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At least 235 records · Page 13Linked to original sources
PubMed1999

Cross-linking and sequence-specific alkylation of DNA by aziridinylquinones. 3. Effects of alkyl substituents.

The cytotoxicities and DNA cross-linking abilities of several alkyl-substituted diaziridinylquinones have been investigated. The cytotoxicities were determined in DT-diaphorase-rich (H460 and HT29) and -deficient (H596 and BE) cell lines. It was shown that the cytotoxicities in these cell lines correlated with the relative rates of reduction by the purified human enzyme and with the cross-linking efficiencies. The rates of reduction by DT-diaphorase were more dependent on the structures of the compounds than the reduction potentials, as determined by cyclic voltammetry. A computer model was also used to explain high efficiency of cross-linking and the GNC sequence selectivity of the reduced methyl-substituted diaziridinylquinones.

Antineoplastic Agents, Alkylating↗
PubMed2000

Rate enhancement with high ratio of the monoalkylated product to the dialkylated product in the alkylation of the lithium enolate of 1-tetralone with reactive alkyl halides.

The reactions of the lithium enolate of 1-tetralone with reactive alkyl halides were examined in the absence and in the presence of 3 eq of various ligands for the lithium. It is shown that the rates of the reactions are enhanced greatly in the presence a tetradentate amine (1,1,4,7,10,10-hexamethyltriethylenetetramine), and the ratio of the monoalkylated product to the dialkylated product is increased under shorter reaction times.

Alkylation↗
PubMed1991

Control over the sequence specificity of DNA alkylation: syntheses and reactions with 32P-end-labelled DNA of N-alkyl-N-nitrosoureas linked to minor groove binding lexitropsins.

The syntheses of N-2-chloroethyl-N-nitrosoureas (Cl-ENU) that are covalently linked to a series of minor groove binding lexitropsins related to distamycin A are reported. The lexitropsins of 2-Cl-ENU show a sequence specificity for alkylating an adenine toward the ends of its DNA affinity binding domains. The reaction of DNA with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea does not yield these products. Therefore, the linking of the 2-Cl-ENU to the minor groove binder qualitatively and quantitatively alters the DNA observed.

Alkylation↗
PubMed2000

The role of the alpha-stereogenic center in the control of stereoselection in the reduction of alpha-alkyl-beta-hydroxy ketones: a highly diastereoselective protocol for the synthesis of 1,2-syn-2-alkyl-1,3-diols

Accurate investigations on the role played by an alpha-stereogenic center in controlling the reduction of various classes of beta-hydroxy ketones allowed us to set up a general and highly diastereoselective protocol for the synthesis of 2-alkyl-1,3-diols with 1,2-syn relationship. This methodology is based on the conversion of a beta-hydroxy ketone into the corresponding titanium alcoholate that permits us to organize the substrate in a stable and rigid structure, which stereofacially favors attacking hydride ions. The use of THF as solvent makes available a variety of hydride donors that cover a large spectrum of steric demand: the choice of the more appropriate one depends on the conformational stability of the cyclic intermediate. Excellent results are obtained also in the presence of an additional stereogenic center in the beta-position, even if it exerts a concordant or an opposite steric effect with respect to the alpha-substituent.

Journal Article↗
PubMed1983

Antileukemic effect of alkyl phospholipids. II. Prolongation of survival times of leukemic mice by alkyl ethyleneglycophospholipids.

Alkyl ethyleneglycophospholipids induced differentiation in vitro of mouse myeloid leukemia M1 cells into mature granulocytes and macrophages. The compounds also prolonged the survival of syngeneic SL mice inoculated with M1 cells. Although in mice with florid leukemia these compounds alone scarcely affected survival, administration of dodecyl ethyleneglycophospholipid with pyridinioethyl as a polar group plus actinomycin D significantly prolonged survival.

Animals↗
PubMed1991

Synthesis of alkyl [(alkyl 6-deoxy-alpha-D-gluco-heptopyranosyl- uronate) 6-deoxy-alpha-D-gluco-heptopyranosid]uronates, a novel type of mirror pseudo cord factor.

The 1-octyl, 1-pentadecyl, 1-hexadecyl, 1-heptadecyl, and 1-octadecyl diesters of (6-deoxy-alpha-D-gluco-heptopyranosyluronic acid) 6-deoxy-alpha-D-gluco-heptopyranosiduronic acid, a new homolog of trehalosuronic acid, were prepared by two procedures. One procedure involved conversion of the peracetylated acid into its dichloride, reaction of the latter with the alkanols, and acid-catalyzed deacetylation of the products, whereas the other consisted of reaction of alkyl mesylates with the potassium salt of the unprotected acid.

