Showing papers on "Carboxylic acid published in 1995"

Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes : role of cytochrome P4502C and 3A subfamily members

Abstract: Losartan is a 4-chloro-5-hydroxymethylimidazole derivative that is a potent and highly selective angiotensin II receptor antagonist. Losartan is metabolized in vivo in rats, monkeys, and humans to a carboxylic acid derivative E3174 that is pharmacologically more active than the parent compound. We have investigated the mechanism of this biotransformation in human liver preparations. The oxidation of both losartan and the putative aldehyde intermediate E3179 was catalyzed by the microsomal fraction, required both NADPH and molecular oxygen, and was inhibited by SKF 525-A, implicating cytochrome P450 (CYP). When incubations with each substrate were performed under an atmosphere of 18O2, the extent of 18O incorporation into the carboxylic acid product was consistent with a mechanism for losartan oxidation involving an aldehyde intermediate. To substantiate the involvement of CYP in these reactions, incubations with losartan and the aldehyde E3179 were performed in the presence of isoform-selective inhibitors. Inhibitors of CYP3A4/5 (gestodene and ketoconazole) and CYP2C9/10 (sulfaphenazole) attenuated the oxidation of both substrates. It was then demonstrated that microsomes containing either recombinant human liver CYP2C9 or CYP3A4 were capable of oxidizing both losartan and the aldehyde E3179 to the carboxylic acid E3174. Subsequently, it was shown that rabbit anti-CYP2C9 and anti-CYP3A3/4 inhibited the oxidation of losartan to E3174 in incubations with human liver microsomes. These studies support the hypothesis that the aldehyde E3179 is an intermediate in the oxidation of losartan and that this two-step reaction is catalyzed in human liver microsomes by members of the CYP3A and CYP2C subfamilies.

Strong-Acid, carboxyl-group structures in fulvic Acid from the suwannee river, georgia. 1. Minor structures.

Abstract: An investigation of the strong-acid characteristics (PK a 3.0 or less) of fulvic acid from the Suwannee River, Georgia, was conducted. Quantitative determinations were made for amino acid and sulfur-containing acid structures, oxalate half-ester structures, malonic acid structures, keto acid structures, and aromatic carboxyl-group structures. These determinations were made by using a variety of spectrometric ( 13 C-nuclear magnetic resonance, infrared, and ultraviolet spectrometry) and titrimetric characterizations on fulvic acid or fulvic acid samples that were chemically derivatized to indicate certain functional groups. Only keto acid and aromatic carboxyl-group structures contributed significantly to the strong-acid characteristics of the fulvic acid ; these structures accounted for 43% of the strong-acid acidity. The remaining 57% ofthe strong acids are aliphatic carboxyl groups in unusual and/or complex configurations for which limited model compound data are available.

pH Dependence of Carboxylic and Mineral Acid Extraction by Amine-Based Extractants: Effects of pKa, Amine Basicity, and Diluent Properties

Abstract: Extraction mechanism strongly depends on the acid-base properties of the extractant as well as on those of the extracted acid. For amines of basicity similar to that of the anion of the extracted acid, or higher, extraction is governed by ion-pair formation. H-bonding of undissociated acid becomes important only for extraction of weak acids by weak bases. Extraction mechanism determines the effect of various parameters. Thus the degree of extraction is most sensitive to pH at about the pK{sub a} of the amine for extraction through ion-pair formation. Extraction by H-bonding, however, is most sensitive at about the pK{sub a} of the acid. Polar and protic diluents enhance extraction through ion-pair formation, but may have no effect on H-bonding or even hinder it. Extraction through ion-pair formation prefers stronger acids at low pH while H-bonding extracts weaker acids more efficiently. Clarification of the extraction mechanism and its dependence on extracted acid properties and on the pH provide for designing extractants of high efficiency and selectivity.

Cocaine and 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid ester and amide analogues. New high-affinity and selective compounds for the dopamine transporter.

