Nanoproteomic Approach for Isolation and Identification of Potential Biomarkers in Human Urine from Adults with Normal Weight,Overweight and Obesity

In this work, previously synthesized and characterized core-shell silica nanoparticles (FCSNP) functionalized with immobilized molecular bait, Cibacron blue, and a porous polymeric bis-acrylamide shell were incubated with pooled urine samples from adult women or men with normal weight, overweight or obesity for the isolation of potential biomarkers. A total of 30 individuals (15 woman and 15 men) were included. FCSNP allowed the capture of a variety of low molecular weight (LMW) proteins as evidenced by mass spectrometry (MS) and the exclusion of high molecular weight (HMW) proteins (>34 kDa) as demonstrated by SDS-PAGE and 2D SDS-PAGE. A total of 36 proteins were successfully identified by MS and homology database searching against the Homo sapiens subset of the Swiss-Prot database. Identified proteins were grouped into different clusters according to their abundance patterns. Four proteins were found only in women and five only in men, whereas 27 proteins were in urine from both genders with different abundance patterns. Based on these results, this new approach represents an alternative tool for isolation and identification of urinary biomarkers.     

An Adjustable Cleft Based on an 8-Sulfonamide-2-Naphthoic Acid with Oxyanion Hole Geometry

Cleft type receptors showing the oxyanion hole motif have been prepared in a straightforward synthesis starting from the commercial 3,7-dihidroxy-2-naphthoic acid. The double H-bond donor pattern is achieved by the introduction of a sulfonamide group in the C-8 position of naphthalene and a carboxamide at the C-2 position. This cleft, for which the geometry resembles that of an oxyanion hole, is able to adjust to different guests, as shown by the analysis of the X-ray crystal structures of associates with methanol or acetic acid. Combination of hydrogen bonds and charge-transfer interactions led to further stabilization of the complexes, in which the electron-rich aromatic ring of the receptor was close in space to the electron-deficient dinitroaromatic guests. Modelling studies and bidimensional NMR experiments have been carried out to provide additional information.     

Gold(I)-Catalyzed Intermolecular Formal [4+2] Cycloaddition of O-Aryl Ynol Ethers and Enol Ethers: Synthesis of Chromene Derivatives

Gold(I)-catalyzed formal [4+2] cycloaddition of O-aryl ynol ethers 1 and enol ethers 2 is described. This intermolecular reaction between two electron-rich unsaturated systems takes place, under mild conditions, in the presence of 5 mol% [IPrAu(CH₃CN)]SbF₆ as catalyst giving chromene derivatives with good yields. The cycloaddition is completely regio- and stereoselective, as well as versatile for both reactives. Silyl enol ethers can also react in the same way and under the same reaction conditions with quantitative yields. A plausible mechanism through a selective addition of the enol ether to the alkyne gold activated complex followed by an intramolecular aromatic electrophilic substitution is proposed. Several experimental results support the presence of a cationic oxonium intermediate prior to the aromatic substitution. The reaction represents a new entry to the chromene core.     

Chromatography-Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur

The development of a new three-component chromatography-free reaction of isocyanides, amines and elemental sulfur allowed us the straightforward synthesis of thioureas in water. Considering a large pool of organic and inorganic bases, we first optimized the preparation of aqueous polysulfide solution from elemental sulfur. Using polysulfide solution, we were able to omit the otherwise mandatory chromatography, and to isolate the crystalline products directly from the reaction mixture by a simple filtration, retaining the sulfur in the solution phase. A wide range of thioureas synthesized in this way confirmed the reasonable substrate and functional group tolerance of our protocol.     

Probing the Catalytically Active Species in POM-Catalysed DNA-Model Hydrolysis**

Phosphoester hydrolysis is an important chemical step in DNA repair. One archetypal molecular model of phosphoesters is para-nitrophenylphosphate (pNPP). It has been shown previously that the presence of molecular metal oxide [Mo₇O₂₄]⁶⁻ may catalyse the hydrolysis of pNPP through the partial decomposition of polyoxomolybdate framework resulting in a [(PO₄)₂Mo₅O₁₅]⁶⁻ product. Real-time monitoring of the catalytic system using electrospray ionisation mass spectrometry (ESI-MS) provided a glance into the species present in the reaction mixture and identification of potential catalytic candidates. Following up on the obtained spectrometric data, Density Functional Theory (DFT) calculations were carried out to characterise the hypothetical intermediate [Mo₅O₁₅(pNPP)₂(H₂O)₆]⁶⁻ that would be required to form under the hypothesised transformation. Surprisingly, our results point to the dimeric [Mo₂O₈]⁴⁻ anion resulting from the decomposition of [Mo₇O₂₄]⁶⁻ as the active catalytic species involved in the hydrolysis of pNPP rather than the originally assumed {Mo₅O₁₅} species. A similar study was carried out involving the same species but substituting Mo by W. The mechanism involving W species showed a higher barrier and less stable products in agreement with the non-catalytic effect found in experimental results.     

The Effect of Auxiliary Nitrogenated Linkers on the Design of New Cadmium-Based Coordination Polymers as Sensors for the Detection of Explosive Materials

Three new cadmium-based coordination polymers, denoted [Cd(hfipbb)(4,4’-bipy)] ( CdPF-1 ), [Cd(hfipbb)(2,2’-bipy)] ( CdPF-2 ), and [Cd(hfipbb)(1,10-phen)] ( CdPF-3 ), have been hydrothermally synthesized by using the well-known V-shaped organic linker 4,4’-(hexafluoroisopropylidene)bis(benzoic acid) (H₂hfipbb), together with different nitrogenated auxiliary linkers. Considering the d¹⁰ configuration of the transition metal selected, the luminescent properties for these CdPF-n materials were explored, finding that materials CdPF-2 and CdPF-3 act as excellent sensors in the detection of explosive nitro aromatic compounds. The photoluminescence properties of CdPF-2 and CdPF-3 revealed that significant and sensitive fluorescence quenching was observed toward NP (nitrophenol) for CdPF-2 and PA (picric acid) for CdPF-3 in MeOH suspensions.     

Comprehensive Characterization of the Self-Folding Cavitand Dynamics

The conformational equilibria and guest exchange process of a resorcin[4]arene derived self-folding cavitand receptor have been characterized in detail by molecular dynamics simulations (MD) and ¹H EXSY NMR experiments. A multi-timescale strategy for exploring the fluxional behaviour of this system has been constructed, exploiting conventional MD and accelerated MD (aMD) techniques. The use of aMD allows the reconstruction of the folding/unfolding process of the receptor by sampling high-energy barrier processes unattainable by conventional MD simulations. We obtained MD trajectories sampling events occurring at different timescales from ns to s: 1) rearrangement of the directional hydrogen bond seam stabilizing the receptor, 2) folding/unfolding of the structure transiting partially open intermediates, and 3) guest departure from different folding stages. Most remarkably, reweighing of the biased aMD simulations provided kinetic barriers that are in very good agreement with those determined experimentally by ¹H NMR. These results constitute the first comprehensive characterization of the complex dynamic features of cavitand receptors. Our approach emerges as a valuable rational design tool for synthetic host-guest systems     

Maschke Type Theorems for Nonassociative Hopf Algebras

In this article, we give necessary and sufficient conditions for a possibly nonassociative comodule algebra over a nonassociative Hopf algebra to have a total integral, thus extending the classical theory developed by Doi in the associative setting. Also, from this result we deduce a version of Maschke's Theorems and the consequent characterization of projectives for (H, B)-Hopf triples associated with a nonassociative Hopf algebra H and a nonassociative right H-comodule algebra B.