Cymantrene radical cation family: spectral and structural characterization of the half-sandwich analogues of ferrocenium ion

The anodic one-electron oxidation of three members of the half-sandwich family of piano-stool compounds MnCp (gamma)(CO) 3, where Cp (gamma) is a generic cyclopentadienyl ligand, has been studied in a CH 2Cl 2/[NBu 4][TFAB] electrolyte (TFAB = [B(C6F5) 4] (-)). The long-sought 17 e (-) radical cation of the parent complex MnCp(CO) 3 (cymantrene, 1, E 1/2 = 0.92 V vs ferrocene) has been shown to be persistent in solutions that use weakly coordinating anions in place of more nucleophilic traditional electrolyte anions. Spectroscopically characterized for the first time, 1 (+) was shown to absorb in the visible (530 nm), near-IR (2066 nm), and IR (2118, 1934 cm (-1)) regions. It was ESR-active at low temperatures (g parallel = 2.213, g perpendicular = 2.079, A parallel (Mn) = 79.2 G, A perpendicular (Mn) = 50 G) and NMR active at room temperature (delta = 22.4 vs TMS). The radical cations of the Cp-functionalized analogues, Mn(eta (5)-C5H 4NH2)(CO) 3, 2, E 1/2 = 0.62 V, and MnCp*(CO) 3 (Cp*= eta (5)-C 5Me 5, 3), E 1/2 = 0.64 V, were generated electrochemically as well by the chemical oxidant [ReCp(CO) 3] (+). The structures of 2 (+) and 3 (+) were determined by X-ray crystallographic studies of their TFAB salts. Compared to the structures of the corresponding neutral compounds, the cations showed elongated Mn-C(O) bonds and shortened C-O bonds, displaying the effect of diminished metal-to-CO backbonding. The bond-length changes in the Mn(CO) 3 moiety were much larger in 3 (+) (avg changes, Mn-C(O) = + 0.142 A, C-O = -0.063 A) than in 2 (+) (avg changes, Mn-C(O) = + 0.006 A, C-O = -0.003 A). Although there were only minor changes in the metal-to-center ring distances upon oxidation of either 2 or 3, there was decidedly less bending of the C(N) atom out of the cyclopentadienyl plane in 2 (+) compared to 2. The optical, vibrational, and magnetic resonance spectra of radicals 2 (+) and 3 (+) were also observed. The spectral data argue for the SOMOs of the 17-electron species being largely located on the Mn(CO) 3 moiety, having 40-50% Mn d-orbital character, with the ground states of the radicals, most likely (2)A', lying close in energy (within about 6000 cm (-1)) to excited states that are responsible for their rapid electronic relaxations. The cymantrenyl moiety is proposed as an anodic redox tag (or label) having physical and chemical properties that are significantly different from those of its ferrocenyl analogue.     

Organolanthanide-based synthesis of 1,2,3-triazoles from nitriles and diazo compounds

The reaction of [(C5Me5)2Ln][(mu-Ph)2BPh2] complexes with the lithium salt of (trimethylsilyl)diazomethane, Li[Me3SiCN2], gave products formulated as the dimeric isocyanotrimethylsilyl amide complexes {(C5Me5)2Ln[mu-N(SiMe3)NC]}2 (Ln = Sm, 1; La, 2). Reactions of (C5Me5)2Sm and [(C5Me5)2Sm(mu-H)]2 with Me3SiCHN2 also form 1. Complexes 1 and 2 react with Me3CCN to form the 1,2,3-triazolato complexes (C5Me5)2Ln(NCCMe3)[NNC(SiMe3)C(CMe3)N] (Ln = Sm, 3; La, 4). Complex 2 reacts with Me3SiN3 to make the isocyanide ligated azide complex {(C5Me5)2La[CNN(SiMe3)2](mu-N3)}3, 5.     

