João Figueira

Dissolved organic carbon quality and sorption of organic pollutants in the Baltic Sea in light of future climate change.

Regional climate change scenarios predict increased temperature and precipitation in the northern Baltic Sea, leading to a greater runoff of fresh water and terrestrial dissolved organic carbon (DOC) within the second part of the 21st century. As a result, the current north to south gradient in temperature and salinity is likely to be shifted further toward the south. To examine if such climate change effects would cause alterations in the environmental fate of organic pollutants, spatial variations of DOC quality and sorption behavior toward organic contaminants were examined using multiple analytical methods. The results showed declining contents of aromatic functional groups in DOC along a north to south gradient. Similarly, the sorption of a diverse set of organic contaminants to DOC also showed spatial differences. The sorption behavior of these contaminants was modeled using poly parameter linear energy relationships. The resulting molecular descriptors indicated clear differences in the sorption properties of DOC sampled in northern and southern parts of the Baltic Sea, which imply that more organic contaminants are sorbed to DOC in the northern part. The extent of this sorption process determines whether individual contaminants will partition to biota via direct uptake or through sorption to DOC, which serves as food source for bacteria-based food-webs.

Poly(alkylidenamines) dendrimers as scaffolds for the preparation of low-generation ruthenium based metallodendrimers

The aim of this article is to highlight the use of nitrile-functionalized poly(alkylidenamines) dendrimers as building blocks for the preparation of low-generation ruthenium based cationic metallodendrimers having in view potential biomedical applications. Air-stable poly(alkylidenamines) nitrile dendrimers, peripherally functionalized with the ruthenium moieties [Ru(η5-C5H5)(PPh3)2]+ or [RuCl(dppe)2]+, have been prepared, characterized and are being studied for their anticancer activity. The followed strategy is based on the biological advantages associated with low-generation dendrimers, the known activity of ruthenium compounds as anticancer drugs and the stability of these dendrimers at the physiological temperature.

NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls

Saliva is a biofluid that is sensitive to metabolic changes and is straightforward to collect in a non-invasive manner, but it is seldom used for metabolite analysis when studying neurodegenerative disorders. We present a procedure for both an untargeted and targeted analysis of the saliva metabolome in which nuclear magnetic resonance (NMR) spectroscopy is used in combination with multivariate data analysis. The applicability of this approach is demonstrated on saliva samples selected from the 25 year prospective Betula study, including samples from dementia subjects with either Alzheimers disease (AD) or vascular dementia at the time of sampling or who developed it by the next sampling/assessment occasion five years later, and age-, gender-, and education-matched control individuals without dementia. Statistically significant multivariate models were obtained that separated patients with dementia from controls and revealed seven discriminatory metabolites. Dementia patients showed significantly increased concentrations of acetic acid (fold change (fc) = 1.25, p = 2 × 10(-5)), histamine (fc = 1.26, p = 0.019), and propionate (fc = 1.35, p = 0.002), while significantly decreased levels were observed for dimethyl sulfone (fc = 0.81, p = 0.005), glycerol (fc = 0.79, p = 0.04), taurine (fc = 0.70, p = 0.007), and succinate (fc = 0.62, p = 0.008). Histamine, succinate, and taurine are known to be important in AD, and acetic acid and glycerol are involved in related pathways. Dimethyl sulfone and propionate originate from the diet and bacterial flora and might reflect poorer periodontal status in the dementia patients. For these seven metabolites, a weak but statistically significant pre-diagnostic value was observed. Taken together, we present a robust and general NMR analysis approach for studying the saliva metabolome that has potential use for screening and early detection of dementia.

Metabolite quantification by NMR and LC-MS/MS reveals differences between unstimulated, stimulated, and pure parotid saliva

