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1.
Methods Mol Biol ; 1735: 439-447, 2018.
Article in English | MEDLINE | ID: mdl-29380334

ABSTRACT

Many chronic diseases are associated with hypothalamic-pituitary-adrenal axis dysfunction. Therefore, proteomic profiling of the pituitary gland has potential to uncover new information on the underlying pathways affected in these conditions. This could lead to identification of new biomarkers or drug targets for development of novel therapeutics. Here we present a protocol for preparation of pituitary protein extracts and analysis of the major hormones and accessory proteins using liquid chromatography tandem mass spectrometry (LC-MS/MS). The same methods can be applied in the study of other tissues of the diffuse neuroendocrine system.


Subject(s)
Chromatography, Liquid , Pituitary Gland/metabolism , Proteome , Proteomics , Tandem Mass Spectrometry , Biomarkers , Humans , Proteomics/methods
2.
Adv Exp Med Biol ; 974: 313-319, 2017.
Article in English | MEDLINE | ID: mdl-28353251

ABSTRACT

Psychiatric disorders have been associated with perturbations of the hypothalamic-pituitary-adrenal axis. Therefore, proteomic studies of the pituitary gland have the potential to provide new insights into the underlying pathways affected in these conditions as well as identify new biomarkers or targets for use in developing improved medications. This chapter describes a protocol for preparation of pituitary protein extracts followed by characterization of the pituitary proteome by label-free liquid chromatography-tandem mass spectrometry in expression mode (LC-MSE). The main focus was on establishing a method for identifying the major pituitary hormones and accessory proteins as many of these have already been implicated in psychiatric diseases.


Subject(s)
Mental Disorders/metabolism , Nerve Tissue Proteins/analysis , Pituitary Gland/chemistry , Proprotein Convertases/analysis , Proteomics/methods , Spectrometry, Mass, Electrospray Ionization/methods , Chromatography, Liquid/methods , Humans , Nerve Tissue Proteins/metabolism , Pituitary Gland/metabolism , Pituitary Hormones/metabolism , Proprotein Convertases/metabolism , Solubility
3.
Adv Exp Med Biol ; 974: 321-326, 2017.
Article in English | MEDLINE | ID: mdl-28353252

ABSTRACT

This chapter describes a protocol for measuring prolyl oligopeptidase (POP) activity using a biotinylated peptide substrate coupled to magnetic microspheres. The complex is incubated in the presence of a pituitary extract and activity can be detected by loss of the biotin label. The assay can be multiplexed for measuring multiple proprotein-cleaving enzymes simultaneously and can be used in analyses of neuropsychiatric diseases in which proteolytic cleavage of biologically active peptides is known to play a role.


Subject(s)
Immunomagnetic Separation/methods , Nerve Tissue Proteins/analysis , Pituitary Gland/enzymology , Serine Endopeptidases/analysis , Biotinylation , Humans , Microspheres , Peptide Fragments/chemistry , Prolyl Oligopeptidases , Schizophrenia/metabolism , Streptavidin
4.
Methods ; 65(2): 165-74, 2014 Jan 15.
Article in English | MEDLINE | ID: mdl-23886911

ABSTRACT

Robust, facile high throughput assays based on non-peptidic probes are available to detect the enzyme activity of protein tyrosine phosphatases. However, these assays cannot replace the use of peptide-based probes in many applications; for example when a closer mimic of the physiological target is desired or in substrate profiling expeditions. Phosphotyrosine peptides are often used in these assays, but their use is complicated by either poor sensitivity or the need for indirect detection methods, among other pitfalls. Novel peptide-based probes for protein tyrosine phosphatases are needed to replace phosphotyrosine peptides and accelerate the field of tyrosine phosphatase substrate profiling. Here we review a type of peptidic probe for tyrosine phosphatases, which is based on the incorporation of the phosphotyrosine-mimic phosphocoumaryl amino propionic acid (pCAP) into peptides. The resulting fluorogenic pCAP peptides are dephosphorylated by tyrosine phosphatases with similar efficiency as the homologous phosphotyrosine peptides. pCAP peptides outperform phosphotyrosine peptides, providing an assay that is as robust, sensitive and facile as the non-peptidic fluorogenic probes on the market. Finally the use of pCAP can expand the range of phosphatase assays, facilitating the investigation of multiphosphorylated peptides and providing an in-gel assay for phosphatase activity.


