Ester Complexes Research Articles

Increase in neutral cholesteryl ester hydrolase activity produced by extralysosomal hydrolysis of high-density lipoprotein cholesteryl esters in rat hepatoma cells (H-35)

The metabolism of high-density lipoprotein-associated cholesteryl esters (HDL-CE) in liver cells is not well understood. We studied the possible role of lysosomal and extralysosomal pathways on such metabolism by measuring the uptake and hydrolysis of HDL-CE in H-35 rat hepatoma cells. Incubation of cells with [ 3H]cholesteryl ester-labeled HDL led to the intracellular accumulation of both 3 H-free cholesterol and [ 3H]cholesteryl ester. The ratio of 3H-free cholesterol/[ 3H]cholesteryl ester increased with an increase in incubation time even in the presence of chloroquine. Because chloroquine did not inhibit the conversion of cholesteryl ester to free cholesterol, the hydrolysis of HDL-CE may have been catalyzed by an extralysosomal enzyme, perhaps by neutral cholesteryl ester hydrolase (NCEH). When we incubated cells with increasing concentrations of HDL, NCEH activity increased. This increase in enzyme activity was not inhibited by the addition of chloroquine. A complex of dimyristoylphosphatidylcholine (DMPC)/apo HDL/cholesteryl ester enhanced the activity as well as native HDL. Neither the DMPC/apo HDL nor the DMPC/cholesteryI ester complex affected the activity, suggesting that apo HDL may be required for the uptake of HDL-CE. The present study demonstrated that the extralysosomal hydrolysis by NCEH is operating in the metabolism of HDL-CE in hepatoma cells.

Cu II—diamine complex catalyzed hydrolysis of phosphate triesters adsorbed on strong-base ion exchange resins. 31P NMR relaxation measurements

The Cu II—diamine complexes, (bipy)CuSO 4 and (tmen)CuSO 4, catalyze the hydrolysis of p-nitrophenyl diphenyl phosphate (PNDP) adsorbed on a strong-base ion exchange resin. Turnover is observed. The major hydrolysis products are diphenyl phosphate, p-nitrophenyl phenyl phosphate, and the ethanolysis product ethyl diphenyl phosphate (EDPP) which are observed in similar amounts in both the presence and absence of the Cu II—diamine catalysts. The apparent bimolecular rate constants found for the (bipy) CuSO 4 and (tmen)CuSO 4 catalysts are 0.023 and 0.024 M −1 s −1, respectively. CuSO 4 is inactive as a catalyst. 31P MAS NMR relaxation measurements of the stable EDPP product reveal that the Cu II—diamine complexes greatly enhance T 1 relaxation, whereas CuSO 4 has only minimal effect. These results are consistent with the complexation of neutral phosphorus esters by the Cu II—diamine catalysts. 31P T 1 measurements of hydrolytically-stable dimethyl methylphosphonate (DMMP) in water solutions of Cu 2+, (tmen)Cu 2+, and Mn 2+ suggest that DMMP exchanges rapidly between inner-sphere and outer-sphere complexes in a nearly identical manner with each of these paramagnetic species.

Synthesis of the new organometallic carboxylic acid complexes [η 5-C 5H 4COOH)M(CO) nMe] (M  Mo, n = 3; M  Fe, n = 2 and their potential as bioconjugates

The new compounds [η 5-C 5H 4COOH)M(CO) n ,Me] [M  Mo, n = 3 ( 2); M  Fe, n = 2 ( 5)] were synthesized in 61% and 63% yields, respectively, and treated with N-hydroxysuccinimide to yield the corresponding activated ester derivatives [(η 5-C 5H 4COONS)-M(CO) n Me] [M  Mo, n = 3 ( 3); M  Fe, n = 2, ( 6). The metal-activated ester complex, [(η(su5)-C 5H 5Mo(CO) 3(CH 2COONS)] ( 8) was obtained similarly, the ester unit being bonded directly to the metal rather than to the π-bonded cyclopentadienyl. The reactivity and potential of the above species as labelling agents for amino-acids is discussed.

