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A fluorescent acridine-containing polyamine receptor assumes upon protonation a folded conformation featuring a cleft of appropriate size for preferential binding and optical sensing of Cl− and Br− over oxo anions and I−.

Triamine-based receptors containing 2 anthracene units are able to signal ketoprofen in H2O/EtOH solution via fluorescence emission enhancement, exploiting a proton transfer process upon substrate coordination.

Binding ability of Zn(ii) complexes of [9]aneN3-based receptors for selective recognition of glyphosate in aqueous media.

The synthesis of three new polyamine receptors based on a common 1,4,8,11-tetraazacyclododecane (cyclen) platform with appended, via a methylene linker, heteroaromatic fluorophores, a single quinoline (Q) or an 8-hydroxy-quinoline (8-OH-Q) moiety (L1 and HL2) or a Q and an 8-OH-Q unit (HL3), is reported. The proton binding features of these receptors, together with those of two similar receptors containing two equal Q moieties (L4) and two Q and two acetate groups (H2L5), have been studied by means of potentiometric, 1H NMR, UV-vis absorption and fluorescence emission measurements in aqueous solution at different pH values. While cyclen is a commonly used binding unit, Q and 8-OH-Q represent classical examples of signalling units in conjugated fluorescent chemosensors and their protonation features can strongly influence their ability in metal cations, and anion coordination and sensing. This study reveals that the structural features of these receptors are controlled by a subtle balance between hydrogen bonding and electrostatic repulsions occurring in their protonated species. At the same time, their emission properties are tuned by photoinduced electron and/or proton transfer processes taking place in the excited state.

The selection of molecular spin qubits with a long coherence time, Tm, is a central task for implementing molecule-based quantum technologies. Even if a sufficiently long Tm can be achieved through an efficient synthetic strategy and ad hoc experimental measurement procedures, many factors contributing to the loss of coherence still need to be thoroughly investigated and understood. Vibrational properties and nuclear spins of hydrogens are two of them. The former plays a paramount role, but a detailed theoretical investigation aimed at studying their effects on the spin dynamics of molecular complexes such as the benchmark phthalocyanine (Pc) is still missing, whereas the effect of the latter deserves to be examined in detail for such a class of compounds. In this work, we adopted a combined theoretical and experimental approach to investigate the relaxation properties of classical [Cu(Pc)] and a CuII complex based on the ligand tetrakis(thiadiazole)porphyrazine (H2TTDPz), characterized by a hydrogen-free molecular structure. Systematic calculations of molecular vibrations exemplify the effect of normal modes on the spin–lattice relaxation process, unveiling a different contribution to T1 depending on the symmetry of normal modes. Moreover, we observed that an appreciable Tm enhancement could be achieved by removing hydrogens from the ligand., The spin dynamics of [Cu(Pc)] and of the hydrogen-free analogue [Cu(TTDPz)] (H2TTDPz = tetrakis(thiadiazole)porphyrazine) were compared through a combined theoretical and experimental approach. A theoretical analysis of the molecular vibrations highlights the crucial effect of normal mode symmetry on the spin−lattice relaxation process. Furthermore, an appreciable enhancement in the coherence time is observed when hydrogen nuclei are removed from the ligand.

The synthesis and coordination properties of two fluorescent chemosensors, featuring [9]aneN3 (1,4,7-triazacyclononane; L1) and [12]aneNS3 (1-aza-4,7,10-trithiacyclododecane; L2) as receptor units, and a quinoline pendant arm with an amide group as a functional group spacer are described. The optical responses of L1 and L2 in the presence of several metal ions were analysed in MeCN/H2 O (1 : 4 v/v) solutions. A selective chelation enhancement of fluorescence (CHEF) effect was observed in the presence of Zn2+ in the case of L1, and in the presence of Cd2+ in the case of L2, following the formation of a 1 : 1 and a 1 : 2 metal/ligand complex, respectively, which was also confirmed by potentiometric measurements. 1 H and 13 C NMR measurements in CD3 CN/CDCl3 in combination with molecular mechanics calculations show that for both complexes of L1 and L2 with Zn2+ and Cd2+ , respectively, the coordination of the carbonyl group from the pendant arm could be the origin of the observed optical selectivity.

The synthesis and characterization of the two new open-chain ligands 1,15-bis-[6-(2,2'-bipyridyl)]-2,5,8,11,14-pentaaza-octadecane (L1) and 1,15-bis-[2-(1,10-phenanthroline)-9-methyl]-2,5,8,11,14-pentaazaoctadecane (L2), both featuring a tetraethylenpentaamine chain linking via methylene bridges the 6 and 2 positions of two identical 2,2'-bipyridyl (bpy) and 9-methyl-1,10-phenanthroline (9-methyl-phen) moieties respectively, are reported. Their protonation and binding ability for Cu2+ , Zn2+ , Cd2+ and Pb2+ have been studied by coupling potentiometric titrations with UV-vis absorption and fluorescence emission measurements in water. L1 and L2 afford stable mono- and dinuclear complexes, in which the metal ion is bound by a single bpy or 9-methyl-phen unit and the amine groups on the aliphatic chain. However, L1 displays a greater binding ability for Cu2+ and Zn2+ with respect to L2, the stability constants of the [ML1]2+ complexes being 21.8 (Cu2+ ) and 19.4 (Zn2+ ) log units vs 20.34 and 16.8 log. units for the corresponding L2 species. Among all the metal ions tested, only the Zn2+ complex with L2 features an enhanced fluorescence emission at neutral pH, thanks to the simultaneous binding of one Zn2+ ion and H+ ion(s), that inhibits any possible photoinduced electron transfer (PET) process from the amine donors to the excited phen moiety. Binding of a second metal switches off the emission again.