Carbohydrate Conformation↗
PubMed1977

Evaluation of genetic risks of alkylating agents. III. Alkylation of haemoglobin after metabolic conversion of ethene to ethene oxide in vivo.

Male CBA mice, exposed to air contaminated with [14C] labelled ethene, were able to metabolize this olefine to ethene oxide. The amount of epoxide formed was quantitatively determined from the degree of alkylation of cysteine and histidine in haemoglobin. These hydroxyethylated amino acids were determined by ion-exchange chromatography of the labelled products. In a separate experiment the formation of S-(2-hydroxyethyl) cysteine was verified by gas chromatography--mass spectrometry. In addition this cysteine derivative was determined in urine by thin-layer chromatography. For unknown reasons, uninduced mice varied strongly in the extent to which they converted ethene to epoxide.

Aerosols↗
PubMed2006

Zeolite-catalyzed Helferich-type glycosylation of long-chain alcohols. Synthesis of acetylated alkyl 1,2-trans glycopyranosides and alkyl 1,2-cis C2-hydroxy-glycopyranosides.

Zeolite-catalyzed glycosylation of long-chain alcohols, using the inexpensive and readily available peracetylated beta-D-gluco- and galactopyranoses as glycosyl donors under solvent free conditions, has been explored for the first time. Among the various forms (H-, Na-, Fe- and Zn) of beta zeolite examined as catalysts in the reaction of 1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose with cetyl alcohol, Fe-beta zeolite gave the maximum yield of 63% of cetyl 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranoside and cetyl 3,4,6-tri-O-acetyl-alpha-D-galactopyranoside. Fe-beta Zeolite-catalyzed glycosylation was found to be general affording the title compounds in each case in a moderate yield, but with a good stereoselectivity. The yield of synthetically valuable acetylated long-chain alkyl 1,2-cis C2-hydroxy-glycopyranosides obtained in the present single-step procedure is considerably higher than that of the previously reported multi-step method employing the Stork silicon tether approach.

Catalysis↗
PubMed1998

Chain-melting transition temperatures of phospholipids with acylated or alkylated headgroups (N-acyl phosphatidylethanolamines and O-alkyl phosphatidic acids), or with alpha-branched chains.

The biphasic dependence of the chain-melting transition temperature on chainlength, nN, of the headgroup-attached chain of N-acyl phosphatidylethanolamines and of O-alkyl phosphatidic acids is interpreted in terms of a different linear dependence of the transition enthalpy and entropy on nN for long and short chains, respectively. A consistent expression of the form [equation: see text], where DeltanN is the critical chainlength at which the packing mode of the headgroup-attached chains changes, is found to apply systematically to the transition temperatures for both sets of lipids, over the range nN=2-18. This thermodynamic analysis demonstrates that the headgroup-attached chain is located in an environment that differs for long and short chains. Similar considerations apply also to phosphatidylcholines with alpha-branched glycerol-attached chains.

Entropy↗
PubMed1999

Surface properties and hemocompatibility of alkyl-siloxane monolayers supported on silicone rubber: effect of alkyl chain length and ionic functionality.

Self-assembled monolayers of alkylsiloxanes supported on poly(dimethylsiloxane) (PDMS) rubber were used as model systems to study the relation between blood compatibility and surface composition. The inner lumen of PDMS tubes were first treated with an oxygen plasma. The resultant oxidized surfaces were post-derivatized by reaction with alkyltrichlorosilanes to form the monolayer films. The alkyl chain lengths used were slightly longer than in a previous study, and this may alter the phase-state of the monolayer from liquid-like to crystalline. The chemical properties of the monolayer were controlled by varying the chemical composition of the alkyltrichlorosilanes used. Terminal functionalities included -CH3, -CF3, -COOH, -SO3H and -(CH2CH2O)4OH. Surface derivatization was verified with static contact angle measurements and X-ray photoelectron spectroscopy. Blood compatibility was evaluated using a canine ex vivo arterio-venous series shunt model. Surfaces grafted with hydrophobic head groups such as -CH3 and -CF3 were significantly less thrombogenic than the surfaces composed of ionic head groups such as -COOH and -SO3H. Surfaces enriched in -(CH2CH2O)4OH had an intermediate thrombogenicity. Silastic pump grade tubing and polyethylene tubing, used as controls, were found to be the least thrombogenic of all the surfaces tested.

Animals↗
PubMed1975

Alkyl isocyanates as active site-specific reagents for serine proteases. Location of alkyl binding site in chymotrypsin by X-ray diffraction.