Photochemical reactions of transition metal organyl complexes with olefins Part 10. Light-induced formal [5+2] cycloadditions at manganese

Tricarbonyl-η 5-2,4-dimethyl-2,4-pentadien-1-yl-manganese ( 1) forms upon UV irradiation in THF at 208 K solvent stabilized dicarbonyl-η 5-2,4-dimethyl-2,4-pentadien-1-yl-tetrahydrofurane-manganese ( 2). With butynedioic acid dimethyl ester ( 3) and diphenylacetylene ( 5) complex 2 yields tricarbonyl-η 5-1,2-dimethoxycarbonyl-4,6-dimethyl- cyclohepta-2,4-dien-1-yl-manganese ( 4) and tricarbonyl-η-4,6-dimethyl-1,2-diphenyl-cyclohepta-2,4-dien-1-yl- manganese ( 6) in a formal [5+2] cycloaddition. Addition of carbon monoxide and a 1,4-H shift completes the reaction. Propynoic acid methyl ester ( 7) forms the 2:1 adduct dicarbonyl-η 5:2-1,3-dimethyl-6-methoxycarbonyl-6- ( E-2′-methoxycarbonylvinyl)-cyclohepta-2,4-dien-1-yl-manganese ( 8). The crystal and molecular structure of 8 was determined by X-ray structure analysis. The molecular structures of the complexes 4 and 6 were established by IR and NMR spectroscopy. Formation mechanisms of 4, 6 and 8 are discussed. Crystal data for 8: monoclinic space group P2 1/ c, a=802.6(3), b=1136.6(1), c=8872.3(3) pm, β=93.14(2)°, V=1.705 nm 3, Z=4.

Synthesis, characterization and crystallization behaviour of stereoregular poly-β-hydroxyoctanoate

(S)-β-Pentyl-β-propiolactone (( S)-PPL) was prepared in five steps with an optical purity in excess of 97% starting from the optically pure copolymer produced by Pseudomonas oleovorans when grown with n-octanoic acid. The copolymer contained approximately 85 mol% of β-hydroxyoctanoate units; x=4, in the structure shown below. ▪ The remainder of the copolymer was hexanoate, x = 2, and decanoate, x = 6, units. (S)-PPL was polymerized to the opticaly active homopolymer, poly-β-hydroxyoctanoate (PHO) by the ring-opening polymerization of this lactone with aluminoxane and zinc alkyl catalysts. The stereochemical configurations and isomeric purities of the repeating units of the polymers obtained were determined by degrading the polymers to methyl β-hydroxyoctanoate and analysis by 250 MHz 1H n.m.r. spectroscopy of the complexes of these methyl esters with a chiral europium shift reagent. The diad stereochemical sequence distributions of the polymers were determined by 50.3 MHz 13C n.m.r. spectroscopy. The isothermal rates of crystallization were determined by differential scanning calorimetry (d.s.c.) for the bacterial copolymer and for two synthetic PHOs: a racemic P[( R,S)-HO], and an optically active P[(R)-HO]. The synthetic P[( R)-HO] had a higher enthalpy of fusion and a faster crystallization rate than the racemic PHO, which had a higher enthalpy of fusion and a faster crystallization rate than the bacterial PHO. These differences were explained in terms of the stereoregularities and compositions of the different polymers.

Substrate properties of site-specific mutant ubiquitin protein (G76A) reveal unexpected mechanistic features of ubiquitin-activating enzyme (E1).

