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1.
Anal Chem ; 94(2): 1333-1341, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-34985268

RESUMO

Proton nuclear magnetic resonance (NMR) N-acetyl signals (Glyc) from glycoproteins and supramolecular phospholipids composite peak (SPC) from phospholipid quaternary nitrogen methyls in subcompartments of lipoprotein particles) can give important systemic metabolic information, but their absolute quantification is compromised by overlap with interfering resonances from lipoprotein lipids themselves. We present a J-Edited DIffusional (JEDI) proton NMR spectroscopic approach to selectively augment signals from the inflammatory marker peaks Glyc and SPCs in blood serum NMR spectra, which enables direct integration of peaks associated with molecules found in specific compartments. We explore a range of pulse sequences that allow editing based on peak J-modulation, translational diffusion, and T2 relaxation time and validate them for untreated blood serum samples from SARS-CoV-2 infected patients (n = 116) as well as samples from healthy controls and pregnant women with physiological inflammation and hyperlipidemia (n = 631). The data show that JEDI is an improved approach to selectively investigate inflammatory signals in serum and may have widespread diagnostic applicability to disease states associated with systemic inflammation.


Assuntos
COVID-19 , Prótons , Biomarcadores , Feminino , Glicoproteínas , Humanos , Inflamação , Espectroscopia de Ressonância Magnética , Fosfolipídeos , Gravidez , SARS-CoV-2 , Soro
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 269: 120768, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34952444

RESUMO

This paper describes the synthesis, structural study, and evaluation of electrochemical and photophysical properties by UV-Vis absorption and fluorescence emission analysis (solution and solid-state) of a series of eight 3,5-aryl-substituted 1-phenyl-2-pyrazolines (5), where 3-aryl = 2-OH-C6H4 (5a-g) or Ph (5h), and 5-aryl = Ph (a, h), 1-naphthyl (b), 4-Br-C6H4 (c), 4-F-C6H4 (d), 4-OCH3-C6H4(e), 4-NO2-C6H4 (f), 4-(N(CH3)2)-C6H4(g). The UV-Vis absorption properties of 2-pyrazolines were evaluated in DCM, MeCN, AcOEt, EtOH, and DMSO as the solvent and showed a fluorescence shift for the polar aprotic solvents. The steady-state fluorescence emission exhibited a band in the blue region when excited at the least energetic transition of each compound, although the excited-state intramolecular proton (ESIPT) effect was not detected. In the solid state, compounds presented similar behavior regarding absorption and emission properties compared to the solution assays. With the electrochemical analyses performed for the synthesized 2-pyrazolines, it was possible to conclude that the redox potentials were influenced by the electronic and steric effects of the substituents on the aryl rings and, according to the electronic nature of the substituents, which electron-donating groups were favored. Finally, the TD-DFT analyses revealed that all compounds had delocalized electron density throughout the 2-pyrazolines unit and were not influenced by the substituent bonded at C-5. Nonetheless, LUMO orbital analysis showed that only derivatives 5b and 5f have this localized density over the substituents.


Assuntos
Elétrons , Prótons , Corantes , Solventes , Espectrometria de Fluorescência
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 269: 120777, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34954479

RESUMO

A novel indole hydrazone tagged moiety, 2-((5-bromo-1H-indol-2-yl) methylene) hydrazono) methyl)-4, 6-diiodophenol (BHDL) has been developed for the selective and sensitive detection of biogenic tryptamine and F- ions. The binding dexterity of probe BHDL towards F-/tryptamine (TryptA) has been investigated by UV-visible/fluorescence spectroscopy. In the presence of TryptA, probe exhibits strong enhancement in the emission band at 433 nm and the band at 555 nm underwent a blue shift accompanied by a decrease in intensity by the inhibition of Excited State Intramolecular Proton Transfer (ESIPT) on BHDL. Excitingly, complexation with F- ions as well triggers an enhancement in a fluorescence band at 430 nm with the concomitant disappearance of the emission band at 555 nm due to the inhibition of ESIPT and deprotonation process initiated by the hydrogen bonding complex formation. Further, Density Functional Theoretical (DFT) calculations have been performed to support the mechanism functioned on the probe BHDL in the presence of TryptA/F-.


Assuntos
Corantes Fluorescentes , Prótons , Ligação de Hidrogênio , Espectrometria de Fluorescência , Triptaminas
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 269: 120780, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34968838

RESUMO

Molecules with Aggregation-Induced Emission (AIE) effects could show strong emission in solid or aggregate form, thus they are suitable for applications in the field of solid luminescent materials. According to former reporting, AIE molecules are always J-aggregates. In this study, a new benzotriazole derivate with electron donor-acceptor structure was synthesized. (E)-4-(2-(1H-benzo[d] [1,2,3] triazol-1-yl) vinyl)-N, N-dimethylaniline (BTADA) has both TICT and AIE effect, even though it is H-aggregate. Furthermore, BTADA could respond to proton in solution and solid form. Due to its multiple binging sites, proton would bind to benzotriazole and dimethylaniline moiety successively when BTADA was exposed to acid, and the fluorescent color changed from green to yellow then blue as the concentration of proton increased. Such phenomena indicate BTADA has potential usage in proton detection.


