Samuele Ciattini

Affinity and nuclease activity of macrocyclic polyamines and their CuII complexes.

The stability constants of Cu(II) complexes that consist of either an oxaaza macrocycle with two triamine moieties linked by dioxa chains, or two macrocyclic ligands with a polyamine chain which are connecting the 2 and 9 positions of phenanthroline, have been determined by means of potentiometric measurements. The results are compared to those reported for other ligands with a similar molecular architecture. Of the complexes that contain phenanthroline in their macrocycle, the Cu(II) ion of the complex with the smallest and most rigid macrocycle (L3) has an unsaturated coordination sphere, while in the complex with the largest macrocycle (L5) the Cu(II) ion is coordinatively almost saturated. These results are corroborated by the crystal structure of the [CuL5](ClO4)2 complex. The affinity of the ligands and the complexes towards nucleic acids was studied by measuring the changes in the melting temperature, which showed that the affinity of the macrocyclic ligands towards double-stranded DNA or RNA is generally smaller than that of their linear analogues that bear a similar charge, with a strong preference for polyA-polyU, a model for RNA. However, the complexes of two of the changed macrocyclic ligands which contain a phenanthroline unit (L4, L5) showed a distinctly larger increase in their melting temperature deltaTm with DNA (polydA-polydT), which is reversed again in favor of RNA upon metallation to the dinuclear copper complex with L5. Experiments with supercoiled plasmid DNA showed a particularly effective cleavage with a mononuclear Cu(II) complex that contains a phenanthroline unit (L6). Related ligands showed less activity towards DNA, but not so towards the biocidic bis(p-nitrophenyl)phosphate (BNPP). In both cases (with DNA and BNPP) the activity seemed to increase with decrease of coordinative saturation of the Cu(II) ion, with the exception of one particular ligand (L6). Experiments with radical scavengers in the DNA experiments showed some decrease in cleavage, which indicates the participation of redox processes.

A new versatile solvatochromic amino-macrocycle. From metal ions to cell sensing in solution and in the solid state

A new fluorescent NBD-polyaza-macrocycle sensor (L) was synthesized. The coordination of Cu(ii) and Zn(ii) in acetonitrile switches on the fluorescence with different emission wavelengths. Cu(ii) complexes showed solid-state fluorescence. Both L and Cu-complex interact with human cell line (U937) highlighting the cell membrane by fluorescence microscopy.

Benzoquinone–imidazole hybrids as selective colorimetric sensors for cyanide in aqueous, solid and gas phases

Five new chemosensors (R1–R5), possessing benzoquinone as the signaling unit and imidazole as the H-bond donor unit, for cyanide sensing have been rationally designed, synthesized and characterized by NMR and mass spectroscopy. The structure of R5 was confirmed by single crystal XRD studies. These receptors exhibited a prominent visual colour change toward the cyanide ion over other common anions in an aqueous HEPES buffer–DMF (9 : 1 v/v) medium. The complexation of receptor–CN− has been addressed by UV-Vis, fluorescence and 1H NMR spectra and was supported by electrochemical and DFT studies. The mechanism of sensing involves formation of H-bonds between imidazole N–H and CN− ions. The stoichiometry of the receptor–CN− complexes was found to be 1 : 2 (receptor–CN−) and the detection limit was observed to be in the range of 1.1–3 nM. The test strips based on R5 were fabricated and could act as convenient and efficient CN− test kits. Notably, the novelty of the present investigation is that the receptor R5 selectively senses CN− ions in solid, aqueous and gas phases i.e. ‘a complete receptor’.