Ubiquitin-mediated proteolysis proceeds via the formation and degradation of ubiquitin-protein conjugates. Ubiquitin (Ub)-activating enzyme (E1) catalyzes the first, MgATP-dependent step in the conjugative reaction sequence. With wild type ubiquitin, the product of the E1 reaction is a ternary complex (E1-Ub-AMP-Ub) containing one thiol-linked ubiquitin (via the Ub COOH terminus, Gly-76) and one tightly bound ubiquitin adenylate. The thiol-linked ubiquitin is subsequently transferred to the thiol of a ubiquitin-conjugating enzyme (E2 protein); the latter adduct is the proximal donor of ubiquitin to the target protein. A mutant ubiquitin, bearing a Gly to Ala substitution at the COOH terminus (G76A-ubiquitin), was characterized as a substrate for E1. G76A-ubiquitin 1) supported PPi-ATP exchange poorly (500-fold decrease in kcat/K(m); 2) did not produce detectable AMP-Ub with native E1; 3) produced stoichiometric AMP-Ub with thiol-blocked E1; 4) gave a stoichiometric burst of ATP consumption (1 mol/mol E1) with either native or thiol-blocked E1; 5) supported E1-ubiquitin thiol ester formation with native E1; 6) supported several downstream reactions of the proteolytic pathway at approximately 20% of the rate of wild type ubiquitin. These results indicate that G76A-ubiquitin gives a binary E1 thiol ester complex with native E1, due to the failure of the E1-ubiquitin thiol ester to undergo another round of adenylate synthesis; thus AMP-Ub is detected only if adenylate to thiol transfer is prevented by alkylating E1. The inability of G76A-ubiquitin to support ternary complex formation has implications for E1 active site structure. In other experiments, occupancy of the nucleotide/adenylate site of E1, by either MgATP or AMP-Ub, was found to stimulate ubiquitin transthiolation between E1 and E2 proteins. The intermediacy of ubiquitin adenylate thus provides a previously unrecognized catalytic advantage in the E1 mechanism.

Catalytic hydrolysis of phosphate esters by metallocomplexes of 1,10‐phenanthroline derivatives in micellar solution

AbstractDivalent metal‐ion complexes of 2,9‐bis[(methyldodecylamino)methyl]‐1,10‐phenanthroline (C12PhenMII) in neutral Brij 35 micelles catalyse the hydrolysis of various phosphate triesters, diesters and monoesters. The catalytic activity of C12PhenMII has been compared with that of the metal‐ion complexes of its water‐soluble counterpart 2,9‐bis[(dimethyl‐amino)methyl]‐1,10‐phenanthroline (C1PhenMII). Saturation kinetics provide evidence for preliminary formation of ligand‐MII‐phosphate ester complexes, which decay to products. The hydrolysis of diphenyl 4‐nitrophenyl phosphate (1b) coordinated to C12PhenZnII proceeds 8700 times faster than the hydrolysis of 1b in the absence of metallocatalyst. Kinetic studies indicate that phosphate triesters containing a metal‐ion‐binding site in close proximity to the phosphoryl bond, i.e., diphenyl 5‐nitro‐2‐pyridyl phosphate (2b) and diphenyl 5‐nitro‐8‐quinolyl phosphate (3), are hydrolysed by the same mechanism as 1b.

Inclusion complexation of p-hydroxybenzoic acid esters with 2-hydroxypropyl-beta-cyclodextrins. On changes in solubility and antimicrobial activity.

To obtain a transparent and effective solution of p-hydroxybenzoic acid esters (parabens), the use of 2-hydroxypropyl-beta-cyclodextrins (2-HP-beta-CyDs) as solubilizers with different degrees of substitution (D.S.) was surveyed. 2-HP-beta-CyDs significantly increased the aqueous solubility of four kinds of parabens (methyl < ethyl < propyl < butyl esters), where the solubilizing ability decreased with an increase in the D.S. of the 2-hydroxypropyl group in beta-CyD. The antimicrobial activity of the parabens tended to decrease by complexation with 2-HP-beta-CyDs. However, the activity could be maintained by lengthening the alkyl chain of the parabens. 1H- and 13C-nuclear magnetic resonance and circular dichroism spectroscopic studies suggest that the hydrophobic alkyl moiety of butyl paraben is preferably included in the cavity, and the phenol group extrudes from the cavity. The present results suggest that a suitable combination of 2-HP-beta-CyDs and hydrophobic, longer alkyl parabens is useful for the preservation of liquid formulations.

