Search Results (117)

Two tri-carbonyl complexes, [Mn(CO)₃(5cpa)Br] (1) and [Re(CO)₃(5cqn)(OCH₃)] (2), were synthesized, where 5cpa is 5-Cl-2-picolinic acid and 5cqn is 5-Cl-8-Hydroxyquinoline. Their structures were determined using X-ray diffraction techniques. The electronic absorption and IR spectra of the complexes were experimentally measured and theoretically assigned through density functional theory (DFT) calculations. The photo-induced CO release was verified using time-resolved infrared spectroscopy, and the transfer of CO to hemoglobin (Hb) was monitored by UV-vis spectroscopy. The rate of CO release and transfer from Mn complex 1 is significantly faster than that from Re complex 2. Complex 2 exhibits higher cytotoxicity against HeLa cells than complex 1, with IC₅₀ values of 40.1 μM and 10.6 μM for 1 and 2, respectively, which decrease to 16.2 μM and 4.9 μM after photo irradiation. Moreover, 1 exhibited a stronger binding constant (K_b) with human serum albumin (HSA) than 2, with values of 1.6 × 10⁶ and 7.0 × 10⁵ M⁻¹, respectively. The structures of HSA complex adducts revealed that both the resulting [Mn(CO)₃(5cpa)]⁻ and [Re(CO)₃(5cqn)]⁻ group coordinate with the N atom of His146, while four additional dissociated Mn-CO groups were observed to bind to HSA for complex 1. This study provides insights into the stability, possible metabolic pathways, and potential applications of these carbonyl complexes. Full article

The selective gas-phase oxidation of γ-picoline (γ-P) to isonicotinic acid (INA)—a key precursor for the anti-tuberculosis drug isoniazid—was investigated over a V–Mn oxide catalyst as a solvent-free, waste-minimizing alternative to conventional liquid-phase synthesis routes. XRD and Raman spectroscopy confirmed the formation of a stable manganese vanadate crystalline phase with a high concentration of terminal vanadyl groups (V=O), providing well-defined redox-active sites. Water vapour proved essential for sustainable process performance: at an optimal H₂O/substrate molar ratio of 98, γ-picoline conversion reached 94.8% with INA selectivity of 86.5%, eliminating the need for hazardous solvents or additives. NH₃-TPD and kinetic analysis revealed that water vapour acts as a competitive adsorbent at vanadium Lewis acid sites, accelerating target product desorption and suppressing deep oxidation to COx—directly reducing carbon waste. Long-term stability was assessed over 96 h of continuous operation: the 23.4% decline in specific surface area correlated with an equivalent reduction in total acidity, while pore diameter expansion from 2.07 to 3.25 nm mitigated diffusion limitations, partially compensating for deactivation. These findings establish the V–Mn oxide system as a promising green catalytic platform for upgrading petrochemical fractions into high-value pharmaceutical intermediates with reduced environmental impact. Full article

Background/Objectives: Chromium picolinate [Cr(pic)₃] supplementation and strength training (ST) have been proposed as strategies to improve metabolic health in obesity; however, their combined effects on cardiac cellular function remain unclear. This study evaluated the impact of Cr(pic)₃ supplementation associated with ST on body composition, metabolic parameters, cardiac morphology, and cardiomyocyte contractile function in diet-induced obese rats. Methods: Male Wistar rats were fed a high-fat diet and allocated into four groups for 8 weeks: obese sedentary (Ob), obese + ST (ObST), obese + Cr(pic)₃ (ObCr(pic)₃), and obese + ST + Cr(pic)₃ (ObSTCr(pic)₃). Chromium picolinate (80 μg/kg/day) was administered by gavage, and ST was performed using a ladder-climbing protocol three times per week. Nutritional, metabolic, cardiac morphological, and isolated cardiomyocyte contractile parameters were assessed. A significance level of 5% was set for all tests. Results: Neither ST nor Cr(pic)₃, alone or combined, modified adiposity index, glucose tolerance, insulin resistance, lipid profile (except HDL), or cardiac morphology. ST improved maximal load capacity in trained groups, confirming protocol efficacy. HDL levels were higher in the combined intervention group compared with obese sedentary rats. Cardiomyocyte fractional shortening and maximal contraction and relaxation velocities were unchanged among groups. However, the association of ST and Cr(pic)₃ resulted in prolonged time to 50% relaxation, indicating delayed relaxation kinetics without alterations in contractile performance. Conclusions: These findings suggest that Cr(pic)₃ supplementation does not enhance metabolic adaptations to ST and may adversely affect cardiomyocyte relaxation dynamics in obesity. Full article

