Biomedical subjects
Publications and source records attributed to Emil Lobkovsky.
Square planar iron methyl complexes containing bis(imino)pyridine (PDI) ligands have been prepared by reductive alkylation of the corresponding ferrous dichloride; dialkylation is observed upon treatment with a larger alkyl lithium.
The geometric preferences of a family of four coordinate, iron(II) d6 complexes of the general form L2FeX2 have been systematically evaluated. Treatment of Fe2(Mes)4 (Mes = 2,4,6-Me3C6H2) with monodentate phosphine and phosphite ligands furnished square planar trans-P2Fe(Mes)2 derivatives. Identification of the geometry has been accomplished by a combination of solution and solid-state magnetometry and, in two cases (P = PMe3, PEt2Ph), X-ray diffraction. In contrast, both tetrahedral and square planar coordination has been observed upon complexation of chelating phosphine ligands. A combination of crystallographic and magnetic susceptibility data for (depe)Fe(Mes)2 (depe = 1,2-bis(diethylphosphino)ethane) established a tetrahedral molecular geometry whereas SQUID magnetometry and Mössbauer spectroscopy on samples of (dppe)Fe(Mes)2 (dppe = 1,2-bis(diphenylphosphino)ethane) indicated a planar molecule. When dissolved in chlorinated solvents, the latter compound promotes chlorine atom abstraction, forming tetrahedral (dppe)Fe(Mes)Cl and (dppe)FeCl2. Ligand substitution reactions have been studied for both structural types and are rapid on the NMR time scale at ambient temperature.
[reaction: see text] Additions of lithium acetylides and n-BuLi to N-alkyl ketimines mediated by BF(3)-Et(2)O in THF afford hindered tert-alkylamines in moderate to good yields. Stereochemical results and crystal structures of three BF(3)-imine complexes suggest that allylic strain strongly influences conformation and may be an important determinant of reactivity and selectivity.
A family of isolable, well-defined bis-indenyl zirconium sandwich complexes, (eta(5)-C(9)H(5)-1,3-R(2))(eta(9)-C(9)H(5)-1,3-R(2))Zr (R = silyl, alkyl), have been prepared by either alkane reductive elimination or alkali metal reduction of a suitable zirconium(IV) dihalide precursor. Crystallographic characterization of two of these derivatives, R = SiMe(2)CMe(3) and CHMe(2), reveals unprecedented eta(9) coordination of one of the indenyl ligands. Variable-temperature and EXSY NMR studies establish that the eta(5) and eta(9) rings are rapidly interconverting in solution. The sandwich complexes serve as effective sources of low-valent zirconium reacting rapidly with both olefins and alkynes at ambient temperature. In contrast to bis-cyclopentadienyl chemistry, the olefin adducts of the bis-indenyl zirconium sandwiches undergo preferential C-H activation to yield the corresponding allyl hydride compounds, although reaction with excess olefin proceeds through the eta(2)-olefin adduct, forming the corresponding zirconacyclopentane.
Alkylation of beta-amino ester enolates proceeds with high diastereoselectivity. Single crystal, powder, and solution X-ray diffraction studies of the enolate show that the racemic enolate forms prismatic hexamers. 6Li NMR spectroscopic studies on partially racemic enolates reveal complex mixtures of homo- and heterochiral hexamers. An implicit fit of the aggregate populations to the Boltzmann distribution provides the free energy differences and equilibrium constants for the ensemble. Rate studies show that enolate alkylation occurs directly from the hexamer with participation by THF. A mechanism based on the alkylation of a ladder-like aggregate is proposed.
The activation of dinitrogen by titanium sandwich complexes of the general form (eta5-C5Me4R)2Ti (R = CHMe2, CMe3, SiMe3) has been systematically investigated. Low-temperature, in situ, solution infrared spectroscopy has allowed detection of monomeric bis-dinitrogen complexes of titanium that are isostructural with more familiar dicarbonyl derivatives. One example, (eta5-C5Me4CHMe2)2Ti(N2)2, has also been characterized by X-ray diffraction and reveals weakly activated dinitrogen ligands. From the solution IR data, the relative azophilicity of the titanium sandwich complexes has been established and increases with smaller cyclopentadienyl substituents.
