Excited state dynamics of Zn-salophen complexes.

Zn-salophen complexes are a promising class of fluorescent chemosensors for nucleotides and nucleic acids. We have investigated, by means of steady state UV-Vis, ultrafast transient absorption, fluorescence emission and time dependent density functional theory (TD-DFT) the behavior of the excited states of a salicylidene tetradentate Schiff base (Sal), its Zn(II) coordination compound (Zn-Sal) and the effect of the interaction between Zn-Sal and adenosine diphosphate (ADP). TD-DFT shows that the deactivation of the excited state of Sal occurs through torsional motion, due to its rotatable bonds and twistable angles. Complexation with Zn(II) causes rigidity so that the geometry changes in the excited states with respect to the ground state structure are minimal. By addition of ADP to a freshly prepared Zn-Sal ethanol solution, a longer relaxation constant, in comparison to Zn-Sal, was measured, indicative of the interaction between Zn-Sal and ADP. After a few days, the Zn-Sal-ADP solution displayed the same static and dynamic behavior of a solution containing only the Sal ligand, demonstrating that the coordination of the ADP anion to Zn(II)leads to the demetallation of the Sal ligand. Fluorescence measurements also revealed an enhanced fluorescence at 375 nm following the addition of ADP to the solution, caused by the presence of 2,3-diamino naphthalene that is formed by demetallation and partial decomposition of the Sal ligand. The efficient fluorescence of this species at 375 nm could be selectively detected and used as a probe for the detection of ADP in solution.

A Newly Designed Water Soluble Uranyl-Salophen Complex for Anion Recognition.

A novel water-soluble uranyl-salophen (salophen=N,N'-disalicylidene-o-phenylenediaminate) complex was obtained. Solubility was achieved in aqueous methyl-ß-cyclodextrin solutions, taking advantage of the host-guest interactions established with the adamantyl moieties present on the ligand skeleton. Such an approach facilitates the synthesis of the receptor and the purification processes and, in perspective, can be definitely applicable to other molecular scaffolds. UV/Vis titration experiments demonstrate that the capacity of the uranyl-salophen core to behave as a receptor for anions is retained in water and appears comparable with that previously reported for other water-soluble uranyl-salophen systems. Hence the presence of cyclodextrins does not interfere with molecular recognition processes.

A Simple and Efficient Mechanochemical Route for the Synthesis of Salophen Ligands and of the Corresponding Zn, Ni, and Pd Complexes.

A number of salophen ligands and their Zn, Ni, and Pd complexes were synthesized by an efficient one-pot mechanosynthesis protocol. The reaction products were characterized by means of complementary solid-state techniques, i.e., powder X-ray diffraction, single-crystal X-ray diffraction, and solid-state NMR spectroscopy. Four new crystal structures of metal salophen complexes as DMSO solvates are here reported. The described simple and relatively fast (about 1 h for all derivatives) procedure is a good alternative to classical methods performed in organic solvents.

MicroRNAs delivery into human cells grown on 3D-printed PLA scaffolds coated with a novel fluorescent PAMAM dendrimer for biomedical applications.

Many advanced synthetic, natural, degradable or non-degradable materials have been employed to create scaffolds for cell culture for biomedical or tissue engineering applications. One of the most versatile material is poly-lactide (PLA), commonly used as 3D printing filament. Manufacturing of multifunctional scaffolds with improved cell growth proliferation and able to deliver oligonucleotides represents an innovative strategy for controlled and localized gene modulation that hold great promise and could increase the number of applications in biomedicine. Here we report for the first time the synthesis of a novel Rhodamine derivative of a poly-amidoamine dendrimer (G = 5) able to transfect cells and to be monitored by confocal microscopy that we also employed to coat a 3D-printed PLA scaffold. The coating do not modify the oligonucleotide binding ability, toxicity or transfection properties of the scaffold that is able to increase cell proliferation and deliver miRNA mimics (i.e., pre-mir-503) into human cells. Although further experiments are required to optimize the dendrimer/miRNA ratio and improve transfection efficiency, we demonstrated the effectiveness of this promising and innovative 3D-printed transfection system to transfer miRNAs into human cells for future biomedical applications.

Synthesis of potential HIV integrase inhibitors inspired by natural polyphenol structures.

Drawing inspiration from the structural features of some natural polyphenols, the synthesis of two different model compounds as potential inhibitors of HIV integrase (IN) has been described. The former was characterised by a diketo acid (DKA) bioisostere, such as a ß-hydroxycarbonyl moiety, between two fragments containing aromatic groups, while in the latter an epoxide linked two polyoxygenated aromatic residues. The moieties present in the structures are thought to function by chelating divalent metal ions on the enzyme catalytic site. Overall, 10 compounds were prepared and some of that submitted to molecular modelling studies (to investigate their interactions with the active site of IN), to metal titration studies (to detect their chelating capability) and to biological assays.