Mongolians have high overweight prevalence linked to their nomadic lifestyle and diet, but gut microbiota studies in this population are scarce. This study used fecal metagenomic and serum metabolomic analyses of 96 Mongolian participants (normal-weight n = 55, overweight n = 41) to characterize gut microbiome alterations and identify weight-related biomarkers. The analyses revealed that Parabacteroides distasonis, Barnesiella intestinihominis, and Alistipes onderdonkii were significantly reduced in overweight individuals (p < 0.05). Concurrently, the metabolites such as beta-cryptoxanthin, p-cresol, and ribothymidine were significantly down-regulated in the overweight group (p < 0.05). Random forest models from the three datasets showed a strong diagnostic ability for microbial families (AUC > 0.70). A subsequent integrated multi-kingdom classifier that combined microbiota and metabolite data achieved the highest performance (AUC = 0.818). Key features with high predictive contributions were identified, including Lactobacillus crispatus, Alistipes onderdonkii, and Parabacteroides distasonis, and metabolites, such as beta-cryptoxanthin, p-cresol, and picolinic acid. These results show the random forest model has high predictive value for distinguishing normal weight and overweight individuals. In summary, this study identified specific gut microbiota and serum metabolomic profiles linked to overweight in Mongolians. Multi-omics integration established a diagnostic biomarker model, laying a theoretical basis for microbiome-targeted weight management interventions. Full article

The creation of new potential metal-based therapeutics largely relies on the development of useful ligand scaffolds. In recent years, our research group has introduced thiophosphoryl-functionalized carboxamides as a convenient framework for obtaining biologically active cyclopalladated derivatives. In continuation of these studies, β-(aminoalkyl)phosphine sulfides bearing additional substituents in the ethylene backbone were synthesized for the first time and reacted with picolinic acid to afford a series of new functionalized amide ligands. The latter readily underwent direct cyclopalladation under the action of PdCl₂(NCPh)₂ under mild reaction conditions. The resulting S,N,N-complexes were studied for in vitro cytotoxicity against several solid and hematopoietic cancer cell lines, as well apoptosis induction and DNA damage ability, which showed their promising anticancer properties. In addition, moderate antibacterial activity was observed for a representative palladocycle of the β-thiophosphorylated derivatives. Full article

Background: The effects of fasting on serum kynurenines (KYNs) have been reported; however, no data are available on whether fasting also modifies their urinary excretion. Kidney organic anion transporters are involved in KYNs excretion, suggesting that changes in serum levels may result from altered urinary elimination. Considering the important role of KYNs in regulating various physiological processes, it is crucial to understand the factors that determine their blood concentrations. The present study aimed to determine the effect of an 8-day fasting period on the concentrations of KYNs in both serum and urine. Methods: Thirteen participants underwent an 8-day fast. The exercise test was performed at baseline after an overnight fast and after 8 days of fasting. Results: Fasting increased the serum concentrations of 3-hydroxykynurenine (3-HK), anthranilic acid (AA), picolinic acid (PA), kynurenic acid (KYNA), and xanthurenic acid (XANA). Conversely, serum kynurenine (KYN) and quinolinic acid (QA) decreased, while 3-hydroxyanthranilic acid (3-HAA) remained unchanged. In urine, KYN, 3-HK, XANA and QA increased after fasting, whereas AA and PA did not change. Conclusions: In conclusion, these findings indicate that fasting generally increases serum kynurenines (KYNs), which are associated with enhanced urinary excretion, suggesting that fasting may stimulate their synthesis. In the case of anthranilic acid (AA) and picolinic acid (PA), their increase in serum does not influence their urinary excretion. Conversely, a decrease in serum KYN and quinolinic acid (QA) may result from enhanced urinary excretion. Full article