Oxidative stress due to excess superoxide anion ($${{\bf{O}}}_{{\bf{2}}}^{{\boldsymbol{\cdot }}{\boldsymbol{-}}}$$ O 2 ⋅ − ) produced by dysfunctional mitochondria is a key pathogenic event of aging and ischemia-reperfusion diseases. Here, a new $${{\bf{O}}}_{{\bf{2}}}^{{\boldsymbol{\cdot }}{\boldsymbol{-}}}$$ O 2 ⋅ − -scavenging MnII complex with a new polyamino-polycarboxylate macrocycle (4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate) containing 2 quinoline units (MnQ2), designed to improve complex stability and cell permeability, was compared to parental MnII complex with methyls replacing quinolines (MnM2). MnQ2 was more stable than MnM2 (log K = 19.56(8) vs. 14.73(2) for the equilibrium Mn2+ + L2−, where L = Q2 and M2) due to the involvement of quinoline in metal binding and to the hydrophobic features of the ligand which improve metal desolvation upon complexation. As oxidative stress model, H9c2 rat cardiomyoblasts were subjected to hypoxia-reoxygenation. MnQ2 and MnM2 (10 μmol L−1) were added at reoxygenation for 1 or 2 h. The more lipophilic MnQ2 showed more rapid cell and mitochondrial penetration than MnM2. Both MnQ2 and MnM2 abated endogenous ROS and mitochondrial $${{\bf{O}}}_{{\bf{2}}}^{{\boldsymbol{\cdot }}{\boldsymbol{-}}}$$ O 2 ⋅ − , decreased cell lipid peroxidation, reduced mitochondrial dysfunction, in terms of efficiency of the respiratory chain and preservation of membrane potential (Δψ) and permeability, decreased the activation of pro-apoptotic caspases 9 and 3, and increased cell viability. Of note, MnQ2 was more effective than MnM2 to exert cytoprotective anti-oxidant effects in the short term. Compounds with redox-inert ZnII replacing the functional MnII were ineffective. This study provides clues which further our understanding of the structure-activity relationships of MnII-chelates and suggests that MnII-polyamino-polycarboxylate macrocycles could be developed as new anti-oxidant drugs.

The main results from the work of the authors, concerning the use of mixed thia/aza medium sized macrocycles for the development of optically selective fluorescent chemosensors for toxic heavy meta...

We describe here the synthesis and coordination properties of three new derivatives of [9]aneN3 containing phenyl/quinoline pendant arm derivatives (L1, L2 and L3, respectively) also featuring urea (L1–L2) or amide (L3) functions as “non-innocent” spacers. At first, L1, L2 and L3 were studied considering the interaction with a series of anions (AcO−, BzO−, H2PO4−, F−, and Cl−) by means of 1H NMR measurements. Subsequently, the optical responses of L2 and L3 in the presence of several metal ions Cd2+, Co2+, Cu2+, Fe3+, Hg2+, K+, Mg2+, Mn2+, Ni2+, Zn2+ and Pb2 were analysed in MeCN/H2O (4 : 1 v/v). As observed by spectrophotometric and spectrofluorimetric titrations, there were significant changes in the absorbance and fluorescent emission of L2 upon addition of increasing amounts of Cd2+, Zn2+, Pb2+ and Cu2+ in MeCN/H2O (4 : 1 v/v). In particular, titrations of L2 with Cd2+, Zn2+ or Pb2+ showed an almost comparable CHEF effect up to an M2+/L2 molar ratio of 1. Overall, no significant optical selectivity was observed in the case of L2. Conversely, L3 revealed an OFF–ON selective response only in the presence of the Zn2+ ion in MeCN/H2O (4 : 1 v/v), which can be attributed to the formation of both 1 : 1 and 1 : 2 metal-to-ligand complexes, as also confirmed by potentiometric measurements. Finally, crystals of [ZnL1(Ac)](Ac) (1), [CuL1(Cl)](Cl)·H2O (2) and [CuL3](NO3) (3) were grown and analysed by X-ray diffraction. 1 and 3 feature the metal center in a pseudo-octahedral coordination geometry coordinated also by the carbonyl group from one pendant arm, while in the case of 2, one of the six coordination sites in the final distorted octahedral geometry is occupied by the nitrogen donor from the urea group of one pendant arm.

