Bis[trans-dichloridobis(propane-1,3-diamine-κ2 N,N′)chromium(III)] tetra­chloridozincate determined using synchrotron radiation

In the title compound, [CrCl2(C3H10N2)2]2[ZnCl4], the CrIII atom is coordinated by four N atoms of propane-1,3-diamine (tn) and two Cl atoms in a trans arrangement, displaying a distorted octa­hedral geometry with crystallographic inversion symmetry; the Zn atom in the [ZnCl4]2− anion lies on a -4 axis. The orientations of the two six-membered chelate rings in the complex cation are in an anti chair–chair conformation with respect to each other. The Cr—N bond lengths are 2.087 (6) and 2.097 (6) Å. The Cr—Cl and Zn—Cl bond lengths are 2.3151 (16) and 2.3255 (13) Å, respectively. Weak inter­molecular hydrogen bonds involving the tn NH2 groups as donors and chloride ligands of the anion and cation as acceptors are observed

Metal-organic frameworks constructed from flexible ditopic ligands: Conformational diversity of an aliphatic ligand

The solvothermal reaction of adipic acid as a flexible ditopic ligand and the metal ions MnII, CoII, and TbIII afforded three novel metal-organic frameworks (MOFs), {[Mn2(adipate) 2(DMA)]} (1), {[Co2(adipate)2(DMF)] ??1DMF??1.5H2O} (2), and {[Tb3(adipate) 4.5(DMF)2]} (3) (DMA = N,N-dimethylacetamide; DMF = N,N-dimethylformamide), respectively, which were structurally characterized by single-crystal X-ray diffraction. Depending on the kind of metal ion and solvent system, the conformations and coordination modes of the adipate ligands were diverse and governed the entire MOF structure. Compound 1 consists of the secondary building units (SBUs) of Mn-O chains that were linked by adipate ligands extending in two-dimensional sheets, which were infinitely stacked in a layer-by-layer manner. Compound 2 presented a three-dimensional MOF constructed from Co-O chains and bridging adipate ligands extending in four different directions. Compound 3 also had a three-dimensional structure which was formed by Tb-O chains connected with adipate ligands in six directions. From these structures, ten different adipate ligands with diverse conformations were found, and the potential energy of each conformation was calculated by the first-principles density function. In addition, the luminescence properties of the Tb-based MOF 3 were investigated in the solid state at room temperature.close0

A microporous metal-organic framework constructed from a 1D column made of linear trinuclear manganese secondary building units

A metal-organic framework (MOF) was prepared based on a 1D column made of a linear trinuclear manganese cluster as a secondary building unit (SBU), where the SBU is connected to two adjacent SBUs by carboxylates to form a 1D column and the column is further connected to four adjacent 1D columns via the SBUs to form a microporous MOF of pcu network topology.close7

Entropically driven self-assembly of a strained hexanuclear indium metal-organic macrocycle and its behavior in solution

The self-assembly of a polyprotic pentadentate ligand, N-cyclopentanoylaminobenzoylhydrazide (H4L4), and an In(III) nitrate hydrate in methanol led to a strained hexanuclear indium metal-organic macrocycle (In-MOM), [In(III)(6)(H2L4)(6)(NO3)(x)(solvent)(6-x)](NO3)(6-x) (where, the solvent is either methanol or a water molecule and x is the number of the nitrate anions ligated). The ligand in the doubly deprotonated state serves as an unsymmetric linear ditopic donor and the alternating indium ions in two different chelation modes serve as two different bent ditopic metal acceptors, which led to a D-3-symmetric hexanuclear In-MOM. Although the hexanuclear In-MOM is enthalpically unfavorable because of the ring strain, the combination of the soft coordination characteristic of the indium ion and the slight ligand deformation from the conjugated planar conformation allows the formation of the entropically favored hexanuclear In-MOM rather than the enthalpically favored octanuclear In-MOM. While the hexanuclear In-MOM is stable in acetonitrile, it partially dissociates into its components in dimethylsulfoxide, and then slowly reaches a new equilibrium state with several different indium species yet to be identified in addition to the free ligand.close4

Characterization of the membrane proteome and N-glycoproteome in BV-2 mouse microglia by liquid chromatography-tandem mass spectrometry

