Novel Luminescent Tricarbonylrhenium(I) Polypyridine Tyramine-Derived Dipicolylamine Complexes as Sensors for Zinc(II) and Cadmium(II) Ions

Abstract

Three luminescent tricarbonylrhenium(I) polypyridine complexes containing a tyramine-derived 2,2′-dipicolylamine (DPAT) unit, [Re(N∧N)(CO)3(py-TU-DPAT)](CF3SO3) (py-TU-DPAT = 3-(2-(4-hydroxy-3-(2,2′-dipicolylaminomethyl)phenyl)ethylthioureidyl)pyridine; N∧N = 1,10-phenanthroline (phen) (1a), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen) (2a), 4,7-diphenyl-1,10-phenanthroline (Ph2-phen) (3a)), and their DPAT-free counterparts, [Re(N∧N)(CO)3(py-TU-Et)](CF3SO3) (py-TU-Et = 3-(ethylthioureidyl)pyridine; N∧N = phen (1b), Me4-phen (2b), Ph2-phen (3b)), have been synthesized and characterized. Their electrochemical and photophysical properties have been studied. Upon photoexcitation, all the complexes exhibited triplet metal-to-ligand charge-transfer (3MLCT) (dπ(Re) → π*(N∧N)) emission in fluid solutions at 298 K and in low-temperature alcohol glass. The DPAT complexes showed lower emission quantum yields and shorter emission lifetimes compared to those of the DPAT-free analogues, indicative of the quenching properties of the appended DPAT unit. The DPAT complexes also exhibited pH-dependent emission, with their emission intensities at pH < 3 being ca. 40 fold higher than those at pH > 11. These complexes displayed emission enhancement and lifetime elongation in the presence of zinc(II) and cadmium(II) ions. The cellular uptake of all the complexes by human cervix epithelioid carcinoma (HeLa) cells has been examined by ICP-MS. We have investigated the cytotoxicity of the complexes by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the results revealed that all the complexes were more cytotoxic than cisplatin. Furthermore, the cellular uptake of complexes 3a and 3b and the intracellular ion-binding properties of the former complex have been studied by laser-scanning confocal microscopy.

Underestimated Potential of Organometallic Rhenium Complexes as Anticancer Agents

“…All compounds screened for cytotoxicity were indeed imaged in the cytoplasm. 28,32,33,39,51 When co-localization experiments were performed on Re organometallic complexes 7i and 9f ( Figure 1A), predominately mitochondrial (up to 80%) localization was reported. 39 A non-negligible percentage of endosomal accumulation (about 20%) has also been detected for compound 7i 39 As a note of caution, although fluorescent microscopy imaging is an important tool in the investigation of the cellular behavior of Re organometallic complexes, their luminescence can sometimes be quenched in cells.…”

“…Their anti-proliferative activity reached or even exceeded the one of cisplatin on various human cancer cell lines. 28,30,32,39,40,45,49,51 The cytotoxicity of the compounds generally increased with lipophilicity, 32,33,39,49,51 most probably due to an improved cellular uptake. Re(I) complexes 9 ( Figure 1A) derivatized with a fluorous pendant were the only exception to this trend.…”

“…49 Re luminescent probes used to sense Cd(II) and Zn(II) (5 on Figure 1A) are, however, taken up via an energy-dependent pathway such as endocytosis as demonstrated by temperature and ATP production inhibition uptake assays. 32 Interestingly, fluorescence microscopy cellular localization studies have never -to the best of our knowledge -identified a cytotoxic Re(I) tricarbonyl bisimine complex located inside the nucleus. All compounds screened for cytotoxicity were indeed imaged in the cytoplasm.…”

A New Luminescent Ruthenium(II) Polypyridine‐derived Dipicolylamine Complex as a Sensor for Cu2+ Ions

“…of Cu 2＋ , also suggesting a ratio of 1∶2 in the bonding between 1 and Cu 2＋ ions (Figure 2, inset a). On the other hand, the binding constant (K s ) was calculated as 5.89 ×10 4 L•mol -1 according to the formula Furthermore, the selectivity of the interaction was also studied using an additional series of metal ions such as Zn [16][17][18][19][20] However, very weak variations of absorption and emission spectra were observed upon addition of 2 equiv. of Zn 2＋ ions and other metal ions ( Figure 3) 27,28 as an elongated octahedral with three N atoms of DPA and three O atoms (from a water, a carbonyl group and a nitrate).…”

“…It is well known that di(2-picolyl)amine (DPA) moiety in particular has been widely employed because of its specificity for Zn 2 ＋ over other metal ions. [16][17][18][19][20] Herein, a Ru(II) polypyridyl complex 1 ([Ru(bpy) 2 (bpy-DPF)](PF 6 ) 2 ) with two DPAs as the recognition group, which are connected to the 4,4'-positions of the bipyridine unit through C＝O, was synthesized and characterized (Scheme 1). Interestingly, this Ru(II) polypyridyl complex demonstrates good selectivity and sensitivity to Cu 2＋ ions by the spectroscopic properties of 1 in response to different metal ions including Zn 23 were prepared by the methods described in the literatures and confirmed by 1 H NMR spectra.…”