Density functional theory (DFT) calculations elucidate the mechanism of diastereoselective cyclization of 2-picoline with 1,5-hexadiene catalyzed by a cationic half-sandwich scandium complex. The catalytic cycle proceeds through four key stages: formation of active species, initial alkene insertion, cis-selective cyclization, and protonation. Central to the mechanism is the dual role of 2-picoline, which initially coordinates as a supporting ligand to facilitate C–H activation and regioselective 1,2-insertion but must dissociate to enable stereocontrol. The mono(2-picoline)-coordinated complex C3 is identified as the thermodynamically favored active species. C–H activation reactivity follows the trend: ortho-C(sp²)–H (2-picoline-free) > ortho-C(sp²)–H (2-picoline-coordinated) > benzylic C(sp³)–H (2-picoline-free) > benzylic C(sp³)–H (2-picoline-coordinated), a preference governed by a wider C_α–Sc–C_α′ angle and shorter Sc···X (X = C_α, C_α′, H) distances that enhance scandium–substrate interaction. Subsequent 1,5-hexadiene insertion proceeds with high 1,2-regioselectivity through a picoline-assisted pathway. The stereoselectivity-determining step reveals a mechanistic dichotomy: while picoline coordination is essential for initial activation, its dissociation is required for intramolecular cyclization. This ligand displacement avoids prohibitive steric repulsion in the transition state, directing the reaction exclusively toward the cis-cyclized product. The cycle concludes with a sterically accessible mono-coordinated protonation. This work establishes a “ligand-enabled then ligand-displaced” mechanism, highlighting dynamic substrate coordination as a critical design principle for achieving high selectivity in rare-earth-catalyzed C–H functionalization. Full article

Background: Zn is an essential mineral nutrient for human health. Its deficiency may result not only from insufficient intake but also from impaired absorption. Dietary components released from the food matrix during digestion can interact in ways that either enhance or inhibit mineral bioavailability. Objectives: The primary aim of this study was to evaluate the bioaccessibility of Zn from dietary supplements, particularly in the context of diet type, chemical form, and pharmaceutical formulation effects. Methods: The experiment was conducted using an in vitro gastrointestinal digestion model with cellulose dialysis membranes. Zn content after digestion was determined using flame atomic absorption spectrometry (F-AAS). The method employed had been previously developed and validated for use in determining the bioaccessibility of mineral nutrients. Results: The bioaccessibility of Zn from the standard, basic, and high-fiber diets was 19.43, 16.18, and 8.12%, respectively. In the presence of a standard diet, the bioaccessibility of Zn from dietary supplements was within the range 1.77–36.09%, in the presence of a basic diet, 1.05–35.86%; and in the presence of a high-fiber diet, 1.37–35.94%. The highest values were observed for zinc picolinate, whereas the lowest were determined for zinc oxide. Conclusions: A high-fiber diet significantly reduced Zn bioaccessibility. Bioaccessibility is also strongly dependent on the chemical form of zinc. Full article

Since 1978, platinum-based drugs have benefited countless cancer patients and come to form the foundation of many cancer pharmacotherapies. These drugs induce apoptosis in cancer cells by forming cross-links between nucleobases in the DNA. Our previous studies have shown that these drugs can also interact with other similar compounds whose structures resemble nucleobases. Therefore, this study analyzed the interactions of Cisplatin, Carboplatin, and Oxaliplatin with Pyridine derivatives (Nicotinic acid, Nicotinamide, Isonicotinic acid, and Picolinic acid). These values were then compared with those for Guanine and Adenine coming from DNA using spectroscopic methods and computational chemistry (B3LYP/6-31G(d,p) and MN15/def2-TZVP methods). Theoretical studies suggest cytostatic affinity, not only for nucleobases but also for Pyridine derivatives. Experimental studies have confirmed these theoretical results. Full article

Background and Objectives: Pituitary adenomas are common intracranial tumors lacking specific non-invasive biomarkers. This study aimed to determine whether key metabolites and enzymes of the kynurenine pathway—including indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), kynurenic acid (KYNA), kynurenine aminotransferase (KAT), quinolinic acid, and picolinic acid—can serve as diagnostic biomarkers distinguishing patients with pituitary adenomas from healthy controls. Materials and Methods: We conducted a single-center, cross-sectional, case–control study with 50 patients with pituitary adenomas and 35 healthy controls. Serum levels of IDO, KYN, KYNA, KAT, quinolinic acid, and picolinic acid were measured via enzyme-linked immunosorbent assay (ELISA). Statistical analyses included group comparisons (t-test/Mann–Whitney U), multivariate logistic regression to identify independent predictors, receiver operating characteristic (ROC) curve analysis to evaluate diagnostic performance (area under the curve, AUC), and partial least squares discriminant analysis (PLS-DA) for multivariate metabolic profiling. Results: Serum kynurenine, kynurenic acid, 3-hydroxykynurenine, picolinic acid, IDO and kynureninase were significantly higher in the pituitary adenoma group than in healthy controls (p < 0.001), while tryptophan, kynurenine aminotransferase, anthranilic acid and quinolinic acid showed no significant differences. ROC analysis demonstrated excellent diagnostic accuracy, with KAT (AUC = 0.923) and KYNA (AUC = 0.901) showing the highest discrimination. Multivariate logistic regression identified IDO, KYN, and KYNA as independent predictors of pituitary adenoma (p < 0.05). PLS-DA of the combined metabolite data also demonstrated clear separation between patients and controls, confirming distinct metabolic profiles between the groups. Conclusions: Kynurenine pathway metabolites and enzymes show strong potential as non-invasive biomarkers for pituitary adenomas. In particular, elevated KAT and KYNA levels demonstrated high diagnostic performance. These findings suggest that a panel of kynurenine pathway metabolites could aid in the early, non-invasive detection of pituitary adenomas. Full article

