Silvana C. Ngo

Inhibition of Isolated Mycobacterium tuberculosis Fatty Acid Synthase I by Pyrazinamide Analogs

ABSTRACT An analog of pyrazinamide (PZA), 5-chloropyrazinamide (5-Cl-PZA), has previously been shown to inhibit mycobacterial fatty acid synthase I (FASI). FASI has been purified from a recombinant strain of M. smegmatis (M. smegmatis Δfas1 attB::M. tuberculosis fas1). Following purification, FASI activity and inhibition were assessed spectrophotometrically by monitoring NADPH oxidation. The observed inhibition was both concentration and structure dependent, being affected by both substitution at the 5 position of the pyrazine nucleus and the nature of the ester or N-alkyl group. Under the conditions studied, both 5-Cl-PZA and PZA exhibited concentration and substrate dependence consistent with competitive inhibition of FASI with Kis of 55 to 59 μM and 2,567 to 2,627 μM, respectively. The results were validated utilizing a radiolabeled fatty acid synthesis assay. This assay showed that FASI was inhibited by PZA and pyrazinoic acid as well as by a series of PZA analogs.

Thermal and structural characterization of a series of homoleptic Cu(II) dialkyldithiocarbamate complexes: bigger is only marginally better for potential MOCVD performance

Abstract A series of Cu(II) dialkyldithiocarbamate complexes, Cu(S2CNRR′)2, with R=R′=n-Bu (1); i-Bu (2); c-Hex (3); CH2Ph (4); R=n-Bu, R′=Et (5); R=n-Pr, R′=c-PrCH2 (6); R=R′=n-Pr (7); i-Pr (8); allyl (9), were prepared. The thermal properties of the complexes were investigated to determine if their potential performance in chemical vapor deposition processes was affected by the nature of the peripheral substituents of the ancillary ligands. Modest gains in volatility were noted for 2 and 7 over the most often utilized complex with R=R′=Et, while 1 and 8 had thermal parameters and stability comparable to this standard. Unsymmetrical substitution, such as in 5, also improved volatility, with some loss of stability for this particular compound. X-ray diffraction studies of complexes 1–6 suggested that long range Cu⋯S interactions in the solid-state have little bearing on the thermal properties of this class of Cu(II) complexes.

Synthesis and physical and structural characterization of Ag(I) complexes supported by non-fluorinated β-diketonate and related ancillary ligands

Abstract A series of Ag(I) complexes, [Ag(X)L], where X is the anion of 2,2,6,6-tetramethyl-3,5-heptanedione (tmhdH), 2,2,7-trimethyl-3,5-octanedione (tmodH), 2-sila-2,2,6,6-tetramethyl-3,5- heptanedione (tmshdH), 5-mercapto-2,2,6,6-tetramethyl-4-hepten-3-one (S-tmhdH), 5-mercapto-2,2,7-trimethyl-4-octen-3-one (S-tmodH), or 5-amino-2,2,6,6-tetramethyl-4-hepten-3-one (N-tmhdH) and L=triphenylphosphine (PPh3) or tri-n-butylphosphine (PBu3), were prepared by treatment of silver nitrate with either the diketone derivative in the presence of a base or with the preformed sodium salt of the diketone derivative. The thermal properties of the new complexes were investigated for potential application in chemical vapor deposition (CVD) processes. Results of thermogravimetric analysis showed that the vast majority of the silver complexes have little promise for CVD, since the ligands dissociate at elevated temperatures without volatilization. The first ever reported single crystal X-ray diffraction studies of silver complexes, with simple, ancillary, non-fluorinated β-diketonate supporting ligands, revealed [Ag(tmhd)(PPh3)] (1a) to be monomeric and [Ag(S-tmhd)(PPh3)]2 (4a) to be dimeric in the solid state, respectively.

Structural investigations of copper(II) complexes containing fluorine-substituted β-diketonate ligands

Abstract The crystal structures of the β-diketonate complexes Cu(pta)2, Cu(pta)2·EtOH, and Cu(F6-thd)2 (where pta is the anion of 1,1,1-trifluoro-5,5-dimethylhexane-2,4-dione and F6-thd is the anion of 2,2-bis(trifluoromethyl)-6,6-dimethylheptane-3,5-dione) were determined. The solid-state structures of Cu(pta)2 and Cu(F6-thd)2 are square planar, while Cu(pta)2·EtOH is approximately square pyramidal with the EtOH ligand occupying the apical position. In each case, only one geometrical isomer (cis or trans) was observed in the crystals; arguments are presented that both isomers are present in bulk samples. Calculations of molecular volumes for structurally related Cu(II) complexes containing non-fluorinated versus fluorinated ancillary ligands show that fluorine substitution does not significantly affect packing efficiency in the solid-state; however, solvent coordination decreases packing efficiency slightly. [Cu(tdf)(py)(μ-C3F7CO2)]2 (where tdf is the anion of 1,1,1,2,2,3,3,7,7,8,8,9,9,9-tetradecafluorononane-4,6-dionate), a derived impurity from preparations of Cu(tdf)2, was isolated in low yield. The copper coordination geometries in the centrosymmetric structure are intermediate between square pyramidal and trigonal bipyramidal, with two unsymmetrically bridging μ,η1:η1-C3F7CO2 ligands.

