A New Biphenol-bis(polyazacyclophane) Receptor with Unusual Photophysical Properties Towards Zn2.

The new ligand 3,3'-bis(((2-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)amino)methyl)-[1,1'-biphenyl]-2,2'-diol (L) has been synthesized and characterized. It contains two pyridinacyclophane macrocycles spaced by a 2,2'-biphenol moiety. The acid-base behaviour of L as well as its binding properties towards Zn2+ ion have been investigated. This work is inserted in the field of fluorescent ditopic receptors, formed by two polyamines spaced by a aromatic fragments. This ligand represents a new example of a peculiar case of polyamine fluorescent receptor in which the interaction with Zn2+ is translated into a deactivation of the emission. Enough data to describe and explain this unusual behaviour was obtained through potentiometric, UV-Vis, fluorescence and NMR titrations as well as theoretical calculations. This studies have shown that the metal cation is indirectly affecting the emission favouring a conformation in which the fluorophore is at stacking distance from the electron poor pyridine moieties. This gives rise to an oxidative photoinduced electron transfer from the excited state of the fluorophore to the electron-poor Zn2+ coordined pyridine.

A new biphenol-dipicolylamine based ligand and its dinuclear Zn2+ complex as fluorescent sensors for ibuprofen and ketoprofen in aqueous solution.

In this work, the study of the new ligand 3,3'-bis[N,N-bis(pyridine-2-ylmethyl)aminomethyl]-2,2'-dihydroxybiphenyl (L) is reported, where a central 2,2'-biphenol (BPH) fluorophore was functionalized at 3,3'-positions with two dipicolylamine (DPA) side arms as receptor units. Following the synthesis and full chemical-physical characterization, the acid-base and Zn2+-coordination abilities of L were investigated through a combination of potentiometric, UV-Vis, fluorescence, NMR, XRD and DFT measurements. The optical properties of the ligand turned out to be strongly dependent on the pH, being straightforwardly associated with the protonation state of the BPH moiety, whereas its peculiar design allowed to form stable mono and dinuclear Zn2+ complexes. In the latter species, the presence of two Zn2+ ions coordinatively unsaturated and placed at close distance to each other, prompted us to test their usefulness as metallo-receptors for two environmental pollutants of great relevance, ibuprofen and ketoprofen. Potentiometric and fluorescence investigations evidenced that these important non-steroidal anti-inflammatory drugs (NSAIDs) are effectively coordinated by the metallo-receptors and, of relevance, both the stability and the fluorescence properties of the resulting ternary adducts are markedly affected by the different chemical architectures of the two substrates. This study aims at highlighting the promising perspectives arising from the use of polyamino phenolic ligands as chemosensors for H+/Zn2+ and other additional anionic targets in their metal-complexed forms.

Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non-Innocent Ligands as Effective Antioxidants in Human Neuroblasts.

Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical-physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS-scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3-DAN)Cl]PF6 (Ru1), featuring a benzoxazole derivative (dpby=2,6-bis(4-methyl-2-benzoxazolyl)pyridine) and the non-innocent 2,3-diamminonaftalene (2,3-DAN) ligand, along with the reference tpy-containing analogue [Ru(tpy)(2,3-DAN)Cl]PF6 (Ru2) (tpy=2,2':6',2''-terpyridine). Following the synthesis and the electrochemical characterization, chemical antioxidant assays highlighted the beneficial role of dpby for the ROS-scavenging properties of Ru1. These data have been corroborated by the highest protective effect of Ru1 against the oxidative stress induced in SH-SY5Y human neuroblastoma, which exerts pro-survival and anti-inflammatory actions. The results herein reported highlight the potential of Ru1 as pharmacological tool in neurodegenerative diseases and specially prove that the antioxidant properties of such compounds are likely the result of a non-trivial synergetic action involving the bioactive ligands in their chemical architectures.

Synthesis and Fluorescence Properties of 4-Cyano and 4-Formyl Melatonin as Putative Melatoninergic Ligands.

Fluorescent ligands are imperative to many facets of chemical biology and medicinal chemistry. Herein, we report the syntheses of two fluorescent melatonin-based derivatives as potential ligands of melatonin receptors. The two compounds, namely, 4-cyano and 4-formyl melatonin (4CN-MLT and 4CHO-MLT, respectively), which differ from melatonin by only two/three atoms that are very compact in size, were prepared using the selective C3-alkylation of indoles with N-acetyl ethanolamines involving the "borrowing hydrogen" strategy. These compounds exhibit absorption/emission spectra that are red-shifted from those of melatonin. Binding studies on two melatonin receptor subtypes showed that these derivatives have a modest affinity and selectivity ratio.