The metoprolol free base has been characterized in the solid state by X-ray diffaction (both single-crystal and variable-temperature powder diffraction) and differential scanning calorimetry. These studies are supplemented by mol­ecular modelling and Hirshfeld surface analysis. Structural relationships with the strictly related betaxolol are discussed., Metoprolol {systematic name: (RS)-1-iso­propyl­amino-3-[4-(2-meth­oxy­eth­yl)phen­oxy]propan-2-ol}, C15H25NO3, is a cardioselective β1-adrenergic blocking agent that shares part of its mol­ecular skeleton with a large number of other β-blockers. Results from its solid-state characterization by single-crystal and variable-temperature powder X-ray diffraction and differential scanning calorimetry are presented. Its mol­ecular and crystal arrangements have been further investigated by mol­ecular modelling, by a Cambridge Structural Database (CSD) survey and by Hirshfeld surface analysis. In the crystal, the side arm bearing the isopropyl group, which is common to other β-blockers, adopts an all-trans conformation, which is the most stable arrangement from modelling data. The crystal packing of metoprolol is dominated by an O—H⋯N/N⋯H—O pair of hydrogen bonds (as also confirmed by a Hirshfeld surface analysis), which gives rise to chains containing alternating R and S metoprolol mol­ecules extending along the b axis, supplemented by a weaker O⋯H—N/N—H⋯O pair of inter­actions. In addition, within the same stack of mol­ecules, a C—H⋯O contact, partially oriented along the b and c axes, links homochiral mol­ecules. Amongst the solid-state structures of mol­ecules structurally related to metoprolol deposited in the CSD, the β-blocker drug betaxolol shows the closest analogy in terms of three-dimensional arrangement and inter­actions. Notwithstanding their close similarity, the crystal lattices of the two drugs respond differently on increasing temperature: metoprolol expands anisotropically, while for betaxolol, an isotropic thermal expansion is observed.

The synthesis of a new RuII complex, in which the metal is coordinated by two 1,10-phenanthroline ligands and a 2,2&prime, bipyridyl unit linked, via methylene bridges in its 4 and 4&prime, positions, to two 1,4,7,10-tetraazacyclododecane (cyclen) macrocycles ([Ru(phen)2L]2+) is reported. Protonation and ZnII binding by [Ru(phen)2L]2+ have been analyzed by potentiometric titration, evidencing the formation of mixed hetero-binuclear and hetero-trinuclear ZnII/RuII complexes. These complexes were tested as bis-phenol A (BPA) binders. Only the dizinc complex with [Ru(phen)2L]2+ is able to bind BPA in aqueous solution, affording a remarkably stable {Zn2[Ru(phen)2L]BPA(H&minus, 2)}4+ adduct at neutral pH, in which BPA is bound in its doubly deprotonated form to the two ZnII ions. BPA binding was found to quench the luminescence emission of the RuII(phen)2bipy core. Although the quenching effect is modest, this study demonstrates that appropriately designed dizinc complexes can be used for binding and optical sensing of BPA in water.

The synthesis of a new RuII complex, in which the metal is coordinated by two 1,10-phenanthroline ligands and a 2,2′-bipyridyl unit linked, via methylene bridges in its 4 and 4′ positions, to two 1,4,7,10-tetraazacyclododecane (cyclen) macrocycles ([Ru(phen)2L]2+) is reported. Protonation and ZnII binding by [Ru(phen)2L]2+ have been analyzed by potentiometric titration, evidencing the formation of mixed hetero-binuclear and hetero-trinuclear ZnII/RuII complexes. These complexes were tested as bis-phenol A (BPA) binders. Only the dizinc complex with [Ru(phen)2L]2+ is able to bind BPA in aqueous solution, affording a remarkably stable {Zn2[Ru(phen)2L]BPA(H−2)}4+ adduct at neutral pH, in which BPA is bound in its doubly deprotonated form to the two ZnII ions. BPA binding was found to quench the luminescence emission of the RuII(phen)2bipy core. Although the quenching effect is modest, this study demonstrates that appropriately designed dizinc complexes can be used for binding and optical sensing of BPA in water.

The metoprolol fumarate (MF) salt has been characterized by a combined use of powder X-ray diffraction (PXRD), variable temperature PXRD (VT-PXRD), and differential scanning calorimetry. Its molecular and crystal structure, as determined from PXRD data, has been thoroughly compared to those of the analogous tartrate (MT-o) and succinate (MS-m) salts. Moreover, Hirshfeld surface analysis and graph sets analysis have been performed to achieve insights into the intermolecular interactions. Despite their evident similarities at the molecular level, the three salts behave differently upon temperature variation: MF expands/contracts anisotropically (as MS-m), but the melt takes 3 days to recover the starting crystalline phase (as MT-o). A rationale for this behavior is provided based on their crystal arrangements.

