Stoichiometric Complex Research Articles

Binuclear isophthaloylbis(N,N-diphenylthioureate) transition metal complexes: Synthesis, spectroscopic, thermal and structural characterization

The isophthaloylbis(N,N-diphenylthiourea) molecule (H2L ligand) reacts with CuI, CuII, MnIII, FeII, FeIII and CoII ions to form binuclear complexes with formula [M2(L-O,S)2] (M = CuII (1), NiII (2)) or [M2(L-O,S)3] (M = FeIII (4), CoIII (5)). In presence of dimethyl sulfoxide, [Mn2(L-O,S)2(dmso)2] (3) was successfully obtained and represents the first manganese complex with any thiourea derivative ligand. The ligand and the complexes were characterized by spectroscopic techniques and elemental analysis. Complexes 1, 3, 4 and 5 were structurally analyzed by single crystal X-ray diffraction data, confirming the O,S chelating coordination mode. The stoichiometries were confirmed by thermal analysis with formation of the corresponding metal oxides. The set of the performed analysis corroborated that some metal ions undergo oxidation or reduction to form stable 2:2 or 2:3 metal to ligand stoichiometric complexes with H2L.

C-H Functionalization via Iron-Catalyzed Carbene-Transfer Reactions.

The direct C-H functionalization reaction is one of the most efficient strategies by which to introduce new functional groups into small organic molecules. Over time, iron complexes have emerged as versatile catalysts for carbine-transfer reactions with diazoalkanes under mild and sustainable reaction conditions. In this review, we discuss the advances that have been made using iron catalysts to perform C-H functionalization reactions with diazoalkanes. We give an overview of early examples employing stoichiometric iron carbene complexes and continue with recent advances in the C-H functionalization of C(sp2)-H and C(sp3)-H bonds, concluding with the latest developments in enzymatic C-H functionalization reactions using iron-heme-containing enzymes.

A deep insight into mechanism for inclusion of 2R,3R-dihydromyricetin with cyclodextrins and the effect of complexation on antioxidant and lipid-lowering activities

2R,3R-Dihydromyricetin (DMY) is a natural flavonoid that has versatile biological activities. However, due to its poor water solubility and low chemical stability, its applications in food and pharmaceutical fields remain limited. Inclusion of DMY with cyclodextrins (CDs) has been shown to improve the solubility and stability of DMY, whereas the mechanism for the inclusion has not been elucidated. This study investigated the characteristic and mechanism for inclusion of DMY with CDs, and evaluated the effects of complexation on antioxidant and lipid-lowering activities of DMY. Phase solubility studies revealed that the solubility of DMY was significantly improved in the presence of natural (α-, β-, γ-) CDs and their derivatives, namely hydroxypropyl-β-cyclodextrin (HP-β-CD) and (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), by forming 1:1 stoichiometric inclusion complexes. Particularly, the complexes of DMY with HP-β-CD and DM-β-CD were prepared and characterized by FT-IR, PXRD, DSC, SEM and NMR analysis. Furthermore, the possible inclusion configuration was verified by molecular docking, which indicated that B-ring of DMY was fully embedded in the cavity of CDs while C-ring and A-ring were partly included, through non-covalent interaction such as hydrogen bonding. The results also showed that inclusion of DMY with HP-β-CD or DM-β-CD enhanced the radical scavenging capacity of DMY and maintained its lipid-lowering effect in hyperlipidemia zebrafish model.