Assuntos
Prótons , Triazóis , Corantes , Luminescência
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 268: 120704, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-34896683

RESUMO

A Schiff-based aggregation induced emission (AIE) fluorescent probe with excited intramolecular proton transfer (ESIPT) mechanism was synthesized by grafting 2-hydrazinobenzothiazole onto 2,6-diformyl-4-methylphenol. The probe recognizes Zn2+ selectively and sensitively, accompanied by a significant fluorescence emission increasement change from light yellow-green to strong green. Additionally, a stabilization time of at least 30 min was kept in the recognition process. Besides, a linear relationship was observed between the concentration of Zn2+ and the fluorescence intensity at 525 nm (0.05-10 µM). And thus, the probe can detect Zn2+ quantitatively in aqueous solution with a low detection limit of 1.9 × 10-8 M. Based on the AIE property and the selective recognition of Zn2+, SCH was strategically loaded on the filter paper to develop a novel paper-based indicator for on-site and high-efficiency detection of Zn2+. The results showed that the paper-based indicator could be conveniently applied to the visual inspection of Zn2+ as expected and SCH in the paper-based indicators fortunately exhibited a better stability. Furthermore, our comprehensive application evaluations have confirmed that SCH was capable of detecting Zn2+ in real water samples and imaging Zn2+ in living cells roundly.


Assuntos
Corantes Fluorescentes , Prótons , Células HeLa , Humanos , Espectrometria de Fluorescência , Zinco
6.
Methods Mol Biol ; 2303: 349-364, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34626393

RESUMO

Recent NMR studies of the exchangeable protons of GAGs in aqueous solution, including those of the amide, sulfamate, and hydroxyl moieties, have demonstrated potential for the detection of intramolecular hydrogen bonds providing insights into secondary structure preferences. GAG amide protons are observable by NMR over wide pH and temperature ranges; however, specific solution conditions are required to reduce the exchange rate of the sulfamate and hydroxyl protons and allow their detection by NMR. Building on the vast body of knowledge on detection of hydrogen bonds in peptides and proteins, a variety of methods can be used to identify hydrogen bonds in GAGs including temperature coefficient measurements, evaluation of chemical shift differences between oligo- and monosaccharides, and relative exchange rates measured through line shape analysis and EXSY spectra. Emerging strategies to allow direct detection of hydrogen bonds through heteronuclear couplings offer promise for the future. Molecular dynamic simulations are important in this effort both to predict and confirm hydrogen bond donors and acceptors.


Assuntos
Prótons , Amidas , Glicosaminoglicanos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio
7.
Cancer Lett ; 524: 172-181, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34688844

RESUMO

The influence of high-linear energy transfer (LET) particle radiation on the functionalities of mesenchymal stromal cells (MSCs) is largely unknown. Here, we analyzed the effects of proton (1H), helium (4He), carbon (12C) and oxygen (16O) ions on human bone marrow-MSCs. Cell cycle distribution and apoptosis induction were examined by flow cytometry, and DNA damage was quantified using γH2AX immunofluorescence and Western blots. Relative biological effectiveness values of MSCs amounted to 1.0-1.1 for 1H, 1.7-2.3 for 4He, 2.9-3.4 for 12C and 2.6-3.3 for 16O. Particle radiation did not alter the MSCs' characteristic surface marker pattern, and MSCs maintained their multi-lineage differentiation capabilities. Apoptosis rates ranged low for all radiation modalities. At 24 h after irradiation, particle radiation-induced ATM and CHK2 phosphorylation as well as γH2AX foci numbers returned to baseline levels. The resistance of human MSCs to high-LET irradiation suggests that MSCs remain functional after exposure to moderate doses of particle radiation as seen in normal tissues after particle radiotherapy or during manned space flights. In the future, in vivo models focusing on long-term consequences of particle irradiation on the bone marrow niche and MSCs are needed.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/genética , Quinase do Ponto de Checagem 2/genética , Histonas/genética , Células-Tronco Mesenquimais/efeitos da radiação , Células-Tronco/efeitos da radiação , Medicina Aeroespacial , Apoptose/genética , Apoptose/efeitos da radiação , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Células da Medula Óssea/efeitos da radiação , Carbono/efeitos adversos , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Linhagem da Célula/genética , Linhagem da Célula/efeitos da radiação , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos da radiação , Hélio/efeitos adversos , Humanos , Células-Tronco Mesenquimais/metabolismo , Oxigênio/efeitos adversos , Prótons/efeitos adversos , Voo Espacial , Células-Tronco/metabolismo
8.
Biochim Biophys Acta Biomembr ; 1864(1): 183809, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34699768

