(E)-2-{[2-(2-Hy­droxy­ethyl­amino)­ethyl­imino]­meth­yl}phenol

The asymmetric unit of the title compound, C11H16N2O2, contains two independent conformational isomers which show intra­molecular aromatic–imine O—H⋯N hydrogen bonds. In the crystal, neighboring mol­ecules are linked through inter­molecular aliphatic–aliphatic O—H⋯N, aliphatic–aromatic N—H⋯O and C—H⋯O inter­actions into hydrogen-bonded layers parallel to the ab plane

(N-{Amino[(diaminomethylidene)amino]methylidene}-N-methylmethanaminium)tribromidozinc(II)

In the title compound, [ZnBr3(C4H12N5)], the ZnII cation is tetrahedrally coordinated by three bromide ions and the (N-{amino[(diaminomethylene)amino]methylene}-N-methylmethanaminium) cation that binds through the central N atom. The complex is of interest as a potential antidiabetic drug of the biguanide family. The crystal structure is stabilized by an extensive series of N—H...Br and C—H...Br hydrogen bonds, which combine to form a three-dimensional structure

An Arabidopsis mutant line lacking the mitochondrial calcium transport regulator MICU shows an altered metabolite profile

Plant metabolism is constantly changing and requires input signals for efficient regulation. The mitochondrial calcium uniporter (MCU) couples organellar and cytoplasmic calcium oscillations leading to oxidative metabolism regulation in a vast array of species. In Arabidopsis thaliana, genetic deletion of AtMICU leads to altered mitochondrial calcium handling and ultrastructure. Here we aimed to further assess the consequences upon genetic deletion of AtMICU. Our results confirm that AtMICU safeguards intracellular calcium transport associated with carbohydrate, amino acid, and phytol metabolism modifications. The implications of such alterations are discussed

Spontaneous Enantiomeric Resolution of 1,3-Diols from the Naphtylidene Derivative of 2,4-Pentanedione

Enantiomers (2S, 4S)- and (2R, 4R)-3-(naphthalene-1-ylmethyl) pentane-2,4-diols were synthesized by the reduction of (Z)-4-hydroxy-3-(naphthalene-1-ylmethyl) pent-3-en-2-one with NaBH4 in methanol (MeOH). Crystallization in dichloromethane of this racemic mixture led to simple crystals with a crystalline habit with similar morphologies; however, in a group of them, it was possible to find a barely observable difference that allowed determining a crystal structure for each of the enantiomers, the 2S,4S, and the 2R,4R

Mechanochemistry: A Green Approach in the Preparation of Pharmaceutical Cocrystals

Mechanochemistry is considered an alternative attractive greener approach to prepare diverse molecular compounds and has become an important synthetic tool in different fields (e.g., physics, chemistry, and material science) since is considered an ecofriendly procedure that can be carried out under solvent free conditions or in the presence of minimal quantities of solvent (catalytic amounts). Being able to substitute, in many cases, classical solution reactions often requiring significant amounts of solvents. These sustainable methods have had an enormous impact on a great variety of chemistry fields, including catalysis, organic synthesis, metal complexes formation, preparation of multicomponent pharmaceutical solid forms, etc. In this sense, we are interested in highlighting the advantages of mechanochemical methods on the obtaining of pharmaceutical cocrystals. Hence, in this review, we describe and discuss the relevance of mechanochemical procedures in the formation of multicomponent solid forms focusing on pharmaceutical cocrystals. Additionally, at the end of this paper, we collect a chronological survey of the most representative scientific papers reporting the mechanochemical synthesis of cocrystals

Relevance of Fluorinated Ligands to the Design of Metallodrugs for Their Potential Use in Cancer Treatment

Fluorination of pharmaceutical agents has afforded crucial modifications to their pharmacological profiles, leading to important advances in medicinal chemistry. On the other hand, metallodrugs are considered to be valuable candidates in the treatment of several diseases, albeit with the caveat that they may exhibit pharmacological disadvantages, such as poor water solubility, low bioavailability and short circulating time. To surmount these limitations, two approaches have been developed: one based on the design of novel metallodrug-delivering carriers and the other based on optimizing the structure of the ligands bound to the metal center. In this context, fluorination of the ligands may bring beneficial changes (physicochemical and biological) that can help to elude the aforementioned drawbacks. Thus, in this review, we discuss the use of fluorinated ligands in the design of metallodrugs that may exhibit potential anticancer activity

Ball-Milling Preparation of the Drug–Drug Solid Form of Pioglitazone-Rosuvastatin at Different Molar Ratios: Characterization and Intrinsic Dissolution Rates Evaluation

Ball-milling using neat grinding (NG) or liquid-assisted grinding (LAG) by varying the polarity of the solvents allowed access to various drug–drug solid forms of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV). Using NG, the coamorphous form was formed from the reaction of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV) in a 2:1 molar ratio. The formation of the expected coamorphous salt could not be corroborated by FT-IR, but DSC data showed that it was indeed a single-phase amorphous mixture. By varying the molar ratios of the reactants, either keeping PGZ·HCl constant and varying RSV or vice versa, another coamorphous form was obtained when a 1:1 molar ratio was employed. In the case of the other outcomes, it was observed that they were a mixture of solid forms coexisting simultaneously with the coamorphous forms (1:1 or 2:1) together with the drug that was in excess. When RSV was in excess, it was in an amorphous form. In the case of PGZ·HCl, it was found in a semicrystalline form. The intrinsic dissolution rates (IDRs) of the solid forms of PGZ·HCl-RSV in stoichiometric ratios (1:1, 2:1, 1:4, 6:1, and 1:10) were evaluated. Interestingly, a synchronized release of both drugs in the dissolution medium was observed. In the case of the release of RSV, there were no improvements in the dissolution profiles, because the acidic media caused the formation of degradation products, limiting any probable modification in the dissolution processes. However, the coamorphous 2:1 form exhibited an improvement of 1.03 times with respect to pure PGZ·HCl. It is proposed that the modification of the dissolution process of the coamorphous 2:1 form was limited by changes in the pH of the media as RSV consumes protons from the media due to degradation processes

p-values of Spearman´s correlation analysis in Fig 1B.

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Correlation analysis of the metabolites and the clinical tests in the severe group.

A. Spearman correlations analysis of metabolites and clinical tests. SpO2 = Oxygen saturation; LDH = Lactate dehydrogenase; Art pH = Arterial pH; PaO2 = Partial pressure of oxygen; PaCO2 = Partial pressure of CO2; Art HCO3 = Arterial bicarbonate; PaFi = PaO2/FiO2; TB = Total bilirubin; DB = Direct bilirubin; IB = Indirect bilirubin; ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; AP = Alkaline phosphatase; Alb = Albumin; INR = International Normalized Ratio; CRP = C reactive protein; CPK = Creatine phosphokinase. Different intensities in blue and red numbers indicate a positive or negative association, respectively (see also the gradient scale at the right side of the figure). B. Proposed model for the main changes identified in our cohort. The graphs were constructed with normalized values. H, healthy controls; M, mild/moderate disease; S, severe disease. ‡Direct involvement of cystine over glutamic acid levels through xCT antiporting system. †Enzymatic involvement over glutamic levels through proline dehydrogenase activity. Statistical differences were calculated employing Kruskal-Wallis and Dunn tests. P*<0.05 **<0.01, ***<0.001, ****<0.0001.</p