The mitochondrial HSP90 paralog TRAP1 forms an OXPHOS-regulated tetramer and is involved in mitochondrial metabolic homeostasis

BackgroundThe molecular chaperone TRAP1, the mitochondrial isoform of cytosolic HSP90, remains poorly understood with respect to its pivotal role in the regulation of mitochondrial metabolism. Most studies have found it to be an inhibitor of mitochondrial oxidative phosphorylation (OXPHOS) and an inducer of the Warburg phenotype of cancer cells. However, others have reported the opposite, and there is no consensus on the relevant TRAP1 interactors. This calls for a more comprehensive analysis of the TRAP1 interactome and of how TRAP1 and mitochondrial metabolism mutually affect each other.ResultsWe show that the disruption of the gene for TRAP1 in a panel of cell lines dysregulates OXPHOS by a metabolic rewiring that induces the anaplerotic utilization of glutamine metabolism to replenish TCA cycle intermediates. Restoration of wild-type levels of OXPHOS requires full-length TRAP1. Whereas the TRAP1 ATPase activity is dispensable for this function, it modulates the interactions of TRAP1 with various mitochondrial proteins. Quantitatively by far, the major interactors of TRAP1 are the mitochondrial chaperones mtHSP70 and HSP60. However, we find that the most stable stoichiometric TRAP1 complex is a TRAP1 tetramer, whose levels change in response to both a decline and an increase in OXPHOS.ConclusionsOur work provides a roadmap for further investigations of how TRAP1 and its interactors such as the ATP synthase regulate cellular energy metabolism. Our results highlight that TRAP1 function in metabolism and cancer cannot be understood without a focus on TRAP1 tetramers as potentially the most relevant functional entity.

A 4,5-quinolimide-based fluorescent sensor for sequential detection of Cu2+ and cysteine in water and living cells with application in a memorized device.

In this study, a new 4,5-quinolimide-based fluorescent sensor BNC was synthesized and characterized. BNC showed single selectivity for Cu2+via the "turn-off" fluorescence among various common metal ions. After forming a 1:1 stoichiometric complex with Cu2+, the detection limit (LOD) of BNC for Cu2+ was measured to be 0.44μM. Subsequently, the in situ generated BNC-Cu2+ complex had been used for sensing Cys with the LOD of 1.5μM through the displacement strategy, resulting in the revivable emission of BNC. According to the "off-on-off" fluorescence cycle of BNC generated by the alternate addition of Cu2+ and Cys, a reversible memorized device with "read-write-read-erase" behavior was constructed at the molecular level. Furthermore, the recoveries of Cu2+ in lake water with BNC were in the range of 95.0-105%. And sequential fluorescence imagings of BNC for Cu2+ and Cys were successfully applied in living yeast cells.

Physicochemical Properties of Acylglutamic Acid-Alkylamine Complexes in Aqueous Media.

We studied the physicochemical properties of 1:1 stoichiometric complexes of acylglutamic acids (CnGlu) with tertiary alkylamines (CnDMA) in water at their low and high concentrations. Static surface tensiometry suggested that the critical micelle concentration (cmc) decreased with increasing hydrophobic chain length of the complexes. In addition, CnGlu-CnDMA yielded lower cmc than the C12Glu single system. In the region of high concentrations, several phase states including isotropic liquid (L1) phase, hexagonal liquid crystal (H1) phase, bicontinuous cubic liquid crystal (V1) phase, and lamellar liquid crystal (Lα) phase were observed. Assemblies with lesser positive curvature tend to be formed with increasing complex concentration, increasing temperature, and increasing hydrophobic chain length. Additionally, the complex formation resulted in the molecular assemblies with lesser positive curvature.

Effect of Transition-Metal Ions on the Conformation of Encephalin Investigated by Hydrogen/Deuterium Exchange and Theoretical Calculations.

