A comparative study of solid carbon acid catalysts for the esterification of free fatty acids for biodiesel production. Evidence for the leaching of colloidal carbon.

The preparation of a variety of sulfonated carbons and their use in the esterification of oleic acid is reported. All sulfonated materials show some loss in activity associated with the leaching of active sites. Exhaustive leaching shows that a finite amount of activity is lost from the carbons in the form of colloids.

Water soluble acyloxy nitroso compounds: HNO release and reactions with heme and thiol containing proteins.

Nitroxyl (HNO) has gained interest as a potential treatment of congestive heart failure through the ability of the HNO donor, Angeli's salt (AS), to evoke positive inotropic effects in canine cardiac muscle. The release of nitrite during decomposition limits the use of AS requiring other HNO sources. Acyloxy nitroso compounds liberate HNO and small amounts of nitrite upon hydrolysis and the synthesis of the water-soluble 4-nitrosotetrahydro-2H-pyran-4-yl acetate and pivalate allows for pig liver esterase (PLE)-catalysis increasing the rate of decomposition and HNO release.

Analysis of the DNA damage produced by a platinum-acridine antitumor agent and its effects in NCI-H460 lung cancer cells.

High-performance liquid chromatography in conjunction with electrospray mass spectrometry (LC-ESMS) was used to structurally characterize the adducts formed by the platinum-acridine agent [PtCl(en)(N-(2-(acridin-9-ylamino)ethyl)-N-methylpropionimidamide)](NO(3))(2) (compound 1) in cell-free DNA. Compound 1 forms monofunctional adducts exclusively with guanine, based on the fragments identified in enzymatic digests (dG*, dGMP*, dApG*, and dTpG*, where the asterisk denotes bound drug). The time course of accumulation and DNA adduct formation of compound 1 and the clinical drug cisplatin in NCI-H460 lung cancer cells at physiologically relevant drug concentrations (0.

Simple synthesis of 1,3-cyclopentanedione derived probes for labeling sulfenic acid proteins.

Facile, two-step synthesis and kinetic characterization of new chemical probes for selective labeling of sulfenic acid (-SOH) in proteins are presented. The synthesis route relies on the simple and highly efficient Michael addition of thiol containing tags or linkers to 4-cyclopentene-1,3-dione, the unsaturated derivative of 1,3-cyclopentanedione.

Water-soluble triarylphosphines as biomarkers for protein S-nitrosation.

S-Nitrosothiols (RSNOs) represent an important class of post-translational modifications that preserve and amplify the actions of nitric oxide and regulate enzyme activity. Several regulatory proteins are now verified targets of cellular S-nitrosation, and the direct detection of S-nitrosated residues in proteins has become essential to better understand RSNO-mediated signaling. Current RSNO detection depends on indirect assays that limit their overall specificity and reliability.

Preparation and Diels-Alder/cross coupling reactions of a 2-diethanolaminoboron-substituted 1,3-diene.

A 2-diethanolamine boronyl substituted 1,3-diene has been synthesized in high yield and characterized spectroscopically as well as by X-ray crystallography. This diene has then subsequently been used in a number of fast, high yielding Diels-Alder/cross coupling reactions.

Preparation of 2-silicon-substituted 1,3-dienes and their Diels-Alder/cross-coupling reactions.

2-Triethoxysilyl-substituted 1,3-butadiene has been prepared in 30-g quantities from chloroprene via a simple synthetic procedure. Silatrane- and catechol-substituted analogues of this main group element substituted diene were then prepared on a 10-g scale by ligand exchange and characterized by X-ray crystallography in addition to standard spectroscopic techniques. 2-Dimethylphenylsilyl-1,3-butadiene has also been prepared from chloroprene on an 8-g scale.

Reductive phosphine-mediated ligation of nitroxyl (HNO).

Nitroxyl (HNO) demonstrates a unique chemical and biological profile compared to nitric oxide (NO). Phosphorus NMR studies reveal that HNO reacts with triarylphosphines to give the corresponding phosphine oxide and aza-ylide. In the presence of a properly situated electrophilic ester, the aza-ylide undergoes a Staudinger ligation to yield an amide with the nitrogen atom being derived from HNO.

Differential potencies of naturally occurring regioisomers of nitrolinoleic acid in PPARgamma activation.

Previous studies demonstrated that the naturally occurring electrophile and PPARgamma ligand, nitrolinoleic acid (NO(2)-LA), exists as a mixture of four regioisomers [Alexander, R. L., et al.

A non-cross-linking platinum-acridine agent with potent activity in non-small-cell lung cancer.

The cytotoxic complex, [PtCl(Am)2(ACRAMTU)](NO3)2 (1) ((Am)2 = ethane-1,2-diamine, en; ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea), is a dual platinating/intercalating DNA binder that, unlike clinical platinum agents, does not induce DNA cross-links. Here, we demonstrate that substitution of the thiourea with an amidine group leads to greatly enhanced cytotoxicity in H460 non-small-cell lung cancer (NSCLC) in vitro and in vivo. Two complexes were synthesized: 4a (Am2 = en) and 4b (Am = NH3), in which N-[2-(acridin-9-ylamino)ethyl]-N-methylpropionamidine replaces ACRAMTU.

