Thermodynamics of spin crossover in a bis(terpyridine) cobalt(II) complex featuring a thioether functionality.

In this contribution, a terpyridine-based ligand bearing a thioether functionality is used to prepare a new cobalt(II) spin crossover complex: [Co(TerpyPhSMe)2](PF6)2 (1), where TerpyPhSMe is 4'-(4-methylthiophenyl)-2,2':6',2''-terpyridine. Its structure, determined by single crystal X-ray diffraction, reveals a mer coordination of the tridentate terpyridine ligands, leading to a tetragonally compressed octahedron. Intermolecular interactions in the crystal lattice freeze the complex in the high spin state in the solid state at all temperatures, as indicated by magnetometry and Electron Paramagnetic Resonance (EPR) spectra. When dissolved in acetonitrile, however, temperature dependent electronic, 1H-NMR and EPR spectra highlight an entropy-driven spin crossover transition, whose thermodynamics parameters have been determined. This is the first report of a cobalt(II) SCO complex featuring a thioether group, allowing its implementation in chemically grown bistable monolayers and may open important perspectives for the use of such systems in molecular spintronics.

Amorphous Solid Forms of Ranolazine and Tryptophan and Their Relaxation to Metastable Polymorphs.

Different methods were explored for the amorphization of ranolazine, a sparingly soluble anti-anginal drug, such as mechanochemistry, quench-cooling, and solvent evaporation from solutions. Amorphous phases, with Tg values lower than room temperature, were obtained by cryo-milling and quench-cooling. New forms of ranolazine, named II and III, were identified from the relaxation of the ranolazine amorphous phase produced by cryo-milling, which takes place within several hours after grinding. At room temperature, these metastable polymorphs relax to the lower energy polymorph I, whose crystal structure was solved in this work for the first time. A binary co-amorphous mixture of ranolazine and tryptophan was produced, with three important advantages: higher glass transition temperature, increased kinetic stability preventing relaxation of the amorphous to crystalline phases for at least two months, and improved aqueous solubility. Concomitantly, the thermal behavior of amorphous tryptophan obtained by cryo-milling was studied by DSC. Depending on experimental conditions, it was possible to observe relaxation directly to the lower energy form or by an intermediate metastable crystalline phase and the serendipitous production of the neutral form of this amino acid in the pure solid phase.

Bioplastics on marine sandy shores: Effects on the key species Talitrus saltator (Montagu, 1808).

Talitrid amphipods are an important component of detritus web, playing a key role in the fragmentation of organic matters of marine and terrestrial origin, and it is well known that sandhoppers ingest microplastics. To assess the effective consumption of bioplastics and their effects on survival rate and on pollutants transfer (i.e. phthalates) on supralittoral arthropods, laboratory experiments were conducted by feeding adult T. saltator with two different types of bioplastic commonly used in the production of shopping bags. Groups of about 20 individuals were fed with 10 × 10 cm sample sheets of the two types of bioplastic for four weeks. The results show that amphipods ingest bioplastics even in the absence of microbial film and that ingestion of bioplastic can have effects on talitrid amphipods. Microtomographic analyses of faecal pellets seem consistent with this finding. The high phthalate concentrations in freshly collected individuals suggest the presence in the environment of these compounds, and the ability of amphipods to assimilate them, while the decrease in phthalate concentrations in bioplastic-fed individuals could be attributed to the scavenging effect of virgin plastic, as already observed in a previous study. In summary, the results indicate that different bioplastics may have effects on T. saltator (i.e. survival rate and faecal pellets structure) and confirm a potential role of amphipods in the degradation of bioplastics in supralittoral zone of marine sandy beaches, even when bioplastics are not colonized by bacterial biofilm that seems to improve palatability.

Temperature Dependence of Spin-Phonon Coupling in [VO(acac)2]: A Computational and Spectroscopic Study.

Molecular electronic spins are good candidates as qubits since they are characterized by a large tunability of their electronic and magnetic properties through a rational chemical design. Coordination compounds of light transition metals are promising systems for spin-based quantum information technologies, thanks to their long spin coherence times up to room temperature. Our work aims at presenting an in-depth study on how the spin-phonon coupling in vanadyl-acetylacetonate, [VO(acac)2], can change as a function of temperature using terahertz time-domain spectroscopy and density functional theory (DFT) calculations. Powder THz spectra were recorded between 10 and 300 K. The temperature dependence of vibrational frequencies was then accounted for in the periodic DFT calculations using unit-cell parameters measured at two different temperatures and the optimized ones, as usually reported in the literature. In this way, it was possible to calculate the observed THz anharmonic frequency shift with high accuracy. The overall differences in the spin-phonon coupling magnitudes as a function of temperature were also highlighted showing that the computed trends have to be ascribed to the anisotropic variation of cell parameters.

