Cyclic Amino Acids Research Articles

Proline: A versatile amino acid in the presence of salinity and drought in the Capsicum genus

Abstract Proline (Pro) is a low-molecular-weight cyclic amino acid that plays an important role as a source of energy and reducing power and as a source of carbon and nitrogen compounds for plant development. In most plant species, Pro is considered a stress marker. It is also a common compatible solute and is used cumulatively by plants under osmotic stress. The pepper genus, which includes species of great economic importance distributed throughout the world, is the target of different types of stresses, both biotic and abiotic, and Pro plays an important role in tolerance to some of these stresses. In this work, we discuss the general aspects of the metabolism, transport, and different functions of Pro in the Capsicum genus. Special focus is given to critical investigations that should be conducted with respect to Pro accumulation under stress conditions, such as salinity and water deficit.

Metabolic Engineering of Saccharomyces cerevisiae for High-Level Production of l-Pipecolic Acid from Glucose.

l-Pipecolic acid (L-PA), an essential chiral cyclic nonprotein amino acid, is gaining prominence in the food and pharmaceutical sectors due to its wide-ranging biological and pharmacological properties. Historically, L-PA has been synthesized chemically for commercial purposes. This study introduces a novel and efficient microbial production method for L-PA using engineered strain Saccharomyces cerevisiae BY4743. Initially, an optimized biosynthetic pathway was constructed within S. cerevisiae, converting glucose to L-PA with a yield of 0.60 g/L in a 250 mL shake flask in vivo. Subsequently, a multifaceted engineering strategy was implemented to enhance L-PA production: substrate-enzyme affinity modification, global transcription machinery engineering modification, and Kozak sequence optimization for enhanced L-PA production. Approaches above led to an impressive 8.6-fold increase in L-PA yield, reaching 5.47 g/L in shake flask cultures. Further scaling up in a 5 L fed-batch fermenter achieved a remarkable L-PA concentration of 74.54 g/L. This research offers innovative insights into the industrial-scale production of L-PA.

SYNTHESIS OF ALDONITRONES OF THE 1-PYRROLINE-1-OXIDE SERIES USING A THREE-COMPONENT DOMINO REACTION OF GLYCINE ESTERS, KETONES AND ACTIVATED OLEFINS

Aldonitrones of pyrroline series are widely used in organic synthesis, in particular in the synthesis of alkaloids and other biologically active compounds, and as spin traps for short-lived radicals. A three-component domino process involving glycine benzyl ester, ketones (cyclohexanone and diethyl ketone) and fumaric acid esters was used to synthesise aldonitrones of the pyrroline series of 1-pyrroline-1-oxide. The benzyl esters of 3,4,5-substituted prolines obtained in the first step were selectively cleaved by hydrogenolysis. Oxidation of the resulting cyclic amino acids in the tungstate - hydrogen peroxide system is accompanied by decarboxylation and leads to the formation of 3,4,5-substituted 1-pyrroline-1-oxides. It is shown that the ester groups in these compounds can be reduced to hydroxymethyl ones by an excess of lithium aluminum hydride, and subsequent treatment with manganese dioxide leads to aldonitrone group recovery.

Synthesis and antibacterial activity of angular tetrahydrocycloamino [1,2-a]quinoxalin-4-one derivatives

