Marina Cindrić

Novel thiosemicarbazone derivatives as potential antitumor agents: Synthesis, physicochemical and structural properties, DNA interactions and antiproliferative activity

The paper describes synthesis of several novel thiosemicarbazone derivatives. Furthermore, crystal and molecular structure of 4-diethylamino-salicylaldehyde 4-phenylthiosemicarbazone revealed planarity of conjugated aromatic system, which suggested the possibility of DNA binding by intercalation, especially for here studied naphthalene derivatives. However, here presented DNA binding studies excluded this mode of action. Physicochemical and structural properties of novel derivatives were compared with previously studied analogues, taken as reference compounds, revealing distinctive differences. In addition, novel thiosemicarbazone derivatives (1, 2 and 5-8) clearly display stronger antiproliferative activity on five tumor cell lines than the reference compounds 3 and 4, which supports their further investigation as potential antitumor agents.

Redox Control of Microglial Function: Molecular Mechanisms and Functional Significance

Neurodegenerative diseases are characterized by chronic microglial over-activation and oxidative stress. It is now beginning to be recognized that reactive oxygen species (ROS) produced by either microglia or the surrounding environment not only impact neurons but also modulate microglial activity. In this review, we first analyze the hallmarks of pro-inflammatory and anti-inflammatory phenotypes of microglia and their regulation by ROS. Then, we consider the production of reactive oxygen and nitrogen species by NADPH oxidases and nitric oxide synthases and the new findings that also indicate an essential role of glutathione (γ-glutamyl-l-cysteinylglycine) in redox homeostasis of microglia. The effect of oxidant modification of macromolecules on signaling is analyzed at the level of oxidized lipid by-products and sulfhydryl modification of microglial proteins. Redox signaling has a profound impact on two transcription factors that modulate microglial fate, nuclear factor kappa-light-chain-enhancer of activated B cells, and nuclear factor (erythroid-derived 2)-like 2, master regulators of the pro-inflammatory and antioxidant responses of microglia, respectively. The relevance of these proteins in the modulation of microglial activity and the interplay between them will be evaluated. Finally, the relevance of ROS in altering blood brain barrier permeability is discussed. Recent examples of the importance of these findings in the onset or progression of neurodegenerative diseases are also discussed. This review should provide a profound insight into the role of redox homeostasis in microglial activity and help in the identification of new promising targets to control neuroinflammation through redox control of the brain.

Anion‐Directed Self‐Assembly of Flexible Ligands into Anion‐Specific and Highly Symmetrical Organic Solids

Template-induced association of molecular species represents one of the main approaches in the control of supramolecular assembling. This strategy can be used in the design of porous materials of importance for inclusion (host–guest) chemistry and coordination polymers, in which the tunable size and nature of pores is a great advantage over their inorganic analogues. Most numerous in this class of compounds are the MOFs (metal–organic frameworks) and, to a minor extent, COFs (covalent organic frameworks). Porous organic architectures, in which the tectons are linked through noncovalent interactions, are very rare and still represent an undeveloped area of research. Both neutral and cationic templates have been known for a long time and are widely used in different fields of synthetic chemistry. However, anionic templates are rarely used in supramolecular chemistry because of the properties of anions, such as low charge to radius ratio, various geometries, high solvation energies, and pH-dependent charge. Templatedirected processes that are anion specific can lead us to the always challenging development of new selective systems with industrial, ecological, and biomedical applications. Systems that show great oxoanion selectivity are of special interest in the area of nuclear and toxic waste management. Herein we report a solid-state study of two supramolecular complexes assembled by an anion-templated reaction of a flexible ligand L (Scheme 1) and anions with trigonal planar (NO3 , 1; Figure 1), and tetrahedral geometry (SO4 2 ; 2) in methanol. The anion organizes folding of three podands to achieve hydrogen bond saturation, resulting in formation of a pseudomacrocyclic host PMH (Figure 2). The PMH assembly is highly anion specific, and the occurrence of the above-mentioned complexes in systems with high concentrations of competing anions has been explored. Expansion of 1 and 2 through hydrogen bonds leads to a highly symmetrical organic solid with voids and channels habited by counterions and more than 300 disordered solvent molecules per unit cell

