectivity of L toward metal ions showed it could rapidly and sensitively detect Hg2+ with a detection limit of 27 nM. Furthermore, the cell imaging and co-staining experiments in HeLa cells demonstrated that the L-Hg2+ probe had selectivity for the Golgi apparatus to a certain degree. Moreover, it had excellent selectivity for biothiols, especially for glutathione. Finally, the probe was successfully applied to sensitively detect glutathione (GSH) in human serum and fetal bovine serum.

Real-time fluorescence assays of alkaline phosphatase and ATP sulfurylase activities based on a novel PPi fluorescent probe.

An anthracene-armed tetraaza macrocyclic fluorescent probe 3-(9-anthrylmethyl)-3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene(l) for detecting Zn(2+) in aqueous medium was synthesized. L-Zn(2+) complex, showed selectivity toward pyrophosphate ion (PPi) by quenching the fluorescence in aqueous HEPES buffer (pH 7.4). Furthermore, L-Zn(2+) was also used to set up a real-time fluorescence assay for monitoring enzyme activities of alkaline phosphatase (ALP) and adenosine triphosphate sulfurylase (ATPS). In the presence of ALP inhibitor Na3VO4 and ATPS inhibitor chlorate, two enzymes activities decreased obviously, respectively.

An NBD-armed tetraaza macrocyclic lysosomal-targeted fluorescent probe for imaging copper(II) ions.

An NBD-armed tetraaza macrocyclic lysosomal-targeted fluorescent probe for detecting Cu(2+) was synthesized and used for fluorescence imaging in HeLa cells. The probe was specifically localized in lysosomes and successfully applied to visualize Cu(2+) as well as to monitor Cu(2+) level changes in the lysosomes of living cells.

Evidence for inhibition of HIF-1α prolyl hydroxylase 3 activity by four biologically active tetraazamacrocycles.

Hypoxia inducible factor 1 (HIF-1) is central to the hypoxic response in mammals. HIF-1α prolyl hydroxylase 3 (PHD3) degrades HIF through the hydroxylation of HIF-1α. Inhibition of PHD3 activity is crucial for up-regulating HIF-1α levels, thereby acting as HIF-dependent diseases therapy. Macrocyclic polyamines which display high stability on iron-chelating may well inhibit the enzyme activity. Thus inhibition and interaction on catalytic PHD3 by four biologically active tetraazamacrocycles (1-4), which have two types of parent rings to chelate iron(ii) dissimilarly, were studied. The apparent IC(50) values of 2.56, 1.91, 5.29 and 2.44 µM, respectively, showed good inhibition potency of the four compounds. K(I) values were 7.86, 3.69, 1.59 and 2.92 µM for 1-4, respectively. Different inhibition actions of the two groups of compounds were identified. Circular dichroism (CD) and fluorescence spectrometries proved that one type of compound has significant effects on protein conformation while another type does not. Computational methodology was constructed to employ the equilibrium geometry of enzyme active site with the presence of substrate competitive inhibitor. Iron(ii) coordination in the active site by inhibitors of this kind induces conformational change of the enzyme and blocks substrate binding.

A potent antitumor Zn2+ tetraazamacrocycle complex targeting DNA: the fluorescent recognition, interaction and apoptosis studies.

A Zn(2+) tetraazamacrocycle complex (2) bearing three naphthalene moieties has been prepared. Complex 2 recognizes, binds and causes damage to DNA, and shows considerable cytotoxicity against human cervical (HeLa), breast (MCF-7) and lung (NCI-H157) cancer cell lines with a different apoptotic pathway from that of cisplatin.

A versatile water soluble fluorescent probe for ratiometric sensing of Hg2+ and bovine serum albumin.

A novel tetraazamacrocycle fluorescent sensor (6-(1-(dimethylamino)-5-naphthalene sulfonyl)-3,6,9,15-tetraazabicyclo[9.3.1] pentadeca-1(15),11,13-triene, 1) has been designed and prepared, which can be utilized for selective and ratiometric sensing of Hg(2+) and bovine serum albumin (BSA) with two different responsive modes in aqueous solution at physiological pH (50 mM Tris-HCl, pH 7.6). Above 0.5 ppb Hg(2+) can be discerned by coordination with 1 and the emission color changes enable 1 to be applied to a fast Hg(2+) test paper assay. Sensor 1 has also been demonstrated to be easily cell-penetrable and applicable for Hg(2+) imaging in living cells. Imaging of BSA in the gel using SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) stained in the medium containing 1 verified that the binding of 1 and BSA was successful in the presence of nonprotein substances. The linear range of 1 towards BSA utilizing ratiometric fluorescent calibration via noncovalent interaction in solution is 0-100 µg mL(-1) with a detection limit of 1 µg mL(-1), and has been successfully employed to determine the albumin concentration in blood serum by means of ratiometric fluorescent measurements for the first time. Finally, sensor 1 behaves as a fluorescent molecular switch composed of triple logic gates upon chemical inputs of Hg(2+) and BSA, which potentially provides intelligent diagnostics for Hg(2+) contaminated serum on the nanoscale.

A Zn2+-specific turn-on fluorescent probe for ratiometric sensing of pyrophosphate in both water and blood serum.

A novel fluorescent sensor composed of a naphthalene functionalized tetraazamacrocycle ligand 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3-methyl naphthalene (1) and Zn(2+) has been designed and prepared, which can be utilized for selective and ratiometric sensing of pyrophosphate (PPi) over other phosphate-containing anions in aqueous solution at physiological pH. Notably, the water soluble 1 itself also exhibits a selective enhanced fluorescent response to Zn(2+), and the complex 1-Zn(2+) thus formed eventually fulfils the synergic Zn(2+) coordination-altered strategy with PPi. Furthermore, the ratiometric sensing of 1-Zn(2+) towards PPi performed well even in blood serum milieu. Finally, the sensor 1-Zn(2+) was successfully employed to monitor a real-time assay of inorganic pyrophosphatase (PPase) by means of ratiometric fluorescent measurements for the first time.