Effect of geometric isomerism on the anticancer property of new platinum complexes with glycine derivatives as asymmetric N, O donate ligands against human cancer.

In this project, to fallow the anticancer ability of new Pt drugs, several new Pt complexes were synthesized with the asymmetric bidentate glycine derivatives, as named propyl- and hexyl glycine (L), in the general formula: [Pt(NH3)2(L)]NO3, and cis- and trans-[Pt(L)2]. The structure of two cis- and trans-[Pt(propylgly)2] complexes was proved by single crystallography analysis. However, all complex structures were characterized by various methods of 1H NMR, 13C NMR, 195Pt NMR, FTIR, LC-Mass, and Raman spectroscopy. To study the passage of water-soluble complexes of [Pt(NH3)2(L)]NO3 via cell membrane, their solubility, and lipophilicity were analyzed. In addition, the cytotoxic properties of these complexes were evaluated against normal and malignant cell lines (skin, breast, and lung cancer cells). The results indicated that they were either comparable to cisplatin or less damaging than carboplatin and oxaliplatin. It was expected that due to less steric effect, and the presence of length aliphatic hydrocarbon chain in the complex structure, trans-[Pt(hexylgly)2] is more toxic on cancerous cell lines than trans-[Pt(propylgly)2]. Cellular accumulation of all complexes was evaluated on A549 and MCF7 cell lines, and the amount of platinum metal (ng) was measured by the ICP method. Results showed that trans-[Pt(hexylgly)2] complex has the highest accumulation inside both mentioned cell lines and [Pt(NH3)2(L)]NO3 complexes behave like clinical Pt-drugs. Ultimately, the interaction patterns of DNA were examined using spectroscopic methods and molecular docking simulations for all substances.

Cluster of Differentiation 36 (CD36) Preferentially Mediates Intestinal Absorption of Dietary Z-Astaxanthin and Especially 9-Z-Isomer via Higher Binding Affinity.

Variances in the biological functions of astaxanthin geometric isomers (i.e., all-E, Z) are related to their intestinal absorption, but the mechanism of isomer absorption mediated by transporters remains unclear. Here, models of in vitro cell overexpression, in situ intestinal perfusion, and in vivo mouse inhibition were employed to investigate the impact of cluster of differentiation 36 (CD36) on the absorption of astaxanthin isomers. Cells overexpressing CD36 notably enhanced the uptake of Z-astaxanthin, particularly the 9-Z-isomer (47.76%). The absorption rate and permeability of Z-astaxanthin surpassed that of the all-E-isomer by the in situ model. Furthermore, the addition of the CD36-specific inhibitor sulfo-N-succinimidyl oleate significantly reduced the absorption of Z-astaxanthin in the mouse duodenum and jejunum, especially the 9-Z-isomer (57.66%). Molecular docking and surface plasmon resonance techniques further validated that 9-Z-astaxanthin binds to more amino acids of CD36 with higher affinity and in a fast-binding, fast-dissociating mode, thus favoring transport. Our findings elucidate, for the first time, the mechanism of the CD36-mediated transmembrane transport of astaxanthin geometric isomers.

Gold-Thiolate Nanocluster Dynamics and Intercluster Reactions Enabled by a Machine Learned Interatomic Potential.

Monolayer protected metal clusters comprise a rich class of molecular systems and are promising candidate materials for a variety of applications. While a growing number of protected nanoclusters have been synthesized and characterized in crystalline forms, their dynamical behavior in solution, including prenucleation cluster formation, is not well understood due to limitations both in characterization and first-principles modeling techniques. Recent advancements in machine-learned interatomic potentials are rapidly enabling the study of complex interactions such as dynamical behavior and reactivity on the nanoscale. Here, we develop an Au-S-C-H atomic cluster expansion (ACE) interatomic potential for efficient and accurate molecular dynamics simulations of thiolate-protected gold nanoclusters (Aun(SCH3)m). Trained on more than 30,000 density functional theory calculations of gold nanoclusters, the interatomic potential exhibits ab initio level accuracy in energies and forces and replicates nanocluster dynamics including thermal vibration and chiral inversion. Long dynamics simulations (up to 0.1 µs time scale) reveal a mechanism explaining the thermal instability of neutral Au25(SR)18 clusters. Specifically, we observe multiple stages of isomerization of the Au25(SR)18 cluster, including a chiral isomer. Additionally, we simulate coalescence of two Au25(SR)18 clusters and observe series of clusters where the formation mechanisms are critically mediated by ligand exchange in the form of [Au-S]n rings.