We have studied the effects of different 3d orbitals in divalent transition-metal ions [G2+ = Mn2+ (d5), Fe2+ (d6), Co2+ (d7), Ni2+ (d8), Cu2+ (d9), or Zn2+ (d10)] on the conformations of leucine encephalin (LE) and methionine encephalin (ME) in the gas phase using hydrogen/deuterium exchange mass spectrometry (HDX-MS) and theoretical calculations at the molecular level. The HDX-MS reveals a 1:1 stoichiometric monovalent complex of [LE/ME + G - H]+ and observed that the different HDX reactivities follow the trend Fe2+ < Co2+ < Ni2+ < Mn2+ < Cu2+ ≈ Zn2+ and that [ME + Mn/Cu/Zn - H]+ > [LE + Mn/Cu/Zn - H]+, while [LE + Fe/Co/Ni - H]+ > [ME + Fe/Co/Ni - H]+. We cross-correlated the collision-induced dissociation energies of the complexes with the HDX results and found that the more stable the complex, the harder it is for it to undergo HDX. Furthermore, we used theoretical calculations to optimize the favorable conformations of the complexes and found the same interaction structure of G2+ coordination with the five carbonyl oxygens of LE/ME that have different bond lengths. Finally, we calculated the proton affinity (PA) values of the optimized complexes in order to interpret the HDX observations that the higher the PA values, the more difficult it is for the complex to undergo HDX. Overall, both the experiments and the theoretical calculations show that the six metal ions have different effects on the LE/ME conformation, with the low-energy stability of the G2+ 3d orbitals corresponding to more dramatic effects on the LE/ME conformation. In addition, the hardness of the ionic acid corresponding to the fully filled Mn2+ and half-filled Zn2+ orbitals also contributes strongly to the coordination effect; the conformation effect of Fe2+/Co2+/Ni2+ on LE is greater than that on ME, whereas the conformation effect of Mn2+/Cu2+/Zn2+ on ME is greater than that on LE.

Conductance studies on complex formation of nano Cu(NO3)2.2.5H2O with 4,6-diacetylresorcinol in mixed solvents

The different complexation thermodynamic parameters for example, formation constants (Kf), free energies of formation (∆Gf), enthalpies of formation (∆Hf) and entropies of formation (∆Sf) for nano copper nitrate hemi pentahydrate (Cu(NO3)2.2.5H2O) with 4,6-diacetylresorcinol as a ligand in pure DMF and in mixed solvents of DMF and water are calculated at different temperatures, 293.15, 303.15, 313.15 and 323.15 K by using conductance measurements. By drawing the relation between molar conductance and ratio of metal to ligand, the figures indicate the formation of two types of complexes with M:L ratios 1:2 and 1:1 stoichiometric complexes.

Exploring the Structure and Stability of Cholesterol Dimer Formation in Multicomponent Lipid Bilayers

For 40 years, the existence and possible functional importance of cholesterol dimer formation has been discussed. Due to challenges associated with structural studies of membrane lipids, there has as yet been no direct experimental verification of the existence and relevance of the cholesterol dimer. Building on recent advances in lipid force fields for molecular simulation, in this work the structure and stability of the cholesterol dimer is characterized in POPC bilayers in absence and presence of sphingomyelin. The cholesterol dimer structural ensemble is found to consist of sub-states that reflect, but also differ from, previously proposed dimer structures. While face-to-face dimer structures predominate, no evidence is found for the existence of tail-to-tail dimers in POPC lipid bilayers. Near stoichiometric complex formation of cholesterol with sphingomyelin is found to effect cholesterol dimer structure without impacting population. Comparison with NMR-derived order parameters provide validation for the simulation model employed and conclusions drawn related to the structure and stability of cholesterol dimers in multicomponent lipid bilayers. © 2016 Wiley Periodicals, Inc.

Protonthérapie des carcinomes épidermoïdes des voies aérodigestives supérieures : de la physique à la clinique

Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.

Medium Controlled Stoichiometric Complexation of Penicillin G—Potassium Drug with Se(IV), Nb(V), Ta(V), and Te(IV) Chlorides: Physicochemical and Antitumor Activity of the Complexes

Medium Controlled Stoichiometric Complexation of Penicillin G—Potassium Drug with Se(IV), Nb(V), Ta(V), and Te(IV) Chlorides: Physicochemical and Antitumor Activity of the Complexes

A New Spiropyran-Based Sensor for Colorimetric and Fluorescent Detection of Divalent Cu2+ and Hg2+ Ions and Trivalent Ce3+, Cr3+ and Al3+ Ions.