Background : Microglial cells are resident macrophages of the central nervous system and important cellular mediators of the immune response and neuroinflammatory processes. In particular, microglial activation and communication between microglia, astrocytes, and neurons are hallmarks of the pathogenesis of several neurodegenerative diseases. Membrane proteins and their N-linked glycosylation mediate this microglial activation and regulate many biological process including signal transduction, cell-cell communication, and the immune response. Although membrane proteins and N-glycosylation represent a valuable source of drug target and biomarker discovery, the knowledge of their expressed proteome in microglia is very limited. Results : To generate a large-scale repository, we constructed a membrane proteome and N-glycoproteome from BV-2 mouse microglia using a novel integrated approach, comprising of crude membrane fractionation, multienzyme-digestion FASP, N-glyco-FASP, and various mass spectrometry. We identified 6928 proteins including 2850 membrane proteins and 1450 distinct N-glycosylation sites on 760 N-glycoproteins, of which 556 were considered novel N-glycosylation sites. Especially, a total of 114 CD antigens are identified via MS-based analysis in normal conditions of microglia for the first time. Our bioinformatics analysis provides a rich proteomic resource for examining microglial function in, for example, cell-to-cell communication and immune responses. Conclusions : Herein, we introduce a novel integrated proteomic approach for improved identification of membrane protein and N-glycosylation sites. To our knowledge, this workflow helped us to obtain the first and the largest membrane proteomic and N-glycoproteomic datesets for mouse microglia. Collectively, our proteomics and bioinformatics analysis significantly expands the knowledge of the membrane proteome and N-glycoproteome expressed in microglia within the brain and constitutes a foundation for ongoing proteomic studies and drug development for various neurological diseases.This work was supported by the Proteogenomic Research Program through the National Research Foundation of Korea and a National Research Foundation of Korea [NRF] grant (No. 2011–0030740), funded by the Korea government [MSIP]. This work was also supported by the Industrial Strategic Technology Development Program (#10045352), funded by the Ministry of Knowledge Economy (MKE, Korea).Peer Reviewe

Identification of TUBB2A by quantitative proteomic analysis as a novel biomarker for the prediction of distant metastatic breast cancer

Background Metastasis of breast cancer to distal organs is fatal. However, few studies have identified biomarkers that are associated with distant metastatic breast cancer. Furthermore, the inability of current biomarkers, such as HER2, ER, and PR, to differentiate between distant and nondistant metastatic breast cancers accurately has necessitated the development of novel biomarker candidates. Methods An integrated proteomics approach that combined filter-aided sample preparation, tandem mass tag labeling (TMT), high pH fractionation, and high-resolution MS was applied to acquire in-depth proteomic data from FFPE distant metastatic breast cancer tissues. A bioinformatics analysis was performed with regard to gene ontology and signaling pathways using differentially expressed proteins (DEPs) to examine the molecular characteristics of distant metastatic breast cancer. In addition, real-time polymerase chain reaction (RT-PCR) and invasion/migration assays were performed to validate the differential regulation and function of our protein targets. Results A total of 9441 and 8746 proteins were identified from the pooled and individual sample sets, respectively. Based on our criteria, TUBB2A was selected as a novel biomarker candidate. The metastatic activities of TUBB2A were subsequently validated. In our bioinformatics analysis using DEPs, we characterized the overall molecular features of distant metastasis and measured differences in the molecular functions of distant metastatic breast cancer between breast cancer subtypes. Conclusions Our report is the first study to examine the distant metastatic breast cancer proteome using FFPE tissues. The depth of our dataset allowed us to discover a novel biomarker candidate and a proteomic characteristics of distant metastatic breast cancer. Distinct molecular features of various breast cancer subtypes were also established. Our proteomic data constitute a valuable resource for research on distant metastatic breast cancer.This work was supported by the Industrial Strategic Technology Development Program (#10079271 and #20000134), funded by the Ministry of Trade, Industry, and Energy (MOTIE, Korea); the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI17C0048); the Basic Science Research Program through the Seoul National University Hospital Research Fund (26-2016-0020); and the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (Grant Number: 2018R1A1A1A05077484)

Taurodeoxycholate Increases the Number of Myeloid-Derived Suppressor Cells That Ameliorate Sepsis in Mice