Supramolecular Self-Assembled Nanostructures Derived from Amplified Structural Isomerism of Zn(II)-Sn(IV)-Zn(II) Porphyrin Triads and Their Visible Light Photocatalytic Degradation of Pollutants.

Two structural isomeric porphyrin-based triads (Zn(II)porphyrin-Sn(IV)porphyrin-Zn(II)porphyrin) denoted as T1 and T2 were prepared from the reaction of meso-[5-(4-hydroxyphenyl)-10,15,20-tris(3,5-di-tert-butylphenyl)porphyrinato]zinc(II) (ZnL) with trans-dihydroxo-[5,10-bis(3-pyridyl)-15,20-bis(phenyl)porphyrinato]tin(IV) (SnP1) and trans-dihydroxo-[5,15-bis(3-pyridyl)-10,20-bis(phenyl)porphyrinato]tin(IV) (SnP2), respectively. All the compounds were characterized using UV-vis spectroscopy, emission spectroscopy, ESI-MS, 1H NMR spectroscopy, and FE-SEM. Most importantly, the two structurally isomeric porphyrin-based triads supramolecularly self-assembled into completely different nanostructures. T1 exhibits a nanosphere morphology, whereas T2 exhibits a nanofiber morphology. The amplified geometric feature in the structural isomeric porphyrin-based triads dictates the physical and chemical properties of the two triads. Both compounds showed the morphology-dependent visible light catalytic photodegradation of rhodamine B dye (74-97% within 90 min) and tetracycline antibiotic (44-71% within 45 min) in water. In both cases, the photodegradation efficiency of T2 was higher than that of T1. The present investigation can significantly contribute to the remediation of wastewater by tuning the conformational changes in porphyrin-based photocatalysts.

Discrimination of Xylene Isomers by Precisely Tuning the Interlayer Spacing of Reduced Graphene Oxide Membrane.

Separating xylene isomers is a challenging task due to their similar physical and chemical properties. In this study, we developed a molecular sieve incorporating a reduced graphene oxide (rGO) membrane for the precise differentiation of xylene isomers. We fabricated GO membranes using a vacuum filtration technique followed by thermal-induced reduction to produce rGO membranes with precisely controllable interlayer spacing. Notably, we could finely tune the interlayer spacing of the rGO membrane from 8.0 to 5.0 Å by simply varying the thermal reduction temperature. We investigated the reverse osmosis separation ability of the rGO membranes for xylene isomers and found that the rGO membrane with an interlayer spacing of 6.1 Å showed a high single component permeance of 0.17 and 0.04 L m-2 h-1 bar-1 for para- and ortho-xylene, respectively, exhibiting clear permselectivity. The separation factor reached 3.4 and 2.8 when 90:10 and 50:50 feed mixtures were used, respectively, with permeance 1 order of magnitude higher than that of current state-of-the-art reverse osmosis membranes. Additionally, the membrane showed negligible permeance and selectivity decay even after continuous operation for more than 5 days, suggesting commendable membrane resistance to solvent swelling and operating pressure.

Dimeric product formation in the self-reaction of small peroxy radicals using synchrotron radiation vacuum ultraviolet photoionization mass spectrometry.

