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The extraction and complexation of trivalent americium (Am) and lanthanides (Ln) using an asymmetric picolinic acid-derived tridentate N,O-hybrid ligand, 6-(dioctylcarbamoyl)picolinic acid (DOAPA), have been studied through both experimental and theoretical methods. DOAPA exhibits effective and fast extraction of Am(III) and Ln(III). The extraction is driven by favorable enthalpy change. Slope analysis, absorption spectroscopy and NMR titration indicate that both Am(III) and Ln(III) coordinate with DOAPA to form complexes of a 1 : 3 stoichiometry (metal to ligand). Meanwhile, luminescence and mass spectral studies suggest that three deprotonated tridentate DOAPA ligands (L−) substitute all the H2O molecules in the primary coordination sphere of Eu(III), resulting in the extraction of a neutral complex into the organic phase. Further theoretical calculations reveal that a more robust interaction between DOAPA and Am(III) relative to Eu(III) as well as a higher degree of covalence in Am–N/O bonds than in Eu–N/O bonds leads to slight selectivity of Am(III) over Eu(III). [ABSTRACT FROM AUTHOR]

Alterations within the tryptophan–kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan–kynurenine pathway metabolites and all‐cause mortality among CRC patients. This study utilizes data from 2102 stage I–III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3‐hydroxykynurenine (HK), xanthurenic acid (XA), 3‐hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography–tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above‐mentioned metabolites with all‐cause mortality, adjusted for potential confounders. During a median follow‐up of 3.2 years (interquartile range: 2.2–4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all‐cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine‐to‐tryptophan ratio, a marker of cell‐mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan–kynurenine pathway metabolites may be prognostic markers of survival in CRC patients. [ABSTRACT FROM AUTHOR]

Three gold(III) nanostructured complexes of nicotinamide (nta), picolinic acid (pica), and isonicotinic acid (inta) were synthesized by the reacted of AuCl3 salt with nta, pica, and inta with 1:2 stoichiometry in the alcoholic medium. The solid products obtained were formulated by comparing experimental and calculated data for microanalytical (C, H, N) and metal. Both produce 1:2 compounds with metal ions. The prepared complexes were characterized by different physico-spectroscopic techniques. The FTIR, and 1H NMR spectral analysis, morphological analysis (scanning electron microscopy SEM, transmittance TEM, and X-ray powder diffraction XRD) of these complexes have been discussed. The conductive behavior of the complexes indicates that all of them behave as electrolytic behavior. The mononuclear gold(III) complexes have formulated as [Au(nta)2(Cl)2].Cl, [Au(pica)2].Cl and [Au(inta)2].Cl. The shifts of the ν(N-H) amino, ν(C=N) pyridine, and ν(C=O) carboxylic stretches have been monitored to find out the donor sites of the ligands. According to the experimental data, the three complexes can be characterized in the solid state as mononuclear, with a four-coordinate stereochemistry. [ABSTRACT FROM AUTHOR]

Three neutral iridium complexes Ir1–Ir3 were synthesized using diphenylphosphoryl-substituted 2-phenylpyridine derivatives as the cyclometalating ligand and picolinic acid as the auxiliary ligand. They exhibited significant aggregation-induced phosphorescent emission (AIPE) properties in H2O/THF and were successfully used as bi-responsive luminescent sensors for the detection of picric acid (PA) and Fe3+ in aqueous media. Ir1–Ir3 possesses high efficiency and high selectivity for detecting PA and Fe3+, with the lowest limit of detection at 59 nM for PA and 390 nM for Fe3+. Additionally, the complexes can achieve naked-eye detection of Fe3+ in aqueous media. Ir1–Ir3 exhibit excellent potential for practical applications in complicated environments. The detection mechanism for PA is attributed to photo-induced electron transfer (PET) and Förster resonance energy transfer (FRET), and the detection mechanism for Fe3+ may be explained by PET and the strong interactions between Fe3+ and the complexes. [ABSTRACT FROM AUTHOR]

Despite the increasing use of copper in C−H functionalizations, the Cu‐catalyzed direct deuteration of C−H bonds remains a significant challenge due to its inherent low reactivity in inverse C−H bond reconstruction. In this paper, a novel strategy had been developed to reverse the copper‐catalyzed concerted metalation‐deprotonation process by inhibiting the unexpected disproportionation of Cu(II) to Cu(III). Picolinic acid was identified as a powerful ligand for facilitating this H/D exchange with D2O as deuterium source, and its inhibition activity was supported by preliminary control experiments and DFT studies. [ABSTRACT FROM AUTHOR]

The synthesis, crystal structure, and Hirshfeld surface analysis of N-(4-meth­oxy­phen­yl)picolinamide (MPPA), C13H12N2O2, are presented. MPPA crystallizes in the monoclinic space group P21/n, with a single mol­ecule in the asymmetric unit. Structural analysis reveals that all non-hydrogen atoms are nearly coplanar, and the mol­ecule exhibits two intra­molecular hydrogen bonds that stabilize its conformation. Supra­molecular features include significant inter­molecular inter­actions, primarily C—H⋯π and various hydrogen bonds, contributing to the overall crystal cohesion, as confirmed by energy framework calculations yielding a total inter­action energy of −138.3 kJ mol−1. Hirshfeld surface analysis indicates that H⋯H inter­actions dominate, followed by C⋯H and O⋯H inter­actions, highlighting the role of van der Waals forces and hydrogen bonding in crystal packing. [ABSTRACT FROM AUTHOR]

Preliminary evidence suggests perturbations of the kynurenine pathway (KP) of tryptophan metabolism in infants with single ventricle heart disease (SVHD). In 72 infants with SVHD undergoing stage 2 palliation (S2P) and 41 controls, we quantified serum KP metabolite concentrations via tandem mass spectroscopy pre‐S2P and post‐S2P at 2, 24, and 48 h and assessed metabolite relationships with post‐S2P outcomes (length of stay, hypoxemia burden, and intubation duration). Pre‐S2P, SVHD infants had lower tryptophan and serotonin levels and higher kynurenic acid, 3‐hydroxykynurenine, and picolinic acid levels than controls. Post‐S2P, metabolites peaked at 2 h, with return to baseline by 48 h for all except kynurenic acid, which remained elevated. Metabolite concentrations pre‐S2P were poorly associated with outcomes. A lower serotonin peak 2 h post‐S2P was associated with longer length of stay and intubation duration. Multiple metabolites at 24 and 48 h correlated with outcomes; notably, elevated kynurenic acid was associated with worse results for all three outcomes. Our results confirm that interstage SVHD infants have altered KP activity compared to controls. Further, the link between outcomes and KP metabolites post‐S2P—but not at baseline—demonstrates that acute, perioperative changes in tryptophan catabolism may be more important to tolerating S2P physiology than chronic interstage changes. [ABSTRACT FROM AUTHOR]

