4-Amino-3-hydroxybenzoic acid

Unveiling self-sensitized photodegradation pathways by DFT calculations: A case of sunscreen p-aminobenzoic acid.[Pubmed:27529387]

Chemosphere. 2016 Nov;163:227-233.

Self-sensitized photodegradation has been observed for diverse aquatic organic pollutants. However, photodegradation pathways have not been clarified in previous experimental studies. Here, we attempted to probe self-sensitized photodegradation pathways of organic pollutants employing both photolytic experiments and density functional theory calculations. By performing photolytic experiments, we found that singlet state oxygen ((1)O2) play an essential role in photodegradation of a sunscreen p-aminobenzoic acid (PABA). PABA can photogenerate (1)O2 and react fast with (1)O2. We hypothesized that PABA underwent (1)O2 induced self-sensitized photodegradation. By calculating transition states, intermediates and reaction barriers, we found that (1)O2 can oxidize PABA through electrophilic attacks on the benzene ring to abstract one H atom of the amino group following a 1,3-addition mechanism or to induce decarboxylation. Either pathway produces a hydroperoxide. O-O bond cleavage of the hydroperoxides occurring at ground states or the lowest triplet excited states can produce phenoxyl radical precursors of 4-Amino-3-hydroxybenzoic acid and 4-aminophenol, which are photodegradation products detected in experiments. Thus, a viable (1)O2 self-sensitized photodegradation mechanism was unveiled for PABA.

Metabolism of 4-amino-3-hydroxybenzoic acid by Bordetella sp. strain 10d: A different modified meta-cleavage pathway for 2-aminophenols.[Pubmed:17090920]

Biosci Biotechnol Biochem. 2006 Nov;70(11):2653-61.

Bordetella sp. strain 10d metabolizes 4-Amino-3-hydroxybenzoic acid via 2-hydroxymuconic 6-semialdehyde. Cell extracts from 4-amino-3-hydroxybenzoate-grown cells showed high NAD(+)-dependent 2-hydroxymuconic 6-semialdehyde dehydrogenase, 4-oxalocrotonate tautomerase, 4-oxalocrotonate decarboxylase, and 2-oxopent-4-enoate hydratase activities, but no 2-hydroxymuconic 6-semialdehyde hydrolase activity. These enzymes involved in 4-amino-3-hydroxybenzoate metabolism were purified and characterized. When 2-hydroxymuconic 6-semialdehyde was used as substrate in a reaction mixture containing NAD(+) and cell extracts from 4-amino-3-hydroxybenzoate-grown cells, 4-oxalocrotonic acid, 2-oxopent-4-enoic acid, and 4-hydroxy-2-oxovaleric acid were identified as intermediates, and pyruvic acid was identified as the final product. A complete pathway for the metabolism of 4-Amino-3-hydroxybenzoic acid in strain 10d is proposed. Strain 10d metabolized 2-hydroxymuconic 6-semialdehyde derived from 4-Amino-3-hydroxybenzoic acid via a dehydrogenative route, not via a hydrolytic route. This proposed metabolic pathway differs considerably from the modified meta-cleavage pathway of 2-aminophenol and those previously reported for methyl- and chloro-derivatives.

Interaction of mushroom tyrosinase with aromatic amines, o-diamines and o-aminophenols.[Pubmed:15279888]

Biochim Biophys Acta. 2004 Aug 4;1673(3):170-7.

3-Amino-L-tyrosine was found to be a substrate of mushroom tyrosinase, contrary to what had previously been reported in the literature. A series of amino derivatives of benzoic acid were tested as substrates and inhibitors of the enzyme. 3-Amino-4-hydroxybenzoic acid, 4-Amino-3-hydroxybenzoic acid and 3,4-diaminobenzoic acid were oxidized by this enzyme, as previously reported for Neurospora crassa tyrosinase, but 4-aminobenzoic acid and 3-aminobenzoic acid were not. Interestingly, 3-amino-4-hydroxybenzoic acid was oxidized five times faster than 4-Amino-3-hydroxybenzoic acid, confirming the importance of proton transfer from the hydroxyl group at C-4 position. All compounds inhibited the monophenolase activity but their effect on the diphenolase activity was small or negligible. 3-Amino-4-hydroxybenzoic acid was a stronger inhibitor than 4-Amino-3-hydroxybenzoic acid, indicating their different binding affinity to the oxy form of the enzyme. Both, however, were weaker inhibitors than 3-amino-L-tyrosine, 4-methoxy-o-phenylenediamine and 3,4-diaminobenzoic acid, which was the strongest inhibitor from among the compounds tested. These results show that the relative positioning of the amino group and the hydroxy group in o-aminophenols with respect to the side chain is important both for binding to the dicopper center and for catalysis.