Peroxy radicals (RO2) are key reactive intermediates in atmospheric oxidation processes and yet their chemistry is not fully unraveled. Little is known about their structures and the structures of the dimeric products (ROOR) in the self-reaction of small RO2, which are among the most abundant RO2 in the atmosphere. The product branching ratios of ROOR and their atmospheric roles are still in controversy. Here, the self-reaction of propyl peroxy radicals (C3H7O2), a typical small RO2 radical in the atmosphere, has been studied using synchrotron radiation vacuum ultraviolet photoionization mass spectrometry. Both radical (C3H7O) and closed-shell molecular (C3H6O, C3H7OH, C3H7OOC3H7) products in the self-reaction are observed in photoionization mass spectra and their elusive isomers are definitely identified in mass-selected photoionization spectra. Three isomers of the C3H7OOC3H7 dimeric products, R1OOR1, R1OOR2, and R2OOR2 (R1 and R2 represent 1-C3H7 and 2-C3H7, respectively), as well as their complex structures have been determined for the first time. Kinetic experiments are performed and compared with chemical simulations to reveal the sources of specific products. The branching ratio of the C3H7OOC3H7 dimeric channel is measured at 10 ± 5%. This work demonstrates that the dimeric product formation in the self-reaction of small RO2 radicals is non-negligible and should provide valuable new insight into atmospheric modelling.

Overtone Transition 2ν1 of HCO+ and HOC+: Origin, Radiative Lifetime, Collisional Quenching.

We present spectra of the first overtone vibration transition of C-H/ O-H stretch (2ν1) in HCO+ and HOC+, recorded using a laser induced reaction action scheme inside a cryogenic 22 pole radio frequency trap. Band origins have been located at 6078.68411(19) and 6360.17630(26) cm-1, respectively. We introduce a technique based on mass selective ejection from the ion trap for recording background free action spectra. Varying the number density of the neutral action scheme reactant (CO2 and Ar, respectively) and collisional partner reactant inside the ion trap, permitted us to estimate the radiative lifetime of the state to be 1.53(34) and 1.22(34) ms, respectively, and the collisional quenching rates of HCO+(2ν1) with He, H2, and N2.

Isomer-specific cardiotoxicity induced by tricresyl phosphate in zebrafish embryos/larvae.

Tricresyl phosphate (TCP) has received extensive attentions due to its potential adverse effects, while the toxicological information of TCP isomers is limited. In this study, 2 h post-fertilization zebrafish embryos were exposed to tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) or tri-p-cresyl phosphate (TpCP) at concentrations of 0, 100, 300 and 600 µg/L until 120 hpf, and the cardiotoxicity and mechanism of TCP isomers in zebrafish embryos/larvae were evaluated. The results showed that ToCP or TmCP exposure induced cardiac morphological defects and dysfunction in zebrafish, characterized by increased distance between sinus venosus and bulbus arteriosis, increased atrium and pericardial sac area, trabecular defects, and decreased heart rate and blood flow velocity, while no adverse effects of TpCP on zebrafish heart were found. Transcriptomic results revealed that extracellular matrix (ECM) and motor proteins, as well as PPAR signaling pathways, were included in the cardiac morphological defects and dysfunction induced by ToCP and TmCP. Co-exposure test with D-mannitol indicated that the inhibition of energy metabolism by ToCP and TmCP affected cardiac morphology and function by decreasing osmoregulation. This study is the first to report the cardiotoxicity induced by TCP in zebrafish from an isomer perspective, providing a new insight into the toxicity of TCP isomers and highlighting the importance of evaluating the toxicity of different isomers.

Stereoselective Solid-State Synthesis of Biologically Active Cyclobutane and Dicyclobutane Isomers via Conformation Blocking and Transference.

Conformations in the solid state are typically fixed during crystallization. Transference of "frozen" C=C conformations in 3,5-bis((E)-2-(pyridin-4-yl)vinyl)methylbenzene (CH3-3,5-bpeb) by photodimerization selectively yielded cyclobutane and dicyclobutane isomers, one of which (Isomer 2) exhibited excellent in vitro anti-cancer activity towards T-24, 7402, MGC803, HepG-2, and HeLa cells.

Structural Elucidation and Relative Quantification of Fatty Acid Double Bond Positional Isomers in Biological Tissues Enabled by Gas-Phase Charge Inversion Ion/Ion Reactions.