Abstract: Several 2 beta-carboxylic acid ester and amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid were prepared. The binding affinities of these compounds, and of some previously prepared analogues, at the dopamine (DA), norepinephrine (NE), and serotonin (5-HT) transporters were determined. The phenyl esters of 3 beta-(4'-methylphenyl)- and 3 beta-(4'-chlorophenyl)tropane-2 beta-carboxylic acid are highly potent and highly selective for the DA transporter. The isopropyl esters of 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid also possess high DA affinity and show significant DA transporter selectivity. Similarly, the phenyl and isopropyl ester analogues of cocaine are much more selective for the DA transporter than cocaine. Tertiary amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acids are more potent inhibitors of radioligand binding at the DA transporter than the primary and secondary amide analogues. In particular, 3 beta-(4'-chlorophenyl)tropane-2 beta-N-morpholinocarboxamide as well as the 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-N- pyrrolidinocarboxamides possess high affinity and selectivity for the DA transporter. The N,N-dimethylamide cocaine analogue is the most selective cocaine amide derivative for the DA transporter. High correlation between the inhibition of radioligand binding and inhibition of uptake at the DA, NE, and 5-HT transporter was found for a selected group of analogues. Within this group, one compound, the isopropyl ester of 3 beta-(4'-iodophenyl)-tropane-2 beta-carboxylic acid, was found to be more potent in the inhibition of radioligand binding than in the inhibition of DA uptake. Taken together with its high potency and selectivity at the DA transporter, this suggests that this compound may be a lead in the development of a cocaine antagonist.

Ketones from monocarboxylic acids: Catalytic ketonization over oxide systems

Abstract: The ketonization of acetic acid was studied in the presence of a series of 20 oxide catalysts supported on SiO2, TiO2 and Al2O3. The reactions were performed in the continuous flow reactor. Ceria-and mangania-containing catalysts exhibited the highest activity. The influence of the oxide phase concentration, liquid hourly space velocity and of the type of the catalyst carrier on the acetone yield was determined. Alumina support showed the most pronounced effect on the activity of deposited oxides. High yields of 3-pentanone, 6-undecanone, and 7-tridecanone were achieved in the ketonization of appropriate acids in the presence of mangania and ceria catalysts in large-scale laboratory experiments.

Enzymatic ring-opening polymerization of lactones to polyesters by lipase catalyst : unusually high reactivity of macrolides

Abstract: Enzymatic ring-opening polymerization of macrolides was carried out by using various lipases as catalysts. The monomers used in this study were 11-undecanolide (12-membered, UDL) and 15-pentadecanolide (16-membered, PDL). Among the enzymes examined, lipases derived from Pseudomonas fluorescens (lipase P) and from Candida cylindracea (lipase B) gave polyUDL with high molecular weight in a high yield. From 1H and 13C NMR analysis, the polymer was found to possess the terminal structure of a carboxylic acid group at one end and a hydroxyl group at the other. The rate of the UDL polymerization using lipase P was larger than that using lipase B, whereas the polymerization of UDL using lipase B produced the polymer of higher molecular weight in comparison with that obtained by using lipase P. Lipases from Pseudomonas sp. and porcine pancreas showed a catalytic activity for the polymerization of UDL. PDL was also polymerized by lipase catalyst to give the corresponding polyester. The enzymatic polymerizations of...

Chemo-enzymatic epoxidation of unsaturated carboxylic acids

Abstract: Unsaturated carboxylic acids are converted to percarboxylic acids catalyzed by an immobilized lipase from Candida antarctica (Novozym 435 R ). These unsaturated percarboxylic acids are only intermediates and epoxidize themselves in good yields and almost without consecutive reactions. The mechanism of the oxygen-transfer is found to be predominantly intermolecular and the formation of the percarboxylic acids proceeds via two different catalytic reactions. The lipase is surprisingly stable under the reaction conditions; it is recovered and reused fifteen times to produce epoxy-stearic acid on a multi-gram scale.