Positively and negatively charged ionic modifications to cellulose assessed as cotton-based protease-lowering and hemostatic wound agents

Recent developments in cellulose wound dressings targeted to different stages of wound healing have been based on structural and charge modifications that function to modulate events in the complex inflammatory and hemostatic phases of wound healing. Hemostasis and inflammation comprise two overlapping but distinct phases of wound healing wherein different dressing material properties are required to bring pathological events under control when they present as a result of trauma or chronic wounds. Thus, we have designed cellulose wound dressings with properties that function through modified fiber surface properties to lower protease levels in the chronic wound and promote clotting in hemorrhaging wounds. With this in mind three finishing chemistries utilizing traditional pad-dry-cure approaches were explored for their potential to confer charged properties to cotton dressings. Cellulose dressings designed to remove cationic serine proteases from highly exudative chronic wounds were created to present negatively charged fibers as an ion exchange mechanism of protease-lowering. Phosphorylated cotton and polycarboxylic acid crosslinked cotton were prepared to examine their ability to remove human neutrophil elastase (HNE) from surrogate wound fluid. A cellulose phosphorylation reaction utilizing sodium hexametaphosphate: urea was explored to optimize cellulose phosphorylation as a function of HNE sequestration efficacy. Acid catalyzed cross linking of cellulose with butane-tetracarboxylic acid also resulted in a negatively charged dressing that removed HNE from solution more effectively than phosphorylated cellulose. Collagenase sequestration was also assessed with phosphorylated cellulose and polycarboxylic acid cross linked cellulose derivatives. Butanetetracarboxylic acid and phosphorylated cellulose functioned to remove collagenase from solution most effectively. Cellulose dressings designed to accelerate thrombosis and aggregation of blood platelets were prepared with a view to examining derivatized cotton fibers bearing a net positive charge to promote hemostasis. Cellulose and chitosan dressings bearing an aminoglucan functionality were created by grafting chitosan on cotton and preparing aminized cotton. The preparation of chitosan-grafted cotton dressings was completed with a citric acid grafting onto cellulose. Aminized cotton was functionalized as an ethylamino-ether cellulose derivative. The chitosan-grafted and aminized cotton demonstrated a dose response gelling of citrated sheep blood.     

Increased productivity in quantitative bioanalysis using a monolithic column coupled with high-flow direct-injection liquid chromatography/tandem mass spectrometry

The feasibility of using a monolithic column as the analytical column in conjunction with high-flow direct-injection liquid chromatography/tandem mass spectrometry (LC/MS/MS) to increase productivity for quantitative bioanalysis has been investigated using plasma samples containing a drug and its epimer metabolite. Since the chosen drug and its epimer metabolite have the same selected reaction monitoring (SRM) transitions, chromatographic baseline separation of these two compounds was required. The results obtained from this monolithic column system were directly compared with the results obtained from a previously validated assay using a conventional C18 column as the analytical column. Both systems have the same sample preparation, mobile phases and MS conditions. The eluting flow rate for the monolithic column system was 3.2 mL/min (with 4:1 splitting) and for the C18 column system was 1.2 mL/min (with 3:1 splitting). The monolithic column system had a run time of 5 min and the conventional C18 column system had a run time of 10 min. The methods on the two systems were found to be equivalent in terms of accuracy, precision, sensitivity and chromatographic separation. Without sacrificing the chromatographic separation, sensitivity, accuracy and precision of the method, the reduced run time of the monolithic column method increased the sample throughput by a factor of two.     

Thioether sulfur oxygenation from O2 or H2O2 reactivity of copper complexes with tridentate N2Sthioether ligands

To model thioether-copper coordination chemistry including oxidative reactivity, such as occurs in the copper monooxygenases peptidylglycine -hydroxylating monooxygenase (PHM) and dopamine beta-hydroxylase (DbetaH), we have synthesized new tridentate N2S ligands LSEP and LSBz [LSEP = methyl(2-phenethylsulfanylpropyl)(2-pyridin-2-ylethyl)amine; LSBz = (2-benzylsulfanylpropyl)methyl(2-pyridin-2-ylethyl)amine)]. Both copper(I) and copper(II) complexes have been prepared, and their respective O2 and H2O2 chemistry has been studied. Under mild conditions, oxygenation of [(LSEP)CuI]+ (1a) and [(LSBz)CuI]+ (2a) leads to ligand sulfoxidation, thus exhibiting copper monooxygenase activity. A copper(II) complex of this sulfoxide ligand product, [(LSOEP)CuII(CH3OH)(OClO3)2], has been structurally characterized, demonstrating Cu-Osulfoxide ligation. The X-ray structure of [(LSEP)CuII(H2O)(OClO3)]+ (1b) and its solution UV-visible spectral properties [S-CuII LMCT band at 365 nm (MeCN solvent); epsilon = 4285 M-1 cm-1] indicate the thioether sulfur atom is bound to the cupric ion in both the solid (CuII-S distance: 2.31 A) and solution states. Reaction of 1b with H2O2 leads to sulfonation via the sulfoxide; excess hydrogen peroxide gives mostly sulfone product. These results may provide some insight into recent reports concerning protein methionine oxidation, showing the potential importance of copper-mediated oxidation processes in certain biological settings.     

