Aromatic Carboxyl Research Articles

Analogues of N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine (PT523) modified in the side chain: synthesis and biological evaluation.

Four heretofore undescribed side chain analogues of N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine (PT523, 4) were synthesized via straightforward methods of antifolate chemistry, and their properties were compared with those of PT523 and two related compounds with the aim of defining the contribution of the hemiphthaloyl-L-ornithine moiety to the exceptional in vitro antitumor activity of this novel non-polyglutamatable aminopterin analogue. The IC50 values of N alpha-(4-amino-4-deoxypteroyl)-N beta-hemiphthaloyl-L-2,3-diaminopropanoic acid (10) and N alpha-(4-amino-4-deoxypteroyl)-N gamma-hemiphthaloyl-L-2,4- diaminobutanoic acid (9) against A549 human non-small-cell lung carcinoma cells in culture were 23 and 22 nM, whereas those of PT523 and N alpha-(4-amino-4-deoxypteroyl)-N epsilon-hemiphthaloyl-L-lysine (8) were 1.3 and 5.2 nM. A decrease in the in vitro activities of 8 and 9 relative to PT523 was also observed against the panel of cell lines used by the National Cancer Institute to screen new drugs. However the potency of 8 and 9 remained several times greater than that of the historical control methotrexate against many of the cell lines in the screening panel. In an in vivo tumor model, SCC-VII murine squamous cell carcinoma, 9 and methotrexate were well tolerated as 5-day continuous infusions at doses of 0.52 and 0.75 mg/kg/day, whereas the highest tolerated dose of PT523 on this schedule was 0.19 mg/kg/day, in agreement with its lower IC50 in culture. To assess the importance of the hemiphthaloyl group in PT523, N alpha-(4-amino-4-deoxypteroyl)-N delta-isophthaloyl-L-ornithine (11), N alpha-(4-amino-4-deoxypteroyl)-N delta-terephthaloyl-L-ornithine (12), and N alpha-(4-amino-4-deoxypteroyl)-N delta-(4,5-dichlorohemiphthaloyl)-L-ornithine (13) were also synthesized. The IC50 values of 11 and 12 against A549 cells were 45 and 3300 nM, as compared with 1.3 nM for PT523 and 23 nM for methotrexate. In a clonogenic assay against SCC25 human squamous cell carcinoma cells, the IC50 values of 11 and 12 were 2.9 and 72 nM, as compared with 0.3 nM for PT523 and 27 nM for methotrexate. Thus, activity was decreased by moving the aromatic carboxyl group in PT523 to the meta position and was further diminished by moving it to the para position. The IC50 of the halogenated analogue 13 against SCC25 human head and neck squamous carcinoma cells was 18 nM, suggesting lack of tolerance for this 4,5-disubstitution in the phthaloyl moiety. Our results suggest that the combination of a hemiphthaloyl group and three CH2 groups in the side chain are critical determinants of the potent in vitro activity of PT523.

Anionic Synthesis of Aromatic Carboxyl Functionalized Polymers. Chain-End Functionalization of Poly(styryl)lithium with 4,5-Dihydro-4,4-dimethyl-2- [4-(1-phenylethenyl)phenyl]oxazole

The novel syntheses of 4-(4,5-dihydro-4,4-dimethyl-2- oxazolyl)benzophenone, 1-[4-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)phenyl]-1-phenylethanol and 4,5-dihydro-4,4-dimethyl-2-[4-(1-phenylethenyl)phenyl]oxazole (1) are described. ω-Oxazolyl polystyrene (2) was synthesized in quantitative yields by the reaction of poly(styryl)lithium with stoichiometric amounts of 4,5-dihydro-4,4-dimethyl-2-[4-(1-phenylethenyl)phenyl]oxazole (1) in toluene/tetrahydrofuran (4 :1 v/v) at -78°C. Deblocking of the oxazoline protecting group by acid hydrolysis followed by saponification quantitatively provides the corresponding aromatic carboxyl chain-end functionalized polystyrene (3). The functionalization agent and functionalized polymers were characterized by HPLC, thin layer chromatography, size exclusion chromatography, vapor phase osmometry, spectroscopy ( 1 H NMR, 13 C NMR and FTIR), potentiometry and elemental analysis.