A New Family of Macrocyclic Polyamino Biphenolic Ligands: Acid-Base Study, Zn(II) Coordination and Glyphosate/AMPA Binding.

In this study, the ligands 23,24-dihydroxy-3,6,9,12-tetraazatricyclo[17.3.1.1(14,18)]eicosatetra-1(23),14,16,18(24),19,21-hexaene, L1, and 26,27-dihidroxy-3,6,9,12,15-pentaazatricyclo[20.3.1.1(17,21)]eicosaepta-1(26),17,19,21(27),22,24-hexaene, L2, were synthesized: they represent a new class of molecules containing a biphenol unit inserted into a macrocyclic polyamine fragment. The previously synthesized L2 is obtained herein with a more advantageous procedure. The acid-base and Zn(II)-binding properties of L1 and L2 were investigated through potentiometric, UV-Vis, and fluorescence studies, revealing their possible use as chemosensors of H+ and Zn(II). The new peculiar design of L1 and L2 afforded the formation in an aqueous solution of stable Zn(II) mono (LogK 12.14 and 12.98 for L1 and L2, respectively) and dinuclear (LogK 10.16 for L2) complexes, which can be in turn exploited as metallo-receptors for the binding of external guests, such as the popular herbicide glyphosate (N-(phosphonomethyl)glycine, PMG) and its primary metabolite, the aminomethylphosphonic acid (AMPA). Potentiometric studies revealed that PMG forms more stable complexes than AMPA with both L1- and L2-Zn(II) complexes, moreover PMG showed higher affinity for L2 than for L1. Fluorescence studies showed instead that the L1-Zn(II) complex could signal the presence of AMPA through a partial quenching of the fluorescence emission. These studies unveiled therefore the utility of polyamino-phenolic ligands in the design of promising metallo-receptors for elusive environmental targets.

A novel 2,6-bis(benzoxazolyl)phenol macrocyclic chemosensor with enhanced fluorophore properties by photoinduced intramolecular proton transfer.

Macrocyclic ligand L, in which a 2,6-bis(2-benzoxazolyl)phenol (bis-HBO) group is incorporated in triethylenetetramine, was designed and synthesized with the aim of creating a chemosensor with high selectivity and specificity for metal cations in an aqueous environment. The availability of several proton acceptors and donors, and amine and phenol hydroxy groups, respectively, affects the keto-enol equilibrium in both the ground and excited states, and the ligand properties show dependence on the pH of the solution. L is fluorescent in the visible range, through an excited-state intramolecular proton transfer (ESIPT) mechanism. The results of an exhaustive characterization of L by spectroscopic techniques and DFT calculations, as well as of its Zn(II), Cd(II) and Pb(II) complexes, show promising properties of L as a ratiometric metal cation chemosensor, since metal coordination prevents the ESIPT and gives rise to a peculiar displacement of the fluorescence emission from green to blue with Zn(II) and Cd(II), while with Pb(II) the fluorescence is quenched.

A Tetranuclear Copper(II)/Calcium(II) Complex as Dual Chemosensor for Colorimetric and Fluorescent Detection of Non-Steroidal Anti-Inflammatory Drugs.

The tetranuclear Cu2+ /Ca2+ /Ca2+ /Cu2+ complex based on Malten ligand has been investigated as a platform for anion binding. Simple organic carboxylates and non-steroidal anti-inflammatory drugs (NSAIDs) have been tested, revealing the ability of the platform to bind them. The receiving platform hosts at least two guests in solution although a third anion can be bound, as suggested by X-ray diffraction analysis. The addition of the anions is accompanied by a color change of the solution, making the system a colorimetric sensor for carboxylates (LOD values comprised between 3.6 and 20.7 ppm). A fluorescent system consisting of the 2-(3-oxido-6-oxoxanthen-9-yl)benzoate (fluorescein anion) linked to the tetranuclear platform has been also prepared and used in a chemosensing ensemble approach to signal the presence of the selected anions (Log K between 2.6 and 5.6 for the addition of two guests). The latter also works in a paper strip test, offering the chemosensor a possible practical application.

Selective Detection of Mg2+ for Sensing Applications in Drinking Water.