From minerals to materials: synthesis of alumoxanes from the reaction of boehmite with carboxylic acids

Abstract: Reaction of pseudo-boehmite, [Al(O)(OH)]n, with carboxylic acids (RCO2H) results in the formation of the carboxylatoalumoxanes, [Al(O)x(OH)y(O2CR)z]n where 2x + y + z = 3 and R = C1–C13. The physical properties of the alumoxanes are highly dependent on the identity of the alkyl substituents, R, and range from insoluble crystalline powders to powders which readily form solutions or gels in hydrocarbon solvents, from which films may be readily spin-coated. The physical and chemical changes that occur during the reaction of boehmite with carboxylic acids, and the resulting alumoxanes, have been characterized by scanning electron and transmission electron microscopy (SEM and TEM), IR and multinuclear NMR spectroscopy, and thermogravimetric/differential thermal analysis (TG/DTA). The carboxylatoalumoxanes reported herein are spectroscopically similar to analogues prepared from small molecule precursors. Based on the IR and NMR spectra of the alumoxanes as well as comparison with the aluminium carboxylate compounds [Me2Al(µ-O2CR)]2 and Al(O2CR)(salen)(R = CH3, n-C5H11), a model structure of the alumoxanes is proposed, consisting of a boehmite-like core with the carboxylate substituents bound in a bridging mode. Furthermore, the alumoxane particles appear as rod or sheet-like particles, not linear polymers. This is proposed to be due to the destruction of hydrogen bonding within the mineral as hydroxide groups are removed and replaced with acid functionalities. All of the alumoxanes decompose under mild thermolysis to yield alumina. Mass spectral studies indicate that upon thermolysis the volatile decomposition products are water and the carboxylic acid.

The substrate binding site of human liver cytochrome P450 2C9: an approach using designed tienilic acid derivatives and molecular modeling.

Abstract: Biochemical experiments, using the well-defined human liver CYP2C9 expressed in yeast, and molecular modeling techniques were used to derive a predictive model for substrates of CYP2C9. The ability of 10 2-aroylthiophenes related to tienilic acid to act as substrates for CYP2C9 was studied. Four of them were original compounds that were synthesized and completely characterized by several spectroscopic techniques. In these 10 compounds various chemical functions, such as ester, amide, alcohol, phenol, ether or tetrazole functions, replaced the OCH2COOH function of tienilic acid. Among them, only the derivatives containing an acidic function (carboxylic acids, phenol, and tetrazole whose pKaS are 4.8, 6.3, and 3.8, respectively) underwent a 5-hydroxylation of their thiophene ring like tienilic acid. Despite their close structural analogy with tienilic acid, all of the other compounds not only did not undergo any 5-hydroxylation of their thiophene ring but also failed to act as inhibitors of CYP2C9. These results strongly suggested that the presence, at pH 7.4, of a negative charge on the substrate is a very important feature in its recognition by CYP2C9. In fact, the four new substrates of CYP2C9 described in this study, a carboxylic acid, phenol, and tetrazole derivative, each of which is related to tienilic acid, and the antiinflammatory drug, suprofen (with Km between 12 and 130 microM and kcat between 0.2 and 1.3 min-1), as well as almost all CYP2C9 substrates reported in the literature, exhibit a pKa below 7 (except phenytoin whose pKa is 8.1). They mainly exist as anions at physiological pH. By using molecular modeling techniques, 12 CYP2C9 substrates were superimposed with respect to their hydroxylation site and fitted onto templates, which were rigid molecules such as (S)-warfarin and phenytoin. It was thus possible to arrange them in order that all their anionic sites were at a distance around 4 A from a common point (a putative cationic site of the protein) in space. These results provide a model of the substrate binding site of CYP2C9, in which substrates interact through their anionic site A- with a cationic residue of the CYP2C9 protein C+. In that model, the distance between the hydroxylation site (Hy) and the anionic site (A-) is 7.8 +/- 1.6 A, and the

Polymers useful as pH responsive thickeners and monomers therefor

Abstract: Novel aqueous thickener or thixotropic polymers are prepared by the copolymerization of (A) about 15-60 weight percent of a C 3 -C 8 alpha, beta-ethylenically unsaturated carboxylic acid monomer, preferably acrylic or methacrylic acid or a mixture thereof with itaconic or fumaric acid, (B) about 15-80 weight percent of a nonionic copolymerizable C 2 -C 12 alpha, beta-ethylenically unsaturated monomer, preferably a monovinyl ester such as ethyl acrylate or a mixture thereof with styrene, acrylonitrile, vinyl chloride or vinyl acetate, and (C) about 1-30 weight percent of a new and novel nonionic ethylenically unsaturated nonionic biphillic monomer such as tristyrylpoly(ethyleneoxy) x methyl acrylate, to provide a stable aqueous colloidal dispersion at an acid pH lower than about 5.0 but becoming an effective thickener for aqueous systems upon adjustment to a pH of about 5.5-10.5 or higher. These polymers adjusted to a pH of about 5.5 or higher are effective thickeners for a wide variety of aqueous systems including cosmetic products, drilling muds, aqueous coating compositions such as latex paint, and high solids compositions such as spackle, grouts, cements, and the like.