Fatty acids (FAs) contain a vast amount of structural diversity, and differences in fatty acid structure have been associated with various disease states. Accurate identification and characterization of fatty acids is critical to fully understand the biochemical roles these compounds play in disease progression. Conventional tandem mass spectrometry (MS/MS) workflows do not provide sufficient structural information, necessitating alternative dissociation methods. Gas-phase charge inversion ion/ion reactions can be used to alter the ion type subjected to activation to provide improved or complementary structural information. Herein, we have used an ion/ion reaction between fatty acid (FA) anions and magnesium tris-phenanthroline [Mg(Phen)3] dications to promote charge remote fragmentation of carbon-carbon bonds along the fatty acid chain, allowing for localization of carbon-carbon double bond (C=C) positions to successfully differentiate monounsaturated fatty acid isomers. Relative quantification was also performed to obtain the relative abundance of fatty acid isomers in different biological tissues. For example, the relative abundance of FA 18:1 (9) was determined to vary across regions of rat brain, rat kidney, and mouse pancreas, and FA 16:1 (9) was found to have a higher relative abundance in the dermis layer compared to the sebaceous glands in human skin tissue.

Spectral Assignment in the [3 + 2] Cycloadditions of Methyl (2E)-3-(Acridin-4-yl)-prop-2-enoate and 4-[(E)-2-Phenylethenyl]acridin with Unstable Nitrile N-Oxides.

The investigation of cycloaddition reactions involving acridine-based dipolarophiles revealed distinct regioselectivity patterns influenced mainly by the electronic factor. Specifically, the reactions of methyl-(2E)-3-(acridin-4-yl)-prop-2-enoate and 4-[(1E)-2-phenylethenyl]acridine with unstable benzonitrile N-oxides were studied. For methyl-(2E)-3-(acridin-4-yl)-prop-2-enoate, the formation of two regioisomers favoured the 5-(acridin-4-yl)-4,5-dihydro-1,2-oxazole-4-carboxylates, with remarkable exclusivity in the case of 4-methoxybenzonitrile oxide. Conversely, 4-[(1E)-2-phenylethenyl]acridine displayed reversed regioselectivity, favouring products 4-[3-(substituted phenyl)-5-phenyl-4,5-dihydro-1,2-oxazol-4-yl]acridine. Subsequent hydrolysis of isolated methyl 5-(acridin-4-yl)-3-phenyl-4,5-dihydro-1,2-oxazole-4-carboxylates resulted in the production of carboxylic acids, with nearly complete conversion. During NMR measurements of carboxylic acids in CDCl3, decarboxylation was observed, indicating the formation of a new prochiral carbon centre C-4, further confirmed by a noticeable colour change. Overall, this investigation provides valuable insights into regioselectivity in cycloaddition reactions and subsequent transformations, suggesting potential applications across diverse scientific domains.

Preparative Fractionation of Brazilian Red Propolis Extract Using Step-Gradient Counter-Current Chromatography.

Propolis is a resinous bee product with a very complex composition, which is dependent upon the plant sources that bees visit. Due to the promising antimicrobial activities of red Brazilian propolis, it is paramount to identify the compounds responsible for it, which, in most of the cases, are not commercially available. The aim of this study was to develop a quick and clean preparative-scale methodology for preparing fractions of red propolis directly from a complex crude ethanol extract by combining the extractive capacity of counter-current chromatography (CCC) with preparative HPLC. The CCC method development included step gradient elution for the removal of waxes (which can bind to and block HPLC columns), sample injection in a single solvent to improve stationary phase stability, and a change in the mobile phase flow pattern, resulting in the loading of 2.5 g of the Brazilian red propolis crude extract on a 912.5 mL Midi CCC column. Three compounds were subsequently isolated from the concentrated fractions by preparative HPLC and identified by NMR and high-resolution MS: red pigment, retusapurpurin A; the isoflavan 3(R)-7-O-methylvestitol; and the prenylated benzophenone isomers xanthochymol/isoxanthochymol. These compounds are markers of red propolis that contribute to its therapeutic properties, and the amount isolated allows for further biological activities testing and for their use as chromatographic standards.

Mechanisms and high-value applications of phthalate isomers degradation pathways in bacteria.

Phthalate isomers are key intermediates in the biodegradation of pollutants including waste polyethylene terephthalate (PET) plastics and plasticizers. So far, an increasing number of phthalate isomer-degrading strains have been isolated, and their degradation pathways show significant diversity. In this paper, we comprehensively review the current status of research on the degrading bacteria, degradation characteristics, aerobic and anaerobic degradation pathways, and degradation genes (clusters) of phthalate isomers, and discuss the current shortcomings and challenges. Moreover, the degradation process of phthalate isomers produces many important aromatic precursor molecules, which can be used to produce higher-value derivative chemicals, and the modification of their degradation pathways holds good prospects. Therefore, this review also highlights the current progress made in modifying the phthalate isomer degradation pathway and explores its potential for high-value applications.