ObjectivesThe resistance of bacteria to current antibiotics is a significant concern in treating infectious diseases, posing a strong threat to global health, food security, and development. This underscores the need for synthesizing new heterocyclic compounds as potential lead candidates in drug discovery. Quinoxalinone derivatives, known for their presence in various therapeutic agents and clinical drugs, are of particular interest. This study aimed to synthesize angular tricyclic tetrahydrocycloamino [1,2-a]quinoxalin-4-one derivatives and evaluate their antibacterial activities. Methods/analysisThe synthesis began with preparing precursors through the condensation of substituted 1-halogeno-2-nitrobenzene and cyclic amino acids in the presence of a base in ethanol, forming 2-nitrophenyl pyrrolidine/piperidine-2-carboxylic acids (acid adducts) 3a-3j. These acid adducts were then converted to amino esters 4a-4e by reacting them with thionyl chloride/ trimethylchlorosilane and methanol. Intramolecular reductive cyclization of the acid adducts or esters produced tetrahydrocycloamino [1,2-a]quinoxalin-4-ones (5a-5j) through catalytic hydrogen transfer hydrogenation. The chemical structures of the synthesized compounds were confirmed using FTIR, 1H and 13C NMR, MS, and CHN analysis. Their in vitro antibacterial activities were evaluated against ten bacterial strains using the broth microdilution method, revealing moderate to excellent activities compared to standard antibiotics streptomycin (STM) and nalidixic acid (NLD). FindingsCompound 5g demonstrated significant antibacterial activity (MIC = 15.6 μg/mL) against S. epidermidis, and compound 5c exhibited activity (MIC = 31.3 μg/mL) against S. aureus, both compared to STM and NLD. The results suggest that some of these compounds with promising antibacterial activity could serve as leads for discovering new antibacterial drugs. Novelty/improvementThe tetrahydrocycloamino [1,2-a]quinoxalin-4-ones were prepared using two methods with higher yields than previously reported, with the second method being novel for synthesizing quinoxalin-4-ones. The in vitro antibacterial studies of these compounds were reported, and substituted quinoxalin-4-ones were synthesized from N’-ethyl-N-(2-nitrophenyl)pyrrolidine-2-carboxamide 7 in good yield.

C–3 alkoxymethylation of 4-oxo-1,4-dihydroquinoline 2-carboxylic acid esters via organic additives

Esters of kynurenic acid, a known neuroprotective agent were reacted with cyclic amino acids to yield novel alkoxymethylated products under optimized reaction conditions. The importance of amino acid based (primary, secondary, biogenic and synthetic) organic additives was proven by the conduction of numerous test reactions. Thoroughly extended investigations, directly focusing on amino acid catalysis, which is an emerging and up-to-date field of catalysis and green chemical processes, have been conducted. The mechanism of the alkoxymethylation reaction was proposed and later the findings supported the hypothesis of the first retro-Mannich step (formation of the ortho-quinone methide intermediate) and subsequent formation of the alkoxymethylated derivatives. As a preparative result, two novel kynurenic acid derivatives bearing an alkoxymethyl moiety and two additional derivatives having amino acid residues at the site C-3 were synthesized, thus setting the scope and limitations of the modified Mannich reaction of kynurenic acid derivatives using amino acid nucleophiles. The mechanistic investigations highlighted the significant physicochemical effects of used nucleophiles on the amino-acid driven one-pot retro-Mannich initiated alkoxylation of kynurenic acid.

Influence of starter cultures on microbiological and physical-chemical parameters of dry-cured products

Using the antagonistic competitive interaction of the microbiological cultures has become one of the potential and modern ways to improve the quality of dry-cured meat products. These studies aim to substantiate the use of the starter cultures for producing fermented pork meat products. The studies' physicochemical, microbiological, organoleptic, and statistical methods were used for their implementation. Two starter cultures were used on the basis of Lactobacillus plantarum, L. rhamnosus and Kocuria rosea (SC 1); Staphylococcus carnosus, L. plantarum, L. Rhamnosus and L. paracasei (SC 2). The dynamics of microbiota development, the dynamics of acidity, the content of sodium nitrite, parameters of water activity, the dynamics of moisture changes, the content of nitrogen-containing substances, the accumulation of free cyclic and acyclic amino acids, as well as the organoleptic characteristics were studied. It had been established that the undesirable microflora is suppressed due to the active development of the starter cultures in fermented meat products. The study results confirm that using the starter cultures while producing the dry-cured meat contributes to their dehydration and reduction of the parameters of water activity. Based on the tasting results, the samples with the addition of the compositions of the starter cultures received a total score higher than the control sample, in particular, they had a beautiful appearance, a cut of red color, an elastic consistency, a delectable flavor with a characteristic sour after-taste. The use of the starter culture based on the combination of Staphylococcus carnosus, L. plantarum, L. rhamnosus, and L. paracasei (SC 2) for the dry-cured meat products to be produced activates the microbiological processes, which improves the structural-mechanical properties of the meat product, increases the water-binding power and, as a whole, positively influences on the quality of the finished product. It has been shown that the use of the drugs SC 2 and SC 1, when the dry-cured pork balyks are produced, decreases the duration of the technological cycle by 3-4 days, as well as ensures a high degree of sanitary and epidemic safety of the finished product: the absence of pathogenic and opportunistic microorganisms, the low residual content of sodium nitrite of up to 0.003%.

