Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

Spatiotemporal variability in radial growth of trees in the Central Pyrenees: climatic and site influences.

To understand how tree growth has responded to recent climate warming, an understanding of the tree-climate-site complex is necessary. To achieve this, radial growth variability among 204 trees established before 1850 was studied in relation to both climatic and site factors. Seventeen forest stands were sampled in the Spanish Central Pyrenees. Three species were studied: Pinus uncinata, Abies alba, and Pinus sylvestris. For each tree, a ring-width residual chronology was built. All trees cross-dated well, indicating a common influence of the regional climate. For the 1952-1993 period, the radial growth of all species, especially P. uncinata, was positively correlated with warm Novembers during the year before ring formation and warm Mays of the year the annual ring formed. Differences in species-stand elevation modulated the growth-climate associations. Radial growth in P. uncinata at high elevation sites was reduced when May temperatures were colder and May precipitation more abundant. In the 20th century, two contrasting periods in radial growth were observed: one (1900-1949) with low frequency of narrow and wide rings, low mean annual sensitivity, and low common growth variation; and another (1950-1994) with the reverse characteristics. The increased variability in radial growth since the 1950s was observed for all species and sites, which suggests a climatic cause. The low shared variance among tree chronologies during the first half of the 20th century may result from a"relaxation" of the elevation gradient, allowing local site conditions to dominate macroclimatic influence. These temporal trends may be related to the recently reported increase of climatic variability and warmer conditions. This study emphasizes the need to carefully assess the relationships between radial growth and site conditions along ecological gradients to improve dendroclimatic reconstructions.

Morphostructure and paleobiology of Mesogean orthophragminids (Discocyclinidae and Orbitoclypeidae, Foraminifera)

Orthophragminids are Paleocene-Eocene bilamellarperforate larger foraminifers characterized by a lenticular test with an equatorial layer of rectangular chamberlets arranged in concentric rings and lateral chamberlets on either side. Usually called 'discocyclinids', orthophragrninids include genera from two families: Discocyclinidae and Orbitoclypeidae.

Identification of new transformation products during enzymatic treatment of tetracycline and erythromycin antibiotics at laboratory scale by an on-line turbulent flow liquid-chromatography coupled to a high resolution mass spectrometer LTQ-Orbitrap

This work describes the formation of transformation products (TPs) by the enzymatic degradation at laboratory scale of two highly consumed antibiotics: tetracycline (Tc) and erythromycin (ERY). The analysis of the samples was carried out by a fast and simple method based on the novel configuration of the on-line turbulent flow system coupled to a hybrid linear ion trap – high resolution mass spectrometer. The method was optimized and validated for the complete analysis of ERY, Tc and their transformation products within 10 min without any other sample manipulation. Furthermore, the applicability of the on-line procedure was evaluated for 25 additional antibiotics, covering a wide range of chemical classes in different environmental waters with satisfactory quality parameters. Degradation rates obtained for Tc by laccase enzyme and ERY by EreB esterase enzyme without the presence of mediators were ∼78% and ∼50%, respectively. Concerning the identification of TPs, three suspected compounds for Tc and five of ERY have been proposed. In the case of Tc, the tentative molecular formulas with errors mass within 2 ppm have been based on the hypothesis of dehydroxylation, (bi)demethylation and oxidation of the rings A and C as major reactions. In contrast, the major TP detected for ERY has been identified as the “dehydration ERY-A”, with the same molecular formula of its parent compound. In addition, the evaluation of the antibiotic activity of the samples along the enzymatic treatments showed a decrease around 100% in both cases

Hydrological evidence for a North Atlantic oscillation during the Little Ice Age outside its range observed since 1850.

An annual-resolved precipitation reconstruction for the last 800 yr in Southern Spain has been performed using stable carbon isotope (δ13C) of Pinus nigra tree rings. The reconstruction exhibits high- to low-frequency variability and distinguishes a Little Ice Age (LIA, AD 13501850) characterized by lower averaged rainfall than both in the transition from the Medieval Climate Anomaly to the LIA and in the 20th century. The driest conditions are recorded during the Maunder solar Minimum (mid 17thearly 18th centuries), in good agreement with the Spanish documentary archive. Similar linkage between solar activity (maximum/minimum) and precipitation (increase/decrease) is observed throughout the entire LIA. Additionally, the relationship between the hydrological pattern in the Iberian Peninsula and Morocco during the LIA suggests different spatial distribution of precipitation in the south-eastern sector of the North Atlantic region such as it is known currently. Whereas in the instrumental record the precipitation evolves similarly in both regions and opposite to the North Atlantic oscillation (NAO) index, the coldest periods of the LIA shows a contrasting pattern with drier conditions in the South of Spain and wetter in Northern Africa. We suggest an extreme negative NAO conditions, accompanied by a southward excursion of the winter rainfall band beyond that observed in the last century, can explain this contrast. The sustained NAO conditions could have been triggered by solar minima and higher volcanic activity during the LIA.

The role of aromaticity in determining the molecular structure and reactivity of (endohedral metallo)fullerenes

The encapsulation of metal clusters in endohedral metallofullerenes (EMFs) takes place in cages that in most cases are far from being the most stable isomer in the corresponding hollow fullerenes. There exist several possible explanations for the choice of the hosting cages in EMFs, although the final reasons are actually not totally well understood. Moreover, the reactivity and regioselectivity of (endohedral metallo)fullerenes have in the past decade been shown to be generally dependent on a number of factors, such as the size of the fullerene cage, the type of cluster that is being encapsulated, and the number of electrons that are transferred formally from the cluster to the fullerene cage. Different rationalizations of the observed trends had been proposed, based on bond lengths, pyramidalization angles, shape and energies of (un)occupied orbitals, deformation energies of the cages, or separation distances between the pentagon rings. Recently, in our group we proposed that the quest for the maximum aromaticity (maximum aromaticity criterion) determines the most suitable hosting carbon cage for a given metallic cluster (i.e. EMF stabilization), including those cases where the IPR rule is not fulfilled. Moreover, we suggested that local aromaticity plays a determining role in the reactivity of EMFs, which can be used as a criterion for understanding and predicting the regioselectivity of different reactions such as Diels-Alder cycloadditions or Bingel-Hirsch reactions. This review highlights different aspects of the aromaticity of fullerenes and EMFs, starting from how this can be measured and ending by how it can be used to rationalize and predict their molecular structure and reactivity