A new series of ligands containing the 2-(2-hydroxy-3- naphthyl)-4-methylbenzoxazole (HNBO) fluorophore showed selectivity for Mg2+ ions, without the interference of Ca2+ . The most promising representative L3 resulted the best performing sensor for Mg2+ both in solution and embedded in an all-solid-state optode, especially towards real samples of drinkable water.

A selective fluorescent probe for gadoliniumIII in water based on a PdII-preorganized chromone-receptor.

The synthesis, solution studies, photochemical properties and the X-ray structure of a chromone based fluorescent PdII complex are reported. The ligand contains two chromone units linked as side arms to an ethylenediamine moiety; in the PdII complex the metal ion preorganizes the two hydroxychromone units forming a rigid structure with a negatively charged pocket formed by four oxygen atoms that is able to interact with hard metal cations, such as ions, giving rise to stable bimetallic complexes. Upon interaction with LaIII and GdIII, in particular, the emission intensity at 423 nm increases by a factor of 2 and 8, respectively, while the other rare earth ions quench the fluorescence. Spectrofluorimetric studies on real matrices showed the possibility to use this system as a selective fluorescence probe to detect and trace the presence of Gadolinium in environmental water acting as an OFF-ON chemosensor, with a LOD of 0.4 ppm and a LOQ of 1.2 ppm.

A Metal-Based Receptor for Selective Coordination and Fluorescent Sensing of Chloride.

A scorpionate Zn2+ complex, constituted by a macrocyclic pyridinophane core attached to a pendant arm containing a fluorescent pyridyl-oxadiazole-phenyl unit (PyPD), has been shown to selectively recognize chloride anions, giving rise to changes in fluorescence emission that are clearly visible under a 365 nm UV lamp. This recognition event has been studied by means of absorption, fluorescence, and NMR spectroscopy, and it involves the intramolecular displacement of the PyPD unit by chloride anions. Moreover, since the chromophore is not removed from the system after the recognition event, the fluorescence can readily be restored by elimination of the bound chloride anion.

Zn(ii) detection and biological activity of a macrocycle containing a bis(oxadiazole)pyridine derivative as fluorophore.

The synthesis, photochemical properties, biological effects and the X-ray crystal structure of a fluorescent polyamine macrocycle L are reported. L is a polyamine cyclophane macrocycle in which 2,6-bis(5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl)pyridine (POXAPy) acts as a fluorescent sensor and the polyamine as a metal ion binding unit. L performs as a PET-mediated chemosensor, with a maximum emission wavelength close to 360 nm. This gives rise to a signal that is visible to the naked eye in the blue visible range. L is able to detect the Zn(ii) and Cd(ii) metal ions in an aqueous solution at pH = 7, with the coordination of the ions switching the emission ON through a CHEF effect. In contrast, paramagnetic metal ions like Cu(ii) and Ni(ii) completely quench the already low emission of L at this pH value. L affects the cell survival of a leukemic cellular model (U937) at micromolar concentrations with cell death starting after only 24 h of exposure; starting from a final concentration of 5 µM, L almost completely abrogates the survival of the leukemic cells over 72 h, with a mechanism that is compatible with a genomic DNA interaction.

Playing with Structural Parameters: Synthesis and Characterization of Two New Maltol-Based Ligands with Binding and Antineoplastic Properties.

Two maltol-based ligands, N,N'-bis((3-hydroxy-4-pyron-2-yl)methyl)-1,4-piperazine (L1) and N,N',N'-tris((3-hydroxy-4-pyron-2-yl)methyl)-N-methylethylendiamine (L2), were synthesized and characterized. L1 and L2, containing, respectively, two and three maltol units spaced by a diamine fragment, were designed to evaluate how biological and binding features are affected by structural modifications of the parent compound malten. The acid-base behavior and the binding properties towards transition, alkaline-earth (AE) and rare-earth (RE) cations in aqueous solution, studied by potentiometric, UV-Vis and NMR analysis, are reported along with biological studies on DNA and leukemia cells. Both ligands form stable complexes with Cu(II), Zn(II) and Co(II) that were studied as metallo-receptors for AE and RE at neutral pH. L1 complexes are more affected than L2 ones by hard cations, the L1-Cu(II) system being deeply affected by RE. The structural modifications altered the mechanism of action: L1 partially maintains the ability to induce structural alterations of DNA, while L2 provokes single strand (nicks) and to a lesser extent double strand breaks of DNA.