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1.
Sci Rep ; 14(1): 10699, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729974

RESUMO

In recent years it became apparent that, in mammals, rhodopsin and other opsins, known to act as photosensors in the visual system, are also present in spermatozoa, where they function as highly sensitive thermosensors for thermotaxis. The intriguing question how a well-conserved protein functions as a photosensor in one type of cells and as a thermosensor in another type of cells is unresolved. Since the moiety that confers photosensitivity on opsins is the chromophore retinal, we examined whether retinal is substituted in spermatozoa with a thermosensitive molecule. We found by both functional assays and mass spectrometry that retinal is present in spermatozoa and required for thermotaxis. Thus, starvation of mice for vitamin A (a precursor of retinal) resulted in loss of sperm thermotaxis, without affecting motility and the physiological state of the spermatozoa. Thermotaxis was restored after replenishment of vitamin A. Using reversed-phase ultra-performance liquid chromatography mass spectrometry, we detected the presence of retinal in extracts of mouse and human spermatozoa. By employing UltraPerformance convergence chromatography, we identified a unique retinal isomer in the sperm extracts-tri-cis retinal, different from the photosensitive 11-cis isomer in the visual system. The facts (a) that opsins are thermosensors for sperm thermotaxis, (b) that retinal is essential for thermotaxis, and (c) that tri-cis retinal isomer uniquely resides in spermatozoa and is relatively thermally unstable, suggest that tri-cis retinal is involved in the thermosensing activity of spermatozoa.


Assuntos
Opsinas , Retinaldeído , Espermatozoides , Vitamina A , Masculino , Animais , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Camundongos , Opsinas/metabolismo , Humanos , Retinaldeído/metabolismo , Vitamina A/metabolismo , Resposta Táctica/fisiologia , Motilidade dos Espermatozoides/fisiologia , Isomerismo
2.
J Mass Spectrom ; 59(6): e5033, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38726726

RESUMO

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.


Assuntos
Antioxidantes , Capsicum , Fenóis , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização por Electrospray/métodos , Antioxidantes/química , Antioxidantes/análise , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Capsicum/química , Isomerismo , Fenóis/química , Fenóis/análise , Flavonoides/química , Flavonoides/análise , Extratos Vegetais/química , População do Leste Asiático
3.
J Chem Inf Model ; 64(9): 3865-3873, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38598310

RESUMO

Previous experimental studies have shown that the isomerization reaction of previtamin D3 (PreD3) to vitamin D3 (VitD3) is accelerated 40-fold when it takes place within a ß-cyclodextrin dimer, in comparison to the reaction occurring in conventional isotropic solutions. In this study, we employ quantum mechanics-based molecular dynamics (MD) simulations and statistical multistructural variational transition state theory to unveil the origin of this acceleration. We find that the conformational landscape in the PreD3 isomerization is highly dependent on whether the system is encapsulated. In isotropic media, the triene moiety of the PreD3 exhibits a rich torsional flexibility. However, when encapsulated, such a flexibility is limited to a more confined conformational space. In both scenarios, our calculated rate constants are in close agreement with experimental results and allow us to identify the PreD3 flexibility restriction as the primary catalytic factor. These findings enhance our understanding of VitD3 isomerization and underscore the significance of MD and environmental factors in biochemical modeling.


Assuntos
Simulação de Dinâmica Molecular , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Catálise , Isomerismo , Vitamina D/química , Vitamina D/metabolismo , Teoria Quântica , Conformação Molecular , Colecalciferol/química , Colecalciferol/metabolismo
4.
Biomacromolecules ; 25(5): 2792-2802, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38602263

