Pyrrole-2-carboxylic Acid Research Articles

Synthesis of pyrrole-2-carboxylic acid from cellulose- and chitin-based feedstocks discovered by the automated route search.

The shift towards sustainable feedstocks for platform chemicals requires new routes to access functional molecules that contain heteroatoms, but there are limited bio-derived feedstocks that lead to heteroatoms in platform chemicals. Combining renewable molecules of different origins could be a solution to optimize the use of atoms from renewable sources. However, the lack of retrosynthetic tools makes it challenging to examine the extensive reaction networks of various platform molecules focusing on multiple bio-based feedstocks. In this study, a protocol was developed to identify potential transformation pathways that allow for the use of feedstocks from different origins. By analyzing existing knowledge on chemical reactions in large databases, several promising synthetic routes were shortlisted, with the reaction of D-glucosamine and pyruvic acid being the most interesting to make pyrrole-2-carboxylic acid (PCA). The optimized synthetic conditions resulted in 50% yield of PCA, with insights gained from temperature variant NMR studies. The use of substrates obtained from two different bio-feedstock bases, namely cellulose and chitin, allowed for the establishment of a PCA-based chemical space.

Insight into the antibacterial activity and membrane-damage mechanism of pyrrole-2-carboxylic acid against Listeria monocytogenes

Natural antimicrobials have potential to suppress the growth of foodborne pathogens. In this work, the antibacterial property and membrane-disruptive mechanism of pyrrole-2-carboxylic acid (PCA), against Listeria monocytogenes were elucidated. Leakage of cell constituents (K+ and nucleotide) and flow cytometric analysis indicated that PCA caused a significant change in the permeability and integrity of cell membrane of L. monocytogenes. Meanwhile, remarkable morphological alterations and membrane hyperpolarization of L. monocytogenes validated the disruptive ability of PCA on cell membrane. Additionally, PCA could interact with membrane protein, and cause changes in the conformation of protein. Untargeted lipidomics revealed that PCA triggered alternations in the composition and architecture of the membrane lipids mainly involved in glycerophospholipid and glycerolipid metabolism, thus leading to cell membrane dysfunction. Furthermore, PCA at concentration of 0.75 mg/mL could inhibit the contamination of L. monocytogenes in lettuce stem and beef, with a decrease of 2.4 log CFU/cm2 (P ＜ 0.05) for lettuce stem and 1.8 log CFU/cm2 (P ＜ 0.05) for beef after 10 days of storage. This work illuminates the key targets of PCA against the cell membrane of L. monocytogenes, facilitating the application of natural organic acids as candidate food preservatives in the food industry.

Pyrrole-2-carboxylic acid inhibits biofilm formation and suppresses the virulence of Listeria monocytogenes

Bacterial adhesion and biofilm formation of Listeria monocytogenes on food-contact surfaces result in serious safety concerns. This study aimed to explore the antibiofilm efficacy of pyrrole-2-carboxylic acid (PCA) against L. monocytogenes. Crystal violet staining assay demonstrated that PCA reduced the biofilm biomass of L. monocytogenes. The 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide reduction and flow cytometric assays indicated that PCA attenuated the metabolic activity of L. monocytogenes biofilm together with a decrease in viability. Morphologic observations revealed that PCA exposure collapsed the biofilm architecture. PCA administration of 0.75 mg ml−1 decreased the excretion of extracellular DNA, protein and polysaccharide by 48.58%, 61.60% and 75.63%, respectively. PCA failed to disperse the mature biofilm, even at 1.5 mg ml−1. However, PCA suppressed L. monocytogenes adhesion on common food-contact surfaces. Additionally, PCA exposure suppressed the hemolytic activity of L. monocytogenes. These findings suggested that PCA might serve as an alternative antibiofilm agent to control L. monocytogenes contamination.