A new spiropyran derivative acts as colorimetric and fluorescent sensor for metal ions. Addition of Cu2+, Al3+, Cr3+ and Ce3+ to the sensor solution brings about marked increase in the absorption intensities while addition of other metal ions (Na+, K+, Li+, Sr2+, Hg2+, Zn2+, Co2+, Ni2+ and Ag+) fails to cause substantial change in the UV-Vis spectra. The sensor can be used for detection of Hg2+, Cu2+, Ce3+, Cr3+ and Al3+ ions by the naked eye and by fluorescence enhancement. The detection limit of Cu2+ and Hg2+ ions by the sensor is estimated to be 10 and 14μM, respectively. Job's plot analysis on the sensor-Cu2+ complexation reveals the formation of a 2:1 stoichiometric complex between the sensor and Cu2+ ion.

Structure and electrophysical properties of carbogels based on the interpolyelectrolyte complex lignosulfonate - chitosan with various composition

Abstract The new approach to the synthesis of highly porous polyfunctional nanomaterials with “fullerene-like” morphology was shown. Obtained materials have developed micro- (mainly supermicropores) and mesoporous structure, narrow particle size distribution (particle size of 35–60 nm), low content of minor elements (metal and sulfur), having electrically conductive properties. The supramolecular systems (interpolyelectrolyte complex) formed by the self-assembly and molecular recognition of two biopolymers with various structural organizations were used as a precursor. The interpolyelectrolyte complex was prepared by mixing of the dendritic-like polyelectrolyte lignosulfonate and the linear polysaccharide chitosan with different molar ratios. The idea of this research consists in the sequential combination of interpolymer complexation, supercritical fluid treatment and high-temperature carbonization. New carbon materials contain up to 91.5% of carbon and nitrogen content is up to 6.9%. Organic sulfur is removed from the samples as volatile compounds during carbonation. Metal ions (K+, Na+, Li+) and nitrogen compounds embedded in the structure of aerogels at the stage of complex formation change the structure. It leads to improve the porous structure and allows to obtain the carbogels with the high total pore volume (up to 0.51 cm3 g−1), average pore width (up to 4.6 nm) and specific surface area up to 465 m2 g−1. The maximum specific surface area of the carbogels is formed in the slow pyrolysis mode at the temperature of 600 °C for carbogels based on interpolyelectrolyte complex lignosulfonate-chitosan with Z = 1.4. The size of the cation in the composition of lignosulfonate does not affect the size distribution of micropores (supermicropores) of the carbogel, however, the presence of an alkali metal cation in the structure leads to an increase in the volume of micropores, the total pore volume and the average pore width. It was shown that new carbon nanomaterials have a specific electrical conductivity of the order of 10−4 S m−1 and possess electrically conductive properties. Electrophysical properties of carbogels directly depend on their molar composition. The specific electrical conductivity of carbogels based on interpolyelectrolyte complex with an excess of chitosan (Z = 1.4) in the composition is in five times higher than for the carbogels based on stoichiometric interpolyelectrolyte complex (Z = 1). Carbon nanomaterials are promising for practical use as electrically conductive dispersed particles in small-sized nanoelectronics devices.

The solid-state synchronous vs. conventional fluorescence spectroscopy and complementary methods to study the interactions of aluminum metal-organic framework Basolite A100 with dimethyl sulfoxide