Oxo carboxylate tin ladder clusters. a new structural class of organotin compounds

Abstract: The hexameric n-butyloxotin benzoate, [n-BuSn(O)O2CC6H4NO2.2]6.3C6H6, 1, and the dimeric methyloxotin cyclohexanoate, [(MeSn(O)O2CC6H11)2MeSn(O2CC6H11)3]2, 4, were prepared by condensing the stannoic acid with the respective carboxylic acid. Reaction of n-butyltin. trichloride with the silver salt of the respective carboxylic acid gave the dimeric n-butyloxotin carboxylate compositions, [(n-BuSn(O)O2CR)2-n-BuSn(O2CR)3]2, 2 (R = Ph) and 3 (R = Me). These represent new substances and, as found by X-ray analysis, form a new structural class of organotin compounds for 2-4 having “unfolded drum” or “ladder” structures. The hexamer composition 1 exists in “drum” form. 119Sn NMR data show that the drum and ladder structures interconvert reversibly. 1 crystallizes in the rhombohedral/space group R3 with a H = 15.283 (4) A, cH, = 34.683 (9) A, and Z = 3. 2 crystallizes in the triclinic space group P1 with a = 13.657 (6) A, b = 14.104 (2) A, c = 14.559 (4) A, a = 99.14 (2)°, β = 111.73 (3)°, γ = 101.57 (3)...

Origins and variations of light carboxylic acids in polar precipitation

Abstract: Central Greenland and East Antarctic ice cores have been studied to investigate the carboxylic acid (acetate, CH 3 COO - ; formate, HCOO - ; glycolate, C 2 H 3 O 3 - ; and oxalate, C 2 O 4 -- ) content of high-latitude precipitation. The two records cover the end of the last glacial age, the last great climatic change having occurred between 10,000 and 15,000 years B.P., and the Holocene period which started some 10,000 years ago. Carboxylic acids were measured using ion chromatography. These measurements are more difficult and require more stringent precautions to prevent sample contamination than inorganic trace species measurements. Carboxylic acids account for up to 25% of the free acidity in Greenland and are one order of magnitude more abundant in Greenland than in Antarctic precipitation. In Greenland precipitation deposited under present climatic conditions, formic and acetic acids are both present at the 10 ng g −1 level and are the most abundant carboxylic acids, while glycolic and oxalic acids with concentrations close to 1 ng g −1 represent minor carboxylic acid species. The level of formic, and to a lesser extent acetic, acid is also found to be strongly pH dependent. There is less formic acid at depths corresponding to periods when the acidity of the atmosphere was enhanced by a volcanic activity. Over the last 12,700 years, the carboxylic acid level of Greenland precipitation has often been sporadically enhanced by several orders of magnitude. Such large perturbations, which are accompanied by large increases of NH 4 + concentrations, are probably caused by biomass-burning events which occurred at high northern latitudes. A particular chemical feature appears in snow layers corresponding to biomass-burning events which occurred during the Younger Dryas (11,550 to 12,700 years B.P.). During this cold stage, the precipitation was alkaline and the events were accompanied by an input of nitrite suggesting that peroxyacetyl nitrate (PAN) was present in the atmosphere and was hydrolyzed in alkaline cloud water. Formate and acetate profiles indicate that background levels of these carboxylic acids were 5 and 2 times lower, respectively, during the last glacial maximum (15,000 to 34,000 years B.P.) than during the Holocene stage in Greenland precipitation. The increases of the acetate and formate snow contents in response to the glacial-interglacial climatic transition exhibit a time lag of some 5000 years. In particular, the formic acid increase follows perfectly the timing of the retreat of the Laurentide ice sheet from 18,000 years B.P. to the mid-Holocene stage (6000 years B.P.). Our data suggest therefore that carboxylic acids in Greenland precipitation are mainly linked to emissions from the high-latitude continental biosphere. In contrast, the incloud oxidation of formaldehyde produced from methane oxidation under acidic conditions likely represents the main source of formic acid in East Antarctica. Finally, the study of recent Greenland snow deposits indicates that the expected trend of carboxylic acid concentrations due to man-made activities is counteracted by a simultaneous increase of the acidity related to growing fossil fuel combustion, which leads to a less efficient uptake of carboxylic acids into precipitation.