In this work, two novel mixed-ligand CPs that has a compositions of [Co2(µ-Hdppa)2(phen)2(H2O)2] (1) and {[Co(µ-Hdppa)(µ-4,4′-bipy)(H2O)]·H2O}n (2) is achieved through reaction of cobalt salts with the 5-(3,4-Dicarboxylphenyl)picolinic acid (H3dppa) with various N-donor co-ligands (1,10-phenanthroline (phen) for 1 and 4,4′-bipyridine (4,4′-bipy) for 2). The structures and characteristics of these two complexes were fully examined via IR, TGA, and SXRD. Furthermore, their superior blue fluorescence properties compared to the original ligands were confirmed through fluorescence spectroscopy. These two complexes prepared in this study have enriched the choices for blue fluorescent materials. [ABSTRACT FROM AUTHOR]

Quantum tunneling conductance of molecular junctions originates from the charge transport through the 𝜋-orbitals (𝜋-transport) and the 𝜎-orbitals (𝜎-transport) of the molecules, but the 𝜎-transport can not be observed due to the more rapid decay of the tunneling conductance in the 𝜎-system compared to that in the 𝜋-system. Here, we demonstrate that dominant 𝜎-transport can be observed in 𝜋-conjugated molecular junctions at the subnanometer scale using the scanning tunneling microscope break junction technique (STM-BJ). We have found that the conductance of meta -connected picolinic acid, which mainly occurs by 𝜎-transport, is ∼35 times higher than that of its para -isomer, which is entirely different from what is expected from 𝜋-transport through these systems. Flicker noise analysis reveals that the transport through the meta -connection exhibits more throughbond transport than the para -counterpart and density functional theory (DFT) shows that the 𝜎-system provides the dominant transport path. These results reveal that the 𝜎-electrons, rather than the 𝜋-electrons, can dominate charge transport through conjugated molecular junctions at the sub-nanometer scale, and this provides a new avenue toward the future miniaturization of molecular devices and materials. [ABSTRACT FROM AUTHOR]

A potential source of novel biomarkers for mTBI is the kynurenine pathway (KP), a metabolic pathway of tryptophan (Trp), that is up‐regulated by neuroinflammation and stress. Considering that metabolites of the KP (kynurenines) are implicated in various neuropsychiatric diseases, exploration of this pathway could potentially bridge the gap between physiological and psychological factors in the recovery process after mTBI. This study, therefore, set out to characterize the KP after mTBI and to examine associations with long‐term outcome. Patients were prospectively recruited at the emergency department (ED), and blood samples were obtained in the acute phase (<24 h; N = 256) and at 1‐month follow‐up (N = 146). A comparison group of healthy controls (HC; N = 32) was studied at both timepoints. Trp, kynurenines, and interleukin (IL)‐6 and IL‐10 were quantified in plasma. Clinical outcome was measured at six months post‐injury. Trp, xanthurenic acid (XA), and picolinic acid (PA) were significantly reduced in patients with mTBI relative to HC, corrected for age and sex. For Trp (d = −0.57 vs. d = −0.29) and XA (d = −0.98 vs. d = −0.32), larger effects sizes were observed during the acute phase compared to one‐month follow‐up, while for PA (d = −0.49 vs. d = −0.52) effect sizes remained consistent. Findings for other kynurenines (e.g., kynurenine, kynurenic acid, and quinolinic acid) were non‐significant after correction for multiple testing. Within the mTBI group, lower acute Trp levels were significantly related to incomplete functional recovery and higher depression scores at 6 months post‐injury. No significant relationships were found for Trp, XA, and PA with IL‐6 or IL‐10 concentrations. In conclusion, our findings indicate that perturbations of the plasma KP in the hyperacute phase of mTBI and 1 month later are limited to the precursor Trp, and glutamate system modulating kynurenines XA and PA. Correlations between acute reductions of Trp and unfavorable outcomes may suggest a potential substrate for pharmacological intervention. [ABSTRACT FROM AUTHOR]

Human exposure to PM2.5 and PM10 has been linked to respiratory and cardiovascular diseases through inflammation activation. The kynurenine pathway is associated with inflammation, and it is necessary to investigate the effects of long-term PM2.5 and PM10 exposure on this pathway. This study aimed to conduct a cross-sectional analysis of long-term PM2.5 and PM10 exposure's impact on the kynurenine pathway using proton NMR spectroscopy (1H-NMR). The participants were divided into a low-PM-exposure group (LG; n = 98), and a high-PM-exposure group (HG; n = 92). The metabolites of tryptophan were determined in blood by 1H-NMR. Serotonin, cinnabarinic acid, xanthurenic acid, 5-hydroxytryptophan, indoleacetic acid, tryptamine, melatonin, L-tryptophan, 5-hydroxy-L-tryptophol, indoxyl, 2-aminobenzoic acid, 5-HTOL, hydroxykynurenine, L-3-hydroxykynurenine, N-formyl kynurenine, 3-hydroxy anthranilic acid, kynurenic acid, and picolinic acid significantly increased (p < 0.05) in the HG group. Conversely, NAD and quinolinic acid significantly decreased in the HG group compared to the LG group. The enzyme activities of indoleamine 2,3-dioxygenase and formamidase significantly decreased, while kynureninase and kynurenine monooxygenase significantly increased. The kynurenine pathway is linked to inflammation and non-communicable diseases. Disruption of the kynurenine pathway from particulate matter might promote diseases. Reducing exposure to the particulate matter is crucial for preventing adverse health effects. [ABSTRACT FROM AUTHOR]

Computational analysis of four antifungal transition metal complexes of Co(II), Ni(II), Cu(II) and Zn(II) with pyridine carboxamide derivates (methyl 2-amino-3- methylbenzoate isonicotinic acid amide (L1) and methyl 2-amino-3-methylbenzoate picolinic acid amide (L2)) as ligands is provided here within the DFT framework. Geometry optimization, binding energy, HOMO-LUMO energy gap, Density of States (DOS) plots, and MEP surfaces have been calculated to rationalize the molecular structure of these complexes. The effect of noncovalent interactions on the crystal structure of these complexes has been deciphered using CE-B3LYP model instigated into CrystalExplorer using experimental geometries accessed from Cambridge Crystallographic Data Center (CCDC). These complexes are docked against Enterococcus Faecalis using AutoDock Vina to quantify binding energy between the complexes and protein accessed from the protein data bank (PDB). [ABSTRACT FROM AUTHOR]

