Direct tissue analysis of phospholipids in rat brain using MALDI-TOFMS and MALDI-ion mobility-TOFMS

After water, lipids are the most common biomolecules found in the brain (12%). A brief perusal of the physiology, anatomy, and pathophysiology of the brain illustrates the importance of lipids. Recent advances in mass spectrometry have allowed the direct probing of tissues. However, most studies have focused on proteins. In the present work, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and MALDI-ion mobility (IM)-TOFMS were employed for direct analysis of phospholipids in rat brain tissue. Molecular ions (MH⁺) corresponding to phosphatidylcholines, phosphatidylethanolamines, and sphingomyelin, were recorded. When studying pharmacology, we learn that many therapeutic compounds are stored in the body’s adipose tissue. MALDI-TOFMS and MALDI- IM-TOFMS were thus used to analyze rat brain tissue with chlorisondamine added directly onto the tissue slice. With both techniques, noncovalent complexes between the tissue phospholipids and chlorisondamine were detected. In addition, MALDI-IM-TOFMS of noncovalent complexes between phospholipids and chlorisondamine displayed a mobility between that of an isobaric lipid and peptide.     

Antimicrobial Triterpenoids and Ingol Diterpenes from Propolis of Semi-Arid Region of Morocco

The chemical composition and antimicrobial activity of propolis from a semi-arid region of Morocco were investigated. Fifteen compounds, including triterpenoids (1, 2, 7–12), macrocyclic diterpenes of ingol type (3–6) and aromatic derivatives (13–15), were isolated by various chromatographic methods. Their structures were elucidated by a combination of spectroscopic and chiroptical methods. Compounds 1 and 3 are new natural compounds, and 2, 4–6, and 9–11 are newly isolated from propolis. Moreover, the full nuclear magnetic resonance (NMR) assignments of three of the known compounds (2, 4 and 5) were reported for the first time. Most of the compounds tested, especially the diterpenes 3, 4, and 6, exhibited very good activity against different strains of bacteria and fungi. Compound 3 showed the strongest activity with minimum inhibitory concentrations (MICs) in the range of 4–64 µg/mL. The combination of isolated triterpenoids and ingol diterpenes was found to be characteristic for Euphorbia spp., and Euphorbia officinarum subsp. echinus could be suggested as a probable and new plant source of propolis.     

Benzochromenopyrimidines: Synthesis,Antiproliferative Activity against Colorectal Cancer and Physicochemical Properties

Ten new differently substituted 3-benzyl-5-aryl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidin-4,6,11-triones 3 were synthesized by a simple and cost-efficient procedure in a one-pot, three-component reaction from readily available ethyl 2-amino-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene-3-carboxylates, benzylamine and triethyl orthoformate under solvent- and catalyst-free conditions. All the new compounds were screened for their antiproliferative activity against two colorectal-cancer-cell lines. The results showed that the compounds 3-benzyl-5-phenyl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidine-4,6,11-trione (3a) and 3-benzyl-5-(3-hydroxyphenyl)-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidine-4,6,11-trione (3g) exhibited the most potent balanced inhibitory activity against human LoVo and HCT-116 cancer cells.     

Synthesis,characterization, magnetic,thermal and electrochemical studies of oxidovanadium (IV) picolyl hydrazones as functional catechol oxidase models

The picolyl hydrazone ligands derived from picolonic acid hydrazide and α-pyridyle ketone (L¹, L² and L³), α-acetyl thiophene (L⁴), α-formyl or α-acetyl phenol (L⁵ and L⁶ respectively) and 2-hydroxy-1-naphthaldehyde (L⁷) react with equimolecular amount of vanadyl sulfate in refluxing methanol to yield oxidovanadium (IV) complexes. The structure of the obtained ligands and their oxidovanadium (IV) complexes were characterized by various physicochemical techniques, viz. elemental analysis, molar conductance, magnetic susceptibility measurements, thermal analysis (TGA & DTG), IR, electronic absorption and ESR spectral studies. Cyclic voltammeteric behavior of the complexes has also been discussed. Five-coordinate square-pyramidal structure was proposed for all complexes. A monomeric nature was reported for complexes (2), (3), (6), and (7), while dimeric structures were suggested for complexes (1), (4) and (5). The ability of the complexes to catalyze the aerobic oxidation of catechol to the light absorbing o-quinone has been investigated. The results obtained show that all complexes catalyze this oxidation reaction and large variations in the rate were observed. Electrochemical data for most complexes show that there is a linear relationship between their ability to oxidize catechole and their E_1/2 potentials. The most effective catalysts were those complexes which exhibited E_1/2 values approached to the E° value of the natural tyrosinase enzyme isolated from mushroom, while those that largely deviated from that potential exhibited lower oxidase catalytic activity. The probable mechanistic implications of the catalytic oxidation reactions are discussed.     