Strong-Acid, Carboxyl-Group Structures in Fulvic Acid from the Suwannee River, Georgia. 1. Minor Structures

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.

Structure and Reactivity of Spruce Mechanical Pulp Lignins. IV:13C-NMR Spectral Studies of Isolated Lignins

Abstract 13C-NMR spectroscopy has been used to characterize the lignins extracted by an organosolv flow-through process from spruce TMP, bleached TMP (BTMP) and yellowed BTMP (YBTMP). In general, the 13C-NMR spectra of these lignins are similar to that of spruce MWL, indicating that the lignins underwent limited structural changes. Thus they may be an acceptable substrate for lignin structural study. However, these lignins appear to have a significant amount of condensed aromatic carbons assigned mainly to β-5, 5-5 and diarylmethane structures. These were likely formed during the organosolv cook, or initially present in TMP and extracted with this organosolv process. On the other hand, the hydrogen peroxide bleaching causes little change in the lignin overall structure. As a favorable effect, elimination of the coniferaldehyde structures can clearly be seen. The photoyellowing appears to result in the creation of aromatic carbonyl and carboxyl groups. This suggests that oxidative cleavage of Cα, Cβb bonds...

Chemical characteristics of soil fulvic acids fractionated using polyvinylpyrrolidone (PVP)

Abstract Elementary composition, IR spectra, 13C-NMR spectra and molecular size distribution were determined for fulvic acids (FAs), polyvinylpyrrolidone (PVP)-adsorbed and non-adsorbed fractions of FAs and humic acids (HAs). The analytical data showed that the properties were distinctly different between the PVP-adsorbed and the non-adsorbed fractions. Atomic ratio, IR spectra and 13C-NMR spectra indicated that the PVP-adsorbed fractions contained a larger number of aromatic rings and carboxyl groups including ester than the non-adsorbed fractions. On the other hand, carbohydrates and N-containing compounds such as peptides or amino acids were concentrated in the PVP-non-adsorbed fractions. Weight average molecular weights (Mw ) of the adsorbed fractions were lower and the range of molecular size distribution was narrower than those of the non-adsorbed fractions. Chemical characteristics of HAs varied depending on the types of soils, while the characteristics of the PVP-adsorbed and non-adsorbed fraction...

Studies of the Photodegradation of Spruce Lignin by Nmr Spectroscopy

ABSTRACT The light-induced degradation of lignin was studied using spruce MWL impregnated on handsheets prepared from cotton linters. The sheets were irradiated with simulated sunlight and the lignin was extracted. Solutions of untreated and irradiated lignin were studied by 1H and 13C NMR spectroscopy. The results showed that α- and β- ether and α-β bond cleavage were the main reactions. The main degradation products were vanillin and vanillic acid. The amount of terminal groups containing aromatic aldehyde and carboxyl groups also incre- ased on irradiation. The existing α- C=O groups were transformed mainly to carboxyl groups. However, the results indicate that new α- C=O groups were generated on irradiation. The methoxyl content decreased and some degradation of aromatic rings took place. However, no formation of quinoid structures was observed. Degradation of phenylcoumaran units was evident, α- Ether cleavage in phenylcoumarans could possibly lead to formation of stilbenes and stilbene derived chrom...

Adducts of nitroimidazole derivatives with rhodium(II) carboxylates: Syntheses, characterization, and evaluation of antichagasic activities

Adducts of several rhodium(II) carboxylates with two antiparasitic nitroimidazole ligands were prepared and characterized by elemental microanalysis, thermogravimetry, spectrophotometry (IR, UV, and visible), and proton magnetic resonance. Results of elemental and thermogravimetric analyses were consistent with the general formula Rh 2(RCOO) 4.2L (R = aliphatic or aromatic carboxylic groups; L = metronidazole or benznidazole). The reddish-brown color of the adducts as well as their visible spectra suggest axial coordination of the nitroimidazole ligands through nitrogen atoms. NMR spectra indicate N 3 as the coordinating atoms. Screening tests performed on cultures of T. cruzi indicate that aliphatic complexes-particularly propionate and acetate adducts-were more active than their aromatic counterparts, the same being observed with benznidazole adducts in relation to their metronidazole analogues. Evaluated for their usefulness as transfusion prophylactic agents against Chagas' disease, propionate derivatives failed to sterilize T. cruzi infected blood. An oral toxicity assay in mice showed mild toxic effects with daily doses of 5 mg/kg for 20 days.