Different orientations of C=O versus P=O in P(O)NHC(O) skeleton: the first study on an aliphatic diazaphosphorinane with a gauche orientation

Different orientations of P(O) versus C(O) in P(O)NHC(O) skeleton have been discussed in two new phosphorus(V)-nitrogen compounds with formula XP(O)Y and XP(O)Z₂ where X = NHC(O)C₆H₄(4-F) and Y = NHCH₂C(CH₃)₂CH₂NH (1), Z = NHC₆H₄(4-CH₃) (2). Compound 1 is the first example of an aliphatic diazaphosphorinane with a gauche orientation which has been studied by X-ray crystallography; the P=O bond is in the equatorial position of the ring. Both compounds show ⁿ J(F,C) and ^m J(F,H) coupling constants (n = 1, 2, 3 and 4; m = 3 and 4) and ³ J(P,C) > ² J(P,C). Quantum chemical calculations were performed with HF and Density Functional Theory (DFT) methods using 6−31+G(d,p) basis set. A tentative assignment of the observed vibrational bands for these molecules is discussed. Compound 1 shows a deshielded C atom of the carbonyl moiety (in ¹³C NMR spectrum) relative to that of 2, which is supported by IR spectroscopy in which the considerably lower C=O frequency is observed for 1. Comparing the X-ray crystallography and IR spectra of 1 and 2 shows that the acyclic compound 2, containing P=O and C=O bonds in an anti position, are involving in a stronger N–H···O=P hydrogen bond in crystal network. This leads to a weaker P=O and N_C(O)NHP(O)–H bonds and stronger N···O interaction. The N_amide–H is involved in an intramolecular N–H···O hydrogen bond.     

Chemical constituents of the new endophytic fungus Mycosphaerella sp. nov. and their anti-parasitic activity

Chemical investigation of a new endophytic fungus, Mycosphaerella sp. nov. strain F2140, associated with the foliage of the plant Psychotria horizontalis (Rubiaceae) in Panama, resulted in the isolation of cercosporin (1) and a new cercosporin analog (3) as the major components. The structures of minor compounds in the extract were elucidated by detailed spectroscopic analysis as 2-(2-butyl)-6-ethyl-3-hydroxy-6-methylcyclohex-2-ene-1,5-dione (4), 3-(2-butyl)-6-ethyl-5-hydroxy-2-methoxy-6-methyl-cyclohex-2-enone (5), and an isomer of 5 (6). To study the influence of the hydroxy groups on the anti-parasitic activity of cercosporin, compound 1 was acetylated to obtain derivative 2. The isolated compounds 1- 6 were tested in vitro to determine their anti-parasitic activity against the causal agents of malaria (Plasmodium falciparum), leishmaniasis (Leishmania donovani), and Chagas disease (Trypanosoma cruzi). Cytotoxicity and potential anticancer activity of these compounds were evaluated using mammalian Vero cells and MCF7 cancer cell lines, respectively. Compounds 1 and 2 displayed high potency against L. donovani (IC50 0.46 and 0.64 microM), T. cruzi (IC50 1.08 and 0.78 microM), P. falciparum (IC50 1.03 and 2.99 microM), and MCF7 cancer cell lines (IC50 4.68 and 3.56 microM). Compounds 3-6 were not active in these assays at a concentration of 10 microg/mL.     

Synthesis of α,α-disubstituted aryl amines by rhodium-catalyzed amination of tertiary allylic trichloroacetimidates

The rhodium-catalyzed regioselective amination of tertiary allylic trichloroacetimidates with unactivated aromatic amines is a direct and efficient approach to the preparation of α,α-disubstituted allylic aryl amines in good yield and with excellent regioselectivity. This method is applicable to a variety of unactivated primary and secondary amines and allows for the preparation of reverse prenylated indoles in two steps.     