The formation of ketones and aldehydes from carboxylic acids, structure-activity relationship for two competitive reactions

Abstract: Four carboxylic acids with a number of α-hydrogen atoms ranging from three to zero were tested in the selective hydrogenation to aldehyde. The acids used were acetic, propanoic, isobutyric, and pivalic acid. The oxides of iron, vanadium, zirconium, and titanium were used as catalysts. It was found that by decreasing the number of α-hydrogen atoms the selectivity to the aldehyde increased, while the formation of the main by-product, ketone, was suppressed. It is suggested that this is due to the fact that the ketonisation proceeds via a ketene-like intermediate, the formation of which needs the presence of α-hydrogen. Furthermore, the reactions to aldehyde and ketone seem to be in competition with each other.

Acid-functionalized amphiphiles, derived from polystyrene-poly (propylene imine) dendrimers, with a pH-dependent aggregation

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Radiofrequency-induced plasma polymerisation of propenoic acid and propanoic acid

Abstract: Inductively coupled, radiofrequency-induced plasmas of propenoic (‘acrylic’) acid and propanoic acid, operated at a low electrical power (1–10 W), have been investigated using a combination of mass spectrometry (MS) and deposition-rate measurements. Thin films of plasma polymers of both compounds were deposited onto silicon substrates and analysed by X-ray photoelectron spectroscopy (XPS). The positive-ion MS data obtained from both compounds indicate the presence of species of the form (M+ H)+, (2M+ H)+ and (3M+ H)+, where M represents the molecular weight of the starting material. No neutral oligomeric species were detected. XPS analysis reveals an inverse relationship between the electrical power supplied to the plasma and the degree of retention of the carboxylic acid functionality in the solid product. Comparison of the MS and XPS results suggests that the above cationic species are responsible for the carboxylic-acid functionalisation of the plasma-polymer product, whereas fragmentation processes lead to the introduction of other functional groups such as alcohol and ketone. The thin film which featured the highest degree of retention of carboxylic acid (65%) was obtained from a plasma of propanoic acid operated at 1 W, and was deposited at the lowest rate (0.90 ng s–1).

Surface Functionalization of Poly(ethylene terephthalate) Film and Membrane by Controlled Wet Chemistry: Chemical Characterization of Carboxylated Surfaces

Abstract: Surface functionalization of poly(ethylene terephthalate) (PET) film or track-etched membrane was performed using the methods of organic synthesis conducted at the solid-liquid interface. Basic hydrolysis in aqueous acetonitrile followed by permanganate oxidation in diluted sulfuric acid created new carboxylic chain-ends. These reactive functions were assayed as follows: (i) activation with water soluble carbodiimide; (ii) coupling to H-3-labeled amino acids; and (iii) liquid scintillation counting of the sample-associated radioactivity. Some samples were also analyzed by X-ray photoelectron spectroscopy. Depending on the experimental conditions (temperature and duration of treatment), about 1-2% of the surface repeated units could be functionalized without deterioration of the polymer bulk. This study establishes the best conditions for the covalent anchorage of bioactive substances on the PET surface. (C) 1995 Academic Press, Inc.