Conversion of nitriles into Δ2-1,3-oxazolines in platinum(II) complexes. Crystal structure of trans-[PtCl2{NC(But)OCH2CH2}2

The reactions of cis- and trans-[PtCl2(NCR)2](R =p-MeC6H4, p-CF3C6H4, o-MeC6H4, Et, Prn, Pri or But) complexes with 2 equivalents of –OCH2CH2Cl, generated by deprotonation of HOCH2CH2Cl with LiBun, afford in high yield the bis(Δ2-1,3-oxazoline) derivatives cis-and trans-[PtCl2{[graphic omitted]H2}2]. The complexes have been characterized by their elemental analyses, IR, 1H NMR, 13C-{1H} NMR and FAB mass spectra. The structure of trans-[PtCl2{[graphic omitted]H2}2] was established also by X-ray crystallography: monoclinic, space group P21/n, a= 11.233(2), b= 8.741(2), c= 9.394(2)A, β= 101.61(3)° and Z= 2; R= 0.038 (R′= 0.042) for 2514 measured reflections with I 3σ(I). The N–C(R) and (R)C–O bond distances of 1.284(5) and 1.335(5)A suggest that there is extensive electron delocalization within the N–C(R)–O system. The co-ordination geometry around PtII is planar and the oxazoline rings are only slightly twisted. The formation of Δ2-1,3-oxazolines from platinum(II)-co-ordinated nitriles has also been examined using HOCH2CH2Cl in the presence of the weak base NEt3. These reactions proceed through the initial formation of the bis(imido ester) complexes [PtCl2{NHC(R)OCH2CH2Cl}2], present as their (Z,Z), (E,E) and (E,Z) conformers, which slowly convert to the final cyclic Δ2-1,3-oxazoline derivatives.

A peptide-aluminum complex as a novel chiral Lewis acid. Asymmetric addition of cyanotrimethylsilane to aldehydes

The enantioselective addition of cyanotrimethylsilane (TMSCN) to aldehydes promoted by the addition of a stoichiometric or catalytic amount of organoaluminum complexes of dipeptide esters or α-amino acid amides whose amino terminals are modified by a variety of protective groups is described.These compounds serve as ligands for chiral Lewis acid catalysts

Electrocatalytic reduction of nitrite and nitrosyl by iron(III) protoporphyrin IX dimethyl ester immobilized in an electropolymerized film

Thin polymeric films formed by anodic electropolymerization of an iron(III) protoporphyrin IX dimethyl ester complex, [Fe III (PP)Cl], on glassy-carbon or optically transparent SnO 2 electrodes are effective catalysts for the electroreduction of HONO/NO 2 - or NO to N 2 O, N 2 , NH 2 OH, and NH 3 . The yield of N 2 is enhanced in the compact environment of the redox polymer.

Synthesis, characterization and release of cromoglycate from dextran conjugates

This paper describes the synthesis of a macromolecular derivative of the anti-asthmatic drug sodium cromoglycate. Cromoglycic acid (CGA) was covalently bound to dextran (Mol. Wt 10 000) by two methods. The first, involving chlorination of the free acid, followed by reaction with dextran in formamide, resulted in low yields (1.5%) of an ester complex (CGA-DEX) containing 2.5% w/w CGA. During hydrolysis experiments in phosphate buffer pH 7.4, this conjugate was found to release cromoglycate with a half-life of 10 h. In the second method, CGA was reacted with dextran via an imidazolide intermediate. This procedure gave higher yields (30–50%) of CGA-DEX, with the complexes containing between 0.8 and 40% w/w CGA, dependent upon reaction conditions. CGA-DEX containing 0.8% w/w CGA released cromoglycate with a half-life of 39 min, whilst another batch containing approx. 40% w/w CGA had a release half-life of 290 min, in buffer of pH 7.4 at 37°C. In contrast to previously reported conjugates of metronidazole and benzoic acid, the dextran conjugates of CGA studied released the drug more rapidly.