Experimental and Computational Investigation of Salophen-Zn Gas Phase Complexes with Cations: A Source of Possible Interference in Anionic Recognition.

We explore the possibility that protonated molecular ions might be an unexpected source of interference in the recognition process of anions and neutral species by Zn-salophen receptors. Zn-salophen complexes are known to bind anions and neutral molecules in solution. We present here evidence (from computational work and IRMPD spectroscopy) that these complexes can also be the binding site for protonated pyridine or quinuclidine. The resulting binding pattern does not involve the Zn ion, but one of the oxygen atoms directly attached to it. The resulting complex therefore turns out to have a positive charge adjacent to the Zn-salophen binding site. This finding seems to point to the existence of an interfering factor in the quantification of the experimental data about the association constant.

Solution and Solid-State Studies on the Halide Binding Affinity of Perfluorophenyl-Armed Uranyl-Salophen Receptors Enhanced by Anion-π Interactions.

The enhancement of the binding between halide anions and a Lewis acidic uranyl-salophen receptor has been achieved by the introduction of pendant electron-deficient arene units into the receptor skeleton. The association and the occurrence of the elusive anion-π interaction with halide anions (as tetrabutylammonium salts) have been demonstrated in solution and in the solid state, providing unambiguous evidence on the interplay of the concerted interactions responsible for the anion binding.

Fluoride binding in water with the use of micellar nanodevices based on salophen complexes.

The use of micelles to transpose lipophilic receptors, such as uranyl-salophen complexes, into an aqueous environment is a valuable and versatile tool. Receptor 1 incorporated into CTABr micelles forms a supramolecular system that exhibits excellent binding properties towards fluoride in water, despite the competition of the aqueous medium. To fully evaluate the potential of micellar nanodevices, we extended our previous study to other types of surfactants and to a uranyl-salophen receptor with a more extended aromatic surface. Paramagnetic relaxation enhancement experiments were used to obtain information on the location of the two receptors within the micelles and complementary information was obtained from dynamic light scattering experiments. With these data it is possible to account for the key factors necessary to obtain an efficient supramolecular device for anion binding in water.

Anion recognition by uranyl-salophen derivatives as probed by infrared multiple photon dissociation spectroscopy and ab initio modeling.

The vibrational features and molecular structures of complexes formed by a series of uranyl-salophen receptors with simple anions, such as Cl(-) , H(-) , and HCOO(-) , have been investigated in the gas phase. Spectra of the anionic complexes were studied in the $\tilde \nu $=800-1800 cm(-1) range by mass-selective infrared multiple photon dissociation (IRMPD) spectroscopy with a continuously tunable free-electron laser. The gas-phase decarboxylation of the formate adducts produces uranyl-salophen monohydride anions, which have been characterized for the first time and reveal a strong UH bond, the nature of which has been elucidated theoretically. The spectra are in excellent agreement with the results obtained from high-quality ab initio calculations, which provided the structure and binding features of the anion-receptor complexes.

Orthohalogen substituents dramatically enhance hydrogen bonding of aromatic ureas in solution.

The phenylurea moiety is a ubiquitous synthon in supramolecular chemistry. Here we report that the introduction of chlorine or bromine atoms in the ortho positions to the urea unit is a simple and very efficient way to improve its intermolecular hydrogen bond (HB) donor character. This effect was demonstrated in solution both in the context of self-association of bis-ureas and hydrogen bonding of mono-ureas to strong HB acceptors.

Paramagnetic relaxation enhancement experiments: a valuable tool for the characterization of micellar nanodevices.

Micellar incorporation of hydrophobic molecular receptors is a promising strategy to obtain efficient nanodevices that work in water. In order to fully evaluate the potential of this approach, information on the localization and orientation of the receptor inside the micelle are necessary. Systematic studies undertaken on a uranyl-salophen receptor incorporated into CTABr and CTACl micelles show that nuclear magnetic resonance paramagnetic relaxation enhancement (NMR-PRE) experiments are particularly suitable to provide this type of information. The effect on the measurements of surfactant concentration, nature of the surfactant polar head, and ionic strength is also reported. Notably the normalization procedure applied to the obtained data can be considered of general application, thus enabling the comparison of information collected for different types of supramolecular micelle/receptor systems.

A route to oligosaccharide-appended salicylaldehydes: useful building blocks for the synthesis of metal-salophen complexes.