Bile acids (BAs) control metabolism and inflammation by interacting with several receptors. Here, we report that intravenous infusion of taurodeoxycholate (TDCA) decreases serum pro-inflammatory cytokines, normalizes hypotension, protects against renal injury, and prolongs mouse survival during sepsis. TDCA increases the number of granulocytic myeloid-derived suppressor cells (MDSCLT) distinctive from MDSCs obtained without TDCA treatment (MDSCL) in the spleen of septic mice. FACS-sorted MDSCLT cells suppress T-cell proliferation and confer protection against sepsis when adoptively transferred better than MDSCL. Proteogenomic analysis indicated that TDCA controls chromatin silencing, alternative splicing, and translation of the immune proteome of MDSCLT, which increases the expression of anti-inflammatory molecules such as oncostatin, lactoferrin and CD244. TDCA also decreases the expression of pro-inflammatory molecules such as neutrophil elastase. These findings suggest that TDCA globally edits the proteome to increase the number of MDSCLT cells and affect their immune-regulatory functions to resolve systemic inflammation during sepsis

Crystal structure of [2,13-bis(acetamido)-5,16-dimethyl-2,6,13,17-tetraazatricyclo[16.4.0.07,12]docosane-κ4N]silver(II) dinitrate from synchrotron X-ray data

The asymmetric unit of the title compound, [Ag(C24H46N6O2)](NO3)2 [C24H46N6O2 is (5,16-dimethyl-2,6,13,17-tetraazatricyclo[16.4.0.07,12]docosane-2,13-diyl)diacetamide, L], consists of one independent half of the [Ag(C24H46N6O2)]2+ cation and one nitrate anion. The Ag atom, lying on an inversion centre, has a square-planar geometry and the complex adopts a stable trans-III conformation. Interestingly, the two O atoms of the pendant acetamide groups are not coordinated to the AgII ion. The longer distance of 2.227 (2) Å for Ag—N(tertiary) compared to 2.134 (2) Å for Ag—N(secondary) may be due to the effects of the attached acetamide group on the tertiary N atom. Two nitrate anions are very weakly bound to the AgII ion in the axial sites and are further connected to the ligand of the cation by N—H...O hydrogen bonds. The crystal packing is stabilized by hydrogen-bonding interactions among the N—H donor groups of the macrocycle and its actetamide substituents, and the O atoms of the nitrate anions and of an acetamide group as the acceptor atoms

Crystal structure of trans-cyclohexane-1,2-diammonium chromate(VI) from synchrotron X-ray diffraction data

The structure of the title hybrid compound, (C6H16N2)[CrO4], has been determined from synchrotron data. The organic cation adopts a chair conformation. The inorganic CrO42− anion is slightly distorted owing to its involvement in N—H...O hydrogen-bonding interactions with neighbouring trans-cyclohexane-1,2-diammonium cations, whereby the two Cr—O bonds to the O atoms acting as acceptor atoms for two hydrogen bonds are slightly longer than the other two Cr—O bonds for which only one acceptor interaction per O atom is observed. In the crystal, cations and anions are packed into layers parallel to (001), held together through the aforementioned N—H...O hydrogen bonds

Crystal structure of cis-dichlorido(1,4,8,11-tetraazacyclotetradecane-κ4N)chromium(III) (oxalato-κ2O1,O2)(1,4,8,11-tetraazacyclotetradecane-κ4N)chromium(III) bis(perchlorate) from synchrotron data

In the asymmetric unit of the title compound, [CrCl2(C10H24N4)][Cr(C2O4)(C10H24N4)](ClO4)2 (C10H24N4 = 1,4,8,11-tetraazacyclotetradecane, cyclam; C2O4 = oxalate, ox), there are two independent halves of the [CrCl2(cyclam)]+ and [Cr(ox)(cyclam)]+ cations, and one perchlorate anion. In the complex cations, which are completed by application of twofold rotation symmetry, the CrIII ions are coordinated by the four N atoms of a cyclam ligand, and by two chloride ions or one oxalate bidentate ligand in a cis arrangement, displaying an overall distorted octahedral coordination environment. The Cr—N(cyclam) bond lengths are in the range of 2.075 (5) to 2.096 (4) Å while the Cr—Cl and Cr—O(ox) bond lengths are 2.3358 (14) and 1.956 (4) Å, respectively. Both cyclam moieties adopt the cis-V conformation. The slightly distorted tetrahedral ClO4− anion remains outside the coordination sphere. The supramolecular architecture includes N—H...O and N—H...Cl hydrogen bonding between cyclam NH donor groups, O atoms of the oxalate ligand or ClO4− anions and one Cl ligand as acceptors, leading to a three-dimensional network structure