Abstract We report, for the first time, an experimental study of interaction of metal-organic framework (MOF) with dimethyl sulfoxide (DMSO). Adsorption of DMSO on aluminum MOF Basolite A100 results in formation of the stoichiometric complex [A100]2[DMSO]3. The solid-state synchronous fluorescence spectroscopy allows observation of the following major excitation/emission transitions in Basolite A100 and its adsorption complex [A100]2[DMSO]3 which are not well-resolved in “conventional” fluorescence spectra: 1) narrow resonance of the isolated BDC linker, 2) excitation across optical bandgap, and 3) excimers. In the adsorption complex [A100]2[DMSO]3, the DMSO molecules interact with the μ2-OH group of Basolite A100 and with its BDC linker through the π-π system. We present, for the first time, the new variety of the solid-state synchronous fluorescence spectroscopy, which we denote as the solid-state enhanced-resolution synchronous fluorescence (excitation) spectroscopy. The accurate measurements of small changes in the optical bandgap of the adsorption complex [A100]2[DMSO]3 and Basolite A100 are described by the solid-state enhanced-resolution synchronous fluorescence (excitation) spectroscopy.

KRAS Prenylation Is Required for Bivalent Binding with Calmodulin in a Nucleotide-Independent Manner

Deregulation of KRAS4b signaling pathway has been implicated in 30% of all cancers. Membrane localization of KRAS4b is an essential step for the initiation of the downstream signaling cascades that guide various cellular mechanisms. KRAS4b plasma membrane (PM) binding is mediated by the insertion of a prenylated moiety that is attached to the terminal carboxy-methylated cysteine, in addition to electrostatic interactions of its positively charged hypervariable region with anionic lipids. Calmodulin (CaM) has been suggested to selectively bind KRAS4b to act as a negative regulator of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway by displacing KRAS4b from the membrane. However, the mechanism by which CaM can recognize and displace KRAS4b from the membrane is not well understood. In this study, we employed biophysical and structural techniques to characterize this mechanism in detail. We show that KRAS4b prenylation is required for binding to CaM and that the hydrophobic pockets of CaM can accommodate the prenylated region of KRAS4b, which might represent a novel CaM-binding motif. Remarkably, prenylated KRAS4b forms a 2:1 stoichiometric complex with CaM in a nucleotide-independent manner. The interaction between prenylated KRAS4b and CaM is enthalpically driven, and electrostatic interactions also contribute to the formation of the complex. The prenylated KRAS4b terminal KSKTKC-farnesylation and carboxy-methylation is sufficient for binding and defines the minimal CaM-binding motif. This is the same region implicated in membrane and phosphodiesterase6-δ binding. Finally, we provide a structure-based docking model by which CaM binds to prenylated KRAS4b. Our data provide new insights into the KRAS4b-CaM interaction and suggest a possible mechanism whereby CaM can regulate KRAS4b membrane localization.

Anion Recognition in Water by Charge-Neutral Halogen and Chalcogen Bonding Foldamer Receptors.

A novel strategy for the recognition of anions in water using charge-neutral σ-hole halogen and chalcogen bonding acyclic hosts is demonstrated for the first time. Exploiting the intrinsic hydrophobicity of halogen and chalcogen bond donor atoms integrated into a foldamer structural molecular framework containing hydrophilic functionalities, a series of water-soluble receptors was constructed for an anion recognition investigation. Isothermal titration calorimetry (ITC) binding studies with a range of anions revealed the receptors to display very strong and selective binding of large, weakly hydrated anions such as I- and ReO4-. This is achieved through the formation of 2:1 host-guest stoichiometric complex assemblies, resulting in an encapsulated anion stabilized by cooperative, multidentate, convergent σ-hole donors, as shown by molecular dynamics simulations carried out in water. Importantly, the combination of multiple σ-hole-anion interactions and hydrophobic collapse results in I- affinities in water that exceed all known σ-hole receptors, including cationic systems (β2 up to 1.68 × 1011 M-2). Furthermore, the anion binding affinities and selectivity trends of the first example of an all-chalcogen bonding anion receptor in pure water are compared with halogen bonding and hydrogen bonding receptor analogues. These results further advance and establish halogen and chalcogen bond donor functions as new tools for overcoming the challenging goal of anion recognition in pure water.