Magnetic Anisotropy Trends along a Full 4f-Series: The fn+7 Effect.

The combined experimental and computational study of the 13 magnetic complexes belonging to the Na[LnDOTA(H2O)] (H4DOTA = tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid and Ln = Ce-Yb) family allowed us to identify a new trend: the orientation of the magnetic anisotropy tensors of derivatives differing by seven f electrons practically coincide. We name this trend the fn+7 effect. Experiments and theory fully agree on the match between the magnetic reference frames (e.g., the easy, intermediate, and hard direction). The shape of the magnetic anisotropy of some couples of ions differing by seven f electrons might seem instead different at first look, but our analysis explains a hidden similarity. We thus pave the way toward a reliable predictivity of the magnetic anisotropy of lanthanide complexes with a consequent reduced need of computational and synthetical efforts. We also offer a way to gain information on ions with a relatively small total angular momentum (i.e., Sm3+ and Eu3+) and on the radioactive Pm3+, which are difficult to investigate experimentally.

New 3-unsubstituted isoxazolones as potent human neutrophil elastase inhibitors: Synthesis and molecular dynamic simulation.

Human neutrophil elastase (HNE) is a proteolytic enzyme belonging to the serine protease family and is involved in a variety of pathologies. Thus, compounds able to inhibit HNE represent promising therapeutics for the treatment of inflammatory diseases. Here, we report the further elaboration of our previously reported 3-methylisoxazolone derivatives, synthesizing a new series of 3-nor-derivatives bearing different substituents at the 4-phenyl ring. The most potent compounds 3a, 3g, and 3h, had IC50 values of 16, 11, and 18 nM, respectively. Molecular modeling studies and molecular dynamic (MD) simulations demonstrated no substantial differences between the 3-methylisoxazole derivatives previously tested and the corresponding 3-unsubstituted derivatives in the snapshot conformations sampled during the MD simulations, which is consistent with their similar levels of HNE inhibitory activity. Thus, we conclude that the isoxazolone scaffold is a good scaffold for developing HNE inhibitors, as it tolerates several modifications when adhering to basic scaffold requirements, and the resulting derivatives are quite potent HNE inhibitors.

A multi-analytical approach for the study of red stains on heritage marble.

Red stains are a common discolouration on stone cultural heritage all over the world. These are very difficult to remove and little is known about the reddish pigmentation. Numerous red stains were mapped on the Baptistery of San Giovanni in Florence, one of the most important monuments in Italy. This paper is focused on red stains on marble stone and the results of a detailed multidisciplinary approach are presented. Several analytical and investigation techniques (such as optical microscopy, X-ray fluorescence mapping, X-ray micro-tomography, micro-Raman spectroscopy, scanning electron microscopy with energy dispersive spectroscopy, microbial isolation, colorimetric measurements and isotopic analyses) were used to better understand the origin and processes involved in this kind of alteration. Analyses of the red stains led us to believe the presence of minium (lead tetroxide) and Pb are usually concentrated in the spaces between calcite grains. Red stains of Pb isotopic composition also overlap with data from Sardinian mines. These preliminary data seem to reinforce the suggestion of a source of lead from some metallic items (during restoration campaigns between 1938 and 1944, damaged parts were removed and replaced, and the new marble cladding was fixed with iron brackets treated with minium).

Ingested microplastic as a two-way transporter for PBDEs in Talitrus saltator.