The structure of octylcarbamoyl-alpha-chymotrypsin to a resolution of 3.0 A is described. The n-octyl side chain of the active site directed irreversible inactivator octyl isocyanate is bound exclusively in the hydrophobic substrate binding pocket. The n-octyl isocyanate forms a planar urethane bond with the Ser-195 Ogamma and extends approximately 1 A deeper into the hydrophobic pocket than the indolyl group of indoleacryloyl-alpha-chymotrypsin (Henderson, R. (1970), J. Mol. Biol. 54, 341). All the structural changes are essentially identical with those observed in indoleacryloyl-alpha-chymotrypsin including the observation of a hydrogen bonded water molecule between the carbonyl oxygen of the octylcarbamoyl group and the imidazole group of His-57. The observed mode of n-octyl alkyl binding to chymotrypsin is consistent with the hypothesis proposed earlier (Brown, W. E. and Wold, F. (1973), Biochemistry 12, 828).

Binding Sites↗
PubMed2006

Synthesis, characterization, properties, and drug release of poly(alkyl methacrylate-b-isobutylene-b-alkyl methacrylate).

Polyisobutylene (PIB)-based block copolymers have attracted significant interest as biomaterials. Poly(styrene-b-isobutylene-b-styrene) (SIBS) has been shown to be vascularly compatible and, when loaded with paclitaxel (PTx) and coated on a coronary stent, has the ability to deliver the drug directly to arterial walls. Modulation of drug release from this polymer has been achieved by varying the drug/polymer ratio, by blending SIBS with other polymers, and by derivatizing the styrene end blocks to vary the hydrophilicity of the copolymer. In this paper, results are reported on the synthesis, physical properties, and drug elution profile of PIB-based block copolymers containing methacrylate end blocks. The preparation of PIB-poly(alkyl methacrylate) block copolymers has been accomplished by a new synthetic methodology using living cationic and anionic polymerization techniques. 1,1-Diphenylethylene end-functionalized PIB was prepared from the reaction of living PIB and 1,4-bis(1-phenylethenyl)benzene, followed by the methylation of the resulting diphenyl carbenium ion with dimethylzinc (Zn(CH(3))(2)). PIB-DPE was quantitatively metalated with n-butyllithium in tetrahydrofuran, and the resulting macroinitiator could initiate the polymerization of methacrylate monomers, yielding block copolymers with high blocking efficiency. Poly(methyl methacrylate-b-isobutylene-b-methyl methacrylate) (PMMA-b-PIB-b-PMMA) and poly(hydroxyethyl methacrylate-b-isobutylene-b-hydroxyethyl methacrylate) (PHEMA-b-PIB-b-PHEMA) triblock copolymers were synthesized and used as drug delivery matrixes for coatings on coronary stents. The PMMA-b-PIB-b-PMMA/PTx system displayed zero-order drug release, while stents coated with PHEMA-b-PIB-b-PHEMA/PTx formulations exhibited a significant initial burst release of PTx. Physical characterization using atomic force microscopy and differential scanning calorimetry of the formulated PMMA-b-PIB-b-PMMA coating matrix indicated the partial miscibility of PTx with the PMMA microphase of the matrix.

Calorimetry, Differential Scanning↗
PubMed2004

Low melting inorganic salts of alkyl-, fluoroalkyl-, alkyl ether-, and fluoroalkyl ether-substituted oxazolidine and morpholine.

N-Alkyl- and N-fluoroalkyl-substituted oxazolidinium- and morpholinium-based quaternary salts and ionic liquids have been synthesized and characterized. Reactions of N-methyloxazolidine (1) or N-methylmorpholine (2) with 3-fluoropropyl bromide or iodopropane in THF at 25 degrees C gave the quaternary salts (3a,b, 4a,b). These salts were metathesized with various metal salts to yield the corresponding ionic liquids (5a-h, 6a-i). N-Alkoxyethyl- and N-(fluoroalkoxy)ethyl-substituted morpholines (8-11) were prepared and quaternized with methyl iodide (8a-11a). Their corresponding ionic liquids (12-18) were obtained by anion exchange and characterized. For both series of compounds, nitrate, hexafluorophosphate, perchlorate, triflate, and bis(trifluoromethanesulfonyl)amide were utilized. Most of the final products are liquids at 25 degrees C and are thermally stable with long liquid ranges as determined by thermal gravimetric analyses. For compounds 12, 16, and 18, thermal stabilities of > or =400 degrees C were observed. All the new compounds were characterized by spectroscopic and elemental analyses. Their densities and viscosities were also determined.