Unearthing a Cryptic Biosynthetic Gene Cluster for the Piperazic Acid-Bearing Depsipeptide Diperamycin in the Ant-Dweller Streptomyces sp. CS113.

Piperazic acid is a cyclic nonproteinogenic amino acid that contains a hydrazine N-N bond formed by a piperazate synthase (KtzT-like). This amino acid, found in bioactive natural products synthesized by non-ribosomal peptide synthetases (NRPSs), confers conformational constraint to peptides, an important feature for their biological activities. Genome mining of Streptomyces strains has been revealed as a strategy to identify biosynthetic gene clusters (BGCs) for potentially active compounds. Moreover, the isolation of new strains from underexplored habitats or associated with other organisms has allowed to uncover new BGCs for unknown compounds. The in-house "Carlos Sialer (CS)" strain collection consists of seventy-one Streptomyces strains isolated from the cuticle of leaf-cutting ants of the tribe Attini. Genomes from twelve of these strains have been sequenced and mined using bioinformatics tools, highlighting their potential to encode secondary metabolites. In this work, we have screened in silico those genomes, using KtzT as a hook to identify BGCs encoding piperazic acid-containing compounds. This resulted in uncovering the new BGC dpn in Streptomyces sp. CS113, which encodes the biosynthesis of the hybrid polyketide-depsipeptide diperamycin. Analysis of the diperamycin polyketide synthase (PKS) and NRPS reveals their functional similarity to those from the aurantimycin A biosynthetic pathway. Experimental proof linking the dpn BGC to its encoded compound was achieved by determining the growth conditions for the expression of the cluster and by inactivating the NRPS encoding gene dpnS2 and the piperazate synthase gene dpnZ. The identity of diperamycin was confirmed by High-Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR) and by analysis of the domain composition of modules from the DpnP PKS and DpnS NRPS. The identification of the dpn BGC expands the number of BGCs that have been confirmed to encode the relatively scarcely represented BGCs for depsipeptides of the azinothricin family of compounds and will facilitate the generation of new-to-nature analogues by combinatorial biosynthesis.

Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting

Intermittent fasting (IF) has been shown to reduce cardiovascular risk factors in both animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction. However, the underlying molecular mechanisms behind these effects remain unclear. To shed light on the molecular and cellular adaptations of the heart to IF, we conducted comprehensive system-wide analyses of the proteome, phosphoproteome, and transcriptome, followed by functional analysis. Using advanced mass spectrometry, we profiled the proteome and phosphoproteome of heart tissues obtained from mice that were maintained on daily 12- or 16 hr fasting, every-other-day fasting, or ad libitum control feeding regimens for 6 months. We also performed RNA sequencing to evaluate whether the observed molecular responses to IF occur at the transcriptional or post-transcriptional levels. Our analyses revealed that IF significantly affected pathways that regulate cyclic GMP signaling, lipid and amino acid metabolism, cell adhesion, cell death, and inflammation. Furthermore, we found that the impact of IF on different metabolic processes varied depending on the length of the fasting regimen. Short IF regimens showed a higher correlation of pathway alteration, while longer IF regimens had an inverse correlation of metabolic processes such as fatty acid oxidation and immune processes. Additionally, functional echocardiographic analyses demonstrated that IF enhances stress-induced cardiac performance. Our systematic multi-omics study provides a molecular framework for understanding how IF impacts the heart’s function and its vulnerability to injury and disease.

Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting.

Intermittent fasting (IF) has been shown to reduce cardiovascular risk factors in both animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction. However, the underlying molecular mechanisms behind these effects remain unclear. To shed light on the molecular and cellular adaptations of the heart to IF, we conducted comprehensive system-wide analyses of the proteome, phosphoproteome, and transcriptome, followed by functional analysis. Using advanced mass spectrometry, we profiled the proteome and phosphoproteome of heart tissues obtained from mice that were maintained on daily 12- or 16 hr fasting, every-other-day fasting, or ad libitum control feeding regimens for 6 months. We also performed RNA sequencing to evaluate whether the observed molecular responses to IF occur at the transcriptional or post-transcriptional levels. Our analyses revealed that IF significantly affected pathways that regulate cyclic GMP signaling, lipid and amino acid metabolism, cell adhesion, cell death, and inflammation. Furthermore, we found that the impact of IF on different metabolic processes varied depending on the length of the fasting regimen. Short IF regimens showed a higher correlation of pathway alteration, while longer IF regimens had an inverse correlation of metabolic processes such as fatty acid oxidation and immune processes. Additionally, functional echocardiographic analyses demonstrated that IF enhances stress-induced cardiac performance. Our systematic multi-omics study provides a molecular framework for understanding how IF impacts the heart's function and its vulnerability to injury and disease.

Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of N-Acetylamino Malonic Acid Derivatives.

Broad application of α,α-disubstituted cyclic amino acid derivatives in medicinal chemistry urges for analogue design with improved pharmacokinetic properties. Herein, we disclose an electrochemical approach toward unnatural THF- and THP-containing amino acid derivatives that relies on anodic decarboxylation-intramolecular etherification of inexpensive and readily available N-acetylamino malonic acid monoesters under Hofer-Moest reaction conditions. The decarboxylative cyclization proceeds under constant current conditions in an undivided cell in an aqueous medium without any added base. A successful bioisosteric replacement of the 1-aminocyclohexane-1-carboxylic acid subunit by the THP-containing amino acid scaffold in cathepsin K inhibitor balicatib helped to reduce lipophilicity while retaining low nanomolar enzyme inhibitory potency and comparable microsomal stability.

Conformationally Restricted Carbocyclic γ-Amino Acids: Synthesis of Diastereomeric 3-Amino-5-arylcyclopentane 1-Carboxylic Acids

AbstractA Trost Pd-catalyzed [3+2] cycloaddition between a p-benzyloxy cinnamate bearing an Evans auxiliary and 1-trimethylsilyl-2-acetoxymethylpropene is disclosed leading to, after functional group manipulation, previously unreported diastereoisomeric 3-amino-5-arylcyclopentane 1-carboxylic acids via the corresponding 3-hydroxy and 3-azido precursors. The availability of these conformationally restricted cyclic amino acids may find utility in the context of CNS-active compounds related to GABA, or as peripheral units of bioactive pharmaceuticals. An expedient alternative 4-step synthesis of 3S-amino-5S-p-hydroxyphenyl-1S-cyclopentane carboxylic acid methyl ester was achieved starting with the (–)-Vince lactam and utilizing a regio- and diastereoselective Pd-catalyzed hydroarylation reaction.

Common alterations in plasma free amino acid profiles and gut microbiota-derived tryptophan metabolites of five types of cancer patients.

Amino acids not only play a vital role in the synthesis of biological molecules such as proteins in cancer malignant cells, they are also essential metabolites for immune cell activation and antitumor effects in the tumor microenvironment. The abnormal changes in amino acid metabolism are closely related to the occurrence and development of tumors and immunity. Intestinal microorganisms play an essential role in amino acid metabolism, and tryptophan and its intestinal microbial metabolites are typical representatives. However, it is known that the cyclic amino acid profile is affected by specific cancer types, so relevant studies mainly focus on one type of cancer and rarely study different cancer forms at the same time. The objective of this study was to examine the PFAA profile of five cancer patients and the characteristics of tryptophan intestinal microbial metabolites to determine whether there are general amino acid changes across tumors. Plasma samples were collected from esophageal (n = 53), lung (n = 73), colorectal (n = 94), gastric (n = 55), breast cancer (n = 25), and healthy control (HC) (n = 139) subjects. PFAA profile and tryptophan metabolites were measured, and their perioperative changes were examined using high-performance liquid chromatography. Univariate analysis revealed significant differences between cancer patients and HC. Furthermore, multivariate analysis discriminated cancer patients from HC. Regression diagnosis models were established for each cancer group using differential amino acids from univariate analysis. Receiver-operating characteristic analysis was applied to evaluate these diagnosis models. Finally, GABA, arginine, tryptophan, taurine, glutamic acid, and melatonin showed common alterations across all types of cancer patients. Metabolic pathway analysis shows that the most significant enrichment pathways were tryptophan, arginine, and proline metabolism. This study provides evidence that common alterations of the metabolites mentioned above suggest their role in the pathogenesis of each cancer patient. It was suggested that multivariate models based on PFAA profiles and tryptophan metabolites might be applicable in the screening of cancer patients.