Subject(s)
Alanine/analogs & derivatives , Biological Assay/methods , Coumarins/chemistry , Fluorescent Dyes/chemistry , Organophosphates/chemistry , Peptides/chemistry , Protein Tyrosine Phosphatases/chemistry , Alanine/chemistry , Electrophoresis, Polyacrylamide Gel , Humans , Peptides/genetics , Protein Tyrosine Phosphatases/genetics , Substrate Specificity
5.
ChemMedChem ; 8(9): 1561-8, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23873737

ABSTRACT

We screened a small library of thiuram disulfides for inhibition of lymphoid tyrosine phosphatase (LYP) activity. The parent thiuram disulfide, disulfiram, inhibited LYP activity in vitro and in Jurkat T cells, whereas diethyldithiocarbamate failed to inhibit LYP at the concentrations tested. Compound 13, an N-(2-thioxothiazolidin-4-one) analogue, was found to be the most potent LYP inhibitor in this series, with an IC50 value of 3 µM. Compound 13 inhibits LYP pseudo-irreversibly, as evidenced by the time-dependence of inhibition, with a K(i) value of 1.1 µM and a k(inact) value of 0.004 s⁻¹. The inhibition of LYP by compound 13 could not be reversed significantly by incubation with glutathione or by prolonged dialysis, but could be partially reversed by incubation with dithiothreitol. Compound 13 also inhibited LYP activity in Jurkat T cells.


Subject(s)
Disulfides/chemistry , Enzyme Inhibitors/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 22/antagonists & inhibitors , Thiazoles/chemistry , Thiram/chemistry , Disulfides/metabolism , Enzyme Inhibitors/metabolism , Humans , Jurkat Cells , Kinetics , Protein Binding , Protein Tyrosine Phosphatase, Non-Receptor Type 22/metabolism , Quantitative Structure-Activity Relationship , Thiazoles/metabolism , Thiram/metabolism
6.
Psychoneuroendocrinology ; 38(6): 752-66, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23084727

ABSTRACT

Despite decades of research, the pathophysiology and aetiology of schizophrenia remains incompletely understood. The disorder is frequently accompanied by metabolic symptoms including dyslipidaemia, hyperinsulinaemia, type 2 diabetes and obesity. These symptoms are a common side effect of currently available antipsychotic medications. However, reports of metabolic dysfunction in schizophrenia predate the antipsychotic era and have also been observed in first onset patients prior to antipsychotic treatment. Here, we review the evidence for abnormalities in metabolism in schizophrenia patients, both in the central nervous system and periphery. Molecular analysis of post mortem brain tissue has pointed towards alterations in glucose metabolism and insulin signalling pathways, and blood-based molecular profiling analyses have demonstrated hyperinsulinaemia and abnormalities in secretion of insulin and co-released factors at first presentation of symptoms. Nonetheless, such features are not observed for all subjects with the disorder and not all individuals with such abnormalities suffer the symptoms of schizophrenia. One interpretation of these data is the presence of an underlying metabolic vulnerability in a subset of individuals which interacts with environmental or genetic factors to produce the overt symptoms of the disorder. Further investigation of metabolic aspects of schizophrenia may prove critical for diagnosis, improvement of existing treatment based on patient stratification/personalised medicine strategies and development of novel antipsychotic agents.


Subject(s)
Glucose Metabolism Disorders/metabolism , Metabolic Diseases/metabolism , Schizophrenia , Brain/metabolism , Glucose Metabolism Disorders/complications , Glucose Metabolism Disorders/diagnosis , Glucose Metabolism Disorders/therapy , Humans , Insulin/metabolism , Metabolic Diseases/complications , Metabolic Diseases/diagnosis , Metabolic Diseases/therapy , Schizophrenia/complications , Schizophrenia/diagnosis , Schizophrenia/etiology , Schizophrenia/metabolism , Schizophrenia/therapy
7.
Annu Rev Pharmacol Toxicol ; 53: 17-36, 2013.
Article in English | MEDLINE | ID: mdl-23020294

ABSTRACT

Elucidating the molecular basis for the regulation of iron uptake, storage, and distribution is necessary to understand iron homeostasis. Pharmacological tools are emerging to identify and distinguish among different iron transport pathways. Stimulatory or inhibitory small molecules with effects on iron uptake can help characterize the mechanistic elements of iron transport and the roles of the transporters involved in these processes. In particular, iron chelators can serve as potential pharmacological tools to alleviate diseases of iron overload. This review focuses on the pharmacology of iron transport, introducing iron transport membrane proteins and known inhibitors.