Purification, Fermentation Optimization, and Antibacterial Activity of Pyrrole-2-carboxylic Acid Produced by an Endophytic Bacterium, Bacillus cereus ZBE, Isolated from Zanthoxylum bungeanum

An antibacterial compound, pyrrole-2-carboxylic acid (PCA), was isolated from an endophyte named Bacillus cereus ZBE in this study. RNA sequencing identified 14 genes encoding 9 key enzymes involved in PCA biosynthesis in B. cereus ZBE. The PCA production was enhanced 21-fold (149.63 mg/L) by optimization with the Plackett–Burman design and the response surface methodology. The optimum fermentation conditions were found to be 0.5% glycerinum, 1% peptone, 25% loaded liquid, initial pH at 7.0, inoculum size of 4%, incubation temperature at 37.72 °C, rotating speed of 120 rpm, and incubation for 48 h. In addition, PCA showed broad-spectrum antibacterial properties against a variety of foodborne pathogens. A further mechanism study demonstrated that PCA might exhibit antibacterial activity by inducing severe membrane damage in bacterial cells with a loss of membrane integrity. These findings suggested that PCA might be a promising source of natural antibacterial compounds used as preservatives in the food industry.

Vibrationally Induced Conformational Isomerization and Tunneling in Pyrrole-2-Carboxylic Acid

The conformational behavior of carboxylic acids has attracted considerable attention, as it can be used as a gateway for the study of more complex phenomena. Here, we present an experimental and computational study of pyrrole-2-carboxylic acid (PCA) conformational space and the vibrational characterization of the compound by infrared spectroscopy. The possibility of promoting conformational transformations using selective vibrational excitation of the 2ν(OH) and 2ν(NH) stretching overtones is explored. Two conformers, exhibiting the cis configuration of the COOH group (O═C-O-H dihedral angle near 0°) and differing by the orientation of the carboxylic group with respect to the pyrrole ring (i.e., showing either a cis or a trans NCC═O arrangement), were found to coexist initially for the compound isolated in a cryogenic nitrogen matrix, in an 86:14 ratio, and were characterized by infrared spectroscopy. A third conformer, with the COOH group in the trans configuration, was produced, in situ, by narrowband near-infrared (NIR) excitation of the most stable PCA form (with a cis NCC═O moiety). The photogenerated PCA conformer was found to decay back to the most stable PCA form, by H-atom quantum mechanical tunneling, with a characteristic half-life time of ∼10 min in the nitrogen matrix at 10 K. Tunneling rates were theoretically estimated and compared for the observed isomerization of pyrrole-2-carboxylic acid and for the structurally similar furan-2-carboxylic acid. This comparison showcases the effect of small modifications in the potential energy surface and the implications of quantum tunneling for the stability of short-living species.

Reagent-less amperometric glucose biosensor based on nanobiocomposite consisting of poly(1,10-phenanthroline-5,6-dione), poly(pyrrole-2-carboxylic acid), gold nanoparticles and glucose oxidase

In this work, a novel reagent-less amperometric glucose biosensor based on nanobiocomposite consisting of poly(1,10-phenanthroline-5,6-dione), poly(pyrrole-2-carboxylic acid) (PPCA), gold nanoparticles (AuNP) and glucose oxidase (GOx) was designed. To achieve this, the graphite rod electrode with adsorbed 1,10-phenanthroline-5,6-dione (PD) was immersed into electrochemical cell filled with a buffer solution containing pyrrole-2-carboxylic acid (PCA) and colloidal AuNP and electrochemical polymerization of PD and PCA was performed by cyclic voltammetry. During this process AuNP were encapsulated into PPCA layer. Carboxylic groups of the PPCA enabled the covalent immobilization of GOx. Optimal conditions for the biosensor working electrode preparation were elaborated and are discussed. The biosensor was characterized by wide linear range (0.2 –150.0 mM), relatively low detection limit (0.08 mM), good reproducibility (RSD 4.22 %, 2.34 % and 1.67 %, respectively for 5.0, 50.0 and 100.0 mM of glucose) and repeatability (RSD 6.93 %, 2.23 % and 1.17 %, respectively for 5.0, 50.0 and 100.0 mM of glucose), excellent stability (only 3.98 % loss of its initial activity over 14 days, when stored at 4 °C), high anti-interference ability to uric acid, acetaminophen and acetylsalicylic acid and demonstrated good accuracy in the analysis of pharmaceutical preparations Orsalit Drink and Rehydron Optim and human serum.