Mechanism of crosslinking of papers with polyfunctional carboxylic acids

Abstract: Brief thermal curing of papers treated with an aqueous solution of polyfunctional carboxylic acids and NaH2PO4 imparts substantial wet strength to the papers. The effectiveness of such carboxylic acids increases with their functionality in the order 1,2,3,4-butanetetracarboxylic acid (BTCA) > tricarballylic acid (TCA) ≫ succinic acid. The two main stages of the curing reaction of papers, i.e., pendant attachment of the polyfunctional carboxylic acids via esterification with cellulosic hydroxyl groups, and its further reaction with another cellulose hydroxyl group producing crosslinks of the cellulose fibers were analyzed separately using a combination of acid-base and conductometric titrations. The extent of reaction of the polyfunctional carboxylic acids with paper was followed by pH titration, which shows the total decrease in acid functions as the curing progresses and is directly related to the total consumption of carboxylic acids groups by ester attachment and ester crosslinking steps. The conductometric titration, on the other hand, measures the increase in carboxylic acids bound to cellulose units of the paper as a direct result of previous esterification steps. Our studies reveal that the reaction of BTCA with papers is essentially quantitative after 15 min of curing. The amount of once-reacted BTCA increases in the initial phases of the curing reaction and then decreases as more and more carboxylic acid units are converted into crosslinking sites, while the amount of crosslinked BTCA increases throughout the curing reaction. The reaction profile of papers with TCA differs from that of BTCA in that the curing reaction is initially dominated by the formation of ester appendages; crosslinking becomes the main reaction only after extended curing times. We attribute this difference to the ability of BTCA to form an highly reactive difunctional crosslinking reagent at the outset of the curing reaction, while TCA is initially monofunctional in its reaction with cellulosic hydroxyl groups (formation of a monoanhydride). The relationship between the wet tensile strength of the treated papers and their degree of crosslinking is also discussed. © 1995 John Wiley & Sons, Inc.

Low-barrier hydrogen bonding in molecular complexes analogous to histidine and aspartate in the catalytic triad of serine proteases.

Abstract: We present spectroscopic evidence for the presence of low-barrier hydrogen bonds (LBHBs) in molecular complexes composed of carboxylic acids and 1-methylimidazole (1-MeIm) dissolved in aprotic organic solvents. A plot of the values of the low-field proton NMR chemical shifts versus the aqueous pKa of the carboxylic acid exhibits a positive slope for pKa values below 2.1 and a negative slope for higher pKa values. The chemical shifts for protons near the maximum in this plot are 18 ppm, similar to that of 18.3 ppm for His57-Asp102 in the protonated catalytic triad of chymotrypsin. The chemical shifts for the proton bonded to C2 of 1-MeIm in these complexes also vary with the pKa of the carboxylic acid and reveal a gradual change from neutral, hydrogen-bonded 1-MeIm in complexes of weaker acids to hydrogen-bonded 1-methylimidazolium ion in complexes of stronger acids. The midpoint chemical shift for the C2 proton corresponds to a carboxylic aqueous pKa of about 2.1. FTIR spectra of the 1-MeIm-carboxylic acid complexes in CHCl3 indicate that hydrogen bonding is strong and that the complexes are of three types: (a) neutral complexes with the weaker acids (pKa > or = 2.2) in which the antisymmetric carbonyl stretching frequencies are lowered relative to the free acids and the ethyl esters of the same acids; (b) ionic complexes of stronger acids (pKa < or = 2.1) in which the carbonyl stretching frequencies are slightly lower than those for the tetrabutylammonium salts of the same acids; (c) ionic complexes of the same acids (pKa < or = 2.1) coexisting with type b, in which the carbonyl stretching frequencies are intermediate between those for the tetrabutylammonium salts (bond order 1.5) and those of the same acids or their esters (bond order 2.0). The latter complexes appear to incorporate a low-barrier hydrogen bond and are presented as models for the protonated triad of chymotrypsin and other serine proteases. These enzymes have been postulated to utilize a low-barrier hydrogen bond between His57 and Asp102 to facilitate the abstraction of the beta-OH proton from Ser195 in the course of catalysis [Frey, P.A., Whitt, S.A., & Tobin, J.B. (1994) Science (Washington, D.C.)264,1927-1930].

Inhibition of farnesyltransferase

Abstract: Peptidomimetics of the formula CβX where C is cysteine, X is any naturally occuring amino acid, and β is a hydrophobic spacer, most notably 2-phenyl-4-aminobenzoic acid. These compounds are effective inhibitors of p2lras farnesyltrasferase, block Ras-dependent oncogenic signalling and inhibit human tumor growth in vivo in animal models. Pro-drugs made by functionalizing terminal amino and carboxylic acid groups of peptides and peptidomimetics are also disclosed. Such functionalized derivatives demonstrate increased cell uptake. Other structural modifications are also disclosed.