RESUMO

Polyesters from furandicarboxylic acid derivatives, i.e., dimethyl 2,5-furandicarboxylate (2,5-DMFDCA) and 2,4-DMFDCA, show interesting properties among bio-based polymers. Another potential heteroaromatic monomer, 3,4-bis(hydroxymethyl)furan (3,4-BHMF), is often overlooked but holds promise for biopolymer synthesis. Cleaning and greening synthetic procedures, i.e., enzymatic polymerization, offer sustainable pathways. This study explores the Candida antarctica lipase B (CALB)-catalyzed copolymerization of 3,4-BHMF with furan dicarboxylate isomers and aliphatic diols. The furanic copolyesters (co-FPEs) with higher polymerization degrees are obtained using 2,4-isomer, indicating CALB's preference. Material analysis revealed semicrystalline properties in all synthesized 2,5-FDCA-based co-FPEs, with multiple melting temperatures (Tm) from 53 to 124 °C and a glass-transition temperature (Tg) of 9-10 °C. 2,4-FDCA-based co-FPEs showed multiple Tm from 43 to 61 °C and Tg of -14 to 12 °C; one of them was amorphous. In addition, all co-FPEs showed a two-step decomposition profile, indicating aliphatic and semiaromatic segments in the polymer chains.


Assuntos
Ácidos Dicarboxílicos , Proteínas Fúngicas , Furanos , Lipase , Poliésteres , Polimerização , Lipase/química , Lipase/metabolismo , Furanos/química , Proteínas Fúngicas/química , Ácidos Dicarboxílicos/química , Poliésteres/química , Poliésteres/síntese química , Isomerismo , Basidiomycota
5.
J Chem Inf Model ; 64(9): 3599-3604, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38620066

RESUMO

Understanding tautomerism and characterizing solvent effects on the dynamic processes pose significant challenges. Using enhanced-sampling molecular dynamics based on state-of-the-art deep learning potentials, we investigated the tautomeric equilibria of glycine in water. We observed that the tautomerism between neutral and zwitterionic glycine can occur through both intramolecular and intermolecular proton transfers. The latter proceeds involving a contact anionic-glycine-hydronium ion pair or separate cationic-glycine-hydroxide ion pair. These pathways with comparable barriers contribute almost equally to the reaction flux.


Assuntos
Glicina , Simulação de Dinâmica Molecular , Solventes , Água , Glicina/química , Água/química , Solventes/química , Isomerismo , Prótons , Conformação Molecular
6.
Int J Biol Macromol ; 267(Pt 1): 131471, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599419

RESUMO

The conversion of glucose into fructose can transform cellulose into high-value chemicals. This study introduces an innovative synthesis method for creating an MgO-based ordered mesoporous carbon (MgO@OMC) catalyst, aimed at the efficient isomerization of glucose into fructose. Throughout the synthesis process, lignin serves as the exclusive carbon precursor, while Mg2+ functions as both a crosslinking agent and a metallic active center. This enables a one-step synthesis of MgO@OMC via a solvent-induced evaporation self-assembly (EISA) method. The synthesized MgO@OMCs exhibit an impeccable 2D hexagonal ordered mesoporous structure, in addition to a substantial specific surface area (378.2 m2/g) and small MgO nanoparticles (1.52 nm). Furthermore, this catalyst was shown active, selective, and reusable in the isomerization of glucose to fructose. It yields 41 % fructose with a selectivity of up to 89.3 % at a significant glucose loading of 7 wt% in aqueous solution over MgO0.5@OMC-600. This performance closely rivals the current maximum glucose isomerization yield achieved with solid base catalysts. Additionally, the catalyst retains a fructose selectivity above 60 % even after 4 cycles, a feature attributable to its extended ordered mesoporous structure and the spatial confinement effect of the OMCs, bestowing it with high catalytic efficiency.


