Study of ruthenium(II) complexes with anticancer drugs as ligands. Design of metal-based phototherapeutic agents

The reaction of trans-[RuCl(2)(PPh(3))(3)] (Ph = C(6)H(5)) with 2-thio-1,3-pyrimidine (HTPYM) and 6-thiopurines (TPs) produced mainly crystalline solids that consist of cis,cis,trans-[Ru(PPh(3))(2)(N,S-TPYM)(2)] (1) and cis,cis,trans-[Ru(PPh(3))(2)(N(7),S-TPs)(2)]X(2) (X = Cl(-), CF(3)SO(3)(-)). In the case of TPs, other coordination isomers have never been isolated and reported. Instead, the mother liquor obtained after filtration of 1 produced red single crystals of trans,cis,cis-[Ru(PPh(3))(2)(N,S-TPYM)(2)].2H(3)O(+).2Cl(-) (2.2H(3)O(+).2Cl(-)). Selected ruthenium(II)-thiobase complexes were studied for their structural, reactivity, spectroscopic, redox, and cytotoxic properties. Single crystals of 1 contain thiopyrimidinato anions chelated to the metal center via N and S. The Ru[bond]N bonds are significantly elongated for 1 [2.122(2) and 2.167(2) A] with respect to 2 [2.063(3) A] because of the trans influence from PPh(3). The coordination pseudo-octahedron for 2 is significantly elongated at the apical sites (PPh(3) ligands). Solutions of cis,cis,trans isomers in air are stable for weeks, whereas those of 2 turn green within 24 h, in agreement with the respective redox potentials. cis,cis,trans- and trans,cis,cis-[Ru(PH(3))(2)(N,S-TPYM)(2)], as optimized through the DFT methods at the Becke3LYP level are in good agreement with experimental geometrical parameters (1 and 2), with cis,cis,trans being more stable than trans,cis,cis by 3.88 kcal. The trend is confirmed by molecular modeling based on semiempirical (ZINDO/1) and molecular mechanics (MM) methods. Cytotoxic activity measurements for cis,cis,trans-[Ru(PPh(3))(N-THZ)(N(7),S -H(2)TP)(2)]Cl(2) (4) (THZ = thiazole, H(2)TP = 6-thiopurine) and cis,cis,trans-[Ru(PPh(3))(2)(N(7),S-HTPR)2]Cl(2) (5) (HTPR = 6-thiopurine riboside) against ovarian cancer cells A2780/S gave IC(50) values of 17 +/- 1 and 29 +/- 9 microM, respectively. Furthermore, the spectral analysis of HTPYM, TPs, and their Ru(II) complexes in solution shows that intense absorptions occur in the UVA/vis region of light, whereas standard nucleobases absorb in the UVB region.     

Au2trien: a dinuclear gold(III) complex with unprecedented structura features

The X-ray structure of a dinuclear gold(III) complex, Au2trien, shows the presence of two square planar gold(III) centers bridged by a nitrogen donor, in a very unusual fashion.     

Volatile fingerprints of artemisinin-rich Artemisia annua cultivars by headspace solid-phase microextraction gas chromatography/ mass spectrometry

The cultivar Anamed (A3) is a hybrid of Artemisia annua with a high content of the secondary metabolite artemisinin, a well-known antimalarial drug. Here we report for the first time the volatile profile of fresh leaves of this hybrid in comparison with that of Artemisia annua L. wild-type species. Evaluation and comparison of the volatile profiles of A. annua genotypes with different content in artemisinin were carried out by headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography/mass spectrometry (GC/MS) that was performed on fresh leaves of the plants under investigation using a polydimethylsiloxane (PDMS) fiber. The chromatograms obtained from hybrids with a high content of artemisinin (A. annua cv. Anamed A3 and A. annua cv. Artemis F2) reveal the total absence of artemisia ketone, one of the major and characteristic compounds of the wild-type A. annua L., along with a significantly lower variety of volatile compounds. In conclusion, HS-SPME coupled with GC/MS is a very useful, non-destructive and efficient method to describe the volatile pattern of Artemisia annua cultivars. It represents a rapid screening method for the evaluation of volatile biomarkers like artemisia ketone, whose absence is typical of artemisinin-rich A. annua cultivars.     

Formation of PAHs and soot platelets: multiconfiguration theoretical study of the key step in the ring closure–radical breeding polyyne‐based mechanism

Polyynes of general formula H? (C?C? )_nH are known to play a significant role in combustion and pyrolysis, possibly being intermediates in the formation of polycyclic aromatic hydrocarbons (PAHs) and soot. They have also been detected in astrophysical investigations. The key step in the polyyne‐based radical breeding mechanism for PAH growth is a cyclization, put forward by Krestinin, which implies disruption of electron couples, plausibly expected to be energy demanding. We explore the electronic features and energy requirements of such a process by quantum mechanical multiconfiguration methods (CASSCF and CASPT2). The features of the wavefunction are analyzed, and the free energy barriers are estimated over a wide range of temperatures, for three molecular models. The initial radical adduct A, generated by H ^. , HC?C ^. (ethynyl), or HC?C? C ^. H₂ ( propargyl ) addition to butadiyne (BD, HC?C? C?CH), undergoes a cyclization with the generation of two new radical centers. However, in most of the cases, one of these new singly occupied sp² orbitals has some overlap with the unpaired electron lobe already existent in A: some sort of bonding builds up and consequently the triradical character cannot be large. Only one model suggests a possible role of the radical breeding mechanism during combustion. Copyright © 2009 John Wiley & Sons, Ltd.     

