Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The variations in the excitation and fluorescence wavelengths and fluorescence intensities of a number of indole and aniline derivatives over a wide range of acidity and alkalinity (36n-sulphuric acid to 10n-potassium hydroxide) have been studied. 2. The changes in fluorescence with pH of the indoles and anilines had many characteristics in common, and the most fluorescent species were found to be the non-ionized or neutral forms showing fluorescence maxima at about lambda 350mmu. 3. In 10n-potassium hydroxide most of the compounds examined, except those containing a tertiary nitrogen atom, showed a bathochromic shift in fluorescence wavelength attributable to an anion due to a negatively charged nitrogen, but in strong acid (3n-sulphuric acid) these compounds were non-fluorescent, except the anisidines and the 5-hydroxyindoles. 4. p-Anisidine but not the o- and m-isomers showed excited-state ionization in acid solution. 5. Of the hydroxyindoles only the 5-hydroxy derivatives showed a fluorescence (lambda(max.) 520-540mmu) in acid solution. It is suggested that this fluorescence is due to a proton-transfer reaction in the excited state, and various arguments for this suggestion are given. 6. Stokes shifts for the various ionic and neutral species of the indoles and anilines have been calculated, and the large shifts found with indole and p-anisidine may be due to solvent-solute interaction.
 ...
PMID:The fluorescence of indoles and aniline derivatives. 564 78

Cods were equipped with cannulae for drainage of the stomach and for the separate perfusion of the stomach (pure seawater containing phenol red as a volume marker) and intestine (diluted seawater). Acidity of the gastric effluence was titrated, its volume calculated from the phenol red concentration. Gastric mucosal plasma flow (MPF) was estimated by gastric 14C-aniline clearance. I.m. injection of angiotensin II (AII) depressed basal acid secretion in a dose-dependent fashion. Also the MPF was reduced, but relatively less than the secretory depression. Therefore, the AII-induced secretory inhibition could not be explained by restrained mucosal blood flow. Perfusion of the intestine with diluted seawater, or a continuous i.m. infusion of 0.6% NaCl both rendered the fishes non-drinking. A high dose of AII (150 micrograms/kg . h) induced drinking in intestinally perfused cod while lower doses (15, 50 micrograms/kg . h) did not. In i.m. saline-injected cod, all three doses were dipsogenic. The results suggest that 0.6% saline infusion induces a permanent satiety and that intestinal perfusion in addition induces a preabsorptive satiety. The preabsorptive satiety appears more resistant to the dipsogenic action of AII than the permanent one.
 ...
PMID:Effects of exogenous angiotensin II in the Atlantic cod, Gadus morhua. Observations on gastric acid secretion, gastric sham drinking and gastric mucosal plasma flow (14C-aniline clearance). 734 2

The influence of intramolecular catalysis and self-association on the kinetics of deamidation at the A-21 Asn residue of human insulin was explored at low pH and 35 degrees C. Observed rate constants of overall insulin degradation were determined as a function of pH over a pH range of 2.0-5.0 and as a function of total insulin concentration between pH 2.0-4.0. The pH-rate behavior of both monomeric and associated insulin degradation from pH 2.0 to 5.0 indicated intramolecular catalysis by the unionized carboxyl terminus of the A chain. Anhydride trapping with aniline at pH 3.0 provided evidence supporting the formation of a cyclic anhydride intermediate in the rate limiting step indicative of intramolecular nucleophilic catalysis. Insulin in the presence of aniline at low pH formed two anilide products, A-21 N delta 2-phenyl asparagine and N delta 2-phenyl aspartic acid human insulin, at the expense of desamido A-21 formation, consistent with the partitioning of a common intermediate. Self-associated insulin degraded at a rate approximately 2.5 times greater than that of the monomer at pH 2.0 and pH 3. However, self-association had a negligible or slight stabilizing effect on insulin decomposition at pH 4.0. An apparent downward shift in the pKa of the carboxyl terminus of approximately 0.75 units upon self-association and a catalytic rate constant which increases with -COOH acidity are proposed to account for these observations.
 ...
PMID:The role of intramolecular nucleophilic catalysis and the effects of self-association on the deamidation of human insulin at low pH. 793 15