Synthesis and bioactivity evaluation of mirror isomer salidroside derivatives as potent antioxidant and anti-inflammatory agents.

A series of derivatives of salidroside with mirror isomer glucose and different phenyl moieties were synthesized by Schmidt glycosylation in satisfactory yields, and their antioxidant and anti-inflammatory activities were evaluated by using LPS-induced RAW264.7 cells. One of the synthesized derivatives ʟ-Sal-4, bearing ʟ-glycosyl and -OMe modification at the phenyl ring, exhibited high activity in inhibiting the production of pro-inflammatory cytokines and oxidative stress biomarker MDA as well as in enhancing the activity of SOD enzyme, compared with the natural product and its corresponding ᴅ-enantiomer. Further proteomic analysis suggested that ʟ-Sal-4 exerted its anti-inflammatory activity through metabolic reprogramming. The in vitro activity showed that ʟ-Sal-4 is a potent antioxidant and anti-inflammatory agent. Our finding indicated that the ʟ-glucose-derived salidroside might be a promising lead compound in the development of salidroside derivatives as therapeutic agents.

Simultaneous chemo- and enantio-separation of 2-, 3- and 4-chloro-methcatinones by high-performance liquid chromatography-tandem mass spectrometry and its application to oral fluid samples.

A method of analysis was developed for the simultaneous chemo- and enantioseparation of 2-, 3-, and 4-chloromethcathinones by high-performance liquid chromatography tandem mass-spectrometry. The fast method enables the reliable identification of positional isomers of chloromethcathinones in biological samples. In addition, the same method can be used for the enantioselective quantitative determination of one of these compounds and its major phase-1 metabolites in biological fluids. The developed method was applied to oral fluid samples collected by police during routine random traffic control in Belgium from January to November, 2023. It was found that 3-CMC was more frequently abused compared to 4-CMC. Although some differences were observed between the concentrations of enantiomers in OF, most likely the drugs were abused in the racemic form. No abuse of 2-CMC was detected at the timepoint of sample collection.

Chlorogenic Acid and its Isomers Attenuate NAFLD by Mitigating Lipid Accumulation in Oleic Acid-Induced HepG2 Cells and High-Fat Diet- Fed Zebrafish.

Chlorogenic acid (Chl), isochlorogenic acid A (Isochl A), and isochlorogenic acid B (Isochl B) are naturally occurring phenolic compounds, which have been shown to exert a regulatory effect on lipid metabolism. However, the mechanism underlying this effect remains unclear. Herein, we investigated the inhibitory effects and underlying mechanisms of these three phenolic compounds on oleic acid (OA)-induced HepG2 cells and high-fat diet (HFD)-fed zebrafish. Lipid accumulation and triacylglycerol levels increased in OA-induced cells, which was attenuated by Chl, Isochl A, and Isochl B. Moreover, the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) decreased, while superoxide dismutase (SOD) levels increased by Chl, Isochl A and Isochl B treatment. Western blot analysis demonstrated that Chl, Isochl A and Isochl B reduced the expression of lipogenesis-related protein, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, peroxisome proliferator-activated receptor alpha gamma (PPARα) was increased by Chl, Isochl A, and Isochl B treatment. In addition, our results indicated that Chl, Isochl A and Isochl B decreased lipid profiles and lipid accumulation in HFD-fed zebrafish. Thus, these findings highlight the potential of Chl, Isochl A, and Isochl B as effective agents for treating or/and ameliorating non-alcoholic fatty liver disease (NAFLD).

Progress in triacylglycerol isomer detection in milk lipids.