Assuntos
Carbono , Frutose , Glucose , Lignina , Óxido de Magnésio , Frutose/química , Lignina/química , Glucose/química , Carbono/química , Porosidade , Óxido de Magnésio/química , Catálise , Isomerismo
7.
Anal Chem ; 96(18): 7111-7119, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38648270

RESUMO

Unsaturated lipids constitute a significant portion of the lipidome, serving as players of multifaceted functions involving cellular signaling, membrane structure, and bioenergetics. While derivatization-assisted liquid chromatography tandem mass spectrometry (LC-MS/MS) remains the gold standard technique in lipidome, it mainly faces challenges in efficiently labeling the carbon-carbon double bond (C═C) and differentiating isomeric lipids in full dimension. This presents a need for new orthogonal methodologies. Herein, a metal- and additive-free aza-Prilezhaev aziridination (APA)-enabled ion mobility mass spectrometric method is developed for probing multiple levels of unsaturated lipid isomerization with high sensitivity. Both unsaturated polar and nonpolar lipids can be efficiently labeled in the form of N-H aziridine without significant side reactions. The signal intensity can be increased by up to 3 orders of magnitude, achieving the nM detection limit. Abundant site-specific fragmentation ions indicate C═C location and sn-position in MS/MS spectra. Better yet, a stable monoaziridination product is dominant, simplifying the spectrum for lipids with multiple double bonds. Coupled with a U-shaped mobility analyzer, identification of geometric isomers and separation of different lipid classes can be achieved. Additionally, a unique pseudo MS3 mode with UMA-QTOF MS boosts the sensitivity for generating diagnostic fragments. Overall, the current method provides a comprehensive solution for deep-profiling lipidomics, which is valuable for lipid marker discovery in disease monitoring and diagnosis.


Assuntos
Aziridinas , Lipídeos , Aziridinas/química , Lipídeos/química , Lipídeos/análise , Isomerismo , Espectrometria de Massas em Tandem/métodos , Espectrometria de Mobilidade Iônica/métodos
8.
J Mass Spectrom ; 59(5): e5026, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38656572

RESUMO

Identification and specific quantification of isomers in a complex biological matrix by mass spectrometry alone is not an easy task due to their identical chemical formula and therefore their same mass-to-charge ratio (m/z). Here, the potential of direct introduction combined with ion mobility-mass spectrometry (DI-IM-MS) for rapid quantification of isomers as human milk oligosaccharides (HMOs) was investigated. Differences in HMO profiles between various analyzed breast milk samples were highlighted using the single ion mobility monitoring (SIM2) acquisition for high ion mobility resolution detection. Furthermore, the Se+ (secretor) or Se- (non-secretor) phenotype could be assigned to breast milk samples studied based on their HMO contents, especially on the response of 2'-fucosyllactose (2'-FL) and lacto-N-fucopentaose I (LNFP I). The possibility of quantifying a specific isomer in breast milk by DI-IM-MS was also investigated. The standard addition method allowed the determination of the 2'-FL despite the presence of other oligosaccharides, including 3-fucosyllactose (3-FL) isomer in breast milk. This proof-of-concept study demonstrated the high potential of such an approach for the rapid and convenient quantification of isomers in complex mixtures.


Assuntos
Espectrometria de Mobilidade Iônica , Leite Humano , Oligossacarídeos , Trissacarídeos , Leite Humano/química , Humanos , Trissacarídeos/análise , Trissacarídeos/química , Oligossacarídeos/análise , Oligossacarídeos/química , Isomerismo , Feminino , Espectrometria de Mobilidade Iônica/métodos , Espectrometria de Massas/métodos
9.
ACS Appl Mater Interfaces ; 16(17): 22369-22378, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38644563