Dental composition and kit

Abstract: A dental composition which comprises (A) a phosphoric acid group-containing monomer, (B) a carboxylic acid groups-containing monomer and (C) water as main components in amounts of 05 to 50 % by weight, 1 to 50 % by weight and 5 to 90 % by weight, based on the composition, respectively; and a dental adhesive kit comprising a dental primer composition containing the monomer (A) ad water and an adhesive containing a carboxylic acid-containing polyfunctional monomer and a polymerizable initiator

7-(1-pyrrolidinyl)-3-quinolone- and - naphthyridone-carboxylic acid derivatives as antibacterial agents and feed additives

Abstract: 7-(1-Pyrrolidinyl)-3-quinolone- and -naphthyridone-carboxylic acid derivatives as antibacterial agents and feed additives, of the formula ##STR1## in which X 1 is halogen, X 2 is hydrogen, halogen, amino or other radical, R 1 is alkyl, cycloalkyl, optionally substituted phenyl or other radical, R 2 is hydrogen, alkyl or a dioxolylmethyl radical, R 3 is ##STR2## and A is N, CH, C-halogen, or the like, or forms a bridge with R 1 , and addition products thereof.

Pharmacology of the inhibitory glycine receptor : agonist and antagonist actions of amino acids and piperidine carboxylic acid compounds

Abstract: To define structure-activity relations for ligands binding to the inhibitory glycine receptor (GlyR), the agonistic and antagonistic properties of alpha- and beta-amino acids were analyzed at the recombinant human alpha 1 GlyR expressed in Xenopus oocytes The agonistic activity of alpha-amino acids exhibited a marked stereoselectivity and was highly susceptible to substitutions at the C alpha-atom In contrast, alpha-amino acid antagonism was not enantiomer dependent and was influenced little by C alpha-atom substitutions The beta-amino acids taurine, beta-aminobutyric acid (beta-ABA), and beta-aminoisobutyric acid (beta-AIBA) are partial agonists at the GlyR Low concentrations of these compounds competitively inhibited glycine responses, whereas higher concentrations elicited a significant membrane current Nipecotic acid, which contains a trans-beta-amino acid configuration, behaved as purely competitive GlyR antagonist Our data are consistent with the existence of a common binding site for all amino acid agonists and antagonists, at which the functional consequences of binding depend on the particular conformation a given ligand adopts within the binding pocket In the case of beta-amino acids, the trans conformation appears to mediate antagonistic receptor binding, and the cis conformation appears to mediate agonistic receptor binding This led us to propose that the partial agonist activity of a given beta-amino acid is determined by the relative mole fractions of the respective cis/trans conformers

Low-haze ionomers of copolymers of alpha-olefins, carboxylic acid esters, and optional comonomers, and processes for making and acidifying these ionomers

Abstract: Ionomer compositions which have improved optical properties are disclosed. These compositions comprise ionomers which can be represented as the polymerization product of alpha-olefins having from two to eight carbon atoms, esters of alpha, beta-ethylenically-unsaturated carboxylic acids, metal salts of acrylic and methacrylic acid, and optional alpha, beta-ethylenically-unsaturated comonomers which impart some desired polymer property or properties, such as acidity and/or solvent resistivity. Also disclosed are methods of making these ionomer compositions in a reactive extruder and treating the compositions with acid to impart acidity to the compositions or to only the surface of the compositions.

The Biosynthesis and Metabolism of Gibberellins in Higher Plants

Abstract: The gibberellins (GAs) are all tetracyclic diterpenoid acids with theent- gibberellane ring system (structure 1). There are two main types of GAs, the C20-GAs which have a full complement of 20 carbon atoms (structure 2), and the C19-GAs in which the twentieth carbon atom has been lost by metabolism (structure 3). In almost all of the C19-GAs, the carboxylic acid at carbon-19 bonds to carbon-10 to give a lactone bridge.