Synthesis of fluorinated α-sila-β-diketones and their copper(II) complexes

Abstract Fluorinated α-sila-β-diketones, synthesized in good yields via the Claisen condensation of the esters of fluorinated acids or fluorinated acid fluorides and the lithium enolates of acetyltrialkylsilanes, were employed in the preparation of volatile copper complexes for copper metallization. The thermal properties of the corresponding copper(II) complexes were determined by TGA and DSC to evaluate the potential of these materials as copper metal–organic chemical vapor deposition (MOCVD) precursors; the new copper compounds have greater volatility and stability than the corresponding copper complexes of non-fluorinated α-sila-β-diketonates.

Facile synthesis of a novel class of organometalloid-containing ligands, the sila-β-diketones: preparation and physical and structural characterization of the copper(II) complexes, Cu[R′C(O)CHC(O)SiR3]2

Abstract The substitution of a carbon atom by silicon provides an attractive, novel approach to modification of the thermal stability and volatility of metal-organic chemical vapor deposition precursors supported by β-diketonate ancillary ligands. The low temperature reaction of the lithium enolates of acetyltrialkylsilanes with acyl chlorides affords the sila-β-diketones, R′C(O)CH 2 C(O)SiR 3 (R′=Me, Et, n -Pr, i -Pr, n -Bu, i -Bu, s -Bu, t -Bu; SiR 3 =SiMe 3 , SiEt 3 , SiMe 2 ( t -Bu), SiMe 2 ( t -hexyl), Si( i -Pr) 3 ), in good yields. Multinuclear NMR studies suggest that the sila-β-diketones exist as the enolic tautomer with a vinylsilane isomeric structure. Homoleptic Cu(II) sila-β-diketonate complexes were prepared in a first pass study to evaluate how precursor performance is affected by modulation of the peripheral substituents in the ligands. Thermal analyses, (TGA, DSC) show that the silylated Cu(II) precursors (SiR 3 =SiMe 3 ; R′= t -Bu or i -Bu) have greater volatility than the corresponding carbon analogues. Some of the new Cu(II) complexes exist as liquids or low melting solids, which are preferred states for industrial deposition processes. X-ray diffraction studies of selected copper complexes showed them to have typical, square planar geometry; calculations of molecular volumes suggest that packing in the solid-state is less efficient for the silicon-containing complexes than for the non-silylated analogues.

Reactions of novel mono- and difluoroacetyltrialkylsilanes with sulfur and phosphorus ylides

Abstract The reactions of difluoroacetyltrialkylsilanes with methylidene triphenylphosphorane and benzylidene triphenylphosphorane are affected by the nature of the silyl substituents giving either the enol silyl ether or normal Wittig product exclusively, or mixture of both. Reactions with Horner–Emmons type ylide gave only the alkene products. Reactions of mono- and difluoroacetyltrialkylsilanes with dimethylsulfoxonium methylide gave the enol silyl ether products exclusively. Conversion of an enol silyl ether to an epoxide was effected with m -CPBA.

Preparation and Characterization of Half‐Sandwich (Pentamethylcyclopentadienyl)(triflato)titanium(IV) Complexes: Solid‐State Structural Motifs and Catalysis Studies

Half-sandwich (pentamethylcyclopentadienyl)(triflato)titanium(IV) complexes of the type [Ti(Cp*)(TfO)2X] (X=MeO (1), Me (2), 2,4,6-Me3C6H2O (5)) or [Ti(Cp*)(o-OC6H4O)(TfO)] (7) were readily synthesized via methathesis of the corresponding chloride complexes with silver triflate (Cp*=(η5-1,2,3,4,5-pentamethylcyclopenta-2,4-dien-1-yl)). In addition, the complex 3 with X=OH was prepared by controlled hydrolysis of 2. The solid-state structures of these new complexes were determined by single-crystal X-ray-diffraction techniques. Three different structural motifs were identified; 1, 2, 3, and 7 are dimeric, while 5 is monomeric. The complexes were screened for their ability to stereospecifically polymerize styrene under homogeneous conditions. In the absence of activators, such as MAO (methylaluminoxane), 1 and 2 readily catalyzed the formation of atactic polystyrene; a strong dependence on the steric size of X was noted. In the presence of MAO, all of the complexes showed high activity and strong preference for the synthesis of syndiotactic polystyrene that was superior to that of [TiCl3(Cp*)]/MAO.