Subject(s)
Iron/metabolism , Membrane Proteins/metabolism , Animals , Biological Transport , Homeostasis , Humans , Membrane Proteins/antagonists & inhibitors
8.
World J Biol Psychiatry ; 14(7): 478-89, 2013 Sep.
Article in English | MEDLINE | ID: mdl-22248022

ABSTRACT

OBJECTIVES: To identify a molecular profile for schizophrenia using post-mortem pituitaries from schizophrenia and control subjects. METHODS: Molecular profiling analysis of pituitaries from schizophrenia (n = 14) and control (n = 15) subjects was carried out using a combination of liquid chromatography tandem mass spectrometry (LC-MS(E)), multiplex analyte profiling (MAP), two-dimensional difference gel electrophoresis (2D-DIGE) and Western blot analysis. RESULTS: This led to identification of differentially expressed molecules in schizophrenia patients including hypothalamic-pituitary-adrenal axis-associated constituents such as cortisol, pro-adrenocorticotropic hormone, arginine vasopressin precursor, agouti-related protein, growth hormone, prolactin and secretagogin, as well as molecules associated with lipid transport and metabolism such as apolipoproteins A1, A2, C3 and H. Altered levels of secretagogin in serum from a cohort of living first onset schizophrenia patients were also detected, suggesting disease association and illustrating the potential for translating some components of this molecular profile to serum-based assays. CONCLUSIONS: Future studies on the molecules identified here may lead to new insights into schizophrenia pathophysiology and pave the way for translation of novel diagnostics for use in a clinical setting.


Subject(s)
Pituitary Gland/metabolism , Proteomics/methods , Schizophrenia/metabolism , Adult , Bipolar Disorder/metabolism , Bipolar Disorder/pathology , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/pathology , Female , Humans , Male , Middle Aged , Pituitary Gland/pathology , Schizophrenia/blood , Schizophrenia/pathology , Young Adult
9.
J Med Chem ; 54(6): 1640-54, 2011 Mar 24.
Article in English | MEDLINE | ID: mdl-21341673

ABSTRACT

The lymphoid tyrosine phosphatase LYP, encoded by the PTPN22 gene, is a critical regulator of signaling in T cells and recently emerged as a candidate target for therapy of autoimmune diseases. Here, by library screening, we identified a series of noncompetitive inhibitors of LYP that showed activity in primary T cells. Kinetic analysis confirmed that binding of the compounds to the phosphatase is nonmutually exclusive with respect to a known bidentate competitive inhibitor. The mechanism of action of the lead inhibitor compound 4e was studied by a combination of hydrogen/deuterium-exchange mass spectrometry and molecular modeling. The results suggest that the inhibitor interacts critically with a hydrophobic patch located outside the active site of the phosphatase. Targeting of secondary allosteric sites is viewed as a promising yet unexplored approach to develop pharmacological inhibitors of protein tyrosine phosphatases. Our novel scaffold could be a starting point to attempt development of "nonactive site" anti-LYP pharmacological agents.


Subject(s)
Protein Tyrosine Phosphatase, Non-Receptor Type 22/antagonists & inhibitors , Quinolones/chemical synthesis , T-Lymphocytes/drug effects , Tetrazoles/chemical synthesis , Allosteric Site , Animals , Catalytic Domain , Cell Membrane Permeability , Cells, Cultured , Deuterium Exchange Measurement , Humans , Hydrophobic and Hydrophilic Interactions , Kinetics , Lymphocyte Activation/drug effects , Mass Spectrometry , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Molecular , Mutation , Protein Conformation , Protein Tyrosine Phosphatase, Non-Receptor Type 22/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Quinolones/chemistry , Quinolones/pharmacology , Small Molecule Libraries , Stereoisomerism , Structure-Activity Relationship , T-Lymphocytes/enzymology , T-Lymphocytes/immunology , Tetrazoles/chemistry , Tetrazoles/pharmacology
10.
Proteomics ; 11(3): 495-500, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21268279

ABSTRACT

Studies of pituitary-related disorders would be facilitated by enhanced knowledge of the pituitary proteome. To construct a data set of human pituitary proteins, separate protein extracts were prepared from 15 post-mortem pituitaries and analyzed by data independent label-free nanoflow liquid chromatography mass spectrometry (nLC-MS(E) ). The detected mass/time features were aligned and quantified using the Rosetta Elucidator(®) system and annotated using results from ProteinLynx Global Server. The resulting data set comprised 1007 unique proteins, with stringent identification by a minimum of two distinct peptides. These proteins consisted predominantly of enzymes, transporters, transcription/translation factors, cell structure and secreted proteins.