In triacylglycerols (TAGs), position differences of fatty acids on the glycerol skeleton produce various TAG isomers. These TAG isomers have different pathways of digestion, absorption, and utilization in infants, thereby affecting TAG nutritional properties of TAGs. Here, we review the progress of research on methods for detecting TAG isomers, and identify direction and thought for improving these methods, including novel chromatographic combinations, perfect algorithm, and improved equipment. The ensuing optimization of these methods is expected to provide robust guarantee for the gradual improvement of milk-derived TAG isomer detection, and is an important prerequisite for infant formula to mimic the structured lipids of human milk.

Biodegradation of phthalic acid and terephthalic acid by Comamonas testosteroni strains.

Phthalic acid isomers are the monomers of phthalate molecules, also known as phthalic acid esters, widely employed in the plastics industry. This study aims to investigate the biodegradation of phthalic acid (PA) and terephthalic acid (TPA) by five industry-borne Comamonas testosteroni strains: 3APTOL, 3ABBK, 2B, 3A1, and C8. To assess the ability of C. testosteroni strains to biodegrade phthalic acid isomers in fermentation media, an analytical method was employed, consisting of high-performance liquid chromatography (HPLC) analyses. Subsequently, molecular screening of the genomic and plasmid DNA was conducted to identify the degradative genes responsible for the breakdown of these chemicals. The genes of interest, including ophA2, tphA2, tphA3, pmdA, and pmdB, were screened by real-time PCR. The five C. testosteroni strains effectively degraded 100% of 100 mg/L PA (p = 0.033) and TPA (p = 0.0114). Molecular analyses indicated that all C. testosteroni strains contained the pertinent genes at different levels within their genomes and plasmids, as reflected in the threshold cycle (Ct) values. Additionally, DNA temperature of melting (Tm) analyses uncovered minor differences between groups of genes in genomic and plasmid DNA. C. testosteroni strains could be excellent candidates for the removal of phthalic acid isomers from environmental systems.

Identification, structure elucidation, and isomer differentiation of phenolic compounds of Chinese pepper cultivars by UPLC-ESI-Q-TOF-MS and their antioxidant activity.

A total of 43 compounds, including phenolic acids, flavonoids, lignans, and diterpene, were identified and characterized using UPLC-ESI-Q-TOF-MS coupled with UNIFI software. The identified flavonoids were mostly isomers of luteolin, apigenin, and quercetin, which were elucidated and distinguished for the first time in pepper cultivars. The use of multivariate data analytics for sample discrimination revealed that luteolin derivatives played the most important role in differentiating pepper cultivars. The content of phenolic acids and flavonoids in immature green peppers was generally higher than that of mature red peppers. The pepper extracts possessed significant antioxidant activities, and the antioxidant activities correlated well with phenolic contents and their molecular structure. In conclusion, the findings expand our understanding of the phytochemical components of the Chinese pepper genotype at two maturity stages. Moreover, a UPLC-ESI-Q-TOF-MS in negative ionization mode rapid methods for characterization and isomers differentiation was described.

A comprehensive study on the identification and characterization of degradation products of lipoglycopeptide Dalbavancin using LC and LC-HRMS/MS.

Dalbavancin is the second-generation approved semisynthetic lipoglycopeptide by the United States Food and Drug Administration (USFDA) for the treatment of acute bacterial skin and skin-structure infections. Unlike other lipoglycopeptides, the stability behavior of Dalbavancin was least explored, which is a prerequisite. The current study endeavors to elucidate the oxidative and hydrolytic stability behavior of Dalbavancin by exposing the drug to oxidative, acidic, and basic stress conditions. A simple liquid chromatography (LC) method was developed, where significant resolution between Dalbavancin, its homologs, and the generated degradation products was achieved. Seven degradation products were identified under acidic, basic, and oxidative stress conditions. Using liquid chromatography and high-resolution mass spectrometry (LC-HRMS), MS/MS studies, the generated degradation products were identified and characterized. Formation of isomeric degradation products was identified especially upon exposure to basic stress conditions. The mechanistic fragmentation pathway for the seven degradation products was established, and the chemical structure for the identified degradation products was elucidated. The results strongly suggest that Dalbavancin is highly susceptible to degradation under oxidative and hydrolytic stress conditions. This study provides insights into the hydrolytic and oxidative stability of Dalbavancin, which can be employed during drug development and discovery in synthesizing relatively stable analogs.