A novel coupled enzyme assay reveals an enzyme responsible for the deamination of a chemically unstable intermediate in the metabolic pathway of 4-amino-3-hydroxybenzoic acid in Bordetella sp. strain 10d.[Pubmed:15265044]

Eur J Biochem. 2004 Aug;271(15):3248-54.

2-amino-5-carboxymuconic 6-semialdehyde is an unstable intermediate in the meta-cleavage pathway of 4-Amino-3-hydroxybenzoic acid in Bordetella sp. strain 10d. In vitro, this compound is nonenzymatically converted to 2,5-pyridinedicarboxylic acid. Crude extracts of strain 10d grown on 4-Amino-3-hydroxybenzoic acid converted 2-amino-5-carboxymuconic 6-semialdehyde formed from 4-Amino-3-hydroxybenzoic acid by the first enzyme in the pathway, 4-amino-3-hydroxybenzoate 2,3-dioxygenase, to a yellow compound (epsilonmax = 375 nm). The enzyme in the crude extract carrying out the next step was purified to homogeneity. The yellow compound formed from 4-Amino-3-hydroxybenzoic acid by this purified enzyme and purified 4-amino-3-hydroxybenzoate 2,3-dioxygenase in a coupled assay was identified as 2-hydroxymuconic 6-semialdehyde by GC-MS analysis. A mechanism for the formation of 2-hydroxymuconic 6-semialdehyde via enzymatic deamination and nonenzymatic decarboxylation is proposed based on results of spectrophotometric analyses. The purified enzyme, designated 2-amino-5-carboxymuconic 6-semialdehyde deaminase, is a new type of deaminase that differs from the 2-aminomuconate deaminases reported previously in that it primarily and specifically attacks 2-amino-5-carboxymuconic 6-semialdehyde. The deamination step in the proposed pathway differs from that in the pathways for 2-aminophenol and its derivatives.

Cloning of a gene encoding 4-amino-3-hydroxybenzoate 2,3-dioxygenase from Bordetella sp. 10d.[Pubmed:14733932]

Biochem Biophys Res Commun. 2004 Feb 6;314(2):489-94.

Bordetella sp. 10d produces a novel dioxygenase catalyzing the meta-cleavage of 4-Amino-3-hydroxybenzoic acid, 4-amino-3-hydroxybenzoate 2,3-dioxygenase (4A3HBA23D). A gene encoding 4A3HBA23D was cloned and named ahdA. The deduced amino acid sequence of ahdA showed 29.2-24.2% identities to those of prokaryotic and eukaryotic 3-hydoxybenzoate 3,4-dioxygenases in reported meta-cleavage dioxygenases. However, no identities were observed in the amino-terminal sequences of the first 29 amino acid residues. An ORF was found downstream of ahdA. The deduced amino acid sequence of the ORF showed identities to those of LysR family regulators involved in protocatechuate metabolism and contained motifs conserved in the regulators. On the basis of these results, the ORF was named ahdR encoding a putative LysR family regulator. The transcription start point of ahdA was localized 414-bp upstream of the start codon of ahdA. Two DNA-binding motifs of LysR family regulators were found upstream of the transcription start point. These observations suggest that a LysR family regulator encoded by ahdR regulates the expression of ahdA.

A novel meta-cleavage dioxygenase that cleaves a carboxyl-group-substituted 2-aminophenol. Purification and characterization of 4-amino-3-hydroxybenzoate 2,3-dioxygenase from Bordetella sp. strain 10d.[Pubmed:12444975]

Eur J Biochem. 2002 Dec;269(23):5871-7.