The presence and accumulation of plastic waste into the marine environment are well known environmental issues. Microplastics (MPs) end up in sea waters and, due to their hydrophobicity and high surface/volume ratio, POPs tend to sorb and accumulate to their surface. The supralittoral amphipod Talitrus saltator (T. saltator) was selected to study the role of MPs in the transfer of organic pollutants and to investigate if ingested MPs could either transfer contaminants to biota or clean it adsorbing pollutants taken from the diet. T. saltator is an established POPs (Persistent Organic Pollutants) biomonitor in coastal environments and it is able to swallow microplastics in natural condition. Two laboratory experiments were performed and T. saltator was exposed to a labelled polybrominated diphenyl ether (13C-labelled BDE-47) to investigate the opposite gradient role of MPs. X Ray Micro-CT (Micro-Computed Tomography) analyses were also performed on sandhopper samples to evaluate the uptake of MPs via digestive tract. The results showed that MPs ingestion could whether transfer and remove contaminants from T. saltator, indicating a partial balance among positive and negative effects. This study has underlined MP potential double role demonstrating that MP can act both as a carrier and scavenger for the bioaccumulation of organic pollutants (i.e. PBDEs), suggesting that chemicals leaching from MPs could have a limited impact to biota.

Design, synthesis, crystal structures and anticancer activity of 4-substituted quinolines to target PDK1.

The induced fit docking of anilino quinoline scaffold results in the required hydrogen bonding interactions with amino acid residues in the orthosteric site of 3 Phosphoinositide dependent kinase (PDK1). The rational design of 4-substituted amino quinolines is carried out and eight compounds are synthesized. Four crystal structures are determined and their binding mode with adenosine triphosphate (ATP) site of PDK1 is analyzed. The anticancer activity in A549 cell lines of the test compounds by MTT assay resulted in an inhibitor with IC50 value of 0.96 µM which is less than the pemetrexed, a marketed lung cancer drug.

Metal complexes of naphthoquinone based ligand: synthesis, characterization, protein binding, DNA binding/cleavage and cytotoxicity studies.

Protein binding, DNA binding/cleavage and in vitro cytotoxicity studies of 2-((3-(dimethylamino)propyl)amino)naphthalene-1,4-dione (L) and its four coordinated M(II) complexes [M(II) = Co(II), Cu(II), Ni(II) and Zn(II)] have been investigated using various spectral techniques. The structure of the ligand was confirmed by spectral and single crystal XRD studies. The geometry of the complexes has been established using analytical and spectral investigations. These complexes show good binding tendency to bovine serum albumin (BSA) exhibiting high binding constant values (105 M-1) when compared to free ligand. Fluorescence titration studies reveal that these compounds bind strongly with CT-DNA through intercalative mode (Kapp 105 M-1) and follow the order: Cu(II) > Zn(II) > Ni(II) > Co(II) > L. Molecular docking study substantiate the strength and mode of binding of these compounds with DNA. All the complexes efficiently cleaved pUC18-DNA via hydroxyl radical mechanism and the Cu(II) complex degraded the DNA completely by converting supercoiled form to linear form. The complexes demonstrate a comparable in vitro cytotoxic activity against two human cancer cell lines (MCF-7 and A-549), which is comparable with that of cisplatin. AO/EB and DAPI staining studies suggest apoptotic mode of cell death, in these cancer cells, with the compounds under investigation.

Isoxazol-5(2H)-one: a new scaffold for potent human neutrophil elastase (HNE) inhibitors.

Human neutrophil elastase (HNE) is an important target for the development of novel and selective inhibitors to treat inflammatory diseases, especially pulmonary pathologies. Here, we report the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with an isoxazol-5(2H)-one scaffold. The most potent compound (2o) had a good balance between HNE inhibitory activity (IC50 value =20 nM) and chemical stability in aqueous buffer (t1/2=8.9 h). Analysis of reaction kinetics revealed that the most potent isoxazolone derivatives were reversible competitive inhibitors of HNE. Furthermore, since compounds 2o and 2s contain two carbonyl groups (2-N-CO and 5-CO) as possible points of attack for Ser195, the amino acid of the active site responsible for the nucleophilic attack, docking studies allowed us to clarify the different roles played by these groups.

Effects of fecal sampling on preanalytical and analytical phases in quantitative fecal immunochemical tests for hemoglobin.