Protonation of the Os(IV) amido complex TpOs(NHPh)Cl(2) (1) to give the aniline complex [TpOs(NH(2)Ph)Cl(2)]OTf (2) requires excess triflic acid (HOTf). Complex 1 is unreactive with HCl and other moderately strong acids. Consistent with the low basicity of 1, the aniline complex 2 is extremely acidic and is deprotonated by stoichiometric addition of weak bases such as Cl(-) or H(2)O. No reaction is observed between 1 and methyl triflate (CH(3)OTf) at ambient temperatures. Upon heating, CH(3)OTf removes the chloride ligands from 1 to give CH(3)Cl and the amidobis(triflate) complex TpOs(NHPh)(OTf)(2) (3). Attack at the amido nitrogen is not observed. Complex 1 is thus very inert to protonation and electrophilic attack at nitrogen. A deprotonated form of 1, TpOs[NPh(MgBr)]Cl(2) (4), is generated on reaction of PhMgBr with TpOs(N)Cl(2). Complex 4 is extremely basic and will protonate to 1 with weak acids such as CH(3)CN, DMSO, and acetic anhydride. Thus, 1 has a low acidity as well as a low basicity; it is both less acidic and less basic than aniline. The inertness of 1 is ascribed to partial Os-N pi bonding and to the oxidizing nature of the Os(IV) center.
 ...
PMID:Protonation and deprotonation of TpOs(NHPh)Cl(2): an unusually inert amido ligand. 1131 46

The formation and properties of poly(phenylenediamine) colloidal dispersions were investigated. Oxidative dispersion polymerization of 1,3-phenylenediamine dihydrochloride stabilized with poly(N-vinylpyrrolidone) was taken as a reference experiment. Conductivity, temperature, and acidity of the reaction mixture were recorded during the polymerization. Oxidations of all three phenylenediamine bases, of corresponding dihydrochlorides, and of dihydrochlorides in excess acid are compared. The effect of the nature of steric stabilizer on the course of polymerization was found to be marginal. Dispersion polymerization was observed to proceed faster than the precipitation one. Dynamic light scattering was used to assess particle sizes in poly(phenylenediamine) dispersions. The results are discussed in relation to an analogous polymerization of aniline leading to polyaniline dispersions. Copyright 2001 Academic Press.
...
PMID:Poly(phenylenediamine) Dispersions. 1140 80

2-Amino-4-nitrophenol and 2-methoxy-5-nitroaniline were converted into the 5-nitroquinolines 6b and 6d, respectively, and then the latter into nitro-acetal 6f. 6,7-Dimethoxy-4-methylquinoline (6g) was nitrated at C-5 and then the methyl substituent converted into aldehyde 6j and then protected giving acetal 6l. Various means, notably a large excess of NiCl(2)/NaBH(4), were used to reduce both nitro group and pyridine ring, forming 1,2,3,4-tetrahydroquinolines such as 7b, 7c, 7d, which under acidic conditions closed to give 1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolines 9a, 9d, 9c, respectively. In some cases it was unnecessary to protect the aldehyde function, for example quinolinium salt 12c gave 9j and nitro-aldehyde 6j gave 9e (after BOC protection) directly by reaction with NiCl(2)/NaBH(4). Substitution of the indole and aniline nitrogens in the 1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinolines was based on a combination of protection, selective deprotection, and the exploitation of the greater acidity of the indole N-hydrogen. 8-Chlorination of 6h and then conversions, as above, gave chloro-diamine-acetal 7e which on acid treatment produced iminoquinone 11b; formylation of the nitrogens in 7e and then acidic treatment allowed formation of the chlorine-substituted 1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline 9m which was then converted into 9p. De-O-methylation and then oxidation of 9b and 9c gave o-quinones 10b and 10a, respectively.
 ...
PMID:Synthesis of Pyrrolo[4,3,2-de]quinolines from 6,7-Dimethoxy-4-methylquinoline. Formal Total Syntheses of Damirones A and B, Batzelline C, Isobatzelline C, Discorhabdin C, and Makaluvamines A-D. 1167 51