RESUMO

Enzymes catalyze almost all material conversion processes within living organisms, yet their natural evolution remains unobserved. Short peptides, derived from proteins and featuring active sites, have emerged as promising building blocks for constructing bioactive supramolecular materials that mimic native proteins through self-assembly. Herein, we employ histidine-containing isomeric tetrapeptides KHFF, HKFF, KFHF, HFKF, FKHF, and FHKF to craft supramolecular self-assemblies, aiming to explore the sequence-activity landscapes of enzyme evolution. Our investigations reveal the profound impact of peptide sequence variations on both assembly behavior and catalytic activity as hydrolytic simulation enzymes. During self-assembly, a delicate balance of multiple intermolecular interactions, particularly hydrogen bonding and aromatic-aromatic interactions, influences nanostructure formation, yielding various morphologies (e.g., nanofibers, nanospheres, and nanodiscs). Furthermore, the analysis of the structure-activity relationship demonstrates a strong correlation between the distribution of the His active site on the nanostructures and the formation of the catalytic microenvironment. This investigation of the sequence-structure-activity paradigm reflects how natural enzymes enhance catalytic activity by adjusting the primary structure during evolution, promoting fundamental research related to enzyme evolutionary processes.


Assuntos
Peptídeos , Peptídeos/química , Isomerismo , Nanoestruturas/química , Relação Estrutura-Atividade , Domínio Catalítico , Histidina/química
10.
J Chromatogr A ; 1722: 464874, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598893

RESUMO

Hydroxypropyl methyl cellulose (HPMC) is a type of cellulose derivative with properties that render it useful in e.g. food, cosmetics, and pharmaceutical industry. The substitution degree and composition of the ß-glucose subunits of HPMC affect its physical and functional properties, but HPMC characterization is challenging due to its high structural heterogeneity, including many isomers. In this study, comprehensive two-dimensional liquid chromatography-mass spectrometry was used to examine substituted glucose monomers originating from complete acid hydrolysis of HPMC. Resolution between the different monomers was achieved using a C18 and cyano column in the first and second LC dimension, respectively. The data analysis process was structured to obtain fingerprints of the monomers of interest. The results revealed that isomers of the respective monomers could be selectively separated based on the position of substituents. The examination of two industrial HPMC products revealed differences in overall monomer composition. While both products contained monomers with a similar degree of substitution, they exhibited distinct regioselectivity.


Assuntos
Derivados da Hipromelose , Espectrometria de Massas , Hidrólise , Derivados da Hipromelose/química , Espectrometria de Massas/métodos , Cromatografia Líquida/métodos , Isomerismo , Glucose/química , Glucose/análise , Espectrometria de Massa com Cromatografia Líquida
11.
Pestic Biochem Physiol ; 201: 105849, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685233

RESUMO

Beta-cypermethrin (ß-CYP) consists of four chiral isomers, acting as an environmental estrogen and causing reproductive toxicity, neurotoxicity, and dysfunctions in multiple organ systems. This study investigated the toxic effects of ß-CYP, its isomers, metabolite 3-phenoxybenzoic acid (3-PBA), and 17ß-estradiol (E2) on HTR-8/SVneo cells. We focused on the toxic mechanisms of ß-CYP and its specific isomers. Our results showed that ß-CYP and its isomers inhibit HTR-8/SVneo cell proliferation similarly to E2, with 100 µM 1S-trans-αR displaying significant toxicity after 48 h. Notably, 1S-trans-αR, 1R-trans-αS, and ß-CYP were more potent in inducing apoptosis and cell cycle arrest than 1R-cis-αS and 1S-cis-αR at 48 h. AO/EB staining and flow cytometry indicated dose-dependent apoptosis in HTR-8/SVneo cells, particularly at 100 µM 1R-trans-αS. Scratch assays revealed that ß-CYP and its isomers variably reduced cell migration. Receptor inhibition assays demonstrated that post-ICI 182780 treatment, which inhibits estrogen receptor α (ERα) or estrogen receptor ß (ERß), ß-CYP, its isomers, and E2 reduced HTR-8/SVneo cell viability, whereas milrinone, a phosphodiesterase 3 A (PDE3A) inhibitor, increased viability. Molecular docking studies indicated a higher affinity of ß-CYP, its isomers, and E2 for PDE3A than for ERα or ERß. Consequently, ß-CYP, its isomers, and E2 consistently led to decreased cell viability. Transcriptomics and RT-qPCR analyses showed differential expression in treated cells: up-regulation of Il24 and Ptgs2, and down-regulation of Myo7a and Pdgfrb, suggesting the PI3K-AKT signaling pathway as a potential route for toxicity. This study aims to provide a comprehensive evaluation of the cytotoxicity of chiral pesticides and their mechanisms.