Introduction: Tryptophan’s (Trp) metabolites are undervalued markers of human health. Their serum concentrations are modified by physical exercise and other factors, among which fasting has a well-documented role. Although this mechanism is hardly explored, thus, the study aimed to determine the effect of the 8-day fasting period and the impact of such a procedure on a single bout of an endurance exercise on the concentration of kynurenine pathway (KP) metabolites. Methods: 10 participants fasted for 8 days, and 10 as a control group participated in the study. The exercise was performed at baseline after an overnight fast and repeated post 8 days. Results: The 8 days of fasting increased the resting 3-hydroxy-L-kynurenine (3HK), picolinic acid (PA), kynurenic acid (KYNA), and xanthurenic acid (XA) serum concentration. Also elevated phenylalanine (Phe) and tyrosine (Tyr) levels were recorded, suggesting expanded proteolysis of muscle proteins. In turn, physical activity caused a decrease in the concentration of 3-hydroxyanthranilic acid (3HAA) and PA after fasting. The obtained results were not recorded in controls. Conclusion: The results of this study show that the health-promoting effects of fasting are associated with changes in the KYN pathway. The increase in the concentration of PA and XA metabolites following fasting is capable of penetrating the blood-brain barrier, and KYNA, which initiates several beneficial changes, supports this assumption. [ABSTRACT FROM AUTHOR]

Fusaric acid (FA), a picolinic acid derivative, is a natural substance produced by a wide variety of fungal plant pathogens belonging to the Fusarium genus. As a metabolite, fusaric acid exerts several biological activities including metal chelation, electrolyte leakage, repression of ATP synthesis, and direct toxicity on plants, animals and bacteria. Prior studies on the structure of fusaric acid revealed a co-crystal dimeric adduct between FA and 9,10-dehydrofusaric acid. During an ongoing search for signaling genes differentially regulating FA production in the fungal pathogen Fusarium oxysporum (Fo), we found that mutants lacking pheromone expression have an increased production of FA compared to the wild type strain. Noteworthy, crystallographic analysis of FA extracted from Fo culture supernatants showed that crystals are formed by a dimeric form of two FA molecules (1:1 molar stoichiometry). Overall, our results suggest that pheromone signaling in Fo is required to regulate the synthesis of fusaric acid. [ABSTRACT FROM AUTHOR]

Objectives. To study the equilibrium distribution of components between KU-2-8 sulfocationite and an aqueous solution containing picolinic acid and Cu(II); to show the possibility of immobilization of cations of picolinic acid and Cu2+ in sulfonic cation exchanger KU-2-8; to calculate the component compositions of the equilibrium solution, in order to obtain the required ionic composition of the KU-2-8 sulfonic cation exchanger according to the selectivity coefficients of binary ion exchange, and the constants of formation of such complexes in water.Methods. The concentrations of the individual components in multicomponent solutions were calculated using the HySS 2009 program (Hyperquad Simulaton and Speciation). The calculation of the equilibrium ionic compositions of KU-2-8 sulfocationite was performed using the selectivity coefficients of binary ion exchanges and the formation constants of complexes of picolinic acid with Cu2+ and H+ cations. Experimental study of the equilibrium distribution of components between aqueous solutions of picolinic acid, copper nitrate, and KU-2-8 sulfocationite was carried out by means of the dynamic method at a temperature of 298 K. Fourier-transform infrared spectroscopy and electron paramagnetic resonance spectroscopy were used, in order to determine the ionic forms of the components contained in the sulfocationite.Results. It was shown that the equilibrium solution contains H+ protons, Cu2+ cations, LH picolinic acid molecules, protonated picolinic acid cations [H2L]+, deprotonated picolinic acid anions L-, Cu2+ complexes with the deprotonated picolinic acid anion [CuL]+, and Cu2+ complexes with two anions of deprotonated picolinic acid [CuL2]. The concentration of H+, Cu2+, and [H2L]+ cations in the solution significantly exceeds the concentration of other components at pH values from 0 to 0.5. The content of [CuL]+ cations and neutral complexes [CuL2] increases significantly in the solution, while the [H2L]+ cations disappear at pH greater than 1. It was experimentally established that the concentrations of picolinic acid and copper in the polymer phase are many times higher than the concentrations of these components in an aqueous solution. The partition coefficients are about 24 and 210 for picolinic acid and Cu(II), respectively. The calculated dependencies of the concentrations of Cu2+, [H2L]+, H+, [CuL]+ cations in the polymer vs pH of an equilibrium solution containing picolinic acid were obtained. The experimental data on the concentrations of all cations in the ion exchanger is in the intervals of the calculated compositions within the limits of measurement errors.Conclusions. KU-2-8 sulfocationite is proposed as a container for obtaining drugs based on picolinic acid and Cu2+ cations. It was shown that the selectivity coefficients of binary ion exchanges and the formation constants of [H2L]+, [CuL]+ complexes can be used to precalculate the ionic compositions of the equilibrium solution, in order to obtain the required compositions of the sulfocationite.

Many biologically active metabolites of the essential amino acid L-tryptophan (Trp) are associated with different neurodegenerative diseases and neurological disorders. Precise and reliable methods for their determination are needed. Variability in their physicochemical properties makes the analytical process challenging. In this case, chemical modification of analyte derivatization could come into play. Here, we introduce a novel fast reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) coupled with tandem mass spectrometry (MS/MS) method for the determination of Trp and its ten metabolites in human plasma samples after derivatization with 2-bromo-4′-nitroacetophenone (BNAP). The derivatization procedure was optimized in terms of incubation time, temperature, concentration, and volume of the derivatization reagent. Method development comprises a choice of a suitable stationary phase, mobile phase composition, and gradient elution optimization. The developed method was validated according to the ICH guidelines. Results of all validation parameters were within the acceptance criteria of the guideline, i.e., intra- and inter-day precision (expressed as relative standard deviation; RSD) were in the range of 0.5–8.2% and 2.3–7.4%, accuracy was in the range of 93.3–109.7% and 94.7–110.1%, limits of detection (LODs) were in the range of 0.15–9.43 ng/mL, coefficients of determination (R2) were higher than 0.9906, and carryovers were, in all cases, less than 8.8%. The practicability of the method was evaluated using the blue applicability grade index (BAGI) with a score of 65. Finally, the developed method was used for the analysis of Alzheimer's disease and healthy control plasma to prove its applicability. Statistical analysis revealed significant changes in picolinic acid (PA), anthranilic acid (AA), 5 hydroxyindole-3-acetic acid (5-OH IAA), and quinolinic acid (QA) concentration levels. This could serve as the basis for future studies that will be conducted with a large cohort of patients. [ABSTRACT FROM AUTHOR]