Thirteen C(6) para-substituted anilinebenzoquinones derived from perezone (PZ) (2-(1,5-dimethyl-4-hexenyl)-3-hydroxy-5-methyl-1,4-benzoquinone) were prepared to analyze the effect of the substituents on quinone electronic properties. The effect of a hydrogen bond between the alpha-hydroxy and carbonyl C(4)-O(4) groups was determined in perezone derivatives by substituting electron-donor and electron-acceptor groups such as -OMe, -Me, -Br, and -CN and comparing the -OH (APZs) and -OMe (APZms) derivatives. Reduction potentials of these compounds were measured using cyclic voltammetry in anhydrous acetonitrile. The typical behavior of quinones, with or without alpha-phenolic protons, in an aprotic medium was not observed for APZs due to the presence of coupled, self-protonation reactions. The self-protonation process gives rise to an initial wave, corresponding to the irreversible reduction reaction of quinone (HQ) to hydroquinone (HQH(2)), and to a second electron transfer, attributed to the reversible reduction of perezonate (Q(-)) formed during the self-protonation process. This reaction is favored by the acidity of the alpha-OH located at the quinone ring. To control the coupled chemical reaction, we considered both methylation of the -OH group (APZms) and addition of a strong base, tetramethylammonium phenolate (Me(4)N(+)C(6)H(5)O(-)), to completely deprotonate the APZs. Methylation led to recovery of reversible, bi-electronic behavior (Q/Q(*)(-) and Q(*)(-)/Q(2)(-)), indicating the nonacidic properties of the NH group. The addition of a strong base resulted in reduction of perezonate (Q(-)) obtained from the acid-base reaction of APZs with Me(4)N(+)C(6)H(5)O(-) to produce the dianion radical (Q(*)(2)(-)). Although the nitrogen atom interferes with direct conjugation between both rings by binding the quinone with the para-substituted ring, the UV-vis spectra of these compounds showed the existence of intramolecular electronic transfer from the respective aniline to the quinone moiety. (13)C NMR chemical shifts of the quinone atoms provided additional evidence for this electron transfer. These findings were also supported by linear variation in cathodic peak potentials (E(pc)) vs Hammett sigma(p) constants associated with the different electrochemical transformations: Q/Q(*)(-), Q(*)(-)/Q(2)(-) for APZms or HQ/HQH(2) and Q(-)/Q(*)(2)(-) for APZs. The electronic properties of model anilinebenzoquinones were determined at a B3LYP/6-31G(d,p) level of theory within the framework of the density functional theory. Our theoretical calculations predicted that all the compounds are floppy molecules with a low rotational C-N barrier, in which the degree of conjugation of the lone nitrogen pair with the quinone system depends on the magnitude of the electronic effect of the substituents of the aniline ring. Natural charges show that C(1) is more positive than C(4) although the LUMO orbital is located at C(4). Hence, if the natural charge distribution in the molecule controls the first electron addition, this should occur at carbon atom C(1). If the process is controlled by the LUMO orbitals, however, electron addition would first occur at C(4). For the APZms series susceptibility of the first reduction wave to the substitution effect (rho(pi) = 147 mV) is lower than that of the second reduction wave (rho(pi) = 156 mV). Thus, the first, one-electron transfer in the quinone system is controlled by the natural charge distribution of the molecule and therefore takes place at C(1).
 ...
PMID:Molecular structure of substituted phenylamine alpha-OMe- and alpha-OH-p-benzoquinone derivatives. Synthesis and correlation of spectroscopic, electrochemical, and theoretical parameters. 1173 13