Methylene blue (MB) can be employed as a photo-activatable antimicrobial drug in photodynamic therapy (PDT) due to its ability to release oxygen free radicals upon photo-activation. However, its poor ability to penetrate bacterial cell walls and bacterial biofilms limits its antimicrobial activity. To overcome these limitations, we propose some formulations of MB based on different cationic liposomes. The liposome-MB systems were characterized using dynamic light scattering (DLS), zeta potential analysis and UV-visible spectroscopy. Their ability to penetrate inside the cytoplasm of E. coli, taken as a bacterial model for Gram-negative strains, was investigated through laser scanning confocal microscopy (CLSM) and compared to the penetration of naked MB. Then, MB-loaded liposomes were photo-activated and their antimicrobial activity was tested against E. coli, showing a strong improvement with respect to MB solutions. The liposomal formulations dramatically enhance MB penetration in bacterial biofilms and reduce the inflammatory response due to lipopolysaccharide exposure in mammalian cells. The observed antimicrobial and anti-inflammatory efficacies show a clear correlation with some structural features of the carriers, namely the size and the surface charge density. Overall, these results provide fundamental knowledge that enables the design of novel efficient PDT treatments, which potentially overcome the rising incidence of antibiotic resistance of bacterial strains.

We describe here the synthesis and coordination properties of three new derivatives of [9]aneN3 containing phenyl/quinoline pendant arm derivatives (L1, L2 and L3, respectively) also featuring urea (L1-L2) or amide (L3) functions as "non-innocent" spacers. At first, L1, L2 and L3 were studied considering the interaction with a series of anions (AcO-, BzO-, H2PO4-, F-, and Cl-) by means of 1H NMR measurements. Subsequently, the optical responses of L2 and L3 in the presence of several metal ions Cd2+, Co2+, Cu2+, Fe3+, Hg2+, K+, Mg2+, Mn2+, Ni2+, Zn2+ and Pb2 were analysed in MeCN/H2O (4 : 1 v/v). As observed by spectrophotometric and spectrofluorimetric titrations, there were significant changes in the absorbance and fluorescent emission of L2 upon addition of increasing amounts of Cd2+, Zn2+, Pb2+ and Cu2+ in MeCN/H2O (4 : 1 v/v). In particular, titrations of L2 with Cd2+, Zn2+ or Pb2+ showed an almost comparable CHEF effect up to an M2+/L2 molar ratio of 1. Overall, no significant optical selectivity was observed in the case of L2. Conversely, L3 revealed an OFF-ON selective response only in the presence of the Zn2+ ion in MeCN/H2O (4 : 1 v/v), which can be attributed to the formation of both 1 : 1 and 1 : 2 metal-to-ligand complexes, as also confirmed by potentiometric measurements. Finally, crystals of [ZnL1(Ac)](Ac) (1), [CuL1(Cl)](Cl)·H2O (2) and [CuL3](NO3) (3) were grown and analysed by X-ray diffraction. 1 and 3 feature the metal center in a pseudo-octahedral coordination geometry coordinated also by the carbonyl group from one pendant arm, while in the case of 2, one of the six coordination sites in the final distorted octahedral geometry is occupied by the nitrogen donor from the urea group of one pendant arm.

Here we report a family of bis-amide receptors for anion binding that contain carboxylic acid groups vicinal to the amide function. Deprotonation of the carboxylic acids decreases the acidity of amide NHs, switching on the anion binding ability of the deprotonated receptors with selectivity for fluoride complexation. The proposed systems represent a unique example of anionic receptors able to bind anions via H-bonding.

A comparative study between two novel, highly water soluble, ruthenium(II) polypyridyl complexes, [Ru(phen)2 L'] and [Ru(phen)2 Cu(II)L'] (L and L-CuII ), containing the polyaazamacrocyclic unit 4,4'-(2,5,8,11,14-pentaaza[15])-2,2'-bipyridilophane (L'), is herein reported. L and L-CuII interact with calf-thymus DNA and efficiently cleave DNA plasmid when light-activated. They also possess great penetration abilities and photo-induced biological activities, evaluated on an A375 human melanoma cell line, with L-CuII being the most effective. Our study highlights the key role of the Fenton active CuII center within the macrocycle framework, that would play a synergistic role with light activation in the formation of cytotoxic ROS species. Based on these results, an optimal design of RuII polypyridyl systems featuring specific CuII -chelating polyamine units could represent a suitable strategy for the development of novel and effective photosensitizers in photodynamic therapy.

This critical review focuses on recent advances (2010–2015) in the detection of cyanide anion via metal-based optical chemosensors in which a change in colour and/or fluorescence intensity (or emission wavelength) of a molecular metal complex is determined by the direct interaction of the metal centre with this anion.