A simple and general synthetic protocol to obtain oligosaccharide-appended salicylaldehydes, key intermediates for the synthesis of water-soluble metal-salophen complexes, is here reported. Six new aldehydes have been prepared and fully characterized as well as the corresponding zinc- and uranyl-salophen complexes. These new derivatives show very good solubility in water. Preliminary studies on the association of compound 19-U, that is, the uranyl maltotetraose derivative, with hydrogen phosphate and fluoride provide very encouraging results and open up the possibility of using such compounds for the efficient recognition of anions in pure water.

Substituent effects on the biological properties of Zn-salophen complexes.

The synthesis, characterization, and luminescent properties of a series of 5,5'-X-substituted salophen ligands, X = OCH3, Br, and NO2, and the corresponding Zn(II) complexes are reported here. Their biological activity has been analyzed and related to the different Lewis acid character of the complexes. In vitro studies (AFM and absorption and emission titrations) show that the strongest interaction with free plasmid DNA is observed for 5,5'-dinitro-substituted Zinc-salophen complex 3b. Semiempirical theoretical calculations together with redox potential measurements suggest that this might be interpreted as a direct consequence of this compound having the hardest Lewis acid character. Cellular uptake and cytotoxicity studies undertaken with these metal complexes show that they enter the cells but are not cytotoxic.

Anion recognition in water with use of a neutral uranyl-salophen receptor.

A new water-soluble uranyl-salophen complex incorporating two glucose units has been synthesized. This neutral derivative shows noteworthy binding affinity for fluoride in water thanks to the Lewis acid-base interaction occurring between the metal and the anion. Such interaction is strong enough to overcome the high hydration enthalpy of fluoride. Moreover this complex effectively binds hydrogen phosphate and exhibits remarkably strong association for nucleotide polyanions ADP(3-) and ATP(4-).

Metal-salophen-based receptors for anions.

In this critical review the use of metal-salophen complexes as anion receptors is discussed with an emphasis on the supramolecular control of selectivity derived by the presence of additional interaction sites on the ligand skeleton. Some examples of application in sensing are also reported (112 references).

A new water soluble Zn-salophen derivative as a receptor for alpha-aminoacids: unexpected chiral discrimination.

A new water soluble zinc-salophen complex with appended D-glucose moieties was synthesized and characterized. Its binding properties toward six aminoacids were investigated by UV-vis spectrophotometric titrations. Association constants showed to be unfavorably affected by increasing steric hindrance of the side chain. Quite surprisingly, different association constants were measured for the L and D enantiomers. These data suggest that aminoacids are bound via two interactions, zinc-carboxylate coordination and two hydrogen bonds between the ammonium group of the aminoacid and two oxygen atoms of one D-glucose moiety. Such conclusion is supported by the result of semiempirical (PM3) calculations. Notably, the K(L)/K(D) value of 9.6 observed for the association of phenylalanine rivals with the highest values found for the chiral recognition of aminoacids in water.

Specific supramolecular interactions between Zn(2+)-salophen complexes and biologically relevant anions.

Recognition of inorganic phosphates PO(4)(3-), P(2)O(7)(4-), and P(3)O(10)(5-) and nucleotides AMP(2-), ADP(3-), and ATP(4-) by Zn(2+)-salophen complexes 1 and 2 in ethanol was investigated by different spectroscopic techniques. (31)P NMR and mass spectrometry showed that anions of both series are bound by 1 and 2, while absorption and emission studies revealed that only nucleotides produce relevant changes in the spectral properties of the two hosts. (1)H NMR studies proved that the adenine aromatic group is involved in the complexation, thus pointing out the role of supramolecular ditopic receptors played by salophen derivatives toward this class of biologically relevant substrates. The lifetime of the photogenerated triplet state of the Zn(2+)-salophen compounds was measured by nanosecond laser flash photolysis, and the observed changes upon increasing the concentration of nucleotides allowed the identification of the formation of a 1:0.5 host/guest intermediate complex additionally to the formation of a 1:1 complex.

The role of attractive van der Waals forces in the catalysis of Michael addition by a phenyl decorated uranyl-salophen complex.

The Et(3)N-assisted addition of beta-ketoester 3 to MVK in chloroform is catalyzed with high turnover efficiency by the phenyl-substituted uranyl-salophen compound 2b but not by the parent compound 1b. A plausible mechanism is suggested, involving concomitant nucleophilic attack at the beta-carbon and hydrogen bonding between the Et(3)NH(+) countercation and the carbonyl oxygen of the s-cis conformation of the enone reactant. The role of the van der Waals interactions with the aromatic side arm of 2b as a crucial driving force for catalysis is discussed.