IntroductionTryptophan’s (Trp) metabolites are undervalued markers of human health. Their serum concentrations are modified by physical exercise and other factors, among which fasting has a well-documented role. Although this mechanism is hardly explored, thus, the study aimed to determine the effect of the 8-day fasting period and the impact of such a procedure on a single bout of an endurance exercise on the concentration of kynurenine pathway (KP) metabolites.Methods10 participants fasted for 8 days, and 10 as a control group participated in the study. The exercise was performed at baseline after an overnight fast and repeated post 8 days.ResultsThe 8 days of fasting increased the resting 3-hydroxy-L-kynurenine (3HK), picolinic acid (PA), kynurenic acid (KYNA), and xanthurenic acid (XA) serum concentration. Also elevated phenylalanine (Phe) and tyrosine (Tyr) levels were recorded, suggesting expanded proteolysis of muscle proteins. In turn, physical activity caused a decrease in the concentration of 3-hydroxyanthranilic acid (3HAA) and PA after fasting. The obtained results were not recorded in controls.ConclusionThe results of this study show that the health-promoting effects of fasting are associated with changes in the KYN pathway. The increase in the concentration of PA and XA metabolites following fasting is capable of penetrating the blood-brain barrier, and KYNA, which initiates several beneficial changes, supports this assumption.

Molecularly imprinted polymers (MIPs) have attracted much attention in recent years due to their structure predictability, recognition specificity, and universal application, as well as robustness, simplicity, and cheapness. In this study, firstly, the pre-polymerization process of molecularly imprinted polymer of dipicolinic acid (DPA) was simulated by molecular dynamics. Then, the appropriate functional monomer molecule for printing was selected and its intermolecular bond with the DPA molecule was evaluated. The monomers 2-vinyl pyridine, acrylic acid (AA), and methacrylic acid (MAA) were selected with potential energies of 3.93 kcal/mol, 3.15 kcal/mol, and 2.78 kcal/mol, respectively. Finally, the ability of functional groups to form hydrogen bonds was estimated, and molecularly imprinted polymers (MIPs) and non-imprinted polymers (NIPs) were synthesized by bulk polymerization. MAA and AA were used as functional monomers to identify DPA molecules. The morphology of MIP and NIP was investigated using a scanning electron microscope (SEM). Their performance was evaluated in the absorption of DPA molecules and picolinic acid (PA) molecules and the printing factor of synthesis polymers. The results showed that fabricated MIPs can be used in the structure of sensors, and the synthesis process is a key factor that significantly affects the polymer properties. The MIP based on the AA monomer showed a higher adsorption rate/capacity and maximum printing factor than MAA monomer-based MIP. [ABSTRACT FROM AUTHOR]

The chemical speciation of binary and ternary VO2+-picolinic acid (HPic) complexes with the amino acids: Leucine (Leu, HL), Isoleucine (Ile, HL), Valine (Val, HL), Tryptophan (Thr, HL), Glutamine (Gln, HL), Lysine (Lys, HL), Arginine (Arg, HL) and Tyrosine (Tyr, H2L) were obtained. This study was performed by potentiometric titrations at 25 °C using 1.0 mol·dm−3 NaCl as the ionic medium. The experimental data were analyzed with the least squares program LETAGROP, and the respective distribution diagrams were obtained with the HYSS program. The relative stability parameters Δlog10K, log10X and %R.S were determined. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is associated with anxiety; however, its exact mechanism is not well understood. Therefore, the aim of the present study was to assess the effect of moderate CKD on anxiety in rats. 5/6 nephrectomy was performed in male Wistar rats. 7 weeks after, anxiety-like behavior was assessed by elevated plus maze (EPM), open field (OF), and marble burying (MB) tests. At weeks 8 and 9, urinalysis was performed, and blood and amygdala samples were collected, respectively. In the amygdala, the gene expression of Avp and the gene and protein expression of Crh, Crhr1, and Crhr2 were analyzed. Furthermore, the plasma concentration of corticosterone, uremic toxins, and tryptophan metabolites was measured by UHPLC-MS/MS. Laboratory tests confirmed the development of CKD. In the CKD group, the closed arm time increased; the central time and the total number of entries decreased in the EPM. There was a reduction in rearing, central distance and time in the OF, and fewer interactions with marbles were detected during MB. CKD evoked an upregulation of gene expression of Crh, Crhr1, and Crhr2, but not Avp, in the amygdala. However, there was no alteration in protein expression. In the CKD group, plasma concentrations of p-cresyl-sulfate, indoxyl-sulfate, kynurenine, kynurenic acid, 3-hydroxykynurenine, anthranilic acid, xanthurenic acid, 5-hydroxyindoleacetic acid, picolinic acid, and quinolinic acid increased. However, the levels of tryptophan, tryptamine, 5-hydroxytryptophan, serotonin, and tyrosine decreased. In conclusion, moderate CKD evoked anxiety-like behavior that might be mediated by the accumulation of uremic toxins and metabolites of the kynurenine pathway, but the contribution of the amygdalar CRH system to the development of anxiety seems to be negligible at this stage. [ABSTRACT FROM AUTHOR]

Thirty-eight new 4-amino-3,5-dicholo-6-(1H-indazolyl)-2-picolinic acids and 4-amino-3,5-dicholo-6-(2H-indazolyl)-2-picolinic acids were designed by scaffold hopping and synthesized to discover potential herbicidal molecules. All the new compounds were tested to determine their inhibitory activities against Arabidopsis thaliana and the root growth of five weeds. In general, the synthesized compounds exhibited excellent inhibition properties and showed good inhibitory effects on weed root growth. In particular, compound 5a showed significantly greater root inhibitory activity than picloram in Brassica napus and Abutilon theophrasti Medicus at the concentration of 10 µM. The majority of compounds exhibited a 100% post-emergence herbicidal effect at 250 g/ha against Amaranthus retroflexus and Chenopodium album. We also found that 6-indazolyl-2-picolinic acids could induce the up-regulation of auxin genes ACS7 and NCED3, while auxin influx, efflux and auxin response factor were down-regulated, indicating that 6-indazolyl-2-picolinic acids promoted ethylene release and ABA production to cause plant death in a short period, which is different in mode from other picolinic acids. [ABSTRACT FROM AUTHOR]