Mechanistic and Structural Insights into a Divergent PLP-Dependent l-Enduracididine Cyclase from a Toxic Cyanobacterium.

Cyclic arginine noncanonical amino acids (ncAAs) are found in several actinobacterial peptide natural products with therapeutically useful antibacterial properties. The preparation of ncAAs like enduracididine and capreomycidine currently takes multiple biosynthetic or chemosynthetic steps, thus limiting the commercial availability and applicability of these cyclic guanidine-containing amino acids. We recently discovered and characterized the biosynthetic pathway of guanitoxin, a potent freshwater cyanobacterial neurotoxin, that contains an arginine-derived cyclic guanidine phosphate within its highly polar structure. The ncAA l-enduracididine is an early intermediate in guanitoxin biosynthesis and is produced by GntC, a unique pyridoxal-5'-phosphate (PLP)-dependent enzyme. GntC catalyzes a cyclodehydration from a stereoselectively γ-hydroxylated l-arginine precursor via a reaction that functionally and mechanistically diverges from previously established actinobacterial cyclic arginine ncAA pathways. Herein, we interrogate l-enduracididine biosynthesis from the cyanobacterium Sphaerospermopsis torques-reginae ITEP-024 using spectroscopy, stable isotope labeling techniques, and X-ray crystallography structure-guided site-directed mutagenesis. GntC initially facilitates the reversible deprotonations of the α- and β-positions of its substrate before catalyzing an irreversible diastereoselective dehydration and subsequent intramolecular cyclization. The comparison of holo- and substrate-bound GntC structures and activity assays on site-specific mutants further identified amino acid residues that contribute to the overall catalytic mechanism. These interdisciplinary efforts at structurally and functionally characterizing GntC enable an improved understanding of how nature divergently produces cyclic arginine ncAAs and generate additional tools for their biocatalytic production and downstream biological applications.

Synthesis and In Vitro Anticancer Evaluation of Chrysin Containing Hybrids and Other Chrysin Derivatives

Chrysin, a well-known naturally occurring flavonoid having several biological effects including antiproliferative activity, was coupled with different pharmacophore structures. Coupling was carried out with spacers of different lengths and types. Structures selected for hybrid formation were amines, cyclic amino acid esters, and (hetero)aromatic compounds. In addition, vindoline, which is a Vinca alkaloid containing an indole skeleton, was also used. The alkylation of amines in the presence of carbonate base resulted in an interesting carbamate side product formation beside the expected amine. We also present the detailed structure elucidation of the carbamates. The in vitro anticancer activities of the synthesized derivatives were examined against 60 human tumor cell lines in National Cancer Institute (NCI, USA).

Oxidative C–N Bond Cleavage of Cyclic Amines with Ammonium Hypochlorite

AbstractAn oxidative C–N bond cleavage of cyclic amines has been developed under metal-free conditions, providing N-Cl-ω-amino acids in moderate to excellent yields. The reactions proceed by using tetramethylammonium hypochlorite (TMAOCl) as an oxidant even on a gram scale. Hofmann–Löffler–Freytag-type reaction of N-Cl-ω-amino acids to form cyclic amino acids has also been demonstrated.

Synthesis of cyclic amino acid baikiain via asymmetric phase transfer catalysis

AbstractThe synthesis of the cyclic, naturally occurring amino acid baikiain from glycine and cis‐1,4‐butenediol is reported. The key step of the synthesis is an enantioselective phase transfer catalyzed allylation of the benzophenone imine of glycine t‐butyl ester, catalyzed by a cinchonidine quaternary ammonium salt, which provided the allylated glycine in 82% yield and 80% e.e. Further deprotection and hydrolysis of the Schiff base followed by an intramolecular Mitsunobu ring closure reaction yielded the corresponding piperidine ring system in 77% yield, which by hydrolysis yielded baikiain hydrochloride in 36% overall yield. Hydrogenation of the double bond could provide access to (S)‐pipecolic acid, which is also an important chiral synthon.

A New Approach in Prebiotic Chemistry Studies: Proline Sorption Triggered by Mineral Surfaces Analysed Using XPS.