A Series of Molybdenum(VI) Complexes with Tridentate Schiff Base Ligands

Mononuclear and polynuclear dioxomolybdenum(VI) complexes with Schiff base ligands have been prepared by the reaction of [MoO2(acac)2] with salicylaldehyde (1 and 4), 2-hydroxy-1-naphthaldehyde (2 and 5) and 2-hydroxy-3-methoxybenzaldehyde (3 and 6) with addition of appropriate amine. All prepared complexes of the general formulae [MoO2LD] and [MoO2L]n consist of cis-MoO22+ core coordinated by Schiff-base ligand (L) in a tridentate manner through two deprotonated hydroxyl groups and one imino nitrogen. The usual octahedral coordination around molybdenum atom is completed by monodentate solvent molecules D (methanol, ethanol or dimethylsulphoxide). All compounds were characterized by means of chemical analysis, IR spectroscopy, thermogravimetric analysis and some of them by X-ray crystallography (1a, 2c, 3a, 4c and 6c). Eine Reihe von Molybdan(VI)-Komplexen mit dreizahnigen Schiff-Basen-Liganden Ein- und vielkernige Dioxomolybdan(VI)-Komplexe mit Schiff-Basen-Liganden wurden durch Reaktion von [MoO2(acac)2] mit Salicylaldehyd (1 und 4), 2-Hydroxy-1-naphthaldehyd (2 und 5) und 2-Hydroxy-3-methoxybenzaldehyd (3 und 6) durch Zugabe von Amin hergestellt. Alle Komplexe der allgemeinen Formeln [MoO2LD] und [MoO2L]n enthalten die cis-MoO22+-Einheit, die durch die Schiff-Basen-Liganden dreifach durch zwei deprotonierte Hydroxyl-Gruppen und durch ein Imino-Stickstoffatom koordiniert ist. Die ubliche oktaedrische Koordination am Molybdanatom wird durch einzahnige Solvens-Molekule D (Methanol, Ethanol oder Dimethylsulfoxid) erganzt. Alle Verbindungen werden durch Elementaranalysen, IR-Spektren, thermogravimetrische Analysen und einige von ihnen durch Kristallstrukturanalysen (1a, 2c, 3a, 4c und 6c) charakterisiert.

Synthesis and structure of K2[HMo6VIVVO22(NH3CH2COO)3]·8H2O: a new example of a polyoxomolybdovanadate coordinated by a glycinato ligand

Abstract A new complex of formula K2[HMo6VIVVO22(NH3CH2COO)3]·8H2O has been prepared from molybdenum(VI) oxide and vanadium(V) oxide in aqueous solution by adding glycine and potassium chloride, and its structure determined by X-ray structure analysis. The molybdovanadate anion is built up of six MoO6 edge-sharing octahedra connected into a ring centered by a VO4 tetrahedron. The MoO6 octahedra are in pairs linked by the bridging glycine-carboxylato ligands.

Synthesis, structure and properties of molybdenum(VI) oxalate complexes of the types M2[Mo2O5(C2O4)2(H2O)2] and M2[MoO3(C2O4)] (M=Na, K, Rb, Cs)

The reaction of molybdenum(VI) oxide with oxalic acid or alkali oxalate and alkali halides results in the formation of two series of molybdenum(VI) oxalate complexes: one of the general formula M-2[Mo2O5(C2O4)(2)(H2O)(2)] containing the Mo2O5 core and the other of the formula M-2[MoO3(C2O4)] with a MoO3 core (M = Na, K, Rb, Cs). Both series were characterized by chemical analysis, ESR, UV and IR spectroscopy, thermogravimetry, differential scanning calorimetry, X-ray powder method and some of them by single-crystal X-ray structure analysis. Complexes of the first series adopt dimeric structures, the second series infinite polymeric structures. In both types of structures molybdenum ions are six-coordinated being surrounded by terminal ore-oxygens, bridging oxygens and bidentate bonded oxalate ligands. When exposed to UV light all these complexes in the solid state exhibit photochromic behavior changing color from colorless to green-brown. These changes are remarkably more pronounced in the complexes with dimeric structures. There is definite correlation between their coloration and the UV induced ESR signal indicative for molybdenum(V). Such behavior is explained by the partial reduction of Mo(VI) to Mo(V) only at the crystal surfaces. This is also the explanation why K-2[Mo2O5(C2O4)(2)(H2O)(2)] was so far described as being red or pale reddish tan. All attempts to prepare the corresponding lithium complexes were unsuccessful. They are most probably very unstable because of the small radius of the lithium ion

Supramolecular stabilization of metastable tautomers in solution and the solid state.

This work presents a successful application of a recently reported supramolecular strategy for stabilization of metastable tautomers in cocrystals to monocomponent, non-heterocyclic, tautomeric solids. Quantum-chemical computations and solution studies show that the investigated Schiff base molecule, derived from 3-methoxysalicylaldehyde and 2-amino-3-hydroxypyridine (ap), is far more stable as the enol tautomer. In the solid state, however, in all three obtained polymorphic forms it exists solely as the keto tautomer, in each case stabilized by an unexpected hydrogen-bonding pattern. Computations have shown that hydrogen bonding of the investigated Schiff base with suitable molecules shifts the tautomeric equilibrium to the less stable keto form. The extremes to which supramolecular stabilization can lead are demonstrated by the two polymorphs of molecular complexes of the Schiff base with ap. The molecules of both constituents of molecular complexes are present as metastable tautomers (keto anion and protonated pyridine, respectively), which stabilize each other through a very strong hydrogen bond. All the obtained solid forms proved stable in various solid-state and solvent-mediated methods used to establish their relative thermodynamic stabilities and possible interconversion conditions.