Assuntos
Apoptose , Piretrinas , Humanos , Piretrinas/toxicidade , Piretrinas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Simulação de Acoplamento Molecular , Estradiol/farmacologia , Proliferação de Células/efeitos dos fármacos , Inseticidas/toxicidade , Inseticidas/farmacologia , Inseticidas/química , Isomerismo , Movimento Celular/efeitos dos fármacos , Benzoatos/farmacologia , Benzoatos/química , Estereoisomerismo , Sobrevivência Celular/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
12.
Environ Sci Technol ; 58(18): 7937-7946, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38669108

RESUMO

Emissions of biogenic reactive carbon significantly influence atmospheric chemistry, contributing to the formation and destruction of secondary pollutants, such as secondary organic aerosol and ozone. While isoprene and monoterpenes are a major fraction of emissions and have been extensively studied, substantially less is known about the atmospheric impacts of higher-molecular-weight terpenes such as sesquiterpenes. In particular, sesquiterpenes have been proposed to play a significant role in ozone chemical loss due to the very high ozone reaction rates of certain isomers. However, relatively little data are available on the isomer-resolved composition of this compound class or its role in ozone chemistry. This study examines the chemical diversity of sesquiterpenes and availability of ozone reaction rate constants to evaluate the current understanding of their ozone reactivity. Sesquiterpenes are found to be highly diverse, with 72 different isomers reported and relatively few isomers that contribute a large mass fraction across all studies. For the small number of isomers with known ozone reaction rates, estimated rates may be 25 times higher or lower than measurements, indicating that estimated reaction rates are highly uncertain. Isomers with known ozone reaction rates make up approximately half of the mass of sesquiterpenes in concentration and emission measurements. Consequently, the current state of the knowledge suggests that the total ozone reactivity of sesquiterpenes cannot be quantified without very high uncertainty, even if isomer-resolved composition is known. These results are in contrast to monoterpenes, which are less diverse and for which ozone reaction rates are well-known, and in contrast to hydroxyl reactivity of monoterpenes and sesquiterpenes, for which reaction rates can be reasonably well estimated. Improved measurements of a relatively small number of sesquiterpene isomers would reduce uncertainties and improve our understanding of their role in regional and global ozone chemistry.


Assuntos
Atmosfera , Ozônio , Sesquiterpenos , Ozônio/química , Sesquiterpenos/química , Atmosfera/química , Poluentes Atmosféricos/química , Isomerismo
13.
Anal Chem ; 96(10): 4163-4170, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38430121

RESUMO

Cyclosporin A (CycA) is a peptide secondary metabolite derived from fungi that plays a crucial role in transplantation surgery. Cyclic traveling wave ion mobility mass spectrometry (IM-MS) revealed an N → O peptidyl shift in singly protonated CycA to isocyclosporin A (isoA), whereas no such isomerization was observed for doubly protonated and sodiated molecules. CycA and isoA were able to be separated by considering doubly protonated precursors using a specific ion fragment. In parallel, sodium ion stabilization facilitated the simultaneous separation and quantitation of singly charged cyclosporin isomers with the limit of detection and coefficient of determination of 1.3% and 0.9908 for CycA in isoA and 1.0% and 0.9830 for isoA in CycA, respectively. Finally, 1H-13C gHSQC NMR experiments permitted parallel recording of up to 11 cyclosporin conformers. The ratios were determined by integrating the volume of cross-peaks of the upfield resonating hydrogen in the diastereotopic methylene group of sarcosine-3.