Despite the progress on cobalt and manganese catalyzed C−C and C−N bond‐forming methodologies, the associated catalyst reusability remains with some unresolved issue, which needs to be addressed. Disclosed herein, a flexible multidentate proton‐responsive ligand (L) bearing 2,6‐bis(1H‐benzo[d]imidazol‐2‐yl)pyridine (BBP), 6‐(1H‐benzo[d]imidazol‐2‐yl)picolinic acid (BPA), and benzene‐1,2‐diamine (BDA) for Co/Mn‐based mono‐ and bi‐metallic supramolecular materials for C‐/N‐alkylation of alcohols. The flexible binding sites and different hydrogen bond donor‐acceptor fragments of L brings the rigidity and self‐assembling to ordered crystalline supramolecular materials, which prevented the coordinatively saturated active sites and thus providing much higher reaction efficiency and selectivity, which is highly unlikely in the case of comparable individual components. The easy synthesis, efficient reactivity and selectivity through cooperativity, broad substrate scope, and efficient recycling via recharging of metals make the catalyst and the protocol economical and sustainable. Importantly, the design strategy based on metallo‐organic hydrogen bonded coordination assembly has the potential to contribute to the development of supramolecular materials for various advanced catalytic applications. [ABSTRACT FROM AUTHOR]

A novel synthetic protocol for the direct oxidation of alkanes, including cyclic and linear ones, to give ketones and alcohols using hydrogen peroxide as terminal oxidant under ambient conditions is presented. The active catalyst for this challenging transformation is conveniently generated by combination of simple Fe salts with N‐methyl bis(picolylamine) (Me‐bpa). Utilizing picolinic acid as additive leads to improved yields of ketones and alcohols (32‐57 %). The reaction can be conveniently scaled up to multi‐g scale. [ABSTRACT FROM AUTHOR]

An experimental study of the equilibrium distribution of cations in the system of Dowex 50 sulfonic cation exchanger and an aqueous solution of picolinic acid and iron chloride was carried out. A high concentration of iron and picolinic acid complexes was obtained in the Dowex 50 sulfonic cationite phase. The possibility of calculating the equilibrium counterionic composition of Dowex 50 sulfonic cationite from the equilibrium constants of binary ion exchanges and the known composition of the solution is shown. Sulfocationite Dowex 50 is proposed as a container for biologically active preparations based on picolinic acid and Fe3+ cations. [ABSTRACT FROM AUTHOR]

A series of novel Ga(III)—pyridine carboxylates ([Ga(Pic)3]·H2O (GaPic; HPic = picolinic acid), H3O[Ga(Dpic)2]·H2O (GaDpic; H2Dpic = dipicolinic acid), [Ga(Chel)(H2O)(OH)]2·4H2O (GaChel; H2Chel = chelidamic acid) and [Ga(Cldpic)(H2O)(OH)]2 (GaCldpic; H2Cldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-H2Dpic systems by potentiometry and 1H NMR spectroscopy and mononuclear complex species were determined; [Ga(Pic)2]+ (logβ021 = 16.23(6)), [Ga(Pic)3] (logβ031 = 20.86(2)), [Ga(Dpic)2]− (logβ021 = 15.42(9)) and [Ga(Dpic)2(OH)]2− (logβ-121 = 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale 1H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC50 (0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant P. aeruginosa. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 μM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin. [ABSTRACT FROM AUTHOR]

Brown spot, caused by Bipolaris oryzae, is one of the most important diseases of rice. The non‐host toxin α‐picolinic acid (PA) has great potential to be used to enhance plant resistance against pathogen infection. The present study investigated the effect of spraying PA [0 (control), 1, 3, and 5 mg/mL] on the photosynthetic performance of rice plants (cultivar Metica‐1) infected or not with B. oryzae. Moreover, whether the PA treatment, especially at the highest concentration, could affect brown spot development was also evaluated. The chlorophyll a fluorescence parameters such as variable‐to‐maximum chlorophyll a fluorescence ratio (Fv/Fm), photochemical yield [Y(II)], yield for dissipation by down‐regulation [Y(NPQ)], the yield for non‐regulated dissipation [Y(NO)], and electron transport rate (ETR) as well as the concentration of photosynthetic pigments were determined. Based on the in vitro assay, PA inhibited mycelial growth of B. oryzae in a dose‐dependent manner and conidial germ tube length only decreased at 5 mg PA/mL. Conidia germination was not affected by the PA treatment. Necrotic lesions caused by PA were observed on leaves of non‐inoculated plants at 3 and 5 mg PA/mL. Symptoms of the brown spot were reduced on plants sprayed with 1 and 3 mg PA/mL compared to the control treatment. Brown spot lesions and those originating from PA toxicity overlapped for inoculated plants sprayed with 3 and 5 mg PA/mL. The photochemical performance of non‐inoculated plants was hampered by treatments with 3 and 5 mg PA/mL. Greater concentration of photosynthetic pigments and less impairment on the photosynthetic performance of inoculated plants sprayed with 1 mg PA/mL were noticed based on the values of Fv/Fm, Y(II), Y(NPQ), Y(NO), and ETR compared to inoculated plants non‐sprayed with PA. In conclusion, spraying rice plants with a low concentration of PA could decrease brown spot severity while preserving the photosynthetic capacity of the infected plants. The cellular damage generated by spraying the plants with the highest PA concentration did not favour the infection process of B. oryzae. [ABSTRACT FROM AUTHOR]

Background and Aim: Picolinic acid (PIC) is a metabolite of the kynurenine pathway, which is involved in the degradation of tryptophan, an essential amino acid. PIC has been suggested to have neuroprotective effects by inhibiting the production of quinolinic acid, a neurotoxic agent that can induce inflammation and oxidative stress in the brain. Several studies have reported the altered levels of PIC and other kynurenine metabolites in patients with suicidal behavior, indicating a possible link between PIC and suicide risk. However, the exact role of PIC in the pathophysiology of suicide is not fully understood and requires further investigation. We aim to assess the levels of PIC in patients with severe depression with and without suicidal attempts. Materials and Methods: A cross-sectional, observation study was conducted at MGM Medical College, Indore. The study consisted of two groups: Group A including patients of depression with suicidal attempt(s) and Group B including patients of depression without any suicidal attempt. After obtaining written informed consent, recruitment of the subjects was done as per strict inclusion criteria and exclusion criteria. Sociodemographic parameters such as age, gender, residence, and marital status were collected along with the clinical parameters such as Hamilton depression rating scale (HAM-D), Suicidal Behavior Questionnaire Revised (SBQ-R) score, and Beck Scale for suicidal ideation (BSSI). Blood samples of both the groups were measured for serum PIC using an auto analyzer. Results: Serum PIC levels were significantly lower (124.33 ± 51.15 ng/L) in the depression with suicidal attempt group than depression without suicide attempt which was 163 ± 41.28 ng/L (P < 0.01). SBQ-R, BSSI score, and number of suicide attempts correlated negatively with serum PIC levels. Conclusion: The depression with suicidal attempt(s) group has shown lower mean serum PIC levels than the depression without suicidal attempt(s) group, which was statistically significant. This indicates serum PIC could be a marker in severe depression.