Effect of alkali metal ions on the pyrrole and pyridine π-electron systems in pyrrole-2-carboxylate and pyridine-2-carboxylate molecules: FT-IR, FT-Raman, NMR and theoretical studies

The FT-IR, FT-Raman and 1H and 13C NMR spectra of pyrrole-2-carboxylic acid (PCA) and lithium, sodium, potassium, rubidium and caesium pyrrole-2-carboxylates were recorded, assigned and compared in the Li → Na → K → Rb → Cs salt series. The effect of alkali metal ions on the electronic system of ligands was discussed. The obtained results were compared with previously reported ones for pyridine-2-carboxylic acid and alkali metal pyridine-2-carboxylates. Calculations for pyrrole-2-carboxylic acid and Li, Na, K pyrrole-2-carboxylates in B3LYP/6-311++G ** level and Møller–Plesset method in MP2/6-311++G ** level were made. Bond lengths, angles and dipole moments as well as aromaticity indices (HOMA, EN, GEO, I 6) for the optimized structures of pyrrole-2-carboxylic acid (PCA) and lithium, sodium, potassium pyrrole-2-carboxylates were also calculated. The degree of perturbation of the aromatic system of ligand under the influence of metals in the Li → Cs series was investigated with the use of statistical methods (linear correlation), calculated aromaticity indices and Mulliken, NBO and ChelpG population analysis method. Additionally, the Bader theory (AIM) was applied to setting the characteristic of the bond critical points what confirmed the influence of alkali metals on the pyrrole ring.

Determination of 4-hydroxyproline-2-epimerase activity by capillary electrophoresis: A stereoselective platform for inhibitor screening of amino acid isomerases

Isomerases involved in the metabolism of D/L-amino acids represent promising therapeutic targets for treatment of disease. Herein, we report a tunable platform for the assessment of enzymatic kinetics involving amino acid isomerization by CE that offers improved selectivity and sensitivity over traditional methods. Enzyme activity and competition assays were evaluated for various hydroxyproline diastereoisomers, proline enantiomers and their structural analogs using 4-hydroxyproline-2-epimerase as a model system. In this work, pyrrole 2-carboxylic acid was found to be a selective inhibitor of 4-hydroxyproline-2-epimerase with a half-maximal inhibition concentration of (2.3 + or - 0.1) mM. Reliable methods for unambiguous characterization of amino acid isomerases are required for the screening of novel inhibitors with epimerase and/or racemase activity.

Pyrrole-2-carboxylic acid as a ligand for the Cu-catalyzed reactions of primary anilines with aryl halides.

Pyrrole 2-carboxylic acid (L5) was found to be an effective ligand for the Cu-catalyzed monoarylation of anilines with aryl iodides and bromides. Under the reported conditions (10% CuI/20% L5/DMSO/K3PO 4/80-100 degrees C/20-24 h), a variety of useful functional groups were tolerated, and moderate to good yields of the diaryl amine products were obtained.

Theoretical study of excited state proton transfer in pyrrole-2-carboxylic acid

Pyrrole 2-carboxylic acid (PCA) shows dual emission (310 nm and 430 nm) in water on photo-excitation, which indicates that more than one species is in the excited state. This paper reports on the quantum chemical analysis of pyrrole 2-carboxylic acid (PCA) in the light of a possible excited state proton transfer. Dipole moment, excited state energy and findings in molecular orbital calculations (HOMO, LUMO) establish that PCA is a likely candidate for transfer of a proton from the pyrrole moiety to the C=O of carboxylic moiety (possible zwitterionic form) in the excited state. Overall, the computed predicted results of intramolecular and intermolecular excited state proton transfer corroborates the experimental results.