Subject(s)
Biomarkers/metabolism , Chromatography, Liquid , Neuropeptides/analysis , Pituitary Gland/metabolism , Proteome/analysis , Tandem Mass Spectrometry , Autopsy , Humans , Neuropeptides/metabolism , Pituitary Gland/cytology , Proteome/metabolism , Proteomics
11.
Psychoneuroendocrinology ; 36(7): 1092-6, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21251762

ABSTRACT

Recently, we showed that the circulating levels of insulin-related peptides and the secretory granule protein chromogranin A were increased in small cohorts of first onset schizophrenia patients. Assuming that this effect was associated with impaired insulin signalling, we investigated the possibility that secretion of other hormones is also affected in schizophrenia. Multiplex immunoassay analysis of 21 hormones and hormone-related molecules was carried out using sera from 236 first and recent onset schizophrenia patients and 230 matched controls. Serum concentrations of insulin and chromogranin A were increased in schizophrenia subjects, consistent with our previous study. In addition, we found elevated concentrations of pancreatic polypeptide, prolactin, progesterone and cortisol, and decreased levels of growth hormone. We also found that growth hormone levels were decreased in post-mortem pituitaries obtained from chronic schizophrenia patients. It will be important to determine whether any of these molecules are involved in the pathosphysiology of schizophrenia or if they reflect the associated insulin resistance. We conclude that function of multiple components of the hypothalamic-pituitary-adrenal-gonadal axis may be affected in schizophrenia. This could have important implications for future biomarker discovery efforts and personalized medicine strategies based on patient stratification for the treatment of this debilitating disorder.


Subject(s)
Hormones/blood , Insulin/blood , Schizophrenia/blood , Schizophrenia/etiology , Adult , Age of Onset , Autopsy , Case-Control Studies , Cohort Studies , Electrophoresis, Gel, Two-Dimensional , Female , Hormones/metabolism , Humans , Hypothalamo-Hypophyseal System/metabolism , Male , Neuroendocrine Cells/metabolism , Pituitary Gland/metabolism , Pituitary Gland/pathology , Pituitary-Adrenal System/metabolism , Pituitary-Adrenal System/pathology , Schizophrenia/epidemiology , Schizophrenia/pathology , Young Adult
12.
J Inorg Biochem ; 104(3): 268-73, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20083307

ABSTRACT

Selective protein tyrosine phosphatase (PTP) inhibition is often difficult to achieve owing to the high degree of similarity of the catalytic domains of this family of enzymes. Selective inhibitors of the lymphoid specific tyrosine phosphatase, LYP, are of great interest due to the involvement of LYP in several autoimmune disorders. This manuscript describes a study into the mechanistic details of selective LYP inhibition by a Au(I)-phosphine complex. The complex, [Au((CH(2)CH(2)CN)(2)PPh)Cl], selectively inhibits LYP activity both in vitro and in cells, but does not inhibit other T-cell derived PTPs including the highly homologous PTP-PEST. The mode of inhibition was probed by investigating inhibition of LYP, the LYP mutant C129/231S, and PTP-PEST. Inhibition of LYP and PTP-PEST was competitive, while the LYP double mutant appeared mixed. Wild-type LYP was inhibited more potently than LYP C129/231S, indicating an important role for at least one of these residues in Au(I) binding. Coordination of Au(I) by both the active site cysteine residue as well as either Cys129 or 231 is suggested as a potential mechanism for LYP selective inhibition.