A series of AIE molecules (BPO, BPM, BPP) with small conjugation were successfully designed and synthesized using 6-(dodecylcarbamyl)picolinic acid. The AIE gels BPO, BPM, and BPP were obtained in different solvents, and the self-assembly process of BPM as a representative sample in 1,4-dioxane was characterized using different technologies. Interestingly, BPM exhibited a 'turn-on' fluorescence response towards Cd2+ with excellent selectivity and a low limit of detection (LOD) of 0.66 nM. The formation of complex BPM-Cd with the stoichiometry of 1 : 1 was confirmed through Job's plot. With the introduction of metal–ligand coordination bonds, complex BPM-Cd showed multiple stimuli responses to polar solvents, including H2O, DMF, DMSO, methanol, and ethanol, with LODs of 0.0039%, 0.0042%, 0.002%, 0.088%, and 0.12% (v/v), respectively. This study provides a new method for constructing AIE self-assembly systems and multifunctional organic probes with improved sensitivity and selectivity. [ABSTRACT FROM AUTHOR]

• New norfloxacin cocrystals synthesized by a mechanochemical method. • The apparent aqueous solubility in the cocrystals is higher compared to pure drug. • Establishment of scale-up conditions from solution crystallization. Cocrystals are recognized as one of the most efficient approaches to improve aqueous solubility of Biopharmaceutical Classification System, BCS, classes II and IV drugs. Cocrystal discovery and the establishment of experimental conditions suitable for scale-up purposes are some of the main challenges in cocrystal investigation. In this work, the investigation of mechanochemical synthesis of norfloxacin cocrystals with picolinic and isonicotinic acids is performed, leading to the discovery of two new cocrystals of this important BCS class IV antibiotic, which were characterized through thermal, spectral and diffractometric analysis. Norfloxacin apparent aqueous solubility using the cocrystals is also presented, with higher values being obtained for all the investigated systems when compared to the pure drug. Norfloxacin has 3 polymorphs and several solvents/hydrates, which represents a challenge for obtaining pure cocrystal forms from solvent crystallization. This challenge was successfully overcome in this work, as experimental conditions to obtain the pure cocrystals (the new ones and also norfloxacin-nicotinic acid and norfloxacin-saccharin) were established using Crystal16 equipment. This is a crucial step to envisage future scale-up procedures and therefore a valuable information for the pharmaceutical industry. [Display omitted] [ABSTRACT FROM AUTHOR]

By utilizing the well-known selective xanthine oxidase inhibitor topiroxostat, a new zinc(II) complex Zn(L)2(H2O)2 (1) [HL = 4-(3-(pyridine-4-yl)-1H-1,2,4-triazol-5-yl)picolinic acid] has been hydrothermally synthesized, involving in-situ ligand formation upon hydrolysis of topiroxostat. The complex has been structurally characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, powder X-ray diffraction, and single-crystal X-ray diffraction. X-ray structural analysis revealed that complex 1 is a N,O-chelating mononuclear Zn(II) complex. Complex 1 shows good thermal stability and exhibits photoluminescence in the solid state at room temperature. Moreover, complex 1 has been shown to be effective in the solvent-free ring-opening polymerization of ε-caprolactone without any co-catalyst or initiator. [ABSTRACT FROM AUTHOR]

• Plasma levels of all kynurenines were positively correlated with those in CSF. • Correlations between plasma and CSF were strongest for QA. • QA showed a tendency for positive associations with CSF Aβ 1-42. • KYN, KA, and KTR in CSF were all positively associated with CSF Aβ 1-42. • KYN, both in plasma and CSF, was negatively associated with CSF p-tau. Altered levels of kynurenines in blood and cerebrospinal fluid (CSF) have been reported in Alzheimer's disease (AD). However, it is still largely unknown whether peripheral kynurenine concentrations resemble those found in CSF and how they relate to AD pathology. We therefore studied correlations between kynurenines in plasma and CSF and their associations with CSF amyloid-beta (Aβ 1-42) and tau levels in patients from the memory clinic spanning the whole cognitive spectrum. The Biobank Alzheimer Center Limburg study is a prospective cohort study of consecutive patients referred to the memory clinic of the Alzheimer Center Limburg. Plasma and CSF concentrations of tryptophan (TRP), eight kynurenines and neopterin from 138 patients were determined by means of LC-MS/MS. Additionally, CSF Aβ 1-42 , total-tau (t-tau) and phosphorylated tau (p-tau) concentrations were determined using commercially available single-parameter ELISA methods. Partial correlations were used to analyze cross-sectional associations between kynurenines in plasma and CSF and their relation to AD related CSF-biomarkers adjusted for age, sex, educational level, and kidney function. Moderate to strong correlations were observed between plasma and CSF levels for quinolinic acid (QA; r = 0.63), TRP (r = 0.47), anthranilic acid (r = 0.59), picolinic acid (r = 0.55), and the kynurenine (KYN)/TRP ratio (KTR; r = 0.55; all p < 0.0001), while other kynurenines correlated only weakly with their corresponding CSF values. No correlations were found between plasma and CSF levels of KA/QA. Several kynurenines were also weakly correlated with Aβ 1-42 , t-tau or p-tau. Plasma levels of KA/QA were negatively correlated with Aβ 1-42 (r = -0.21, p < 0.05). Plasma levels of TRP were negatively correlated with t-tau (r = -0.19) and levels of KYN with p-tau (r = -0.18; both p < 0.05). CSF levels of KYN (r = 0.20, p < 0.05), KA (r = 0.23, p < 0.01), and KTR (r = 0.18, p < 0.05) were positively correlated with Aβ 1-42. Finally, TRP and KYN were negatively (r = -0.22 and r = -0.18, respectively), and neopterin positively (r = 0.19) correlated with p-tau (all p < 0.05). Plasma concentrations of TRP, KP metabolites, KTR, and neopterin all significantly correlated positively with their corresponding CSF concentrations, but many correlations were weak. Additionally, our results suggest a relation between higher kynurenine levels and lower AD pathology load. These results need verification in future studies and require more research into (shared) underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background and Aim: Picolinic acid (PIC) is a metabolite of the kynurenine pathway, which is involved in the degradation of tryptophan, an essential amino acid. PIC has been suggested to have neuroprotective effects by inhibiting the production of quinolinic acid, a neurotoxic agent that can induce inflammation and oxidative stress in the brain. Several studies have reported the altered levels of PIC and other kynurenine metabolites in patients with suicidal behavior, indicating a possible link between PIC and suicide risk. However, the exact role of PIC in the pathophysiology of suicide is not fully understood and requires further investigation. We aim to assess the levels of PIC in patients with severe depression with and without suicidal attempts. Materials and Methods: A cross-sectional, observation study was conducted at MGM Medical College, Indore. The study consisted of two groups: Group A including patients of depression with suicidal attempt(s) and Group B including patients of depression without any suicidal attempt. After obtaining written informed consent, recruitment of the subjects was done as per strict inclusion criteria and exclusion criteria. Sociodemographic parameters such as age, gender, residence, and marital status were collected along with the clinical parameters such as Hamilton depression rating scale (HAM-D), Suicidal Behavior Questionnaire Revised (SBQ-R) score, and Beck Scale for suicidal ideation (BSSI). Blood samples of both the groups were measured for serum PIC using an auto analyzer. Results: Serum PIC levels were significantly lower (124.33 ± 51.15 ng/L) in the depression with suicidal attempt group than depression without suicide attempt which was 163 ± 41.28 ng/L (P < 0.01). SBQ-R, BSSI score, and number of suicide attempts correlated negatively with serum PIC levels. Conclusion: The depression with suicidal attempt(s) group has shown lower mean serum PIC levels than the depression without suicidal attempt(s) group, which was statistically significant. This indicates serum PIC could be a marker in severe depression. [ABSTRACT FROM AUTHOR]