A bacterial strain that grew on 4-Amino-3-hydroxybenzoic acid was isolated from farm soil. The isolate, strain 10d, was identified as a species of Bordetella. Cell extracts of Bordetella sp. strain 10d grown on 4-Amino-3-hydroxybenzoic acid contained an enzyme that cleaved this substrate. The enzyme was purified to homogeneity with a 110-fold increase in specific activity. The purified enzyme was characterized as a meta-cleavage dioxygenase that catalyzed the ring fission between C2 and C3 of 4-Amino-3-hydroxybenzoic acid, with the consumption of 1 mol of O2 per mol of substrate. The enzyme was therefore designated as 4-amino-3-hydroxybenzoate 2,3-dioxygenase. The molecular mass of the native enzyme was 40 kDa based on gel filtration; the enzyme is composed of two identical 21-kDa subunits according to SDS/PAGE. The enzyme showed a high dioxygenase activity only for 4-Amino-3-hydroxybenzoic acid. The Km and Vmax values for this substrate were 35 micro m and 12 micro mol.min-1.(mg protein)-1, respectively. Of the 2-aminophenols tested, only 4-aminoresorcinol and 6-amino-m-cresol inhibited the enzyme. The enzyme reported here differs from previously reported extradiol dioxygenases, including 2-aminophenol 1,6-dioxygenase, in molecular mass, subunit structure and catalytic properties.

B-535a, b and c, new sphingosine kinase inhibitors, produced by a marine bacterium; taxonomy, fermentation, isolation, physico-chemical properties and structure determination.[Pubmed:11079796]

J Antibiot (Tokyo). 2000 Aug;53(8):753-8.

In the course of our screening for inhibitors of sphingosine kinase, we found a series of active compounds in a culture broth of a novel marine bacterium, SANK 71896. The structures of the compounds, named B-5354a, b and c, were elucidated by a combination of spectroscopic analyses to be new esters of 4-Amino-3-hydroxybenzoic acid with long-chain unsaturated alcohols. B-5354a, b and c inhibit sphingosine kinase activity with IC50 values of 21, 58 and 38 microm, respectively.

The photochemistry of p-aminobenzoic acid.[Pubmed:1528977]

Photochem Photobiol. 1992 May;55(5):647-56.

We have studied the photoreactions occurring when p-aminobenzoic acid (PABA), a component of some sunscreens, is irradiated in aqueous solution. These studies were carried out in the presence and absence of oxygen, using light of lambda = 254 nm as well as light of wavelengths greater than 290 nm. In deoxygenated solution between pH 7.5 and 11.0, we found two photoproducts that were identified as 4-(4'-aminophenyl)aminobenzoic acid (I) and 4-(2'-amino-5'-carboxyphenyl)aminobenzoic acid (V); we used 1H and 13C NMR, electron impact mass spectrometry and synthesis by an independent route to identify each of these compounds. Rapid discoloration of the photolyzed sample was observed when PABA was irradiated in aerated solution. Although a number of products were detected under these conditions, the three most abundant stable compounds have been isolated and identified as 4-Amino-3-hydroxybenzoic acid, 4-aminophenol and 4-(4'-hydroxyphenyl)aminobenzoic acid (IV). The latter compound was shown to result from rapid photo-induced oxidation of I in the presence of oxygen. Even in the presence of trace amounts of oxygen, the yield of I was significantly reduced in favor of IV. Studies of the thermal oxidation of I, coupled with evidence gathered from studies of the photochemistry of incompletely deoxygenated PABA solutions, indicate that 4-(2,5-cyclohexadien-4-one)iminobenzoic acid (III) is an intermediate on the pathway between I and IV. Qualitatively, we found that the photochemical reactions resulting from irradiation of PABA solutions with lambda = 254 nm light and light with lambda greater than 290 nm were the same. The quantum yields for formation of I and V are highly pH dependent, both being less than 10(-4) at pH 7 and rising steadily to values greater than 10(-3) at pH 11. The detailed pH dependence suggests that the deprotonated PABA radical cation may be an important intermediate entering into the reactions forming I and IV.