Assuntos
Ciclosporina , Ciclosporinas , Peptídeos , Ciclosporina/química , Peptídeos/química , Íons , Isomerismo
14.
Proc Natl Acad Sci U S A ; 121(12): e2318996121, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38478688

RESUMO

Bestrhodopsins constitute a class of light-regulated pentameric ion channels that consist of one or two rhodopsins in tandem fused with bestrophin ion channel domains. Here, we report on the isomerization dynamics in the rhodopsin tandem domains of Phaeocystis antarctica bestrhodopsin, which binds all-trans retinal Schiff-base (RSB) absorbing at 661 nm and, upon illumination, converts to the meta-stable P540 state with an unusual 11-cis RSB. The primary photoproduct P682 corresponds to a mixture of highly distorted 11-cis and 13-cis RSB directly formed from the excited state in 1.4 ps. P673 evolves from P682 in 500 ps and contains highly distorted 13-cis RSB, indicating that the 11-cis fraction in P682 converts to 13-cis. Next, P673 establishes an equilibrium with P595 in 1.2 µs, during which RSB converts to 11-cis and then further proceeds to P560 in 48 µs and P540 in 1.0 ms while remaining 11-cis. Hence, extensive isomeric switching occurs on the early ground state potential energy surface (PES) on the hundreds of ps to µs timescale before finally settling on a metastable 11-cis photoproduct. We propose that P682 and P673 are trapped high up on the ground-state PES after passing through either of two closely located conical intersections that result in 11-cis and 13-cis RSB. Co-rotation of C11=C12 and C13=C14 bonds results in a constricted conformational landscape that allows thermal switching between 11-cis and 13-cis species of highly strained RSB chromophores. Protein relaxation may release RSB strain, allowing it to evolve to a stable 11-cis isomeric configuration in microseconds.


Assuntos
Diterpenos , Retinaldeído , Rodopsina , Isomerismo , Conformação Proteica , Rodopsina/metabolismo , Retinaldeído/química
15.
J Lipid Res ; 65(4): 100529, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38467328

RESUMO

FASN, the sole cytosolic enzyme responsible for de novo palmitate synthesis in mammalian cells, has been associated with poor prognosis in cancer and shown to cause drug and radiation resistance by upregulating DNA damage repair via suppression of p65 expression. Targeting FASN by repurposing proton pump inhibitors has generated impressive outcomes in triple-negative breast cancer patients. While p65 regulation of DNA damage repair was thought to be due to its suppression of poly(ADP-ribose) polymerase 1 gene transcription, the mechanism of FASN regulation of p65 expression was unknown. In this study, we show that FASN regulates p65 stability by controlling its phosphorylation at Thr254, which recruits the peptidyl-prolyl cis/trans isomerase Pin1 that is known to stabilize many proteins in the nucleus. This regulation is mediated by palmitate, the FASN catalytic product, not by FASN protein per se. This finding of FASN regulation of p65 stability via phosphorylation of Thr254 and isomerization by Pin1 implicates that FASN and its catalytic product palmitate may play an important role in regulating protein stability in general and p65 more specifically.


Assuntos
Ácido Graxo Sintase Tipo I , Peptidilprolil Isomerase de Interação com NIMA , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/genética , Humanos , Fosforilação , Estabilidade Proteica , Fator de Transcrição RelA/metabolismo , Isomerismo
16.
Phys Chem Chem Phys ; 26(13): 10343-10356, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38501246