Mitochondrial impairment is a hallmark feature of neurodegenerative disorders, such as Parkinson disease, and PRKN/parkin-mediated mitophagy serves to remove unhealthy mitochondria from cells. Notably, probiotics are used to alleviate several symptoms of Parkinson disease including impaired locomotion and neurodegeneration in preclinical studies and constipation in clinical trials. There is some evidence to suggest that probiotics can modulate mitochondrial quality control pathways. In this study, we screened 49 probiotic strains and tested distinct stages of mitophagy to determine whether probiotic treatment could upregulate mitophagy in cells undergoing mitochondrial stress. We found two probiotics, Saccharomyces boulardii and Lactococcus lactis, that upregulated mitochondrial PRKN recruitment, phospho-ubiquitination, and MFN degradation in our cellular assays. Administration of these strains to Drosophila that were exposed to paraquat, a mitochondrial toxin, resulted in improved longevity and motor function. Further, we directly observed increased lysosomal degradation of dysfunctional mitochondria in the treated Drosophila brains. These effects were replicated in vitro and in vivo with supra-physiological concentrations of exogenous soluble factors that are released by probiotics in cultures grown under laboratory conditions. We identified methyl-isoquinoline-6-carboxylate as one candidate molecule, which upregulates mitochondrial PRKN recruitment, phospho-ubiquitination, MFN degradation, and lysosomal degradation of damaged mitochondria. Addition of methyl-isoquinoline-6-carboxylate to the fly food restored motor function to paraquat-treated Drosophila. These data suggest a novel mechanism that is facilitated by probiotics to stimulate mitophagy through a PRKN-dependent pathway, which could explain the potential therapeutic benefit of probiotic administration to patients with Parkinson disease. [ABSTRACT FROM AUTHOR]

In this work, the inhibitory ability and mechanism of ω3‐nicotinic acid (ω3‐NA) and ω3‐Picolinic acid (ω3‐PA) complexes on the activity of mushroom tyrosinase (MT) were scrutinized for progressing a novel MT inhibitor. The complexes were synthesized. It was shown to have a considerable inhibition on the MT activity and Ki value of ω3‐NA and ω3‐PA on MT equal to 5.2 and 5.1 mM, respectively. ω3‐NA and ω3‐PA inhibited MT with Vmax values in the range of 0.134 mM and 0.14 mM, respectively. The outputs obtained from fluorescence quenching specified that ω3‐NA and ω3‐PA could interact with MT. Especially, the decrease in fluorescence intensity was due to the formation of a ligand‐enzyme complex which was mostly motivated by hydrogen bonding and hydrophobic forces. The presence of ω3‐NA and ω3‐PA altered the structure of MT and reduced the α‐helix of the enzyme. Molecular docking investigation along with molecular dynamics simulation exhibited that ligands‐MT formation is directed by hydrogen binding with Trp136, His263, and Val299 residues. The results highlight that ω3‐NA and ω3‐PA can be considered as possible inhibitors in treating hyperpigmentation via MT enzyme inhibition. [ABSTRACT FROM AUTHOR]

A cobaltaelectro‐catalyzed dehydrogenative [4+2] annulation of arylphosphinamides with alkynes was proposed in the present study to selectively construct a range of cyclic phosphinamide derivatives. Picolinic acid acted as a ligand to promote this transformation. A total of 38 examples demonstrated broad substrate scope, sufficient functional tolerance and excellent regioselectivity. Moreover, no additional oxidants and electrolytes were needed and it was possible to achieve gram scale synthesis, late‐stage diversification and the removal of the directing group. Cyclic voltammetry and kinetic isotope experiments provided a better understanding to the reaction mechanism. [ABSTRACT FROM AUTHOR]

Nelumbo nucifera Gaertn. (N. nucifera) tea is used as food and folk medicine to reduce toxicity in Southeast Asia. Mancozeb (Mz) is used for controlling fungi in agriculture and contains heavy metals. This study aimed to examine the effect of white N. nucifera petal tea on cognitive behavior, hippocampus histology, oxidative stress, and amino acid metabolism in rats poisoned with mancozeb. Seventy-two male Wistar rats were divided into nine groups (n = 8 in each). Y-maze spontaneous alternation test was used to assess cognitive behavior, and amino acid metabolism was investigated by nuclear magnetic resonance spectroscopy (1H-NMR) from blood. There was a significant increase in relative brain weight in the Mz co-administered with the highest dose (2.20 mg/kg bw) of white N. nucifera group. The levels of tryptophan, kynurenine, picolinic acid, and serotonin in blood showed a significant decrease in the Mz group and a significant increase in the Mz co-administered with low dose (0.55 mg/kg bw) of white N. nucifera group. However, there was no significant difference in cognitive behavior, hippocampus histology, oxidative stress, and corticosterone. This study demonstrated that a low dose of white N. nucifera petal tea has a neuroprotective effect against mancozeb. [ABSTRACT FROM AUTHOR]

[Display omitted] 3-[2-(Aminocarbonyl)pyridinium-1-yl]propane-1-sulfonate, a promising medicinal betain, was prepared by a one-pot synthesis with a 89% yield via N -alkylation of ethyl picolinate with 1,3-propanesultone in MeCN followed by ammonolysis. The reaction involving picolinamide in MeOH followed by the treatment with acetone afforded a novel 3,3-dimethyl- 1-oxo-2,3-dihydro-1 H -imidazo[1,5-a]pyridin-4-ium 3-methoxypropane-1-sulfonate. [ABSTRACT FROM AUTHOR]