Subject(s)
Enzyme Inhibitors/pharmacology , Organogold Compounds/pharmacology , Protein Tyrosine Phosphatase, Non-Receptor Type 22/antagonists & inhibitors , Amino Acid Sequence , Animals , Catalytic Domain , Cysteine/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Humans , Jurkat Cells , Ligands , Molecular Sequence Data , Molecular Structure , Organogold Compounds/chemistry , Organogold Compounds/metabolism , Protein Conformation , Protein Tyrosine Phosphatase, Non-Receptor Type 12/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 12/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 12/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 22/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 22/metabolism , Sequence Alignment
13.
J Med Chem ; 52(21): 6912-8, 2009 Nov 12.
Article in English | MEDLINE | ID: mdl-19888762

ABSTRACT

Therapeutic inhibition of protein tyrosine phosphatase activity is a compelling yet challenging approach to the treatment of human disease. Toward this end, a library of 40 gold complexes with the general formula R(3)P-Au-Cl was screened to identify novel inhibitors of PTP activity. The most promising inhibitor obtained for the lymphoid tyrosine phosphatase LYP, (2-pyridine)(Ph(2))P-Au-Cl, is one of the most potent and selective LYP inhibitors identified to date with an IC(50) of 1.5 +/- 0.3 microM, 10-fold selectivity for LYP over PTP-PEST, HePTP, and CD45 in vitro, and activity in cellular studies as well.


Subject(s)
Coordination Complexes/chemical synthesis , Gold , Organogold Compounds/chemical synthesis , Phosphines/chemical synthesis , Protein Tyrosine Phosphatases/antagonists & inhibitors , Animals , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Databases, Factual , Humans , In Vitro Techniques , Mice , Mice, Inbred C57BL , Organogold Compounds/chemistry , Organogold Compounds/pharmacology , Phosphines/chemistry , Phosphines/pharmacology , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 12/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 2/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 2/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 22/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 22/metabolism , Structure-Activity Relationship , T-Lymphocytes/drug effects , T-Lymphocytes/enzymology
14.
Curr Opin Chem Biol ; 13(4): 375-81, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19716756

ABSTRACT

The protein tyrosine phosphatases are a family of enzymes that play critical roles in regulating physiological processes including cellular signaling, growth, differentiation, and the immune response. As new roles emerge for these enzymes in human disease, interest in understanding their mechanism of regulation and function has increased correspondingly. The recent development of mechanism-based probes for phosphatase activity has paved the way for detailed studies of tyrosine phosphatase activity and regulation in both physiological and pathological cellular signaling.


Subject(s)
Protein Tyrosine Phosphatases/analysis , Protein Tyrosine Phosphatases/metabolism , Proteomics , Animals , Humans , Proteomics/methods
15.
J Med Chem ; 51(15): 4790-5, 2008 Aug 14.
Article in English | MEDLINE | ID: mdl-18605719

ABSTRACT

Gold(I) complexes containing N-heterocyclic carbene ligands were synthesized, characterized, and along with the antiarthritic drug, auranofin, tested as inhibitors of the cysteine-dependent protein tyrosine phosphatases, which are implicated in several disease states. These compounds exhibit potencies in the low micromolar range against the enzymes in vitro. At therapeutically relevant concentrations, all compounds inhibit PTP activity in Jurkat T leukemia cells with some selectivity. In addition, the gold-carbene compounds inhibit phosphatase activity in primary mouse thymocytes.


Subject(s)
Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Gold Compounds/chemical synthesis , Gold Compounds/pharmacology , Protein Tyrosine Phosphatases/antagonists & inhibitors , Cell Line , Enzyme Inhibitors/chemistry , Gold Compounds/chemistry , Humans , Hydrogen-Ion Concentration , Molecular Structure , Protein Tyrosine Phosphatases/metabolism
16.
J Am Chem Soc ; 128(44): 14222-3, 2006 Nov 08.
Article in English | MEDLINE | ID: mdl-17076472