New Fluoro Derivatives of the Pyrazolo[5,1-c][1,2,4]benzotriazine 5-Oxide System: Evaluation of Fluorine Binding Properties in the Benzodiazepine Site on γ-Aminobutyrric Acid Type A (GABAA) Receptor. Design, Synthesis, Biological, and Molecular Modeling Investigation

In the search for potent ligands at the benzodiazepine site on the GABA(A) receptor, new fluoro derivatives of the pyrazolo[5,1-c][1,2,4]benzotriazine system were synthesized to evaluate the importance of the introduction of a fluorine atom in this system. Biological and pharmacological studies indicate that the substitution at position 8 with a trifluoromethyl group confers pharmacological activity due to potential metabolic stability in comparison to inactive 8-methyl substituted analogues. In particular, the compound 3-(2-methoxybenzyloxycarbonyl)-8-trifluoromethylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide (21) emerges because of its selective anxiolytic profile without side effects. An analysis of all the newly synthesized compounds in our pharmacophoric map confirms the essential interaction points for binding recognition and the important areas for affinity modulation. The fluorine atom was able to form a hydrogen bond interaction only when it is not in position 3.

Binding of nucleobases to a dizinc macrocyclic complex. Supramolecular assembling of dinuclear clusters through N-H···O and C-H···O hydrogen bonding

The interaction of cytosine (CyH), thymine (TH) and uracil (UH) with the dinuclear Zn(II) complexes of ligand 1,4,7,16,19,22hexaza-10,13,25,28-tetraoxacyclotriacontane (L) has been studied by means of potentiometric titrations (0.1 mol dm −3 NMe4NO3, 298.1 K), and 1 H NMR measurements. The equilibrium constants for the formation of the ternary complexes with the nucleobases indicate that the [Zn2L] 4 + complex displays similar binding features towards thymine and uracil. The dizinc complex forms stable 1:1 and 1:2 complexes with both deprotonated thymine and uracil at neutral or slightly alkaline pH values. The constants for the addition of first and second substrate molecules are almost equal indicating that each nucleobase is coordinated, almost independently, by one metal ion of [Zn2L] 4 + . This feature is confirmed by the crystal structures of [Zn2LT2] 2 + and [Zn2LU2] 2 + . In the [Zn2LA2] 2 + (A − =T − ,U − ) complexes the two metal ions have almost the same coordination environment and each Zn(II) is coordinated to three nitrogens of the macrocycle and to a deprotonated nitrogen of the nucleobases. In the crystal packing the dinuclear clusters give rise to a supramolecular architecture based on infinite pillars of [Zn2LA2] 2 + (A − =T − , U − ) assembled via hydrogen bonding. Cytosine forms only 1:1 adducts with the dizinc complex and the stability constants values suggest that the deprotonated nucleobase bridges the two metal ions.

Supramolecular Assembling of Dizinc Macrocyclic Complexes with Thymine and Uracil — The Role of Intra- and Intermolecular Hydrogen Bonding

A binuclear ZnII complex with an oxa-aza macrocyclic ligand can bind two deprotonated thymine or uracil moieties, giving versatile building blocks for the assembly of supramolecolar structures, by hydrogen bond pairing of the nucleobases.

Synthesis and Characterization of Homoleptic and Heteroleptic Complexes Involving Dithiocarbamates, Triphenylphosphine, and Nickel(II)

Abstract Six new nickel complexes of two dithiocarbamate ligands (cyfdtc = N-cyclohexyl-N- furfuryldithiocarbamate and bztpedtc = N-benzyl-N-[2-thiophenylethyl]dithiocarbamate) namely, (Ni[cyfdtc]2) (1), (Ni[bztpedtc]2) (2), (Ni[cyfdtc][NCS][PPh3]) (3), (Ni[bztpedtc] [NCS][PPh3]) (4), (Ni[cyfdtc][PPh3]2)ClO4 (5), and (Ni[bztpedtc][PPh3]2)ClO4 (6) have been prepared and characterized using IR, electronic, and NMR (1H and 13C) spectra. A single crystal X-ray structural analysis was carried out for complex 3 and showed that nickel is in a distorted square planar arrangement with the NiS2PN chromophore. The shift in νC˭N of the heteroleptic complexes to higher frequencies compared with the parent complex is assigned to mesomeric delocalization of electron density from the dithiocarbamate ligand toward the metal atom, which increases the contribution of polar thioureide form in mixed ligand complexes. Electronic spectral studies suggest square planar geometry for the complexes. In the 13C NMR spectra, the upfield shift of NCS2 carbon signal for 3 and 4 from the chemical shift value of 1 and 2 is due to effect of PPh3 on the mesomeric drift of electron density toward nickel throughout thioureide C˭N bond. GRAPHICAL ABSTRACT