BACKGROUND: Information on preanalytical variability is mandatory to bring laboratories up to ISO 15189 requirements. Fecal sampling is greatly affected by lack of harmonization in laboratory medicine. The aims of this study were to obtain information on the devices used for fecal sampling and to explore the effect of different amounts of feces on the results from the fecal immunochemical test for hemoglobin (FIT-Hb). METHODS: Four commercial sample collection devices for quantitative FIT-Hb measurements were investigated. The volume of interest (VOI) of the probes was measured from diameter and geometry. Quantitative measurements of the mass of feces were carried out by gravimetry. The effects of an increased amount of feces on the analytical environment were investigated measuring the Hb values with a single analytical method. RESULTS: VOI was 8.22, 7.1 and 9.44 mm3 for probes that collected a target of 10 mg of feces, and 3.08 mm3 for one probe that targeted 2 mg of feces. The ratio between recovered and target amounts of devices ranged from 56% to 121%. Different changes in the measured Hb values were observed, in adding increasing amounts of feces in commercial buffers. CONCLUSIONS: The amounts of collected materials are related to the design of probes. Three out 4 manufacturers declare the same target amount using different sampling volumes and obtaining different amounts of collected materials. The introduction of a standard probes to reduce preanalytical variability could be an useful step for fecal test harmonization and to fulfill the ISO 15189 requirements.

Magnetic Anisotropy of Tetrahedral CoII Single-Ion Magnets: Solid-State Effects.

This study reports the static and dynamic magnetic characterization of two mononuclear tetrahedral CoII complexes, [Co{iPr2P(E)NP(E)iPr2}2], where E = S (CoS4) and Se (CoSe4), which behave as single-ion magnets (SIMs). Low-temperature (15 K) single-crystal X-ray diffraction studies point out that the two complexes exhibit similar structural features in their first coordination sphere, but a disordered peripheral iPr group is observed only in CoS4. Although the latter complex crystallizes in an axial space group, the observed structural disorder leads to larger transverse magnetic anisotropy for the majority of the molecules compared to CoSe4, as confirmed by electron paramagnetic resonance spectroscopy. Static magnetic characterization indicates that both CoS4 and CoSe4 show easy-axis anisotropy, with comparable D values (∼-30 cm-1). Moreover, alternating-current susceptibility measurements on these CoII complexes, magnetically diluted in their isostructural ZnII analogues, highlight the role of dipolar magnetic coupling in the mechanism of magnetization reversal. In addition, our findings suggest that, despite their similar anisotropic features, CoS4 and CoSe4 relax magnetically via different processes. This work provides experimental evidence that solid-state effects may affect the magnetic behavior of SIMs.

Pyrazolo[1,5-a]quinazoline scaffold as 5-deaza analogue of pyrazolo[5,1-c][1,2,4]benzotriazine system: synthesis of new derivatives, biological activity on GABAA receptor subtype and molecular dynamic study.

To investigate the binding affinity of GABAA receptor subtype, new pyrazolo [1,5-a]quinazolines were designed, synthesized, and in vitro evaluated. These compounds, 5-deaza analogues of pyrazolo[5,1-c][1,2,4]benzotriazine derivatives which were already studied in our research group, permit us to evaluate the relevance of the nitrogen or the oxygen atom at 5-position of the tricyclic scaffold. Molecular dynamic study was done on a set of the new and known ligands to rationalize and to explain the lack of affinity on the 4- or 5-substituted new derivative. In fact, from biological results, it can be found that the only 5-unsubstituted new derivative, compound 15, has receptor recognition (Ki = 834.7 nM).

Synthesis and characterization of Ni(II) and Zn(II) complexes of (furan-2-yl)methyl(2-(thiophen-2-yl)ethyl)dithiocarbamate (ftpedtc): X-ray structures of [Zn(ftpedtc)2(py)] and [Zn(ftpedtc)Cl(1,10-phen)].

Seven complexes of a new dithiocarbamate ligand (ftpedtc = (furan-2-yl)methyl(2-(thiophen-2-yl)ethyl)dithiocarbamate) namely [Ni(ftpedtc)2] (1), [Ni(ftpedtc)(NCS)(PPh3)] (2), [Ni(ftpedtc)(PPh3)2]ClO4 (3), [Zn(ftpedtc)2] (4), [Zn(ftpedtc)2(py)] (5), [Zn(ftpedtc)2(1,10-phen)] (6) and [Zn(ftpedtc)2(2,2'-bipy] (7) have been prepared. The complexes were characterized by IR, UV-Vis and NMR ((1)H and (13)C) spectroscopy. Single crystal X-ray structural analysis was carried out for complexes 5 and [Zn(ftpedtc)Cl(1,10-phen)] (8). Electronic spectral studies suggest square planar geometry for nickel complexes. The (13)C NMR peaks of the group N(13)CS2 are found in all the cases, at around 205.0 ppm, which indicates the bidentate character of the dithiocarbamate ligand. X-ray structures of 5 and 8 show bidentate coordination by dithiocarbamate ligands and a distorted trigonal bipyramidal geometry for zinc, defined by NS4 and ClN2S2 donor sets, respectively. The packing in 8 involves π-π stacking interactions involving the 1,10-phenanthroline ring systems with the distance between ring centroids being 3.587 Å.