Background One of the most discomfortable dose-limiting adverse reactions of effective drugs for the treatment of solid tumors is a peripheral neuropathy which is the main reason for dose reduction and discontinuation of the therapy. We identified oxidative stress as one target of oxaliplatin toxicity in the search of possible adjuvant therapies to prevent neuropathy and alleviate pain. Therefore, we studied an effective SOD mimetic compound, MnL4, as a possible adjuvant treatment in in vitro cellular cultures and in vivo on a rat model of oxaliplatin-induced neuropathy. Methods and results All rat manipulations were carried out according to the European Community guidelines for animal care. We performed experiments on SH-SY5Y, HT-29 and primary cortical rat astrocytes. Incubation with 100 µM oxaliplatin increased superoxide anion production and caspase 3/7 activity in the neuronal cell line SH-SY5Y and cortical astrocytes. MnL4 (10 µM) significantly reduced the increase in superoxide anion in both cell types, but prevented caspase 3/7 activity only in astrocytes. MnL4 reduced lipid peroxidation induced by oxaliplatin and normalized the intracellular calcium signal evoked by ATP and acetylcholine in astrocytes, preincubated with oxaliplatin. MnL4 did not interfere with the concentration- and time-dependent cytotoxic effects of oxaliplatin on the cancer cell lines HT-29 and LoVo. In vivo MnL4 reduced the response at mechanical noxious and mechanical and thermal non-noxious stimuli in oxaliplatin treated animals. Rat rota-rod performances were improved. Conclusion Since MnL4 exerts its beneficial effects without interfering with the anticancer activity of oxaliplatin, it could be proposed as adjuvant to prevent and reduce oxaliplatin induced neuropathy.

Oxidative stress plays a major role in cardiovascular injury and dysfunction induced by cigarette smoke. Smoke-borne pro-oxidants impair endothelial function and predispose to thrombosis, inflammation and atherosclerosis. This in vitro study evaluates whether Mn II (4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate).2H 2 O (Mn II (Me 2 DO2A)), a polyamine–polycarboxilate, Mn II -containing O 2 − scavenger, has a direct protective action on guinea pig coronary endothelial (GPCE) cells exposed to cigarette smoke extracts (CSE). Mn II (Me 2 DO2A) (1–10 μmol/l) was added to the culture medium together with CSE and maintained for 4 h. In parallel experiments, the inactive congener Zn II (Me 2 DO2A), in which Zn II replaced the functional Mn II center in the same organic scaffold, was used as negative control. Mn II (Me 2 DO2A), mostly at the higher doses (5 and 10 μmol/l), significantly increased GPCE cell viability (trypan blue assay), improved mitochondrial activity (MTT test, mitochondrial membrane potential Δψ), reduced cellular apoptosis (mPTP, caspase-3 activity, TUNEL assay), decreased intracellular ROS levels (H 2 DCFDA), lipoperoxidation (BODIPY 581/591) and decreased protein nitrosylation. Of note, Zn II (Me 2 DO2A) did not preserve cell viability. These findings suggest that Mn II (Me 2 DO2A) is a promising O 2 − scavenging compound able to protect from cigarette smoke-induced oxidative cell injury. In perspective, should its efficacy be confirmed in future in vivo studies, this molecule might represent a therapeutic or preventive drug to counteract cigarette smoke toxicity.

Oxidative stress due to excess superoxide anion (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\bf{O}}}_{{\bf{2}}}^{{\boldsymbol{\cdot }}{\boldsymbol{-}}}$$\end{document}O2⋅−) produced by dysfunctional mitochondria is a key pathogenic event of aging and ischemia-reperfusion diseases. Here, a new \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\bf{O}}}_{{\bf{2}}}^{{\boldsymbol{\cdot }}{\boldsymbol{-}}}$$\end{document}O2⋅−-scavenging MnII complex with a new polyamino-polycarboxylate macrocycle (4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate) containing 2 quinoline units (MnQ2), designed to improve complex stability and cell permeability, was compared to parental MnII complex with methyls replacing quinolines (MnM2). MnQ2 was more stable than MnM2 (log K = 19.56(8) vs. 14.73(2) for the equilibrium Mn2+ + L2−, where L = Q2 and M2) due to the involvement of quinoline in metal binding and to the hydrophobic features of the ligand which improve metal desolvation upon complexation. As oxidative stress model, H9c2 rat cardiomyoblasts were subjected to hypoxia-reoxygenation. MnQ2 and MnM2 (10 μmol L−1) were added at reoxygenation for 1 or 2 h. The more lipophilic MnQ2 showed more rapid cell and mitochondrial penetration than MnM2. Both MnQ2 and MnM2 abated endogenous ROS and mitochondrial \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\bf{O}}}_{{\bf{2}}}^{{\boldsymbol{\cdot }}{\boldsymbol{-}}}$$\end{document}O2⋅−, decreased cell lipid peroxidation, reduced mitochondrial dysfunction, in terms of efficiency of the respiratory chain and preservation of membrane potential (Δψ) and permeability, decreased the activation of pro-apoptotic caspases 9 and 3, and increased cell viability. Of note, MnQ2 was more effective than MnM2 to exert cytoprotective anti-oxidant effects in the short term. Compounds with redox-inert ZnII replacing the functional MnII were ineffective. This study provides clues which further our understanding of the structure-activity relationships of MnII-chelates and suggests that MnII-polyamino-polycarboxylate macrocycles could be developed as new anti-oxidant drugs.

