Antiproliferative activity of a new xanthone derivative from leaves of Garcinia nobilis Engl.

A new xanthone, mboudiexanthone (1), together with five known compounds, euxanthone (2), isogarcinol (3), garcinol (4), betulinic acid (5) and zeorin (6) were isolated from the leaves of Garcinia nobilis Engl. The structures were determined by 1D and 2D NMR techniques and X-ray diffraction for 6. The in vitro antiproliferative properties of isolated compounds were evaluated against the human breast cancer cell line MCF-7. All compounds showed an antiproliferative activity with an IC50 value down to ∼11 µM for isogarcinol.

pH Dependence of Photoinduced Electron Transfer with [Ru(TAP)3]2.

The quenching of the excited state of [Ru(TAP)3]2+ (TAP = 1,4,5,8-tetraazaphenanthrene) by guanosine-5'-monophosphate (GMP), N-acetyltyrosine (N-Ac-Tyr), and hydroquinone (H2Q) has been studied in aqueous solution over a wide range of pH values including, for the first time, strongly acidic media. This quenching by electron transfer was examined by steady-state 1H photochemically induced dynamic nuclear polarization (photo-CIDNP) as well as by more conventional techniques, among which are pulsed laser-induced transient absorption and emission experiments. A deeper knowledge of the photochemical behavior of [Ru(TAP)3]2+ has been gained thanks to the combined use of these two approaches, photo-CIDNP and electronic spectroscopies, highlighting their complementarity. In contrast to what was believed, it is found that the protonated excited state of [Ru(TAP)3]2+ may give rise to an electron transfer with N-Ac-Tyr and H2Q. Such a photoinduced electron transfer does not occur with protonated GMP, however. 1H photo-CIDNP experiments are expected to be particularly promising for characterization of the reductive quenching of excited-state ruthenium(II) polypyridyl complexes comprising several nonequivalent protonation sites.

Insights into the structure-activity relationships of chiral 1,2-diaminophenylalkane platinum(II) anticancer derivatives.

The structure-activity relationships of chiral 1,2-diaminophenylalkane platinum(II) anticancer derivatives are studied, including interactions with telomeric- and genomic-like DNA sequences, the pKa of their diaqua species, structural properties obtained from DFT calculations and resonant X-ray emission spectroscopy. The binding modes of the compounds to telomeric sequences were elucidated, showing no major differences with conventional cis-platinum(II) complexes like cisplatin, supporting that the cis-square planar geometry governs the binding of small Pt(II) complexes to G4 structures. Double-stranded DNA platination kinetics and acid-base constants of the diaqua species of the compounds were measured and compared, highlighting a strong steric dependence of the DNA-binding kinetics, but independent to stereoisomerism. Structural features of the compounds are discussed on the basis of dispersion-corrected DFT, showing that the most active series presents conformers for which the platinum atom is well devoid of steric hindrance. If reactivity indices derived from conceptual DFT do not show evidences for different reactivity between the compounds, RXES experiments provide new insight into the availability of platinum orbitals for binding to nucleophiles.

Effect of magnetic field and iron content on NMR proton relaxation of liver, spleen and brain tissues.

Iron accumulation is observed in liver and spleen during hemochromatosis and important neurodegenerative diseases involve iron overload in brain. Storage of iron is ensured by ferritin, which contains a magnetic core. It causes a darkening on T2 -weighted MR images. This work aims at improving the understanding of the NMR relaxation of iron-loaded human tissues, which is necessary to develop protocols of iron content measurements by MRI. Relaxation times measurements on brain, liver and spleen samples were realized at different magnetic fields. Iron content was determined by atomic emission spectroscopy. For all samples, the longitudinal relaxation rate (1/T1 ) of tissue protons decreases with the magnetic field up to 1 T, independently of iron content, while their transverse relaxation rate (1/T2 ) strongly increases with the field, either linearly or quadratically, or a combination thereof. The extent of the inter-echo time dependence of 1/T2 also varies according to the sample. A combination of theoretical models is necessary to describe the relaxation of iron-containing tissues. This can be due to the presence, inside tissues, of ferritin clusters of different sizes and densities. When considering all samples, a correlation (r(2) = 0.6) between 1/T1 and iron concentration is observed at 7.0 T. In contrast the correlation between 1/T2 and iron content is poor, even at high field (r(2) = 0.14 at 7.0 T). Our results show that MRI methods based on T1 or T2 measurements will easily detect an iron overloading at high magnetic field, but will not provide an accurate quantification of tissue iron content at low iron concentrations.

Tailored functionalization of polyphenol-based molecular platforms.