Dimers of Formic Acid, Acetic Acid, Formamide and Pyrrole-2-carboxylic Acid: an Ab Initio Study

The intermolecular hydrogen bonds in dimers of formic acid, acetic acid, and formamide were investigated. Additionally, three configurations of the pyrrole-2-carboxylic acid (PCA) dimer were studied to analyze how the pyrrole pi-electron system influences the carboxylic groups connected by double O-H...O hydrogen bonds. The ab initio calculations for the systems investigated were performed at MP2/6-311++G(d,p), MP2/aug-cc-pVDZ, and MP2/aug-cc-pVTZ//MP2/aug-cc-pVDZ levels of theory. The "atoms in molecules" theory of Bader was used and the analysis of the critical points was performed to study the nature of hydrogen bonds. The decomposition of the total interaction energy applied here reveals that the delocalization energy term is a particularly important attractive contribution in these systems, more important in the case of systems forming homonuclear O-H...O double hydrogen bonds than in the case of those connected through heteronuclear N-H...O bonds. Because the systems analyzed may be formally classified as the resonance-assisted hydrogen bonds (RAHBs), it seems that the dominant contribution from the delocalization interaction energy term is a distinguished feature of such interactions.

Crystal and Molecular Structure of Pyrrole-2-carboxylic Acid; π-Electron Delocalization of Its Dimers−DFT and MP2 Calculations

The crystal and molecular structure of pyrrole-2-carboxylic acid (PCA) determined by single-crystal X-ray diffraction is presented. Intermolecular H-bonds for this structure are analyzed. The DFT calculations at the B3LYP/6-311++G(d,p) level of theory and ab initio calculations at the MP2/6-311++G(d,p) level are performed for dimers of pyrrole-2-carboxylic acid and for similar model species. The X-ray data and calculations show that the pyrrole moiety within pyrrole-2-carboxylic acid influences the π-electron delocalization and hence the strength of the hydrogen bonds. The geometrical and energetic features of H-bonds of PCA dimers and of model complexes are analyzed. Additionally, the Bader theory is applied, and the characteristics of the bond critical points and ring critical points confirm the influence of the pyrrole moiety on the strength of H-bond interactions.

Pyrrole-2-carboxylic Acid and Its Dimers: Molecular Structures and Vibrational Spectrum

The infrared and Raman spectroscopic study of pyrrole-2-carboxylic acid (PCA) confirms the formation of the cyclic acid dimer species in the solid state. The molecular structure, vibrational frequencies, and binding energies of cyclic dimers have been also examined using the density functional theory (DFT) at the B3LYP/6-311+G(d) level. In addition, a complete vibrational assignment is proposed for the both s-cis and s-trans PCA conformers. The vibrational assignments are supported by normal coordinate calculations utilizing force constants predicted using the DFT method. The “atoms in molecules” theory of Bader is also used to characterize hydrogen bonds.

Selective enhancement of ligand and flavin Raman modes in charge‐transfer complexes of sarcosine oxidase