A rapid method for the quantification of artemisinin in Artemisia annua L. plants cultivated for the first time in Burundi

We describe a simple, rapid combined method for extracting the antimalarial compound artemisinin from the leaves of Artemisia annua L. cultivated for the first time in Burundi, and quantitating the active principle by high-performance liquid chromatography-electrospray mass spectrometry.     

Flavonoids: A Myth or a Reality for Cancer Therapy?

Nutraceuticals are biologically active molecules present in foods; they can have beneficial effects on health, but they are not available in large enough quantities to perform this function. Plant metabolites, such as polyphenols, are widely diffused in the plant kingdom, where they play fundamental roles in plant development and interactions with the environment. Among these, flavonoids are of particular interest as they have significant effects on human health. In vitro and/or in vivo studies described flavonoids as essential nutrients for preventing several diseases. They display broad and promising bioactivities to fight cancer, inflammation, bacterial infections, as well as to reduce the severity of neurodegenerative and cardiovascular diseases or diabetes. Therefore, it is not surprising that interest in flavonoids has sharply increased in recent years. More than 23,000 scientific publications on flavonoids have described the potential anticancer activity of these natural molecules in the last decade. Studies, in vitro and in vivo, show that flavonoids exhibit anticancer properties, and many epidemiological studies confirm that dietary intake of flavonoids leads to a reduced risk of cancer. This review provides a glimpse of the mechanisms of action of flavonoids on cancer cells.     

Structural features of a new dinuclear platinum(II) complex with significant antiproliferative activity

A novel dinuclear platinum(II) complex, [Pt(2)-N,N'-bis(2-dimethylaminoethyl oxamide)Cl(4)], showing peculiar structural features, has been prepared and characterized. X-ray diffraction data reveal that the two platinum ions are simultaneously bound to the N,N'-bis(2-dimethylaminoethyl) oxamide ligand, on opposite sides. The coordination environment of both platinum centers is square planar, with identical NOCl(2) donor sets. The complex is poorly soluble within a physiological buffer but moderately soluble in DMSO. Preliminary in vitro studies point out that this dinuclear platinum complex exhibits significant growth-inhibiting properties on a panel of cultured human tumor cell lines, although less pronounced than those of cisplatin.     

Surface plasmon resonance for detection of genetically modified organisms in the food supply

A review is presented demonstrating that biospecific interaction analysis, using surface plasmon resonance (SPR) and biosensor technologies is a simple, rapid, and automatable approach to detect genetically modified organisms (GMOs). Using SPR, we were able to monitor in real-time the hybridization between oligonucleotide or polymerase chain reaction (PCR)-generated probes and target single-stranded PCR products obtained by using as substrates DNA isolated from normal or transgenic soybean and maize. This procedure allows a one-step, nonradioactive detection of GMOs. PCR-generated probes are far more efficient in detecting GMOs than are oligodeoxyribonucleotide probes. This is expected to be a very important parameter, because information on low percentage of GMOs is of great value. Determination of the ability of SPR-based analysis to quantify GMOs should be considered a major research field for future studies, especially for the analyses of food supplies.     

Border reactivity of polycyclic aromatic hydrocarbons and soot platelets toward ozone. A theoretical study

PAH-based models, with an even or odd number of unsaturated carbon atoms and π electrons (even and odd PAHs for short), are selected to investigate, by molecular and periodic methods, their electron distribution and border reactivity toward ozone, and also to represent local features and edge reactivity of even or odd soot platelets. These results will contrast those previously collected for the internal positions of similar even (J. Phys. Chem. A 2005, 109, 10929.) or odd systems (J. Phys. Chem. A 2008, 112, 973.). Topologically different peripheral positions, representative of armchair and zigzag borders, exhibit different reactivity right from the beginning. Ozone attacks start off either to give primary ozonides by concerted addition or, nonconcertedly, to first produce trioxyl intermediates. Then, a variety of pathways are described, whose viability depends on both model and position. They can open the way to the possible formation of epoxide, aldehyde, and phenol groups (all entailing O(2) production) or ether (+CO(2)), lactone (+H(2)CO), and ketone functionalities. To sum up, functionalization, regardless of how achieved, can give a number of groups, most of which actually observed in PAH ozonization experimental studies. This picture can be matched up to the results on internal sites of our preceding papers, for which epoxidation was the only outcome. Most interestingly, formation of a ketone group may turn an even system into an odd one (and conversely) while involving production of HOO(?).