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).

A new approach to the synthesis of heteronuclear propeller-like single molecule magnets.

Propeller-like [Fe(4)(L)(2)(dk)(6)] complexes, in which Hdk is a ß-diketone and H(3)L is a tripodal alcohol, R-C(CH(2)OH)(3), exhibit tunable magnetic anisotropy barriers and retain their magnetic memory effect when chemically anchored on metal surfaces. Heteronuclear analogues of these M(4) complexes have been sought to afford a library of compounds with different total spin (S) values, but synthetic efforts described so far gave solid solutions containing M(4) in addition to the desired M(3)M' species. We now present a novel synthetic route to M(3)M' complexes featuring a central chromium(III) ion. The three-step preparation goes through coordination of Cr(III) by two equivalents of tripodal alkoxide (R = Et and Ph), followed by reaction of this complex "core" with the peripheral +III metal ions. Products have been characterised by chemical analyses together with (1)H-NMR, FTIR, W-band EPR, DC/AC magnetic susceptibility measurements and single crystal X-ray diffractometry. Due to the chemical inertness of Cr(III), this route yields 100% pure Fe(3)Cr complexes without metal scrambling; what is more, it is suitable for designing novel heteronuclear single molecule magnets (SMMs) with a variety of d- and f-metals and R groups.

Preparation of ZnS nanosheets from (2,2'-bipyridine)bis(1,2,3,4-tetrahydroquinolinecarbodithioato-S,S')zinc(II).

(2,2'-Bipyridine)bis(1,2,3,4-tetrahydroquinolinecarbodithioato-S,S')zinc(II), [Zn(thqdtc)(2)(2,2'-bipy)] (1) has been synthesized from bis(1,2,3,4-tetrahydroquinolinecarbodithioato-S,S')zinc(II), [Zn(thqdtc)(2)] (2) and characterized by elemental analysis, IR and NMR spectroscopy and single crystal X-ray analysis. In the (13)C NMR spectrum, complex 1 showed a single low-field resonance associated with back bone carbon of dithiocarbamate (N(13)CS(2)) at 209.2 ppm. Single crystal X-ray analysis of 1 showed that the zinc ion is in a distorted octahedral environment of two nitrogen atoms and four sulfur atoms around it. The complex 1 has been used as single source precursor for the preparation of ZnS nanosheets via solvothermal method. The ZnS nanosheets have been characterized by powder XRD, EDAX, TEM, UV-Vis and fluorescence spectroscopy. TEM studies indicate that the nanosheets are very thin. The nanosheets obtained show quantum size effect in their UV-Vis absorption spectrum. The strong emission peak centered at 415 nm in fluorescence spectrum could be attributed to the electron-hole recombination from internal vacancies for Zn and S atoms.

Proton and metal binding by cyclen-based highly rigid cryptands.

The basicity properties of the two cryptands L1 and L2, featuring, respectively, a dibenzofuran or a diphenyl ether moiety bridging the 1,7 positions of a 1,4,7,10-tetraazacyclododecane macrocycle (cyclen) have been studied by means of potentiometric, UV-vis and fluorescence emission measurements. Both ligands show a high basicity in the first protonation step, the first basicity constant of L1 being too high to be measured in aqueous solution. The crystal structure of {[HL1]L1}(+) shows that the NH(2)(+) group is involved in an intramolecular hydrogen bonding network, which justifies the observed high basicity in solution. (1)H, (13)C NMR, UV-vis and fluorescence emission measurements show that, among first row divalent metal cations, both L1 and L2 selectively bind in acetonitrile Cu(II) and Zn(II), which are encapsulated within the ligand cavities. Zn(II) coordination is accompanied by a remarkable increase of the fluorescence emission of the ligands, pointing out that the molecular architecture displayed by L1 and L2 can be used to develop new OFF/ON chemosensors for this metal cation.

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 (GABA(A)) 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.