The effects of silk sericin (SS) supplementation on the functionality of chromium picolinate (CrPic) and lipid metabolism were assessed in male Sprague–Dawley rats to determine whether SS improves the bioavailability of CrPic and contributes to beneficial changes in lipid profiles and cardiovascular risk markers. Rats were administered different doses of SS (0, 1, 10, and 100 mg kg⁻¹ body weight (BW)) in conjunction with CrPic (300 µg kg⁻¹ BW) for 8 weeks through oral gavage. Body and organ weights, lipid profiles, glucose levels, chromium (Cr) accumulation, total protein, and adipocyte size were evaluated. Additionally, FTIR analysis was conducted to investigate the binding and release behavior of SS with CrPic. Although body weight and daily feed intake were comparable among groups, a significant increase in pancreas weight and reduction in omentum weight were observed across all CrPic-SS groups. Increased dosages of SS resulted in a significant reduction in triglyceride and plasma glucose levels. All CrPic and CrPic-SS treatments reduced LDL and total cholesterol while increasing HDL. Cr accumulation was elevated in the liver and kidneys of groups administered 10 and 100 mg kg⁻¹ BW of SS, accompanied by a significant increase in total protein levels and a reduction in adipocyte size to less than 50 µm in all rats. FTIR analysis indicated that SS binds to CrPic at pH 2.0 and releases it at pH 7.0, demonstrating pH-dependent delivery similar to the gastrointestinal tract and possibly improved CrPic functionality. These findings indicate that SS improves the bioavailability of CrPic and positively affects lipid metabolism and cardiovascular risk markers in vivo. Full article

Reactions of (pyH)₅[MoOCl₄(H₂O)]₃Cl₂ with picolinic and pyrazinoic acids yielded three new dinuclear molybdenum(V) complexes: (pyH)₂[Mo₂O₄Cl₂(pic)₂]·CH₃CN (1), (pyH)₂[Mo₂O₄Cl₂(pic)₂]·CH₃CH₂CN (2) and (pyH)₂[Mo₂O₄Cl₂(pyraz)₂]·CH₃CN (3) (pic⁻ = picolinate, pyraz⁻ = pyrazinoate and pyH⁺ = protonated pyridine). The compounds were characterized by single-crystal X-ray diffraction, infrared and ¹H NMR spectroscopy, elemental analysis, and TG/DSC measurements. All display a robust {Mo^V₂O₄}²⁺ core with the heteroaromatic ligands bound in a N,O-bidentate chelating manner. Full article