Oxidative decarbonylation of m-terphenyl isocyanide complexes of molybdenum and tungsten: precursors to low-coordinate isocyanide complexes

Synthetic studies are presented addressing the oxidative decarbonylation of molybdenum and tungsten complexes supported by the encumbering m-terphenyl isocyanide ligand CNAr(Dipp2) (Ar(Dipp2) = 2,6-(2,6-(i-Pr)(2)C(6)H(3))(2)C(6)H(3)). These studies represent an effort to access halide or pseudohalide M/CNAr(Dipp2) species (M = Mo, W) for use as precursors to low-coordinate, low-valent group 6 isocyanide complexes. The synthesis and structural chemistry of the tetra- and tricarbonyl tungsten complexes trans-W(CO)(4)(CNAr(Dipp2))(2) and trans-W(NCMe)(CO)(3)(CNAr(Dipp2))(2) are reported. The acetonitrile adducts trans-M(NCMe)(CO)(3)(CNAr(Dipp2))(2) (M = Mo, W) react with I(2) to form divalent, diiodide complexes in which the extent of decarbonylation differs between Mo and W. In the molybdenum example, the diiodide, dicarbonyl complex MoI(2)(CO)(2)(CNAr(Dipp2))(2) is generated, which has an S = 1 ground state in solution. Paramagnetic group 6 MX(2)L(4) complexes are rare, and the structure of MoI(2)(CO)(2)(CNAr(Dipp2))(2) is discussed in relation to other diamagnetic and C(2v)-distorted MX(2)L(4) complexes. Diiodide MoI(2)(CO)(2)(CNAr(Dipp2))(2) reacts further with I(2) to effect complete decarbonylation, producing the paramagnetic tetraiodide complex trans-MoI(4)(CNAr(Dipp2))(2). The reactivity of the trans-M(NCMe)(CO)(3)(CNAr(Dipp2))(2) (M = Mo, W) complexes toward benzoyl peroxide is also surveyed, and it is shown that dicarboxylate complexes can be obtained by oxidative or salt-elimination routes. The reduction behavior of the tetraiodide complex trans-MoI(4)(CNAr(Dipp2))(2) toward Mg metal and sodium amalgam is studied. In benzene solution under N(2), trans-MoI(4)(CNAr(Dipp2))(2) is reduced by Na/Hg to the η(6)-arene-dinitrogen complex, (η(6)-C(6)H(6))Mo(N(2))(CNAr(Dipp2))(2). The diiodide-η(6)-benzene complex (η(6)-C(6)H(6))MoI(2)(CNAr(Dipp2))(2) is an isolable intermediate in this reduction reaction, and its formation and structure are discussed in context of putative low-coordinate, low-valent molybdenum isocyanide complexes.     

Models of the low-spin iron(III) hydroperoxide intermediate of heme oxygenase: magnetic resonance evidence for thermodynamic stabilization of the d(xy) electronic state at ambient temperatures

The (13)C pulsed ENDOR and NMR study of [meso-(13)C-TPPFe(OCH(3))(OO(t)Bu)](-) performed in this work shows that although the unpaired electron in low-spin ferrihemes containing a ROO(-) ligand resides in a d(pi) orbital at 8 K, the d(xy) electron configuration is favored at physiological temperatures. The variable temperature NMR spectra indicate a dynamic situation in which a heme with a d(pi) electron configuration and planar porphyrinate ring is in equilibrium with a d(xy) electron configuration that has a ruffled porphyrin ring. Because of the similarity in the EPR spectra of the hydroperoxide complexes of heme oxygenase, cytochrome P450, and the model heme complex reported herein, it is possible that these two electron configurations and ring conformations may also exist in equilibrium in the enzymatic systems. The ruffled porphyrinate ring would aid the attack of the terminal oxygen of the hydroperoxide intermediate of heme oxygenase (HO) on the meso-carbon, and the large spin density at the meso-carbons of a d(xy) electron configuration heme suggests the possibility of a radical mechanism for HO. The dynamic equilibrium between the ruffled (d(xy)) and planar (d(pi)) conformers observed in the model complexes also suggests that a flexible heme binding cavity may be an important structural motif for heme oxygenase activity.