The role of minerals in the origin of life and prebiotic evolution remains unknown and controversial. Mineral surfaces have the potential to facilitate prebiotic polymerization due to their ability to adsorb and concentrate biomolecules that subsequently can catalyse reactions; however, the precise nature of the interaction between the mineral host and the guest biomolecule still needs to be understood. In this context, we spectroscopically characterized, using infrared, X-ray photoemission spectroscopy (XPS) and X-ray diffraction (XRD) techniques, the interaction between L-proline and montmorillonite, olivine, iron disulphide, and haematite (minerals of prebiotic interest), by evaluating their interaction from a liquid medium. This work provides insight into the chemical processes occurring between proline, the only cyclic amino acid, and this selection of minerals, each of them bearing a particular chemical and crystal structures. Proline was successfully adsorbed on montmorillonite, haematite, olivine, and iron disulphide in anionic and zwitterionic chemical forms, being the predominant form directly related to the mineral structure and composition. Silicates (montmorillonite) dominate adsorption, whereas iron oxides (haematite) show the lowest molecular affinity. This approach will help to understand structure-affinity relationship between the mineral surfaces and proline, one of the nine amino acids generated in the Miller-Urey experiment.

Toxicological effects of cyanobacterial metabolites on zebrafish larval development

Freshwater cyanobacteria are known worldwide for their potential to produce toxins. However, these organisms are also found in marine, terrestrial and extreme environments and produce unique compounds, other than toxins. Nevertheless, their effects on biological systems are still barely known. This work tested extracts of different cyanobacterial strains against zebrafish (Danio rerio) larvae and analyzed their metabolomic profiles using liquid chromatography combined with mass spectrometry. Strains Desertifilum tharense, Anagnostidinema amphibium, and Nostoc sp. promoted morphological abnormalities such as pericardial edema, edema in the digestive system region, curvature of the tail and spine in zebrafish larvae in vivo. In contrast, Microcystis aeruginosa and Chlorogloeopsis sp. did not promote such changes. Metabolomics revealed unique compounds belonging to the classes of terpenoids, peptides, and linear lipopeptides/microginins in the nontoxic strains. The toxic strains were shown to contain unique compounds belonging to the classes of cyclic peptides, amino acids and other peptides, anabaenopeptins, lipopeptides, terpenoids, and alkaloids and derivatives. Other unknown compounds were also detected, highlighting the rich structural diversity of secondary metabolites produced by cyanobacteria. The effects of cyanobacterial metabolites on living organisms, mainly those related to potential human and ecotoxicological risks, are still poorly known. This work highlights the diverse, complex, and unique metabolomic profiles of cyanobacteria and the biotechnological potential and associated risks of exposure to their metabolites.

Enantioselective synthesis of unprotected 2-quinolinone-based cyclic amino acids via sequential palladium-catalyzed asymmetric allylation/desymmetrization

Enantioselective synthesis of unprotected 2-quinolinone-based cyclic amino acids via sequential palladium-catalyzed asymmetric allylation/desymmetrization

Oxidation of Pharmaceuticals by Ferrate(VI)-Amino Acid Systems: Enhancement by Proline.

The occurrence of micropollutants in water threatens public health and ecology. Removal of micropollutants such as pharmaceuticals by a green oxidant, ferrate(VI) (FeVIO42-, Fe(VI)) can be accomplished. However, electron-deficient pharmaceuticals, such as carbamazepine (CBZ) showed a low removal rate by Fe(VI). This work investigates the activation of Fe(VI) by adding nine amino acids (AA) of different functionalities to accelerate the removal of CBZ in water under mild alkaline conditions. Among the studied amino acids, proline, a cyclic AA, had the highest removal of CBZ. The accelerated effect of proline was ascribed by demonstrating the involvement of highly reactive intermediate Fe(V) species, generated by one-electron transfer by the reaction of Fe(VI) with proline (i.e., Fe(VI) + proline → Fe(V) + proline•). The degradation kinetics of CBZ by a Fe(VI)-proline system was interpreted by kinetic modeling of the reactions involved that estimated the rate of the reaction of Fe(V) with CBZ as (1.03 ± 0.21) × 106 M-1 s-1, which was several orders of magnitude greater than that of Fe(VI) of 2.25 M-1 s-1. Overall, natural compounds such as amino acids may be applied to increase the removal efficiency of recalcitrant micropollutants by Fe(VI).