Synthesis, structure, and reactivity of chiral rhenium carboxylic and carbonic acid ester complexes of the formula [(.eta.5-C5H5)Re(NO)(PPh3)(.eta.1-O:C(X)X')]+ X''-

Synthesis, structure, and reactivity of chiral rhenium carboxylic and carbonic acid ester complexes of the formula [(.eta.5-C5H5)Re(NO)(PPh3)(.eta.1-O:C(X)X')]+ X''-

Preparation of cobalt(II) complexes of β-keto esters

Abstract Using the ethyl, (−)-menthyl and (1-methyl-2-methoxy)ethyl esters of 3-ketobutanoic acid as model compounds, three procedures have been developed for preparing cobalt(II) complexes of β-keto esters in non-aqueous media. These procedures involve the reaction between the lithium enolate, the caesium enolate and the trimethylsilyl enolate of the β-keto ester with an appropriate cobalt(II) compound. All three procedures appear applicable to the preparation of other metal(II) complexes and to β-diketones.

Metallkomplexe mit biologisch wichtigen Liganden, LVIII. C‐Allylglycin‐ und C‐Vinylglycin‐Komplexe von Palladium(II), Platin(II), Rhodium(III), Iridium(III) und deren Reaktionen mit Nucleophilen

Metal Complexes of Biologically Important Ligands, LVIII. – C‐Allylglycine and C‐Vinylglycine Complexes of Palladium(II), Platinum(II), Rhodium(III), Iridium(III) and Reactions with NucleophilesThe synthesis of the complexes (R13P)(Cl2Pt(C‐allylglycine ester) (1), (2) and of (η5‐C5Me5)Ir(C‐allylglycinate) (6) with tridentate O,N,η2;‐CC allylglycinate as ligand is described. Addition of enolates (Nu−) to the coordinated CC bond of 2 gives the γ‐C‐metallated α‐amino acid ester complexes (3). In most cases the platination occurs stereoselectively to yield the five‐membered metallacycle with the substitutents CH2Nu and CO2R2 in trans position. From 3d the new α‐amino acid H2NCH(CO2Me)‐(CH2)3C(Ph)(CO2Et)21 (4) is cleaved. The structures of 3c and 6 have been determined by X‐ray diffraction. C‐Vinylglycinate can be stabilized at the metal atom in the complexes (10) (MRh, Ir).

Metabolism of 99mTc- l,l-Ethyl cysteinate dimer in healthy volunteers

99mTc- l,l-Ethyl cysteinate dimer (ECD) is a brain-perfusion imaging agent, which exhibits selective retention in brain and rapid renal excretion. The pharmacokinetics and metabolism of ECD were studied in vivo in healthy humans and its metabolism in vitro was evaluated in tissue from human brain. In vitro studies showed 99mTc- l,l-ECD to be metabolized to a polar 99mTc-complex. It has been shown previously that most of the activity of 99mTo retained in the brain of the monkey in vivo is in the form of a polar 99mTc complex (Walovitch, Hill, Garrity, Cheesman, Burgess, O'Leary, Watson, Ganey, Morgan and Williams, 1989). Whole body images of the distribution of 99mTc- l,l-ECD (10mCi i.v.) in four adult males showed good uptake in brain, with slow elimination (6.8 ± 0.3% injected dose [mean ± SE] at 5 min), with less than 25% decrease in activity during 4 hr of imaging. Background areas in the head and lungs washed out rapidly, providing ideal imaging conditions. Elimination of 99mTc from venous blood was biphasic, with a plateau of activity between 2–15 min (7–8% injected dose) before a terminal phase, with a t 1 2 of a few hours. Organic extraction of whole venous blood showed greater than 50% of the 99mTc- l,l-ECD to be in the form of polar metabolite(s) at 5 min. They were identified in the urine as the 99mTc ethylenediylbis- l-cysteine, monoethyl ester complex (ECM) and the 99mTc-ethylenediybis- l-cysteine complex (EC). These metabolites were excreted rapidly (75% injected dose in urine within 6hr). The results of this study support the hypothesis that the selective retention in brain, rapid blood elimination and renal excretion of 99mTc- l,l-ECD is due to its metabolic transformation to polar end products.