Background/Objectives: In this proof-of-concept study, the objective was to evaluate the phenotypic CarbaLux combination rapid test in terms of guiding the therapy of infections caused by multidrug-resistant Gram-negative bacteria with carbapenemase inhibitors and carbapenems, and to compare its results and practicability with standard diagnostic methods. Methods: In the classical CarbaLux test, a fluorescent carbapenem serves as a UV–visible diagnostic surrogate for clinically used carbapenem antibiotics. When exposed to extracted carbapenemases from bacterial colony growth on agar plates, fluorescence rapidly disappears, showing whether monotherapy with carbapenems is possible or must be rejected. It was expected that a specific inhibitor that protects imipenem or meropenem from enzymatic deactivation during antibacterial therapy would perform the same in vitro with fluorescent carbapenem and preserve its fluorescence. The new additional CarbaLux combination test is used if the classic test is positive for carbapenemases: a classic test tube pre-dosed with fluorescent carbapenem is spiked with cloxacillin; with recently launched carbapenemase inhibitors, e.g., avibactam, relebactam, zidebactam, nacubactam, or vaborbactam; or with picolinic acid. Fourteen Enterobacterales and six Acinetobacter baumannii isolates were analyzed. Results: At fixed concentrations, the new inhibitors protected fluorescent carbapenem from bacterial KPC-mediated inactivation and partially from AmpC beta-lactamase-mediated inactivation. In addition, avibactam also effectively inhibited OXA-48-like enzymes. Cloxacillin selectively inhibited AmpC beta-lactamases extracted from Enterobacter complex species. Non-therapeutic picolinic acid was specific for metallo-beta-lactamases and thus identified infections by pathogens that cannot be treated with carbapenems alone or in combination. Conclusions: Inhibitor/fluorescent carbapenem mixtures corresponding to therapeutic inhibitor/carbapenem combinations allow us to visualize the efficacy of carbapenemase inhibitors. The in vitro results are consistent with clinical experience regarding combination therapy. Enzymatic assays provide a rapid yes/no answer for carbapenem mono- or combination therapy and offer several advantages over current carbapenemase testing methods. In contrast to PCR and lateral flow tests, which only target a selection of carbapenemases, enzymatic assays work by employing a reproducible phenotypic mechanism. They are simpler, broader in scope, and more cost-effective; they can also detect antimicrobial heteroresistance or AmpC beta-lactamase hyperproduction, which is normally undetected when performing automated antibiotic susceptibility testing. The new tests are suitable for clinical diagnosis, public health purposes, and infection control. Full article

The aim of the present study is to evaluate the impact of chromium (Cr) supplementation on glucose and lipid metabolism in breast muscle in broilers under heat stress. A total of 220 day-old broiler chicks were reared in cages. At 29 days old, 180 birds were randomly assigned to three treatments (0, 400, and 800 µg Cr/kg, as chromium picolinate) and transferred to climate chambers (31 ± 1 °C, 60 ± 7% humidity) for 14 days. Growth performance, carcass traits, serum biochemical indices, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), as well as muscle metabolomic profiles and gene expression related to energy and lipid metabolism were analyzed. The results showed that, compared with the heat stress group, the groups supplemented with 400 and 800 µg Cr/kg showed higher dry matter intake and average daily gain, breast muscle ratio, and lower feed conversion ratio and abdominal fat ratio; chickens supplemented with 400 and 800 µg Cr/kg showed significantly lower serum corticosterone (CORT), free fatty acids, and cholesterol levels compared with the heat stress (HS) group (p < 0.05). Fasting blood glucose and HOMA-IR were also significantly reduced, while fasting insulin was significantly increased in the Cr-supplemented groups (p < 0.05). Metabolomic analysis revealed that Cr supplementation regulated lipid and amino acid metabolism by altering key metabolites such as citric acid, L-glutamine, and L-proline, and modulating pathways including alanine, aspartate, and glutamate metabolism, and glycerophospholipid metabolism. Furthermore, Cr supplementation significantly upregulated the expression of Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 α (PGC-1α), ATP Binding Cassette Subfamily A Member 1 (ABCA1), Peroxisome Proliferator-Activated Receptor α (PPARα), and ATP Binding Cassette Subfamily G Member 1 (ABCG1) in both the hepatic and muscle tissue. This paper suggested that chromium supplementation may enhance energy metabolism and lipid transport like the findings of our study suggested. Full article

Cyclen-based ligands are among the most preferred ones in radiopharmacy, where they are mainly applied for transferring radioisotopes through the human body. A crucial criterion is the stability of their metal–ligand complexes, which depends on the stabilization of the free ligand in solution. However, these flexible ligands can have numerous conformations, and for a reliable evaluation of the dissociation energy, the most stable one(s) in solution must be known. In the present study, the low-energy conformational space of four anionic (2-) cyclen-based ligands has been elucidated in aqueous solution by a joint molecular mechanics (MM)/Density Functional Theory (DFT) procedure. The results revealed a significant preference for C₂ symmetric structures, more or less resembling the arrangements in their metal complexes. The computed dissociation energies agree with the experimentally found stability trend for the Pb²⁺ complexes with ligands containing picolinate pendant arms. For complexes with mixed donor groups (carboxyl, amide, pyridine), significant thermodynamic stabilities were predicted. Full article