RESUMO

Rhodopsins are light-responsive proteins forming two vast and evolutionary distinct superfamilies whose functions are invariably triggered by the photoisomerization of a single retinal chromophore. In 2018 a third widespread superfamily of rhodopsins called heliorhodopsins was discovered using functional metagenomics. Heliorhodopsins, with their markedly different structural features with respect to the animal and microbial superfamilies, offer an opportunity to study how evolution has manipulated the chromophore photoisomerization to achieve adaptation. One question is related to the mechanism of such a reaction and how it differs from that of animal and microbial rhodopsins. To address this question, we use hundreds of quantum-classical trajectories to simulate the spectroscopically documented picosecond light-induced dynamics of a heliorhodopsin from the archaea thermoplasmatales archaeon (TaHeR). We show that, consistently with the observations, the trajectories reveal two excited state decay channels. However, inconsistently with previous hypotheses, only one channel is associated with the -C13C14- rotation of microbial rhodopsins while the second channel is characterized by the -C11C12- rotation typical of animal rhodopsins. The fact that such -C11C12- rotation is aborted upon decay and ground state relaxation, explains why illumination of TaHeR only produces the 13-cis isomer with a low quantum efficiency. We argue that the documented lack of regioselectivity in double-bond excited state twisting motion is the result of an "adaptation" that could be completely lost via specific residue substitutions modulating the steric hindrance experienced along the isomerization motion.


Assuntos
Rodopsina , Rodopsinas Microbianas , Animais , Isomerismo , Rodopsinas Microbianas/química , Rodopsina/química , Rotação
17.
Rapid Commun Mass Spectrom ; 38(10): e9736, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533576

RESUMO

RATIONALE: Pesticide isomers are widely available in agricultural production and may vary widely in biological activity, potency, and toxicity. Chromatographic and mass spectrometric analysis of pesticide isomers is challenging due to structural similarities. METHODS: Based on liquid chromatography time-of-flight mass spectrometry, identification of cis-trans isomeric pesticides was achieved through retention time, characteristic fragment ions, and relative abundance ratio. Furthermore, theoretical and basic research has been conducted on the differences in characteristic fragment ions and their relative abundance ratios of cis-trans isomers. On the one hand, the cleavage pathways of six cis-trans isomers were elucidated through collision-induced dissociation to explain different fragment ions of the isomers. On the other hand, for those with the same fragment ions but different abundance ratios, energy-resolved mass spectrometry combined with computational chemical density functional theory in terms of kinetics, thermodynamics, and bond lengths was employed to explain the reasons for the differences in characteristic fragment ions and their abundance ratios. RESULTS: A high-resolution mass spectrometry method was developed for the separation and analysis of cis-trans isomers of pesticides in traditional Chinese medicine Radix Codonopsis, and six pesticide isomers were distinguished by retention time, product ions, and relative abundance ratios. The limits of quantification of the six pesticides were up to 10 µg/kg, and the linear ranges of them were 10-200 µg/kg, with coefficients of determination (R2) > 0.99, which demonstrated the good linearity of the six pesticides. The recoveries of the pesticides at spiked concentrations of 10, 20, and 100 µg/kg reached 70-120% with relative standard deviations ≤20%. CONCLUSIONS: It was demonstrated that the application of the method was well suited for accurate qualitative and quantitative analysis for isomers with different structures, which could avoid false-negative results caused by ignoring other isomers effectively.


Assuntos
Resíduos de Praguicidas , Praguicidas , Praguicidas/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodos , Isomerismo , Íons/análise , Resíduos de Praguicidas/análise
18.
J Chromatogr A ; 1720: 464773, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38432106

RESUMO

Although the co-occurrences of isomeric chalcones and dihydroflavones widely appear in medicinal plants, the differentiation of such isomerism seldom succeeds using MS/MS, attributing to totally identical MS/MS spectra. Here, efforts were paid to pursue an eligible tool allowing to address the technical challenge. Being inspired by that one more proton signal is observed in 1H NMR spectrum of isoliquiritigenin than liquiritigenin when employing DMSO­d6 as solvent, hydrogen-deuterium exchange (HDX)-MS/MS was evaluated towards differentiating isomeric chalcones and dihydroflavones through replacing H2O with D2O to prepare the mobile phase. As a result, differences were observed for either MS1 or MS2 spectrum when comparing two pairs of isomers, such as liquiritigenin vs. isoliquiritigenin and liquiritin vs. isoliquiritin, because the isomeric precursor and fragment ion species owned different amounts of hydroxyl protons and those reactive protons could be partially or completely substituted by deuterium protons at the exposure in D2O to result in n × 1.006 mass increments. Moreover, utmost four hydrogen/deuterium exchanges occurred for a single glucosyl moiety. Thereafter, HDX-MS/MS was applied to characterize the flavonoids of Snow chrysanthemum, a precious edible herbal medicine that is rich in isomeric chalcones and dihydroflavones. Through paying special attention to the deuterium labeling styles of (de)protonated molecules as well as those featured fragment ions, five pairs of isomeric chalcones and dihydroflavones were confirmatively differentiated, in addition to that 28 flavonoids were structurally annotated by applying those well-defined mass fragmentation rules. Hence, this study offered an in-depth insight towards the flavonoids-focused characterization of Snow chrysanthemum, and more importantly, HDX-MS/MS is a superior tool to differentiate, but not limited to, isomeric chalcones and dihydroflavones.