Preparation of 2-trialkylsiloxy- substituted 1,3-dienes and their diels-alder/cross-coupling reactions.

[reaction: see text] 2-Triethylsiloxy-substituted 1,3-butadiene has been prepared in gram quantities from chloroprene via a simple synthetic procedure. Silatrane and catechol-substituted analogues of this main group element substituted diene were prepared by ligand exchange and characterized by X-ray crystallography in addition to standard spectroscopic techniques. Diels-Alder reactions of these dienes are reported as well as subsequent TBAF assisted/Pd-catalyzed Hiyama cross-coupling reactions of those Diels-Alder adducts.

Modulation of nitrated lipid signaling by multidrug resistance protein 1 (MRP1): glutathione conjugation and MRP1-mediated efflux inhibit nitrolinoleic acid-induced, PPARgamma-dependent transcription activation.

Recent data has shown that nitrolinoleic acid (LNO(2)), an electrophilic derivative of linoleic acid, has several important bioactivities including antiinflammatory, antiplatelet, vasorelaxation, and-as a novel potent ligand of PPARgamma-transcription regulating activities. Moreover, LNO(2) is formed in abundance in vivo at levels sufficient to mediate these bioactivities. In order to investigate the role of glutathione conjugation and MRP1-mediated efflux in the regulation of PPARgamma-dependent LNO(2) signaling, regioisomers of LNO(2) were synthesized and characterized.

Guanine binding of a cytotoxic platinum-acridin-9-ylthiourea conjugate monitored by 1-D 1H and 2-D [1H,15N] NMR spectroscopy: hydrolysis is not the rate-determining step.

The reaction of [PtCl(en)(ACRAMTU)](NO(3))(2) (PT-ACRAMTU, 1; ACRAMTU=1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, en=ethane-1,2-diamine) and the [(15)N]-en labeled analogue, 1', with 2'-deoxyguanosine (dG) was studied by (1)H NMR and two-dimensional [(1)H,(15)N] HSQC (heteronuclear single quantum coherence) spectroscopy. Reactions were performed in phosphate buffered solution at 37 degrees C at various ratios and total concentrations of reactants. The (1)H NMR data suggest that the hydrolyzed form of the drug, [Pt(H(2)O)(en)(ACRAMTU)](3+) (1a), forms at a rate (k(1)) similar to that observed in classical platinum chloroam(m)ines but to only a minor extent ( approximately 15%).

Solution structural study of a DNA duplex containing the guanine-N7 adduct formed by a cytotoxic platinum-acridine hybrid agent.

[PtCl(en)(ACRAMTU-S)](NO(3))(2) (PT-ACRAMTU; en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) is a dual metalating/intercalating DNA binding drug conjugate that shows cytotoxicity at micromolar to nanomolar concentrations in a wide range of solid tumor cell lines. In approximately 80% of its adducts, PT-ACRAMTU binds to guanine-N7 in the major groove, selectively at 5'-CG sites [Budiman, M. E.

Role of phenoxyl radicals in DNA adduction by chlorophenol xenobiotics following peroxidase activation.

Chlorophenol (CP) toxins are classified as probable human carcinogens and are known to undergo bioactivation to generate benzoquinone (BQ) electrophiles that react covalently with biopolymers. Recently, we characterized the ability of pentachlorophenol (PCP) to react covalently with deoxyguanosine (dG) following treatment with horseradish peroxidase (HRP)/H2O2 or myeloperoxidase to yield a C8-dG oxygen (O)-adduct that suggested the intermediacy of the pentachlorophenoxyl radical in covalent bond formation [Dai, J., Wright, M.

Nitroxyl (HNO) release from new functionalized N-hydroxyurea-derived acyl nitroso-9,10-dimethylanthracene cycloadducts.

A thermal retro-Diels-Alder decomposition of N-hydroxyurea-derived acyl nitroso compounds and 9,10-dimethylanthracene cycloadducts followed by acyl nitroso compound hydrolysis produces nitrous oxide, evidence for the formation of nitroxyl, the one-electron reduced form of nitric oxide that has drawn considerable attention for its potential roles in biological systems. EPR and NMR spectroscopy provide further evidence for nitroxyl formation and kinetic information, respectively. Such compounds may prove to be useful alternative nitroxyl donors.

Metal-intercalator-mediated self-association and one-dimensional aggregation in the structure of the excised major DNA adduct of a platinum-acridine agent.

The crystal structure of the excised major DNA monoadduct, [Pt(en)(ACRAMTU-S)(dGuo-N7)]3+ ("dGuo*"; en = ethane-1,2-diamine; ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, acridinium cation; dGuo = 2'-deoxyguanosine), of a platinum-acridine cytotoxic agent is reported. The adduct dGuo*, previously identified in enzymatic digests of native DNA treated with this drug, is partially deprotonated and dimerizes through formation of a rare GG- mismatch base pair, which is sandwiched between the planar chromophores of the acridine nonleaving groups linked to platinum. NMR evidence exists that indicates that the dimeric form persists in neutral aqueous solution.