The silver(I) N-heterocyclic carbene (NHC) complex bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride ([Ag(EIA)2 ]Cl), bearing two anthracenyl fluorescent probes, has been synthesized and characterized. [Ag(EIA)2 ]Cl is stable in organic solvents and under physiological conditions, and shows potent cytotoxic effects in vitro toward human SH-SY5Y neuroblastoma cells. The interactions of [Ag(EIA)2 ]Cl with a few model biological targets have been studied as well as its ability to be internalized in cells. The in vitro anticancer activity is apparently related to the level of drug internalization. Notably, [Ag(EIA)2 ]Cl does not react with a few model proteins, but is capable of binding the C-terminal dodecapeptide of thioredoxin reductase hTrxR(488-499) and to strongly inhibit the activity of this enzyme. Binding occurs through an unconventional process leading to covalent binding of one or two carbene ligands to the C-terminal dodecapeptide with concomitant release of the silver cation. To the best of our knowledge, this mode of interaction is reported here for the first time for Ag(NHC)2 complexes.

The first example of a fluorescent highly stable pure binary ionic liquid (IL)-in-water emulsion is here described. The system is inexpensive, easy to synthesize and can be used as a selective fluorescent probe for metal ions. In particular, the system is able to recognize Fe3+ ions in pure water by a fluorescence “turn-off” mechanism.

This review deals on the interaction of inorganic phosphate anions with zinc(II)-based luminescent dyes, with particular attention to the effects on their emission spectra observed upon binding of these anions to zinc(II). Interaction with phosphates induces different effects, including electron and charge transfer processes as well as structural rearrangements of the complex structures, which can remarkably change the photophysical properties of zinc(II)-based dyes. These effects have been exploited to develop luminescent systems for the selective recognition of inorganic phosphates, which are discussed on the basis of their structural architecture and mechanism involved in the sensing process triggered by the anion binding at the metal centre(s).

Progress in nanotechnology has determined new strategies concerning drug delivery into the central nervous system for the treatment of degenerative and inflammatory diseases. To date, brain targeting through systemic drug administration, even in a nano-composition, is often unsuccessful. Therefore, we investigated the possibility of loading T lymphocytes with PGLA–PEG COOH magnetite nanoparticles (30 nm), which can be built up to easily bind drugs and monoclonal antibodies, and to exploit the ability of activated T cells to cross the blood–brain barrier and infiltrate the brain parenchyma. Iron oxide nanoparticles have been widely used in biomedical applications due to their theranostic properties and are therefore a well-established nanomaterial. The magnetite core is easily hybridized with polymeric compounds that may enhance the possibility of the nanoparticles entering cells with low phagocytic properties. Taking advantage of these material characteristics, after in vitro assessment of the viability and functionality of nano-loaded MOG35–55 specific T cells, we transferred cells containing the nano-cargo into naïve mice affected by experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. By means of histological and immunohistological methods, we were able to identify the nano-loaded T cells in the central nervous system. Our data demonstrated that T cells containing nanomaterials hold the possibility of carrying and releasing nanoparticles in the brain.

Recently, a number of photoacoustic (PA) agents with increased tissue penetration and fine spatial resolution have been developed for molecular imaging and mapping of pathophysiological features at the molecular level. Here, we present bio-conjugated near-infrared light-absorbing magnetic nanoparticles as a new agent for PA imaging. These nanoparticles exhibit suitable absorption in the near-infrared region, with good photoacoustic signal generation efficiency and high photo-stability. Furthermore, these encapsulated iron oxide nanoparticles exhibit strong super-paramagnetic behavior and nuclear relaxivities that make them useful as magnetic resonance imaging (MRI) contrast media as well. Their simple bio-conjugation strategy, optical and chemical stability, and straightforward manipulation could enable the development of a PA probe with magnetic and spectroscopic properties suitable for in vitro and in vivo real-time imaging of relevant biological targets.

A new acridine-based fluorescent chemosensor, L2, featuring two sulfurated macrocyclic units has been synthesised. Proton and metal binding properties of L2 have been studied in H2O/CH3CN (1:1 v/v) by potentiometric and spectrophotometric measurements and compared with those of the analogous and previously published bis-macrocyclic receptor featuring two [9]aneN3units (L1). Despite a thermodynamic selectivity observed for Zn2+with both L1 and L2, L2 shows a marked sensing selectivity towards Cd2+via a chelation enhancement of fluorescence (CHEF) effect both in H2O/CH3CN (1:1 v/v) and in H2O using silica core-PEG shell nanoparticles as vehiculant. On the other hand, L1 shows a selective optical sensing towards Zn2+in agreement with the thermodynamic selectivity observed for the same metal ion.

The role of metal complexes with polyamine ligands in selective binding of anions and their possible use as optical chemosensors or biologically relevant hydrolytic agents for anionic substrates will be discussed on the basis of some study cases from the work of the authors, with particular emphasis on the cooperative action of metal cation and polyamine receptor in both the processes of interaction and sensing/activation.