AbstractMonomeric sarcosine oxidase, from a bacterial source, is a 43.8 kDa flavoenzyme that catalyzes the oxidation of sarcosine (N‐methylglycine). The enzyme forms charge‐transfer (CT) complexes with substrate analogs such as (methylthio)acetic acid (MTA), pyrrole‐2‐carboxylic acid (PCA) and (methylseleno)acetic acid (MSA). The structure of sarcosine oxidase complexed to either of the former two ligands has been solved recently and shows that the ligands are binding close to the re face of the isoalloxazine ring. More structural detail can be adduced from Raman spectroscopic studies of these complexes. These involve collecting Raman difference data using 647.1 nm excitation, a wavelength that is in the resonance or pre‐resonance regime with regard to the CT bands. Selective intensity enhancements are observed and the difference spectra reveal a rich assortment of isoalloxazine modes and a few features due to the bound ligands. Within the CT complexes, intensity enhancement for the isoalloxazine ring vibrations is typically 1–2 orders of magnitude and is greatest for vibrations associated with the N5—C4a—C10a—N1 region of the ring. This identifies the region of the isoalloxazine ring that receives the charge transfer from the ligand and confirms, at the same time, that this region is a prime candidate for nucleophilic attack or electron transfer in any reaction scheme. Intensity enhancements for the ligand modes are much higher, typically a few thousand‐fold. Isotopic substitutions combined with quantum mechanical and vibrational calculations were used to identify the ligand modes showing high intensity enhancement. For MTA and MSA these are the methyl symmetric bending and methylene wag. For PCA the pyrrole ring CH deformations show the highest intensity enhancement. Copyright © 2001 John Wiley & Sons, Ltd.

The suppressive effect of pyrrole-2-carboxylic acid on platelet aggregation

In the course of a search for novel antibiotics, an antiplatelet substance was isolated from the fermentation broth of Streptomyces sp. No. 82-85. Thereafter, the active substance was identified as pyrrole-2-carboxylic acid (P2C) by structural studies. The effects of P2C on adenosine diphosphate (ADP)-, arachidonic acid-, collagen- or tumor cell-induced platelet aggregation were examined in vitro and ex vivo. In in vitro studies, P2C (25-100 micrograms/ml) suppressed the aggregation of platelets of normal Wistar rats. The intraperitoneal administration of P2C (200 mg/kg) to rats and rabbits suppressed platelet aggregation induced by ADP, arachidonic acid and collagen when examined for 0.5-3 hours after administration. The agent also suppressed platelet aggregation induced by both mouse syngenic tumors, Meth-A fibrosarcoma and IMC carcinoma in vitro.

Collagen metabolism. I. Significance of urinary pyrrole-2-carboxylic acid.

ABSTRACT In the hyperthyroid condition in both man and rat the urinary excretion of pyrrole- 2-carboxylic acid (PCA) is elevated and accompanied by increased hydroxyproline. PCA, a metabolite of free L-hydroxyproline, appears to reflect changes in collagen metabolism as well as hydroxyproline.

CONVERSION OF HYDROXYPROLINE TO PYRROLE-2-CARBOXYLIC ACID

Although studies on the degradative metabolism of hydroxyproline have revealed that this amino acid is converted at least in part to glutamic acid (I-G), knowledge of the intermediates in this conversion and of other products of hydroxyproline metabolism is not yet complete. In the course of experiments on the metabolism of hydroxyproline, it was observed that incubation of hydroxyproline with kidney pre.parations led to the formation of a compound which we have identified as pyrrole-2-carboxylic acid (PCA) (7).’ Subsequent study revealed that kidney D-amino acid oxidase oxidizes hydroxy-n-proline and allohydroxy-n-proline to an intermediate compound which appears to be Al-pyrroline-4-hydroxy-2-carboxylic acid. The int’ermediate is spontaneously converted (at pH 8.3) to PCA; this conversion occurs much more rapidly in acid solution. PCA formation was also observed as a product of t,ransamination of y-hydroxyornithine with glyoxylate, pyruvate, or wketoglutarate. The evidence suggests that such transamination, in contrast to that of ornithine (8, 9), involves the a-amino group rather than the b-amino group. This report describes experiments on the formation of PCA by enzymatic oxidation, by enzymatic and non-enzymatic transamination, and also by non-enzymatic oxidation of hydroxyproline by hydrogen peroxide. Some implications of these findings in terms of the metabolism of hydroxyproline are discussed.