Starting from phenethanolamine aniline leads 3a and 3b, we have identified a series of functionally potent and selective beta(3) adrenergic receptor (AR) agonists containing acylsulfonamide, sulfonylsulfonamide, or sulfonylurea groups within the aniline phenethanolamine series. In beta(3), beta(2), and beta(1) AR cAMP functional assays, 3a and other right-hand side (RHS) carboxylate analogues were found to be full agonists that were modestly selective against beta(1) or beta(2) ARs, while analogues lacking RHS acid functionality were active at beta(3) AR but not selective. Replacement of the carboxylate with acylthiazole and acylmethylsulfone gave potent, but only modestly selective, compounds. Increasing the size of the RHS sulfonamide substituent with phenyl or p-toluene afforded compounds with good potency and functional selectivity (beta(3) AR pEC(50) greater than 8; beta(1) and beta(2) AR selectivity greater than 40- and 500-fold, respectively). Our SAR studies suggest that the potency and selectivity profile of the best analogues reported here is a result of both the steric bulk and acidity of the RHS sulfonamide NH group. Although all of the analogues had a pharmacokinetic half-life of less than 2 h, acylsulfonamides 43 and 44 did show moderately low clearance in dogs. These two compounds were further evaluated by thermographic imaging in mice and were found to produce a robust thermogenic response via oral administration.
 ...
PMID:Synthesis and evaluation of potent and selective beta(3) adrenergic receptor agonists containing acylsulfonamide, sulfonylsulfonamide, and sulfonylurea carboxylic acid isosteres. 1180 9

A kinetic method for the determination of aromatic amines is reported. The method involves the formation of an azo dye between 1-(4-hydroxy-6-methylpyrimidin-2-yl)-3-methylpyrazolin-5-one and a diazonium salt formed from the amine in the presence of nitrite in weakly acidic media. The reaction is monitored via the initial rate of change of the absorbance of the azo dye at 420 nm, because this is proportional to the aniline concentration. The optimum acidity and concentration of reagents were established. The concentration ranges for which the calibration lines are linear are quite large. Detection limits were estimated. The effect of several metal ions usually present in real samples, e.g. waste water, was examined to assess interference.
 ...
PMID:Kinetic determination of aromatic amines at millimolar level. 1220 34

The linear-solvent strength (LSS) model of gradient elution has been applied to estimate parameters of lipophilicity and acidity of a series of drugs and model chemicals. Apparent pKa values and log kw values for individual analytes were determined in 2-3 gradient runs. The first experiment (or first two experiments) uses a wide-range organic modifier gradient with pH chosen for suppressed ionization of the analyte. The result of this experiment allows an estimate of contents of organic modifier of the mobile phase (%B) providing the required retention coefficient, k, for the non-ionized analyte. The following experiment is carried out with the latter %B and a pH-gradient of the aqueous component of the eluent that is sufficient to overlap the possible pKa-value of the analyte. The initial pH of the buffer used to make the mobile phase is selected to insure that the analyte is in non-ionized form. The resulting retention time allows an estimate of PKa in a solvent of the selected %B. At the same time, estimates of log kw can also be obtained. The log kw parameter obtained from gradient HPLC by the approach proposed correlated well with the corresponding value obtained by standard procedure of extrapolation of retention data determined in a series of isocratic measurements. Correlation between log kw and the reference parameter of lipophilicity, log P, was very good for a series of test analytes and satisfactory for a structurally diverse series of drugs. The approach supported with specific detection procedures can be recommended for fast screening of lipophilicity of individual components of complex mixtures like those produced by combinatorial chemistry. The values of pKa obtained in a study were found to correlate with the literature pKa data determined in water for a set of aniline derivatives studied. In case of a series of drugs the correlation was less than moderate if the general procedure of pKa determination was applied.
 ...
PMID:Lipophilicity and pKa estimates from gradient high-performance liquid chromatography. 1223 21


1 2 3 4 5 6 Next >>