Heat capacities, self-association and complex formation in alcohol–ester systems

The apparent molar heat capacity, Φc, its associative part, Φc(assoc), and the excess heat capacity, CEp, have been obtained at 25 °C through the concentration range for methanol, hexan-1-ol and decan-1-ol in a series of proton acceptor solvents: methyl acetate, ethyl acetate, octyl acetate, methyl octanoate, decyl acetate and methyl tetradecanoate. The results are explained quantitatively by the Treszczanowicz–Kehiaian (TK) association model and the Flory lattice model in terms of alcohol self-association into tetramers, characterized by an OH—OH equilibrium constant and enthalpy, and by alcohol–ester complex formation characterized by an OH—COO equilibrium constant and enthalpy, each independent of alcohol and ester chain length. As predicted, Φc(assoc) at infinite alcohol dilution is independent of the choice of alcohol, but increases with increasing ester chain length. With increasing alcohol concentration Φc(assoc) passes through a maximum which is much reduced compared with the inert solvent case. For each alcohol, CEp increases with increasing ester chain length, while for the same ester, CEp decreases with increasing alcohol chain length. dCEp/dT is positive for mixtures of methanol and methyl acetate, as predicted by the TK model. It is negative for decanol with methyl acetate, contrary to the TK model, but consistent with a non-random distribution of alcohol tetramers in the solution.

ChemInform Abstract: Comparative Studies on Reactions of α,β‐ and β,γ‐Unsaturated Amides and Acids with Nickel(0), Palladium(0), and Platinum(0) Complexes. Preparation of New Five‐ and Six‐Membered Nickel‐ and Palladium‐Containing Cyclic Amide and Ester Complexes.

AbstractThe zerovalent Ni complex (I) forms with α,β‐unsaturated amides and acids nickel‐containing five‐membered cyclic amide and ester complexes, which are mainly polymeric.

Cyclopentadienyl-ruthenium and -osmium chemistry Part XXXIV. Reactions of 1-alkynes with σ-vinyl-ruthenium complexes. X-ray structures of Ruη 3-CH(CO 2Me)C(CO 2Me)CCHPh(PPh 3)(η-C 5H 5) and Ru(η-C 5H 5)η 5-C 3(CO 2Me) 3CHC tBuCH(CO 2Me)

Reactions between HC 2R (R = Ph, tBu) and the chelate vinyl ester complex RuC(CO 2Me)CHC(O )OMe(PPh 3)(η-C 5H 5) have given η 3-allyl derivatives Ruη 3-CH(CO 2Me)C(CO 2Me)CCHR(PPh 3)(η-C 5H 5), as shown by an X-ray structure of the phenyl derivative. Similarly, the reaction between HC 2Ph and RuC(OMe)CH(CO 2Me)(PPh 3) 2(η-C 5H 5) gave Ruη 3-CH(CO 2Me)C(OMe)CCHPh(PPh 3)(η-C 5H 5). These reactions probably proceed via displacement of the ester carbonyl group or PPh 3 by the 1-alkyne, which isomerises to the corresponding vinylidene before a formal insertion into the Ru-C( sp 2) bond. Complexes containing cyclic adducts of the 1-alkyne and the butadienyl ligand, namely Ru(η-C 5H 5)η 5- C 3(CO 2Me) 3CHCRC H(CO 2Me), were obtained from Ru C(CO 2Me)C(CO 2Me)C(CO 2Me)CH(CO 2Me)(PPh 3)(η-C 5H 5) and HC 2R (R = Ph, tBu), as shown by an X-ray structure of the t-butyl derivative. A small amount of an η 5-vinylcyclohexadienyl complex was also obtained from the reaction with HC 2Ph. In these reactions, the 1-alkyne does not isomerise, probably for steric reasons; the first step may involve replacement of PPh 3 by the alkyne, rather than formation of an η 1-butadienyl complex.

Comparative studies on reactions of .alpha.,.beta.- and .beta.,.gamma.-unsaturated amides and acids with nickel(0), palladium(0), and platinum(0) complexes. Preparation of new five- and six-membered nickel- and palladium-containing cyclic amide and ester complexes [Erratum to document cited in CA113(15):132466t

Comparative studies on reactions of .alpha.,.beta.- and .beta.,.gamma.-unsaturated amides and acids with nickel(0), palladium(0), and platinum(0) complexes. Preparation of new five- and six-membered nickel- and palladium-containing cyclic amide and ester complexes [Erratum to document cited in CA113(15):132466t