Expression of an aromatic-dependent decarboxylase which provides growth-essential CO2 equivalents for the acetogenic (Wood) pathway of Clostridium thermoaceticum

The acetogen Clostridium thermoaceticum generates growth-essential CO2 equivalents from carboxylated aromatic compounds (e.g., 4-hydroxybenzoate), and these CO2 equivalents are likely integrated into the acetogenic pathway (T. Hsu, S. L. Daniel, M. F. Lux, and H. L. Drake, J. Bacteriol. 172:212-217, 1990). By using 4-hydroxybenzoate as a model substrate, an assay was developed to study the expression and activity of the decarboxylase involved in the activation of aromatic carboxyl groups. The aromatic-dependent decarboxylase was induced by carboxylated aromatic compounds in the early stages of growth and was not repressed by glucose or other acetogenic substrates; nonutilizable carboxylated aromatic compounds did not induce the decarboxylase. The decarboxylase activity displayed saturation kinetics at both whole-cell and cell extract levels, was sensitive to oxidation, and was not affected by exogenous energy sources. However, at the whole-cell level, metabolic inhibitors decreased the decarboxylase activity. Supplemental biotin or avidin did not significantly affect decarboxylation. The aromatic-dependent decarboxylase was specific for benzoates with a hydroxyl group in the para position of the aromatic ring; the meta position could be occupied by various substituent groups (-H, -OH, -OCH3, -Cl, or -F). The carboxyl carbon from [carboxyl-14C] vanillate went primarily to 14CO2 in short-term decarboxylase assays. During growth, the aromatic carboxyl group went primarily to CO2 under CO2-enriched conditions. However, under CO2-limited conditions, the aromatic carboxyl carbon went nearly totally to acetate, with equal distribution between the carboxyl and methyl carbons, thus demonstrating that acetate could be totally synthesized from aromatic carboxyl groups. In contrast, when cocultivated (i.e., supplemented) with CO under CO2-limited conditions, the aromatic carboxyl group went primarily to the methyl carbon of acetate.

Gewinnung niedermolekularer organischer Verbindungen aus komplexen wäßrigen Gemischen durch Extraktion

AbstractRecovery of low‐molecular organic compounds from complex aqueous mixtures by extraction. This article considers the recovery of alcohols, aliphatic and aromatic carboxyl acids, amino acids, and penicillins from complex media as well as the separation of chemically similar compounds by extraction from complex mixtures.

PH‐induced reversible permeability control of the 4‐carboxy acrylanilide‐methyl methacrylate copolymer membrane

AbstractTo develop a polymer membrane whose permeability of water‐soluble compounds could be controlled in response to a pH change of the medium, a polyelectrolyte membrane containing an aromatic carboxyl group, i.e., 4‐carboxyacrylanilide (CAAn)‐methyl methacrylate(MMA) copolymer membrane, was prepared. The water content of the CAAn‐MMA copolymer membrane increased with increasing pH owing to ionization change in the CAAn moiety. This increase was particularly remarkable in the pH range from 5 to 7. The change in water content was reversible and could be controlled by the CAAn composition in the copolymer. Permeation of 1,4‐bis(2‐hydroxyethoxy)benzene(DHEB) through the CAAn‐MMA copolymer membrane was investigated in solutions of various pH. Change in the permeability of DHEB in function of the pH was similar to the change in membrane water content. This was explained by an increase in the permeation pathway of DHEB in the membrane, in proportion to that in the water content. Moreover, when a pH‐sensitive membrane was placed in a solution in which an enzymatic reaction occurred, substrate‐induced permeation control of DHEB through the CAAn‐MMA copolymer membrane was possible.