Radiation-induced synthesis of copper nanostructures in the films of interpolymer complexes

The composites with localization of copper nanoparticles on the surface of interpolymer films were prepared by X-ray irradiation of poly(1-vinyl-1,2,4-triazole) – poly(acrylic acid) – Cu2+ complexes. The kinetics of radiation-chemical reduction of ions Cu2+ in films of stoichiometric and nonstoichiometric complexes of poly(1-vinyl-1,2,4-triazole) – poly(acrylic acid) (PVT – PAA) was studied by EPR. The use of transmission electron microscopy with micro-diffraction mode showed that the preparation of metal nanoparticles occurs through the intermediate formation of copper protoxide. The efficiency of nanoparticle formation is determined by the ratio PVT/PAA in interpolymer films. The contrast of X-ray absorption by water-alcohol medium and interpolymer complexes with copper ions provides the favorable conditions for the formation of metal nanostructures in the near-surface layer of the films.

Oligopeptide-CB[8] complexation with switchable binding pathways.

Host-guest complexes exhibiting a 1 : 1 binding stoichiometry need not consist of a single host and guest. A series of oligopeptides, which were previously reported to have abnormally high binding enthalpies were investigated to deduce whether they exist as a 2 : 2 quaternary or a 1 : 1 binary complex with cucurbit[8]uril (CB[8]). Through a systematic study of the sequence-specific binding pathways of peptide-CB[8] association, a phenylalanine-leucine dipeptide was found to be capable of switching from a 1 : 1 stoichiometric complex to a 2 : 1 complex. By studying the differences in size-based diffusion properties of these two binding modes, the presence of a 1 : 1 pairwise inclusion complex was verified for the regime where CB[8] is in excess. Findings in this study can be utilised to 'customise' the precise CB[8]-oligopeptide self-assembly pathway, acting as a useful toolbox in the design of supramolecular systems.

Physicochemical properties of catechin/β-cyclodextrin inclusion complex obtained via co-precipitation

ABSTRACTInclusion complex of catechin (CAT) with β-cyclodextrin (β-CD) was prepared using co-precipitation method to enhance antioxidant stability of CAT and the physicochemical properties of the inclusion complex were studied. The CAT/β-CD inclusion complex was analyzed through phase solubility study, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Phase solubility study indicated that CAT and β-CD formed 1:1 stoichiometric inclusion complex. Results of FT-IR indicated that CAT was stabilized in β-CD cavity by intra-molecular hydrogen bonds. Results of DSC and SEM proved that CAT/β-CD inclusion complex formed. XRD results showed that the formation of new solid crystalline phases in the CAT/β-CD inclusion complex. CAT was effectively protected through encapsulation into β-CD and the antioxidant stability of CAT was improved after encapsulation. In addition, the release behavior of CAT from the inclusion complex increased with increasing of the temperature.

Designing a Formulation of the Nootropic Drug Aniracetam Using 2-Hydroxypropyl-β-Cyclodextrin Suitable for Parenteral Administration.

The nootropic drug aniracetam is greatly limited in its application by low aqueous solubility and a poor oral bioavailability. The primary aim of this study was to design a parenteral formulation of aniracetam that can be administered intravenously. Complexation of aniracetam with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated as a strategy to enhance solubility. A phase solubility analysis was performed to quantify the extent of improvement. An 819% increase in the solubility of aniracetam was obtained, reaching 36.44 mg/mL. This marked increase enables aniracetam to exist in an aqueous solvent at levels sufficient for parenteral dosing. A stability test was then devised using a design of experiment approach. The aniracetam-HP-β-CD formulation was subjected to different relative humidity and temperature and cyclodextrin concentrations over a 12-week period. Key changes in FTIR vibrational frequencies suggest the benzene moiety of aniracetam was introduced into the hydrophobic cavity of HP-β-CD. These results are highly supportive of the formation of a predictable 1:1 molar stoichiometric inclusion complex, explaining the improvement seen in physiochemical properties of aniracetam following formulation with HP-β-CD. This novel formulation of aniracetam suitable for parenteral administration will have utility in future studies to further elucidate the pharmacokinetics of this drug.