Mechanosensitive metal–ligand bonds in the design of new coordination compounds

This article describes the selective cleavage of coordination bonds by mechanochemical methods and the further application of the thus obtained precursors for a facile preparation of new coordination compounds. In the class of dioxomolybdenum(VI) coordination compounds, [MoO2L(ROH)], where L stands for a tridentate dianionic ONO ligand and ROH represents different alcohol molecules, mechanical treatment induces an exclusive cleavage of the molybdenum–alcohol bond, which can thus be considered as a mechanosensitive bond. Alcohol removal can also be accomplished by heating. Both grinding and heating resulted in highly reactive, coordinatively unsaturated compounds, an orange amorphous pentacoordinated [MoO2L] (I) and the brown polymeric [MoO2L]n ((I)nnn), respectively. Even though both I and (I)nn are stable at room temperature, they can be interconverted using only solvent-free techniques, a conversion followed by a colour change of the sample. The tendency of such unsaturated complexes to complete their coordination spheres was exploited for the efficient solution and solvent-free syntheses of octahedral molybdenum complexes with selected O- and N-donating ligands. Both approaches herein used, solution and solvent-free, have proved to be superior under specific conditions and their respective advantages and weaknesses are discussed.

Vanadium-induced formation of thiadiazole and thiazoline compounds. Mononuclear and dinuclear oxovanadium(V) complexes with open-chain and cyclized thiosemicarbazone ligands

Reactions of the salicylaldehyde 4-phenylthiosemicarbazone (H(2)L) with selected vanadium(iv) and vanadium(v) precursors ([VO(acac)(2)], [VO(OAc)(2)], VOSO(4), [V(2)O(4)(acac)(2)]) were investigated under aerobic conditions in different alcohols (methanol, ethanol, propanol). In all examined cases mononuclear alkoxo vanadium(v) complexes [VOL(OR)] (1) (OR = OMe, OEt, OPr) were isolated as major products. On prolonged standing, mother liquids afforded dinuclear vanadium(v) complexes [V(2)O(3)(L(cycl))(2)(OR)(2)] (3) (OR = OMe, OEt, OPr), where L(cycl)(-) represents 1,3,4-thiadiazole ligand, formed by vanadium-induced oxidative cyclization of H(2)L. When [VO(acac)(2)] or [V(2)O(4)(acac)(2)] were used as precursors, in addition to products 1 and 3, a thiazoline derivative HL(acac)(cycl) (2) was isolated. This compound, formed by a reaction between acetylacetone and H(2)L, represented the second type of cyclic product. The products were characterized by IR and NMR spectroscopies, TG analysis, and in some cases by single-crystal X-ray diffraction. To the best of our knowledge, compounds [V(2)O(3)(L(cycl))(2)(OR)(2)] represent the first structurally characterized dinuclear vanadium(v) complexes with a thiadiazole moiety acting as a bridging ligand. Complexes 1 and 3, when dissolved in an appropriate alcohol, underwent substitution of the alkoxo ligand as confirmed by XRPD. The kinetics of reactions in methanolic solutions was qualitatively studied by UV-Vis and ESMS spectrometries. Under the experimental conditions applied, a relatively slow formation of the mononuclear complex [VOL(OMe)] and an even slower formation of the cyclic species 2 were observed, whereas the presence of dinuclear compound [V(2)O(3)(L(cycl))(2)(OMe)(2)] in the reaction mixture could not be detected.

New Dinuclear Molybdenum(V) Complexes With β′‐Hydroxy‐β‐enaminones Containing a 4‐Hydroxy‐2‐pyrone Ring

New dinuclear molybdenum(V) complexes of the general formula [Mo2O4L2D2], were prepared by the reaction of [Mo2O3(acac)4] (acac = acetylacetonate ion) with β′-hydroxy-β-enaminones (L). All prepared complexes consist of Mo2O42+ cores coordinated by two ligands L via two donor oxygen atoms as in the analogous β-diketonates. The usual octahedral coordination around the molybdenum atoms is completed by the monodentate solvent molecules D (methanol, ethanol, or 2-propanol). All compounds were characterized by elemental analyses, IR, one- and two-dimensional NMR spectra, and thermal analysis, and some of them by X-ray crystallography (1a, 4a, 8b, and 9a). (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)