Spectral, magnetic and thermal studies of transition metal complexes of δ(3-carboxy, 4-hydroxy benzoyl) pentanoic acid

Cu(II), Ni(II), Co(II), Mn(II) and Zn(II) form 1:2 complexes while Fe(III) forms 1:3 complex with δ(3-carboxy, 4-hydroxy benzoyl) pentanoic acid. Their structures have been proposed on the basis of analytical, spectral, thermal and magnetic measurements. The infrared spectra provide an evidence for the replacement of the aromatic carboxylic group hydrogen but not the phenolic group hydrogen.

Studies on dental self-curing resins (27). Adhesion of monomers with aromatic carboxylic group to the metals and alloys

Studies on dental self-curing resins (27). Adhesion of monomers with aromatic carboxylic group to the metals and alloys

Fulvic acids: structure and metal binding. I. A random molecular model

SummaryWe have investigated a model of fulvic acid based on randomized positioning of functional groups and aromatic rings which can be used to deduce the types of metal chelating sites and provide statistical estimates of their concentrations. A FORTRAN program ‘RANDOM’ has been written which generates random molecules of fulvic acid. For each molecule generated the program also searches for and counts 14 types of binding site and calculates average concentrations over one thousand such molecules. A formula relating percentage aromatic carbon to the molar hydrogen/carbon ratio is also derived. The results show that the predominant bidentate sites are likely to be phthalate‐ and salicylate‐type sites with a significant proportion of aromatic carboxyl and phenolic hydroxyl not participating in chelating sites.

Thermal degradation of polyquinones used as coal models

A series of polyquinone samples has been pyrolysed in order to elucidate the gaseous product formation from macromolecules involving aromatic segments and carboxyl side groups, as well as carbonyl, ether, methylene, sulfide bridges and oxygen-, sulfur- and nitrogen-containing heterocyclic segments. The amount of the various pyrolysis products was related to the molar ratio of the corresponding groups in the macromelecule thermally decomposed to these product molecules. The effects of pyrolysis temperature, of other molecular sequences present and of pyrolysis residue on the product formation reactions are discussed.

Adhesive bonding of various materials to hard tooth tissues: improvement in bond strength to dentin.

Used in sequence, solutions of an acidic mordant, a surface-active comonomer, and a coupling agent having methacrylate and aromatic carboxyl groups were used to prepare dentin surfaces in vitro for strong bonding with a composite resin.

Inhibition of phenylalanine ammonia-lyase by cinnamic acid derivatives and related compounds

Thirty-five derivatives of cinnamic acid and related compounds were tested for inhibition against phenylalanine ammonia-lyase (PAL) derived from sweet potato, pea and yeast. Caffeic and gallic acids showed inhibition against PAL originating from higher plants, but not against yeast PAL. In contrast, yeast PAL was specifically inhibited by p-hydroxycinnamic and p-hydroxybenzoic acids. The results suggest that caffeic and gallic acids may act as regulatory substances in phenylpropanoid metabolism in higher plants. Inhibition experiments with synthetic cinnamic acid derivatives have revealed that the presence of a hydrophobic aromatic ring, α,β-double bond and carboxyl group is essential for inhibitory activity. 2-Naphthoic acid which fulfills these structural requirements showed a strong inhibition. The size and shape of the active site is discussed from structure-activity relationships of cinnamic acid derivatives. o-Chlorocinnamic acid, one of the strongest inhibitors found in this study showed an inhibitory effect on the growth of the roots of rice seedlings.

13 C chemical shift tensors in organic single crystals

It is described how 13 C chemical shift tensors can be determined from proton enhanced 13 C n.m.r. experiments on single crystals. 13 C chemical shift tensors of aromatic ring carbons, carbonyl carbons, carboxyl carbons and methyl carbons are discussed and compared for groups of related molecules.