General and efficient methods for selective modification of macrocyclic oligomers are rare, mostly because restricting a reaction to a defined number of identical functional groups is difficult to achieve. This work describes a unique, general, and rational methodology for the iteroselective functionalization of polyphenolic platforms by N-tert-butylaminocarbonyl (Bac) groups. The methodology consists of reacting the oligomeric platform with t-BuNCO and an inorganic base in an apolar solvent. This very simple one-step procedure has been applied to various calix[4, 5, 6, and 8]arenes, and in all cases, calixarenes with a single leftover phenolic moiety were isolated in high yields (>90%). Interestingly, this so-called "all-but-one" methodology gives a straightforward access to calixarenes displaying inherent chirality. It is also shown that the Bac group can be used as a protective group. Thus, the all-but-one methodology has been used for the efficient monofunctionalization of a key precursor platform, illustrating its huge potential for the tailored synthesis of sophisticated macrocyclic oligomers.

A Ru(II)-TAP complex, photoreagent for tryptophan-containing peptides: structure of the covalent photoadduct.

We report the first structure determination of a covalent photoadduct between a Ru(II)-tap complex and a tryptophan-containing peptide (AlaTrpAla) by mass spectrometry and NMR spectroscopy. Ru(II)-tap complexes could thus be exploited as photodamaging agents of Trp-containing polypeptides or proteins.

Variable-field relaxometry of iron-containing human tissues: a preliminary study.

Excess iron is found in brain nuclei from neurodegenerative patients (with Parkinson's, Alzheimer's and Huntington's diseases) and also in the liver and spleen of cirrhosis, hemochromatosis and thalassaemia patients. Ferritin, the iron-storing protein of mammals, is known to darken T(2)-weighted MR images. Understanding NMR tissue behavior may make it possible to detect those diseases, to follow their evolution and finally to establish a protocol for non-invasive measurement of an organ's iron content using MRI methods. In this preliminary work, the MR relaxation properties of embalmed iron-containing tissues were studied as well as their potential correlation with the iron content of these tissues. Relaxometric measurements (T(1) and T(2)) of embalmed samples of brain nuclei (caudate nucleus, dentate nucleus, globus pallidus, putamen, red nucleus and substantia nigra), liver and spleen from six donors were made at different magnetic fields (0.00023-14 T). The influence of the inter-echo time on transverse relaxation was also studied. Moreover, iron content of tissues was determined by inductively coupled plasma atomic emission spectroscopy. In brain nuclei, 1/T(2) increases quadratically with the field and depends on the inter-echo time in CPMG sequences at high fields, both features compatible with an outer sphere relaxation theory. In liver and spleen, 1/T(2) increases linearly with the field and depends on the inter-echo time at all fields. In our study, a correlation between 1/T(2) and iron concentration is observed. Explaining the relaxation mechanism for these tissues is likely to require a combination of several models. The value of 1/T(2) at high field could be used to evaluate iron accumulation in vivo. In the future, confirmation of those features is expected to be achieved from measurements of fresh (not embalmed) human tissues.

Novel method for the measurement of xenon gas solubility using 129Xe NMR spectroscopy.

A novel method is presented for determining xenon partitioning between a gas phase and a liquid phase. An experimental setup which permits the simultaneous measurement of the 129Xe chemical shift in both the gas and the liquid phases, that is, under the same experimental conditions, has been designed. Xenon solubility is obtained via 129Xe chemical shift measurements in the gas phase. The method was validated against xenon solubility data from the literature; in general, the agreement is found to be within 3%. The solubility of xenon in three solvents for which data have not been previously reported (acetone, acetonitrile, and 1,1,2,2-tetrachloroethane) was determined using this novel method. 129Xe chemical shifts for dissolved xenon are also reported; it is found that xenon-xenon interactions may play a significant role in the liquid phase even at low equilibrium xenon pressures.

A sugar ester and an iridoid glycoside from Scrophularia ningpoensis.

From cytotoxic extracts of the roots of Scrophularia ningpoensis Hemsl. (Scrophulariaceae) a new sugar ester, ningposide D (3-O-acetyl-2-O-p-methoxycinnamoyl-alpha(beta)-L-rhamnopyranose) (1) and a new iridoid glycoside, scrophuloside B4 (6-O-(2''-O-acetyl-3''-O-cinnamoyl-4''-O-p-methoxycinnamoyl-alpha-L-rhamnopyranosyl) catalpol) (2) along with known compounds: oleanonic acid (3), ursolonic acid (4), cinnamic acid (5), 3-hydroxy-4-methoxy benzoic acid (6), 5-(hydroxymethyl)-2-furfural (7) and beta-sitosterol (8) were isolated. The structures of the new compounds were elucidated by spectral data (1, 2D NMR, EI, HRESI-MS and MS/MS). Oleanonic acid (3) and ursolonic acid (4) were found to be cytotoxic against a series of human cancer cell lines with IC50=4.6, 15.5 microM on MCF7; 4.2, 14.5 microM on K562; 14.8, 44.4 microM on Bowes; 24.9, 43.6 microM on T24S; 61.3, 151.5 microM on A549, respectively. Beta-sitosterol (8) inhibited Bowes cells growth at IC50=36.5 microM. Scrophuloside B4 (2) showed activity on K562 and Bowes cells at IC50=44.6, 90.2 microM, respectively.