ABSTRACT

The synthesis of a mononuclear, five-coordinate ferrous complex [([15]aneN4)FeII(SPh)](BF4) (1) is reported. This complex is a new model of the reduced active site of the enzyme superoxide reductase (SOR), which is comprised of a [(NHis)4(Scys)FeII] center. Complex 1 reacts with alkylhydroperoxides (tBuOOH, cumenylOOH) at low temperature to give a metastable, dark red intermediate (2a: R = tBu; 2b: R = cumenyl) that has been characterized by UV-vis, EPR, and resonance Raman spectroscopy. The UV-vis spectrum (-80 degrees C) reveals a 526 nm absorbance (epsilon = 2150 M-1 cm-1) for 2a and a 527 nm absorbance (epsilon = 1650 M-1 cm-1) for 2b, indicative of alkylperoxo-to-iron(III) LMCT transitions, and the EPR data (77 K) show that both intermediates are low-spin iron(III) complexes (g = 2.20 and 1.97). Definitive identification of the Fe(III)-OOR species comes from RR spectra, which give nu(Fe-O) = 612 (2a) and 615 (2b) cm-1, and nu(O-O) = 803 (2a) and 795 (2b) cm-1. The assignments for 2a were confirmed by 18O substitution (tBu18O18OH), resulting in a 28 cm-1 downshift for nu(Fe-18O), and a 46 cm-1 downshift for nu(18O-18O). These data show that 2a and 2b are low-spin FeIII-OOR species with weak Fe-O bonds and suggest that a low-spin intermediate may occur in SOR, as opposed to previous proposals invoking high-spin intermediates.


Subject(s)
Alkanes/chemistry , Iron/chemistry , Organometallic Compounds/chemistry , Oxidoreductases , Oxygen/chemistry , Peroxides/chemistry , Binding Sites , Cations , Molecular Structure , Oxidation-Reduction , Oxidoreductases/chemistry , Oxidoreductases/metabolism , Spectrophotometry, Ultraviolet , Spectrum Analysis, Raman
17.
Chemistry ; 11(24): 7328-41, 2005 Dec 09.
Article in English | MEDLINE | ID: mdl-16144021

ABSTRACT

The mixed N3S(thiolate) ligand 1-[bis[2-(pyridin-2-yl)ethyl]amino]-2-methylpropane-2-thiol (Py2SH) was used in the synthesis of four iron(II) complexes: [(Py2S)FeCl] (1), [(Py2S)FeBr] (2), [(Py2S)4Fe5II(mu-OH)2](BF4)4 (3), and [(Py2S)2Fe2II(mu-OH)]BF4 (4). The X-ray structures of 1 and 2 revealed monomeric iron(II)-alkylthiolate complexes with distorted trigonal-bipyramidal geometries. The paramagnetic 1H NMR spectra of 1 and 2 display resonances from delta = -25 ppm to +100 ppm, consistent with a high-spin iron(II) ion (S = 2). Spectral assignments were made on the basis of chemical shift information and T1 measurements and show the monomeric structures are intact in solution. To provide entry into hydroxide-containing complexes, a novel synthetic method was developed involving strict aprotic conditions and limiting amounts of H2O. Reaction of Py2SH with NaH and Fe(BF4)2.6 H2O under aprotic conditions led to the isolation of the pentanuclear, mu-OH complex 3, which has a novel dimer-of-dimers type structure connected by a central iron atom. Conductivity data on 3 show this structure is retained in CH2Cl2. Rational modification of the ligand-to-metal ratio allows control over the nuclearity of the product, yielding the dinuclear complex 4. The X-ray structure of 4 reveals an unprecedented face-sharing, biooctahedral complex with an [S2O] bridging arrangement. The magnetic properties of 3 and 4 in the range 1.9-300 K were successfully modeled. Dinuclear 4 is antiferromagnetically coupled [J = -18.8(2) cm(-1)]. Pentanuclear 3 exhibits ferrimagnetic behavior, with a high-spin ground state of S(T) = 6, and was best modeled with three different exchange parameters [J = -15.3(2), J' = -24.7(3), and J'' = -5.36(7) cm(-1)]. DFT calculations provided good support for the interpretation of the magnetic properties.


Subject(s)
Ferric Compounds/chemistry , Hydroxides/chemistry , Magnetics , Sulfhydryl Compounds/chemistry , Ligands , X-Ray Diffraction
18.
Chem Commun (Camb) ; (23): 2772-3, 2002 Dec 07.
Article in English | MEDLINE | ID: mdl-12478739

ABSTRACT

The new sterically encumbered, tripodal N2S(alkylthiolate) ligand, LIm2SH, has been synthesized and used to prepare [(LIm2S)ZnCH3], which upon protonolysis under acidic conditions leads to the synthesis of a novel dinucleating ligand and a zinc dimer with an unusual structure.


Subject(s)
Organometallic Compounds/chemical synthesis , Zinc/chemistry , Dimerization , Disulfides/chemistry , Hydroxides/chemistry , Ligands , Molecular Structure , Organometallic Compounds/chemistry , Organophosphates
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