Reduction of the five-coordinate iron(II) dihalide complexes (iPrPDI)FeX2 (iPrPDI = ((2,6-CHMe2)2C6H3N=CMe)2C5H3N; X = Cl, Br) with sodium amalgam under 1 atm of dinitrogen afforded the square pyramidal, high spin iron(0) bis(dinitrogen) complex (iPrPDI)Fe(N2)2. In solution, (iPrPDI)Fe(N2)2 loses 1 equiv of N2 to afford the mono(dinitrogen) adduct (iPrPDI)Fe(N2). Both dinitrogen compounds serve as effective precatalysts for the hydrogenation and hydrosilation of olefins and alkynes. Effecient catalytic reactions are observed with low catalyst loadings (< or = 0.3 mol %) at ambient temperature in nonpolar media. The catalytic hydrosilations are selective in forming the anti-Markovnikov product. Structural characterization of a high spin iron(0) alkyne and a bis(silane) sigma-complex has also been accomplished and in combination with isotopic labeling studies provides insight into the mechanism of both catalytic C-H and catalytic C-Si bond formation.
Low-temperature 6Li NMR spectroscopic studies on a chiral beta-amino ester enolate reveal a complex mixture of homo- and heterochiral aggregates. Subsequent warming of the samples led to rapid intra-aggregate exchange, resulting in four distinct resonances consistent with an ensemble of hexamers. An implicit fit of the aggregate populations to the Boltzmann distribution provided the free energy differences and equilibrium constants. An X-ray crystal structure obtained from the racemic enolate is consistent with the predominant aggregate in solution.
A reinvestigation of Auletta sp. yielded the novel compound milnamide C (3) plus the known compounds milnamide A (1), milnamide B (hemiasterlin) (2), jasplakinolide (5), and geodiamolides A (6), D (7), E (8), and G (9). The isolation work was guided by cytoskeletal bioactivity data. Compounds 2 and 3 were shown to cause microtubule depolymerization, and 6-9 were shown to cause microfilament disruption. This biological activity and the structural elucidation of 3, including X-ray analysis, are reported here. [structure: see text]
The preparation of the iridium tetrahydride ((iPr)BDI)IrH(4)[BDI = ArNC(Me)CH(Me)CNAr, Ar = 2,6-(i)Pr(2)C(6)H(3)] and its activity in the catalytic C-H activation of arenes is described.
Molecular nitrogen is relatively inert owing to the strength of its triple bond, nonpolarity and high ionization potential. As a result, the fixation of atmospheric nitrogen to ammonia under mild conditions has remained a challenge to chemists for more than a century. Although the Haber-Bosch process produces over 100 million tons of ammonia annually for the chemical industry and agriculture, it requires high temperature and pressure, in addition to a catalyst, to induce the combination of hydrogen (H2) and nitrogen (N2). Coordination of molecular nitrogen to transition metal complexes can activate and even rupture the strong N-N bond under mild conditions, with protonation yielding ammonia in stoichiometric and even catalytic yields. But the assembly of N-H bonds directly from H2 and N2 remains challenging: adding H2 to a metal-N2 complex results in the formation of N2 and metal-hydrogen bonds or, in the case of one zirconium complex, in formation of one N-H bond and a bridging hydride. Here we extend our work on zirconium complexes containing cyclopentadienyl ligands and show that adjustment of the ligands allows direct observation of N-H bond formation from N2 and H2. Subsequent warming of the complex cleaves the N-N bond at 45 degrees C, and continued hydrogenation at 85 degrees C results in complete fixation to ammonia.
The lithium diisopropylamide-mediated 1,2-elimination of 1-bromocyclooctene to provide cyclooctyne is investigated using approximately 50 potentially hemilabile polyethers and amino ethers. Rate laws for selected ligands reveal chelated monomer-based pathways. The dependence of the rates on ligand structure shows that anticipated rate accelerations based on the gem-dimethyl effect are nonexistent and that substituents generally retard the reaction. With the aid of semiempirical and DFT computational studies, the factors influencing chelation are discussed. It seems that severe buttressing within chelates of the substitutionally rich ligands precludes a net stabilization of the chelates relative to nonchelated (eta(1)-solvated) forms. One ligand-MeOCH(2)CH(2)NMe(2)-appears to promote elimination uniquely by a higher-coordinate monomer-based pathway.