Structure-activity relationships in platinum-acridinylthiourea conjugates: effect of the thiourea nonleaving group on drug stability, nucleobase affinity, and in vitro cytotoxicity.

The synthesis, cytotoxicity, and nucleoside binding of some platinum-acridinylthiourea conjugates derived from the prototypical compound [PtCl(en)(ACRAMTU)](NO3)2 ("PT-ACRAMTU"; en=ethane-1,2-diamine, ACRAMTU=1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, protonated form) are reported. To establish structure-activity relationships within this class of compounds, systematic changes were made to the thiourea nonleaving group, which links the intercalator to platinum. Three new derivatives of ACRAMTU, one di-, one tri-, and one tetraalkylated, were generated, where the degree of alkylation indicates the number of alkyl groups attached to the SCN2 framework.

An oxygen-bonded c8-deoxyguanosine nucleoside adduct of pentachlorophenol by peroxidase activation: evidence for ambident c8 reactivity by phenoxyl radicals.

The ability of the carcinogenic environmental toxin pentachlorophenol (PCP, 1) to react with DNA bases has been assessed using MS and NMR. Treatment of PCP (100 microM) with horseradish peroxidase (HRP/H(2)O(2)) or myeloperoxidase (MPx/H(2)O(2), from human leukocytes) in the presence of excess deoxyguanosine (dG, 2 mM) led to the isolation and identification of the oxygen-bonded C8-dG nucleoside adduct 4. The reaction was absolutely specific for dG; no detectable adduct(s) was observed from HRP/H(2)O(2) and PCP in the presence of deoxyadenosine, deoxycytidine, or thymidine.

trans-Bis(dimethylglyoximato-kappa2N,N')(1-hexenyl)(pyridine-kappaN)cobalt(III): a cobaloxime-substituted terminal alkene that rapidly isomerizes to a cobaloxime-substituted internal alkenyl complex.

An unusual cobaloxime-substituted terminal alkene, [Co(C(6)H(11))(C(4)H(7)N(2)O(2))(2)(C(5)H(5)N)], has been isolated and characterized by X-ray crystallography. The double bond in the alkene readily isomerizes, but the title compound could be isolated and structurally characterized at low temperature.

Ochratoxin a forms a carbon-bonded c8-deoxyguanosine nucleoside adduct: implications for c8 reactivity by a phenolic radical.

The ability of the carcinogenic fungal toxin Ochratoxin A (OTA, 1) to react with deoxyguanosine (dG) has been assessed using electrospray mass spectrometry and NMR. Photoexcitation of OTA (100 muM) in the presence of 50 mol equiv of dG led to the isolation and identification of the C8-deoxyguanosine nucleoside adduct 4. Importantly, the same adduct was formed upon oxidative activation of OTA using horseradish peroxidase (HRP)/H2O2 or the transition metals Fe(II) and Cu(II), as evidenced by mass spectrometry.

Zinc and copper complexes of prodigiosin: implications for copper-mediated double-strand DNA cleavage.

[reaction: see text] Zinc(II) and copper(II) complexes of prodigiosin (1) have been characterized. All N-atoms of 1 bind Cu(II) to generate 5: the complex exhibits regiospecific oxidation of the C-pyrrole. In contrast, coordination by Zn(II) to 1 produces Zn(1)(2) (8), a 4-coordinate tetrahedral complex.

Photochemically catalyzed reaction of ochratoxin A with D- and L-cysteine.

The photolysis (>300 nm) of ochratoxin A (OTA, N-[[(3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-7-isochromanyl]carbonyl]-3-phenyl-L-alanine, 1) in the presence of excess (2 and 12 molar equiv) cysteine (CySH) has been investigated and found to yield sulfur adducts 5 and 6 that are characterized by liquid chromatography-mass spectrometry and 1H-NMR spectroscopy. The adduct 5 was ascribed to the Michael addition conjugate resulting from covalent attachment of CySH to the ochratoxin quinone (4) generated by photooxidation of OTA. This species was also formed by photolysis of a synthetic sample of the hydroquinone of OTA (ochratoxin hydroquinone, 3) in the presence of 12 equiv L-CySH.

Detection and characterization of a glutathione conjugate of ochratoxin A.

The ability of the carcinogenic mycotoxin ochratoxin A (OTA) to react with reduced glutathione (GSH) has been assessed using electrospray ionization (ES)-MS techniques. On the basis of the assumption that OTA undergoes biotransformation into the reactive quinone species OTQ (6), a synthetic sample of the reduced form of OTQ (6), hydroquinone OTHQ (5), was prepared and photoreacted with 6 M equiv of GSH to yield an authentic sample of the conjugate 8 that was definitively identified by mass spectrometry, UV-vis spectroscopy and NMR. With the authentic sample of 8 in hand, it was demonstrated that the same conjugate is produced from reaction of 100 microM OTA (1) in the presence of 5 mM GSH following incubation for 1 h with either horseradish peroxidase (HRP)/H(2)O(2), rat liver microsomes (RLM)/NADPH or free Fe(II).