&NA; Saliva is a readily available biofluid that is sensitive to metabolic changes and can be collected through rapid and non‐invasive collection procedures, and it shows great promise for clinical metabolomic studies. This work studied the metabolite composition of, and the differences between, saliva samples collected by unstimulated spitting/drooling, paraffin chewing‐stimulated spitting, and parotid gland suction using targeted nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled to tandem mass spectrometry (LC‐MS/MS) for metabolite quantification. As applied here, these two analytical techniques provide complementary metabolite information and together extend the metabolome coverage with robust NMR quantification of soluble metabolites and sensitive targeted LC‐MS/MS analysis of bioactive lipids in specific metabolic pathways. The NMR analysis was performed on ultrafiltrated (3 kDa cutoff) saliva samples and resulted in a total of 45 quantified metabolites. The LC‐MS/MS analysis was performed on both filtered and unfiltered samples and resulted in the quantification of two endocannabinoids (AEA and PEA) and 22 oxylipins, which at present is the most comprehensive targeted analysis of bioactive lipids in human saliva. Important differences in the metabolite composition were observed between the three saliva sample collection methods, which should be taken into consideration when designing metabolomic studies of saliva. Furthermore, the combined use of the two metabolomics platforms (NMR and LC‐MS/MS) proved to be viable for research and clinical studies of the salivary metabolome. Graphical abstract Figure. No caption available. HighlightsUnstimulated, stimulated and parotid saliva were analyzed by NMR and LC‐MS/MS.NMR quantified up to 45 metabolites.LC‐MS/MS quantified 24 bioactive lipids, at present the largest panel in saliva.Clear differences in the metabolite composition between saliva types were observed.The outcome will affect future study design of metabolomics in clinical research.

Three 2,5-dialkoxy-1,4-diethynylbenzene derivatives.

2,5-Diethoxy-1,4-bis[(trimethylsilyl)ethynyl]benzene, C(20)H(30)O(2)Si(2), (I), constitutes one of the first structurally characterized examples of a family of compounds, viz. the 2,5-dialkoxy-1,4-bis[(trimethylsilyl)ethynyl]benzene derivatives, used in the preparation of oligo(phenyleneethynylene)s via Pd/Cu-catalysed cross-coupling. 2,5-Diethoxy-1,4-diethynylbenzene, C(14)H(14)O(2), (II), results from protodesilylation of (I). 1,4-Diethynyl-2,5-bis(heptyloxy)benzene, C(24)H(34)O(2), (III), is a long alkyloxy chain analogue of (II). The molecules of compounds (I)-(III) are located on sites with crystallographic inversion symmetry. The large substituents either in the alkynyl group or in the benzene ring have a marked effect on the packing and intermolecular interactions of adjacent molecules. All the compounds exhibit weak intermolecular interactions that are only slightly shorter than the sum of the van der Waals radii of the interacting atoms. Compound (I) displays C-H...pi interactions between the methylene H atoms and the acetylenic C atom. Compound (II) shows pi-pi interactions between the acetylenic C atoms, complemented by C-H...pi interactions between the methyl H atoms and the acetylenic C atoms. Unlike (I) or (II), compound (III) has weak nonclassical hydrogen-bond-type interactions between the acetylenic H atoms and the ether O atoms.

Poly(alkylidenimine) Dendrimers Functionalized with the Organometallic Moiety [Ru(η5-C5H5)(PPh3)2]+ as Promising Drugs Against Cisplatin-Resistant Cancer Cells and Human Mesenchymal Stem Cells

Here and for the first time, we show that the organometallic compound [Ru(η5-C5H5)(PPh3)2Cl] (RuCp) has potential to be used as a metallodrug in anticancer therapy, and further present a new approach for the cellular delivery of the [Ru(η5-C5H5)(PPh3)2]+ fragment via coordination on the periphery of low-generation poly(alkylidenimine) dendrimers through nitrile terminal groups. Importantly, both the RuCp and the dendrimers functionalized with [Ru(η5-C5H5)(PPh3)2]+ fragments present remarkable toxicity towards a wide set of cancer cells (Caco-2, MCF-7, CAL-72, and A2780 cells), including cisplatin-resistant human ovarian carcinoma cell lines (A2780cisR cells). Also, RuCp and the prepared metallodendrimers are active against human mesenchymal stem cells (hMSCs), which are often found in the tumor microenvironment where they seem to play a role in tumor progression and drug resistance.

4,4′-[Thio­phene-2,5-diylbis(ethyne-2,1-di­yl)]dibenzonitrile

In the solid state, the title compound, C22H10N2S, forms centrosymmetric dimers by pairs of non-classical C—H⋯S hydrogen bonds linking approximately coplanar molecules. The benzene ring involved in this interaction makes a dihedral angle of only 7.21 (16)° with the thiophene ring, while the other benzene ring is twisted somewhat out of the plane, with a dihedral angle of 39.58 (9)°. The hydrogen-bonded dimers stack on top of each other with an interplanar spacing of 3.44 Å. C—H⋯N hydrogen bonds link together stacks that run in approximately perpendicular directions. Each molecule thus interacts with 12 adjacent molecules, five of them approaching closer than the sum of the van der Waals radii for the relevant atoms. Optimization of the inter-stack contacts contributes to the non-planarity of the molecule.