Potentiometric measurements were used to determine the stability constants of cobalt(II) complexes with a series of pyridine mono and dicarboxylic acids. The following pyridinecarboxylic acids were used: pyridine-2-carboxylic acid (also known as picolinic acid (HPic, HL)), pyridine-3-carboxylic acid (also known as nicotinic acid (HNic, HL)), and pyridine-4-carboxylic acid, known as isonicotinic acid (HIso, HL), the 2-chloropyridine-3-carboxylic acid (HCl-Nic, HL), pyridine-2,6-dicarboxylic acid known as dipicolinic acid (H2Dipic, H2L), pyridine-2,4-dicarboxylic acid (H22,4-Dipic, H2L), pyridine-2,5-dicarboxylic acid (H22,5-Dipic, H2L) and pyridine-3,4-dicarboxylic acid (H23,4-Dipic, H2L). 1.0 mol·dm−3 NaNO3 was used as the ionic medium at 25 °C. Additionally, the hydrolytic cobalt(II) constants were determined under the same experimental conditions. A spectrophotometric study based on Job's plot and the molar ratio method was completed to validate the potentiometric measurements. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a serious public health problem characterized by progressive kidney function loss leading to end-stage renal disease (ESRD) that demands dialysis or kidney transplantation. Early detection can prevent or delay progression to ESRD. The study aimed to gain new insights into the perturbed biochemical reactions and to identify novel distinct biomarkers between ESRD and CKD. Serum samples of 32 patients with ESRD (n = 13) and CKD (n = 19) were analyzed using chemical isotope labeling liquid chromatography-mass spectrometry metabolomics approach. A total of 193 metabolites were significantly altered in ESRD compared to CKD and were mainly involved in aminoacyl-tRNA biosynthesis, branched-chain amino acid (BCAA) biosynthesis, taurine metabolism, and tryptophan metabolism. Three kynurenine derivatives, namely, 2-aminobenzoic acid, xanthurenic acid, and hydroxypicolinic acid were upregulated in ESRD compared to CKD due to the significant decrease in glomerular filtration rate with the progression of CKD to ESRD. N-Hydroxy-isoleucine, 2-aminobenzoic acid, and picolinic acid yielded AUC > 0.99 when analyzed using Receiver Operating Characteristic (ROC) analysis. Our findings suggest that inhibiting the kynurenine pathway might be a promising target to delay CKD progression and that metabolites with high discriminative ability might serve as potential prognostic biomarkers to monitor the progression of CKD to ESRD or used in combination with current markers to indicate the status of kidney damage better. [ABSTRACT FROM AUTHOR]

The kynurenine pathway (KP) is the primary route for the catabolism of the essential amino acid tryptophan. The central KP metabolites are neurologically active molecules or biosynthetic precursors to critical molecules, such as NAD+. Within this pathway are three enzymes of interest, HAO, ACMSD, and AMSDH, whose substrates and/or products can spontaneously cyclize to form side products such as quinolinic acid (QA or QUIN) and picolinic acid. Due to their unstable nature for spontaneous autocyclization, it might be expected that the levels of these side products would be dependent on tryptophan intake; however, this is not the case in healthy individuals. On top of that, the regulatory mechanisms of the KP remain unknown, even after a deeper understanding of the structure and mechanism of the enzymes that handle these unstable KP metabolic intermediates. Thus, the question arises, how do these enzymes compete with the autocyclization of their substrates, especially amidst increased tryptophan levels? Here, we propose the formation of a transient enzyme complex as a regulatory mechanism for metabolite distribution between enzymatic and non-enzymatic routes during periods of increased metabolic intake. Amid high levels of tryptophan, HAO, ACMSD, and AMSDH may bind together, forming a tunnel to shuttle the metabolites through each enzyme, consequently regulating the autocyclization of their products. Though further research is required to establish the formation of transient complexation as a solution to the regulatory mysteries of the KP, our docking model studies support this new hypothesis. [ABSTRACT FROM AUTHOR]

Picolinic acid (PA) is a typical mono-carboxylated pyridine derivative produced by human/animals or microorganisms which could be served as nutrients for bacteria. Most Bordetella strains are pathogens causing pertussis or respiratory disease in humans and/or various animals. Previous studies indicated that Bordetella strains harbor the PA degradation pic gene cluster. However, the degradation of PA by Bordetella strains remains unknown. In this study, a reference strain of genus Bordetella, B. bronchiseptica RB50, was investigated. The organization of pic gene cluster of strain RB50 was found to be similar with that of Alcaligenes faecalis, in which the sequence similarities of each Pic proteins are between 60% to 80% except for PicB2 (47% similarity). The 3,6-dihydroxypicolinic acid (3,6DHPA) decarboxylase gene (BB0271, designated as picCRB50) of strain RB50 was synthesized and over-expressed in E. coli BL21(DE3). The PicCRB50 showed 75% amino acid similarities against known PicC from Alcaligenes faecalis. The purified PicCRB50 can efficiently transform 3,6DHPA to 2,5-dihydroxypyridine. The PicCRB50 exhibits optimal activities at pH 7.0, 35 °C, and the Km and kcat values of PicCRB50 for 3,6DHPA were 20.41 ± 2.60 μM and 7.61 ± 0.53 S−1, respectively. The present study provided new insights into the biodegradation of PA by pathogens of Bordetella spp. [ABSTRACT FROM AUTHOR]

Eleven new and three reported half-sandwich Ru(II) arene complexes were synthesized using [Ru(η6-benzene)Cl(μ-Cl)]2 and [Ru(η6-toluene)Cl(μ-Cl)]2 and four pyridine carboxylic acid-based ligands (dicarboxylic acids and halogen derivatives). The structures and purity of synthesized compounds were confirmed using 1H and 13C NMR spectroscopy, infrared spectroscopy, mass spectrometry, and elemental analysis. The stability of synthesized compounds in dimethyl sulfoxide solution was confirmed using 1H NMR spectroscopy. The seven ligands, two complex precursors (CP1 and CP2), and 14 half-sandwich Ru(II) picolinate complexes (C1–C14) were evaluated for in vitro antibacterial and antifungal activity against pathogens, such as Staphylococcus aureus, Bacillus cereus, Proteus mirabilis, Klebsiella pneumoniae, Ecsherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Enterobacter aerogenes, and yeast Candida albicans, using the microwell-dilution method. Among the tested samples, the ligands showed better inhibitory effect against Gram-positive bacteria when compared to the metal complexes. The most susceptible Gram-negative bacteria was Ecsherichia coli, with a MIC value of 1.25 mg/mL, for C3, C6, and C10. All synthesized complexes showed similar, slightly better activity against Candida albicans. [ABSTRACT FROM AUTHOR]