Hydrolysis of mefenpyrdiethyl: an analytical and DFT investigation

The hydrolysis of the herbicide safener mefenpyrdiethyl (1-(2, 4-dichlorophenyl)-4, 5-dihydro-5-methyl-1H-pyrazole-3,5-dicarboxylic acid diethyl ester) was investigated in aqueous solutions in the pH range from 2 to 9 and the temperature range from 298 to 323 K. The kinetics of hydrolysis were pseudo first order and were found to be strongly pH and temperature dependent. While near-constant in acidic medium, the hydrolysis rates strongly increased in alkaline pH, and total hydrolysis was observed at pH 11. Two main hydrolysis products, mefenpyrethyl (monoester) and mefenpyr (dicarboxylic acid) were isolated by ultrahigh-pressure liquid chromatography (UHPLC) and characterized using high-resolution Fourier transform ion cyclotron resonance mass spectroscopy (ICR-FT/MS) as well as ¹H, ¹³C and 2D NMR analyses. Additionally, a density functional theory (DFT) investigation explained the stability of the pesticide at pH 7 and the high reactivity of the pesticide in alkaline medium. The key nucleophilic reaction partner is hydroxyl ions instead of neutral water molecules. Furthermore, the calculated activation barrier for hydrolysis in alkaline medium is in agreement with the extrapolated and experimentally determined activation barrier at pH 14.     

A Mathematical Programming Based Procedure for Breast Cancer Classification

In this paper we propose a new procedure for classification based on a hybrid approach. The classification problem is solved by minimizing the distance between the components of each clusters and the centers of the clusters. The determination of the cluster centers is therefore a critical step in our approach and was addressed used the k-means algorithm. Once the centers of each class are determined, the rule of center neighbourhood is applied to assign an element to a class using mathematical programming. The implementation of our hybrid approach was validated on benchmark datasets and applied to an original biological dataset on 84 breast cancer tumours. Each tumour was measured for five parameters corresponding to the expression of five biomarkers (proteins). The obtained classification was discussed using biological knowledge and classical clinical experts’ classification of breast tumors.     

Metaheuristic methods based on Tabu search for assigning judges to competitions

Two metaheuristic methods based on Tabu search are introduced to assign judges to individual competitions in a tournament. The complexity of the mathematical formulation accounting for the assignment rules, leads us to use such an approach. The first metaheuristic includes two different Tabu searches that are combined with a diversification strategy. The second metaheuristic is applied to a penalized version of the original model formulated as an assignment problem. This metaheuristic is also based on a Tabu search procedure including a diversification strategy driven by the constraints violated. Numerical results are provided to indicate the efficiency of the methods to generate very good solutions.     

Convenient Synthesis of 11-Aryl-1,12-dihydro-11H-naphthopyrano[2,3-d]pyrimidin-12-ones

Various imidates 3 were successfully synthesized from naphthopyrans and ethyl orthoesters in moderate yields. These intermediates undergo rapid condensation with several primary amines to give the corresponding 11-aryl-1,12-dihydro-11H-naphthopyrano[2,3-d] pyrimidin-12-ones 4.     

Reversible Soft Mechanochemical Control of Biaryl Conformations through Crosslinking in a 3D Macromolecular Network

Tuning the dihedral angle (DA) of axially chiral compounds can impact biological activity, catalyst efficiency, molecular motor performance, or chiroptical properties. Herein, we report gradual, controlled, and reversible changes in molecular conformation of a covalently linked binaphthyl moiety within a 3D polymeric network by application of a macroscopic stretching force. We managed direct observation of DA changes by measuring the circular dichroism signal of an optically pure BINOL-crosslinked elastomer network. Stretching the elastomer resulted in a widening of the DA between naphthyl rings when the BINOL was doubly grafted to the elastomer network; no effect was observed when a single naphthyl ring of the BINOL was grafted to the elastomer network. We have determined that ca. 170 % extension of the elastomers led to the transfer of a mechanical force to the BINOL moiety of 2.5 kcal mol⁻¹ Å⁻¹ (ca. 175 pN) in magnitude and results in the opening of the DA of BINOL up to 130°.