Superoxide anion () is overproduced in joint inflammation, rheumatoid arthritis, and osteoarthritis. Increased production leads to tissue damage, articular degeneration, and pain. In these conditions, the physiological defense against , superoxide dismutases (SOD) are decreased. The complex MnL4 is a potent SOD mimetic, and in this study it was tested in inflammatory and osteoarticular rat pain models.In vivoprotocols were approved by the animal Ethical Committee of the University of Florence. Pain was measured by paw pressure and hind limb weight bearing alterations tests. MnL4 (15 mg kg−1) acutely administered, significantly reduced pain induced by carrageenan, complete Freund’s adjuvant (CFA), and sodium monoiodoacetate (MIA). In CFA and MIA protocols, it ameliorated the alteration of postural equilibrium. When administered by osmotic pump in the MIA osteoarthritis, MnL4 reduced pain, articular derangement, plasma TNF alpha levels, and protein carbonylation. The scaffold ring was ineffective. MnL4 (10−7 M) prevented the lipid peroxidation of isolated human chondrocytes when was produced by RAW 264.7. MnL4 behaves as a potent pain reliever in acute inflammatory and chronic articular pain, being its efficacy related to antioxidant property. Therefore MnL4 appears as a novel protective compound potentially suitable for the treatment of joint diseases.

International audience; A giant-size polyamine macrocycle L, composed of four 1,4,8,11-tetraazacyclotetradecane (cyclam) units linked by 1,3-dimethylenbenzyl spacers, strongly interacts in aqueous solution with four pH indicators (bromocresol purple (H2BCP), phenol red (H2PR), phenolphthalein (H2PP) and fluorescein (H2F)) in their anionic forms. Besides 1 : 1 complexes, L also forms assemblies with an unusual 1 : 2 receptor to dye stoichiometry, thanks to its large dimensions, which allow for the simultaneous interaction of the receptor protonated forms with two anionic dyes. The formation of the assemblies markedly affects the pKa values of the phenol groups of the dyes, which change colour upon complexation in well-defined pH ranges. This property can be effectively exploited for optical detection of anions. The L-H2BCP 1 : 2 assembly is able to selectively detect the triphosphate anion at slightly acidic pH values, thanks to the release, upon triphosphate coordination, of the dye from the ensemble, with a consequent colour change of the solution from purple-violet (complexed BCP2− dye) to yellow (free BCP2−). No effect is caused by other inorganic anions. The L-H2BCP 1 : 2 assembly represents a rare case of an optical chemosensor for the triphosphate anion.

The synthesis of a new ligand (L1) containing two 1,4,7-triazacyclononane ([9]aneN3 ) moieties linked by a 4,5-dimethylenacridine unit is reported. The binding and fluorescence sensing properties toward Cu2+ , Zn2+ , Cd2+ , and Pb2+ of L1 and receptor L2, composed of two [9]aneN3 macrocycles bridged by a 6,6''-dimethylen-2,2':6',2''-terpyridine unit, have been studied by coupling potentiometric, UV/Vis absorption, and emission measurements in aqueous media. Both receptors can selectively detect Zn2+ thanks to fluorescence emission enhancement upon metal binding. The analysis of the binding and sensing properties of the Zn2+ complexes toward inorganic anions revealed that the dinuclear Zn2+ complex of L1 selectively binds and senses the triphosphate anion (TP), whereas the mononuclear Zn2+ complex of L2 displays selective recognition of diphosphate (DP). Binding of TP or DP induces emission quenching of the Zn2+ complexes with L1 and L2, respectively. These results are exploited to discuss the role played by pH, number of coordinated metal cations, and binding ability of the bridging units in metal and/or anion coordination and sensing.

Proton and Cu II , Zn II , Cd II and Pb II binding by ligands L1 and L2, containing a triethylentetraamine and a tetraethylentetraamine aliphatic chain, respectively, linking the 2,7 positions of an acridine moiety, has been analysed by means of potentiometric, UV–Vis and fluorescence emission measurements in aqueous solution. Considering proton binding, L1 and L2 bind up to four and six acidic protons in the pH range 2–11. These protonation steps preferentially occur on the aliphatic amine groups; protonation of acridine takes place only at strongly acidic pH values. In metal complexation, L1 displays a marked selectivity for Zn II over Cd II and Pb II , due to the better accommodation of the smaller Zn II ion within the macrocyclic cavity. The fluorescence emission study points out that Zn II binding at neutral pH is accompanied by a marked increase of the acridine emission. Cd II binding gives rise to a much less intense increase of the emission, whereas Cu II and Pb II complexation leads to fluorescence quenching. Both thermodynamic and sensing selectivity are lost in the case of the larger macrocycle L2.

The reciprocal influence of the thermodynamic (binding) selectivity and the sensing (optical response) selectivity of fluorescent chemosensors in determining their efficiency in probing biologically and environmentally important metal ions in real matrices will be discussed on the basis of some study cases from the work of the authors.

l-Tryptophan containing anion receptors 1 and 2 have shown interesting features. Receptor 1 behaves as a hetero-ditopic dicompartimental receptor for fluoride and chloride with a certain selectivity for fluoride as supported by 1H NMR titrations and molecular modeling, while receptor 2 forms only 1:1 complexes. Moreover, receptor 1 reveals a certain affinity towards the l enantiomers of amino acids alanine and serine.