[structure: see text] Structurally unique steroids, isocyclocitrinol A (1) and 22-acetylisocyclocitrinol A (2), were isolated from the extract of a saltwater culture of sponge-derived Penicilliun citrinum. The structures were established by analysis of 1D and 2D NMR data. The absolute structures were determined on the basis of X-ray structure analysis and application of modified Mosher's method. Furthermore, the structure of cyclocitrinol (3a) previously isolated from a terrestrial P. citrinum was revised as 3b. Compounds 1 and 2 showed weak antibacterial activity against Staphylococcus epidermidis and Enterococcus durans.
Reductive elimination of alkane from a silylated bis-indenyl zirconium isobutyl hydride affords a zirconium sandwich complex with an unusual eta6 indenyl ligand. Crystallographic characterization of its adduct with tetrahydrofuran has been achieved and reveals significant localization in the six-membered ring. Complexation of more potent ligands such as carbon monoxide and diphenylacetylene are effective in promoting haptotropic rearrangement of the eta6 indenyl ligand and provides familiar bent zirconocene derivatives. The zirconium sandwich compound also undergoes oxidative addition of carbon-hydrogen bonds of pyridyl ligands, resulting in a crystallographically characterized dimethylamino pyridyl hydride complex of zirconium.
[reaction: see text] An expeditious procedure for the direct formation of stereochemically well-defined macrodiolides is described. Cyclodimerizations of enantioenriched C7 and C8 hydroxy esters 6 in the presence of catalytic amounts of distannoxane transesterification catalysts afford 14- to 22-membered macrodiolides 7-9 bearing up to six stereocenters. Additional structural diversity is introduced by further stereoselective reactions on selected macrodiolides 7a, 7g, 10a, and 11.
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The rate of reductive elimination for a family of zirconocene isobutyl hydride complexes, Cp(CpR(n)())Zr(CH(2)CHMe(2))H (Cp = eta(5)-C(5)Me(5), CpR(n)() = substituted cyclopentadienyl), has been measured as a function of cyclopentadienyl substituent. In general, the rate of reductive elimination increases modestly with the incorporation of sterically demanding substituents such as [CMe(3)] or [SiMe(3)]. A series of isotopic labeling experiments was used to elucidate the mechanism and rate-determining step for the reductive elimination process. From these studies, a new zirconocene isobutyl hydride complex, Cp' '(2)Zr(CH(2)CHMe(2))(H) (Cp' ' = eta(5)-C(5)H(3)-1,3-(SiMe(3))(2)), was designed and synthesized such that facile reductive elimination of isobutane and activation of dinitrogen was observed. The resulting dinitrogen complex, [Cp' '(2)Zr](2)(mu(2), eta(2),eta(2)-N(2)), has been characterized by X-ray diffraction and displays a bond length of 1.47 A for the N(2) ligand, the longest observed in any metallocene dinitrogen complex. Solution magnetic susceptibility demonstrates that [Cp' '(2)Zr](2)(mu(2), eta(2), eta(2)-N(2)) is a ground-state triplet, consistent with two Zr(III), d(1) centers. Mechanistic studies reveal that the dinitrogen complex is derived from the reaction of N(2) with the resulting cyclometalated zirconocene hydride rather than directly from reductive elimination of alkane.
Trichodermamides A (1) and B (2), two modified dipeptides, have been isolated from cultures of the marine-derived fungus Trichoderma virens. The trichodermamides possess a rare cyclic O-alkyl-oxime functionality incorporated into a six-membered ring. The structure of trichodermamide B was established by X-ray diffraction analysis, while the structure assignment of trichodermamide A, and determination of the absolute stereochemistry, was accomplished by spectral and chemical methods. Trichodermamide B displayed significant in vitro cytotoxicity against HCT-116 human colon carcinoma with an IC(50) of 0.32 microg/mL.