Journal Article↗
PubMed1995

[[[(Thienylcarbonyl)alkyl]oxy]phenyl]- and [[[(pyrrylcarbonyl)alkyl]oxy]phenyl]oxazoline derivatives with potent and selective antihuman rhinovirus activity.

As an approach to more extensive structural modifications of [(oxazolylphenoxy)alkyl]isoxazoles, we synthesized new compounds characterized by the replacement of the isoxazole nucleus with furan, pyrrole, and thiophene rings and by the presence of a ketocarbonyl group in the aliphatic chain connecting these pentatomic heterocycles to the 4-(4,5-dihydro-2-oxazolyl)phenoxy, 4-(ethoxycarbonyl)phenoxy, and 4-carboxyphenoxy moieties. Some pentamethylene derivatives were also prepared, and their antirhinovirus activity was compared to that of the corresponding ketomethylene derivatives. Syntheses were carried out by Friedel-Crafts acylation of the above pentatomic heterocycles and subsequent reaction of chloroalkyl ketones with the proper 4-substituted phenol. Reduction of the ketone function afforded the related polymethylene derivatives. The new compounds were tested for antirhinovirus activity and cytotoxicity in comparison with WIN 51711, used as reference drug. Inspection of the structure-activity relationships revealed that the thiophene ring and the carbonyl group are the structural components which to a large extent contribute to the positive biological profile in terms of both wideness of spectrum and low cytotoxicity. Among the various derivatives, compounds 8e,d showed in vitro the same potency of WIN 51711 but a cytotoxicity at least 10 times lower.

Antiviral Agents↗
PubMed2000

Alkyl- and arylthiodediazoniations of dry arenediazonium o-benzenedisulfonimides. Efficient and safe modifications of the stadler and ziegler reactions to prepare alkyl aryl and diaryl sulfides

The reaction between dry arenediazonium o-benzenedisulfonimides 1 and sodium thiolates in anhydrous methanol represents an efficient and safe procedure, of general validity, for the preparation of unfunctionalized or variously functionalized alkyl aryl and diaryl sulfides. As a rule, the reaction temperature was maintained at 0-5 degrees C for the alkylthiodediazoniations and at room temperature (20-25 degrees C) for the arylthiodediazoniations. The sulfide yields are generally high; of the 63 considered examples, 43 gave yields greater than 80% and 13 were between 70% and 80%. Lower yields were obtained only when sterically hindered diazonium salts or thiols were used. A good amount of the o-benzenedisulfonimide (8) was always recovered from the reactions and could be reused to prepare salts 1. The copious experimental data collected in homogeneous conditions have offered several starting points for the study of the mechanism of these reactions.

Journal Article↗
PubMed2001

Intracellular oxidation of dipeptides. Base-promoted elimination from N-halodipeptides to 2-[N-alkyl-N-(2-N-alkylimino-2-alkyl-ethanoyl)amino]-2,2-dialkylethanoic acids.

One of the possible ways of intracellular oxidation of peptides is via the formation of the corresponding (N-X)-dipeptides, that then undergo base-promoted elimination to yield intermediate 2-[N-alkyl-N-(2-N-alkylimino-2-alkylethanoyl)amino]-2,2-dialkylethanoic acids, which subsequently hydrolyze. Such an elimination process is general-base catalyzed, with Brønsted beta values ranging from 0.26 to 0.31, which suggests an essentially constant degree of proton transfer at the TS. For (N-X)-dipeptides, the ratio k(N-Br)/k(N-Cl) ranges from 2.5 to 15, suggesting a structural dependence of the degree of N-X bond breaking at the TS. The values of beta and k(N-Br)/k(N-Cl) support a concerted asynchronous A(xh)D(H)D(N) mechanism, its TS changing from reactant-like to slightly nitrenium-like depending on the structure of the starting dipeptide. As a consequence of the antiperiplanarity requirements of the reaction, the steric interaction between the leaving group and the substituent on the C bearing the H to be eliminated controls the reaction rate. Such steric interaction is rather important, as indicated by the steric crossed-interaction coefficient (p(ssy') = 0.33). Semiempirical calculations show that bulky substituents in the vicinity of the reaction center imply additional energy requirements for the system to achieve the antiperiplanarity needed at the TS for the reaction to proceed. From the observations reported it follows that (N-X)-dipeptides lose their oxidizing power more readily than analogous (N-X)-amino acids or (N-X)-amines, opening a possible pathway to lessen intracellular halogen-based oxidative stress.

Acetates↗