An interpretation of the conductometric titration curve of humic acid

Methods of fractionating the functional groups of humic acid by conductometric titration were examined. Replacement titration, in which a sample solution is titrated with a standard acid solution after adding an excess amount of a standard base, seems to be a suitable method. By this method, the functional groups of humic acid were fractionated into three clusters of different dissociation constants, designated as VW (very weak), W (weak), and S (strong) clusters. The VW cluster was presumed to include phenolic hydroxyl residues, carboxyl residues and nitrogenous bases of very high pK's. The W cluster was presumed to include various aliphatic and aromatic carboxyl residues and nitrogenous bases of medium pK's, whereas the S cluster was presumed to include carboxyl residues of low pK 1 of salicylate or phthalate. A humic acid sample obtained from the A horizon of Shitara “kuroboku” soil had 0.78 me/g of the VW cluster, 3.24 me/g of the W cluster and 1.90 me/g of the S cluster.

Studies on Properties and Structure of Regenerated Humic Acid (III)

The reaction of ethylene carbonate with the regenerated humic acid prepared from Takamatsu coal (C: 75.7%) by oxidation with nitric acid has been investigated.Hydroxyethylation of humic acid with ethylene carbonate easily occured and carboxyl group and phenolic hydroxy group in humic acid were converted into ester and ether, respectively.In the case of alkali (Na2CO3) catalyst, the formation of polyether followed after hydroxyethylation of humic acid. In the case of acid (H2SO4) catalyst, the crosslinkage formation through ethylene group occured after hydroxyethylation of humic acid.Humic acid became insoluble in an aqueous alkali solution by reaction with ethylene carbonate. In the case of acid catalyst, it was possible to obtain the product which was insoluble in an aqueous alkali solution but retained the most part of acidic group of the original regenerated humic acid.The reaction products showed a strong absorption band at 1, 250cm-1 (C-O-C stretching vibration of ester) in IR spectrum so that the carboxyl group in the regenerated humic acid is considered to be the aromatic carboxyl group.

Biosynthesis of phenylalanine, tyrosine, 3-(3-carboxyphenyl)alanine and 3-(3-carboxy-4-hydroxyphenyl)alanine in higher plants: Examples of the transformation possibilities for chorismic acid

14C-labelled shikimic acid and double labelled shikimic acid tritiated stereospecifically at C-6 are incorporated into 3-(3-carboxyphenyl)alanine, 3-(3-carboxyl-4-hydroxyphenyl)alanine, phenylalanine, and tyrosine in Resda lutea L., Reseda odoratta L., Iris x Hollandica cv. Prof. Blauw, and Iris x hollandica cv. Wedgwood. The experiments with 14C-labelled shikimic acid confirm that the aromatic carboxyl groups and rings in 3-(3-carboxyphenyl)-alanine and 3-(3-carboxy-4-hydroxyphenyl)alanine derive from the carboxyl group and ring in shikimic acid whereas the experiments with double labelled shikimic acid demonstrate that the pro-6S-hydrogen atom is retained and the pro-6R-hydrogen atom lost in the biosynthesis of 3-(3-carboxyphenyl)alanine, phenylalanine, and tyrosine in the plants used. 3H was located in the ortho-position in the aromatic rings of phenylalanine and tyrosine but in a position para to the alanine side chain of 3-(3-cabroxyphenyl)alanine. No 3H was found in 3-(3-carboxy-4-hydroxyphenyl)alanine. This supports a derivation of the last two compounds from chorismic acidvia isochorismic acid, isoprephenic acid, and 3′-carboxyphenylpyruvic acid and 3′-carboxy-4′-hydroxyphenylpyruvic acid. The 3H/14 C ratio in 3-(3-carboxyphenyl)alanine was found higher than in the precursor used. This isotope effect must operate by competition between the pathways from isoprephenic acid to 3′-carboxyphenylpyruvic acid and to 3′-carboxy-4′-hydroxyphenylpyruvic acid. The proposed biosynthetic pathways for the two carboxy-substituted amino acids are in agreement with their distribution patterns in the plant kingdom and suggest that they may derive from minor changes of enzymes involved in the general pathways of aromatic biosynthesis.