International audience; Synthesis and characterization of three new polyamine receptors, composed of a cyclam unit (cyclam=1,4,8,11-tetraazacyclotetradecane) linked by a 2,6-dimethylpyridinyl spacer to the linear polyamines 1,4,8,11-tetraazaundecane (), 1,4,7-triazaheptane (), and to a quaternary ammonium group (L3 py+), are reported. All receptors form highly charged polyammonium cations at neutral pH, suitable for anion recognition studies. ATP recognition was analyzed by using potentiometric, calorimetric, 1H and 31P NMR measurements in aqueous solution. All receptors form 1:1 adducts with ATP in aqueous solution, stabilized by charge–charge and hydrogen-bonding interactions between their ammonium groups and the anionic triphosphate chain of ATP. The binding ability of the three receptors for ATP increases in the order of L3 py+<

This review will cover the developments in the chemistry of phenanthroline-based ligands in the last 10–15 years. 1,10-Phenanthroline (phen) is a classic ligand in coordination chemistry, which couples versatility in metal ion binding with peculiar properties of its complexes. For instance, metal complexes with phenanthroline can be featured by an intense luminescence or can interact with DNA in an intercalative fashion inducing, in some cases, DNA cleavage. For this reason a number of phenanthroline-containing ligands has been recently synthesized by inserting phenanthroline within open-chain or macrocyclic backbone, in order to develop new molecular chemosensors for metal cations and anions, ionophores as well as new intercalating agents for polynucleotides. Furthermore, phenanthroline is rigid and its insertion within cyclic or acyclic structures can impart to the resulting ligand a high degree of pre-organization, affording selective complexing agents. This review will discuss on the coordination, luminescence and intercalating and/or DNA cleaving properties as well as on analytical applications of metal complexes with phenanthroline-based ligands. Particular attention will be devoted to macrocyclic receptors or open-chain ligands that, beside the phenanthroline nitrogen atoms, contain other donor atoms able to interact with the metal cations or anions.

A novel fluorescence chemical sensor for the highly sensitive and selective determination of Pb(2+) ions in aqueous solutions is described. The preliminary potentiometric and spectrofluorimetric complexation studies in solution revealed that the lipophilic ligand 5,8-bis((5'-chloro-8'-hydroxy-7'-quinolinyl)methyl)-2,11-dithia-5,8-diaza-2,6-pyridinophane (L2) forms a highly stable and selective [PbL2](2+) and [Pb(L2)(2)](2+) complexes which results in a strong fluorescence quenching of the ligand. Thus, a novel fluorescence Pb(2+) sensing system was prepared by incorporating L2 as a neutral lead-selective fluoroionophore in the plasticized PVC membrane containing tetrakis(p-chlorophenyl) borate as a liphophilic anionic additive. The response of the sensor is based on the strong selective fluorescence quenching of L2 by Pb(2+) ions. At pH 5.5, the proposed sensor displays a calibration curve over a wide concentration range of 3.0 x 10(-7) to 2.5x 10(-2)M with a relatively fast response time of less than 5 min. In addition to high stability, reversibility and reproducibility, the sensor shows a unique selectivity towards Pb(2+) ion with respect to common coexisting cations. The proposed fluorescence optode was successfully applied to the determination of lead in plastic toys and tap water samples.

The synthesis of the macrocyclic receptor L1, which contains a tetraamine chain linking the 6,6'-positions of a 2,2'-dipyridine moiety, is reported. Its basicity properties and complexation features toward Cu(II), Zn(II), Cd(II) and Pb(II) have been studied in aqueous solutions by means of potentiometric, UV/Vis spectroscopy and fluorescence emission measurements and compared with those of ligand L2, in which a 1,10-phenanthroline moiety replaces the dipyridine unit of L1. In metal coordination, L1 shows a marked selectivity toward Cd(II) over Zn(II) and Pb(II). The crystal structures of its metal complexes shows that L1 possesses a preferential tetradentate binding site for metal cations, composed of the dipyridine unit and the two adjacent benzylic amine groups. This binding site has the proper dimension and conformation to selectively coordinate the Cd(II) ion, as confirmed by DFT calculations carried out on the complexes. This coordinative zone is lost in L2. The rigidity of phenanthroline does not allow the simultaneous binding of both the benzylic amine groups to Zn(II) and Cd(II) and, in fact, one benzylic amine is not coordinated to these metal cations. The fluorescence emission properties of the L1 and L2 complexes are strongly pH dependent. Only the Zn(II) and Cd(II) complexes with L1 display fluorescence emission at neutral pH. This feature is related to the formation in solution at pH 7 of emissive protonated complexes of the type [M(H(x)L)]((2+x)+) (x=1-3), in which all the nitrogen donors are involved in metal or proton binding. The emissive characteristics of these protonated complexes are confirmed by the fluorescence emission spectra collected on the [Zn(HL1)Br][ClO(4)](2) and [Cd(HL1)Br][ClO(4)](2) solid compounds dissolved in CH(3)CN. Conversely, the Zn(II) and Cd(II) complexes with L2 are not emissive; in fact, they contain a benzylic amine group not involved in metal or proton binding that can quench the fluorescence emission of the fluorophore, thanks to a photoinduced electron-transfer process.