Synthesis and spectral studies on nitrogen donor adducts of bis(4-ethylpiperazinecarbodithioato-S,S′)M(II) (M = Zn, Cd) and use of adducts of cadmium dithiocarbamate for the preparation of cadmium sulfide

[M(4-epzdtc)2(py)], [M(4-epzdtc)2(1,10-phen)], and [M(4-epzdtc)2(2,2′-bipy)] (where M = Zn(II), Cd(II); 4-epzdtc− = 4-ethylpiperazinecarbodithioate) were synthesized and characterized by IR and NMR (1H, 13C, HSQC and HMBC) spectra. A single-crystal X-ray analysis was carried out for [Zn(4-epzdtc)2(py)]. The N13CS2 chemical shifts of [M(4-epzdtc)2] and its adducts follow the order: [M(4-epzdtc)2] (ca 202 ppm) < [M(4-epzdtc)2(py)] (ca 204 ppm) < [M(4-epzdtc)2(N,N)] (N,N = 1,10-phen, 2,2′-bipy) (ca 206 ppm), due to the change in coordination number. Single-crystal X-ray structural analysis of [Zn(4-epzdtc)2(py)] showed that zinc is five-coordinate with four sulfurs from dithiocarbamate and one nitrogen from pyridine. This complex adopts a geometry intermediate between the tetragonal pyramid (C4v) and trigonal bipyramid (D3h). [Cd(4-epzdtc)2] and its adducts were used as single source precursors for preparation of CdS. The as-prepared CdS was characterized by powder X-ray diffraction, UV-Vis absorption, and fluorescence spectroscopy. The UV-Vis absorption spectra of CdS particles indicate a blue shift in the absorption spectra due to the quantum size effect.

Synthesis of novel cognition enhancers with pyrazolo[5,1-c][1,2,4]benzotriazine core acting at γ-aminobutyric acid type A (GABA(A)) receptor.

Memory dysfunction associated with aging, neurodegenerative and psychiatric disorders represents an increasing medical need. Advances in research exploring the biological mechanisms underlying learning and memory have opened new potential approaches for development of memory-enhancing therapies addressed to selective neuronal targets. In this work, we synthesized some derivatives with a pyrazolo[5,1-c][1,2,4]benzotriazine core to identify ligands on GABAA receptors subtype (benzodiazepine site on GABAA-receptor) endowed with the potential of enhancing cognition activity without the side effects usually associated with non-selective GABAA modulators. In fact, there is much evidence that GABAA-R (γ-aminobutyric acid, type A receptor) subtype ligands have relevance in learning and memory. In vitro and in vivo tests have been performed. Pharmacological data indicate that compounds 7, 13, 14 and 22 act as dual functional modulators of GABAA-Rs (promnemonic and anxiolytic agents) while only compounds 3 and 10 stand out as selectively displaying good antiamnesic and procognitive activity (1 and 3 mg/kg, respectively).

Selective colorimetric sensing of fluoride in an aqueous solution by amino-naphthoquinone and its Co(II), Ni(II), Cu(II) and Zn(II) complexes – effect of complex formation on sensing behaviour

An amino-naphthoquinone ligand and its Co(II), Ni(II), Cu(II) and Zn(II) complexes have been synthesized and characterized using analytical and spectral techniques. The anion sensing behaviour of these receptors is investigated using UV-vis, fluorescence and 1H NMR spectral studies. Electrochemical and DFT computations are also carried out to substantiate the results of spectral studies. The receptors colourimetrically sense fluoride ions selectively and sensitively in aqueous DMF mixtures. The mechanism of sensing involves formation of an H-bond between the N–H group and fluoride ion. The binding constants for the formation of 1 : 1 receptor–fluoride complexes are found to be in the order of 105 M−1. The results indicate that complexation with metal ions not only enhanced the HBD property of the N–H group but also accommodates ≥50% of water in the sensing medium.