Assuntos
Chalconas , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Hidrogênio/química , Deutério , Flavonoides , Isomerismo , Prótons , Medição da Troca de Deutério/métodos , Cromatografia Líquida , Íons
19.
J Chromatogr A ; 1720: 464782, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38442498

RESUMO

Semicarbazide, as a derivative of urea, constitutes a great variety of functional molecules for different needs. Herein, novel stationary phases with an incorporated semicarbazide group were proposed. Using aliphatic (docosanoyl, C22) and aromatic (benzoyl, Bz) hydrazides, the semicarbazide-embedded ligands were synthesized before chemical modification of the silica gel, allowing for an accurate interpretation of the chromatographic properties of the corresponding packings. The new stationary phases were water-wettable, due to the presence of highly polar groups. In particular, Bz-semicarbazide (Bz-SCD) stationary phase was sufficiently hydrophilic to run in hydrophilic interaction (HILIC) mode, whilst the C22 (C22-SCD) equivalent, in spite of its reversed-phase nature, was markedly less hydrophobic than the referenced polar-embedded ones. The versatility of C22-SCD was demonstrated with a large selection of analytes, including geometric isomers and standard mixtures of polycyclic aromatic hydrocarbons, sulfonamides, sulfonylurea, substituted ureas, pyridines and carbamates, fat-soluble colorants, antifungal metabolites, angiotensin II receptor blockers and calcium channel blockers.


Assuntos
Cromatografia de Fase Reversa , Semicarbazidas , Dióxido de Silício , Cromatografia Líquida/métodos , Interações Hidrofóbicas e Hidrofílicas , Isomerismo , Dióxido de Silício/química
20.
J Agric Food Chem ; 72(11): 5503-5525, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38442367

RESUMO

Conjugated linoleic acid (CLA) has been extensively characterized due to its many biological activities and health benefits, but conjugated linolenic acid (CLnA) is still not well understood. However, CLnA has shown to be more effective than CLA as a potential functional food ingredient. Current research has not thoroughly investigated the differences and advantages between CLnA and CLA. This article compares CLnA and CLA based on molecular characteristics, including structural, chemical, and metabolic characteristics. Then, the in vivo research evidence of CLnA on various health benefits is comprehensively reviewed and compared with CLA in terms of effectiveness and mechanism. Furthermore, the potential of CLnA in production technology and product protection is analyzed. In general, CLnA and CLA have similar physicochemical properties of conjugated molecules and share many similarities in regulation effects and pathways of various health benefits as well as in the production methods. However, their specific properties, regulatory capabilities, and unique mechanisms are different. The superior potential of CLnA must be specified according to the practical application patterns of isomers. Future research should focus more on the advantageous characteristics of different isomers, especially the effectiveness and safety in clinical applications in order to truly exert the potential value of CLnA.


Assuntos
Ingredientes de Alimentos , Ácidos Linoleicos Conjugados , Ácido alfa-Linolênico/química , Ácidos Linoleicos Conjugados/química , Isomerismo , Alimento Funcional
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