RESUMO

Human aquaporin 10 (hAQP10) is an aquaglyceroporin that assists in maintaining glycerol flux in adipocytes during lipolysis at low pH. Hence, a molecular understanding of the pH-sensitive glycerol conductance may open up for drug development in obesity and metabolically related disorders. Control of hAQP10-mediated glycerol flux has been linked to the cytoplasmic end of the channel, where a unique loop is regulated by the protonation status of histidine 80 (H80). Here, we performed unbiased molecular dynamics simulations of three protonation states of H80 to unravel channel gating. Strikingly, at neutral pH, we identified a water coordination pattern with an inverted orientation of the water molecules in vicinity of the loop. Protonation of H80 results in a more hydrophobic loop conformation, causing loss of water coordination and leaving the pore often dehydrated. Our results indicate that the loss of such water interaction network may be integral for the destabilization of the loop in the closed configuration at low pH. Additionally, a residue unique to hAQP10 (F85) reveals structural importance by flipping into the channel in correlation with loop movements, indicating a loop-stabilizing role in the closed configuration. Taken together, our simulations suggest a unique gating mechanism combining complex interaction networks between water molecules and protein residues at the loop interface. Considering the role of hAQP10 in adipocytes, the detailed molecular insights of pH-regulation presented here will help to understand glycerol pathways in these cells and may assist in drug discovery for better management of human adiposity and obesity.


Assuntos
Adiposidade/genética , Aquaporinas/genética , Glicerol/metabolismo , Água/metabolismo , Aquaporinas/química , Citoplasma/química , Citoplasma/genética , Histidina/genética , Humanos , Concentração de Íons de Hidrogênio , Lipólise/genética , Simulação de Dinâmica Molecular , Obesidade/genética , Obesidade/metabolismo , Prótons
9.
Chem Phys Lipids ; 242: 105164, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34906552

RESUMO

The selection of an animal model is based on the pathological mechanism appropriate for experimental investigation because the therapeutic effect was low depending on the pathological occurrence mechanism. The purpose of this study is to elucidate the changes in lipid proton concentration in two animal models of nonalcoholic fatty liver disease (NAFLD): methionine and choline-deficient (MCD) diet and high-fat diet (HFD). We calculated the T2 relaxation time of 7 lipid protons (LP) in the 9.4 T MRS phantom experiment. The concentrations of LPs were adjusted for T2 and T2* of MCD, HFD, and CCl4 fatty liver animal models. Multivariate analysis and Pearson correlation were performed to analyze LP concentration, and the difference was investigated via Kendall correlation and independent t-test using LP composition ratio. The T2 relaxation time of each LP was accurately determined using phantom experiments. The in vivo magnetic resonance spectroscopy (MRS) data were obtained by quantifying the t2/t2* corrected LP concentration in the liver of the animal model. In case of MCD and HFD, there was an average difference in all LPs except 0.9 ppm LP, and the MCD and CCl4 groups showed differences in the average of all LPs. However, there was no difference between LP of HFD and CCl4 groups. A higher level of unsaturated fatty acids was found in the MCD fatty liver model than in HFD induced fatty liver.


Assuntos
Metionina , Hepatopatia Gordurosa não Alcoólica , Animais , Colina , Dieta Hiperlipídica , Modelos Animais de Doenças , Lipídeos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Prótons
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120390, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536889

RESUMO

Excited-state intramolecular proton transfer (ESIPT) has recently received considerable attention due to its dual fluorescent changes and large Stokes shift. Hydrogen sulfide (H2S) is a gas signal molecule that plays important roles in modulating the functions of different systems. Herein, by modifying 2-(2́-hydroxyphenyl) benzothiazole (HBT) scaffold, a novel near-infrared mitochondria-targeted fluorescent probe HBTP-H2S has been rationally designed based on excited-state intramolecular proton transfer (ESIPT) effect. The nucleophilic addition reaction of the H2S with probe HBTP-H2S caused the break of the conjugated skeleton, resulting the shifting of maximum emission peak from 658 nm to 470 nm. HBTP-H2S showed fast-response response time, good selectivity and a large Stokes shift (188 nm) toward H2S. Most importantly, inspired by the inherent advantages of the probe, HBTP-H2S was successfully employed to monitor mitochondrial H2S in HepG2 cells.


Assuntos
Corantes Fluorescentes , Sulfeto de Hidrogênio , Células Hep G2 , Humanos , Mitocôndrias , Prótons
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120383, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536893

RESUMO

In this work, we explore the excited-state intramolecular proton transfer (ESIPT) mechanisms and relative solvent effects for three novel 3-hydroxylflavone derivatives (i.e., HOF, SHOF, and NSHOF) in acetonitrile, dichloromethane, and toluene solvents. Through calculations, we optimize the structures of HOF, SHOF, and NSHOF. Through the analysis of a series of structural parameters related to hydrogen bonding interactions, it could be found that the hydrogen bonds of the three derivatives are all enhanced in the S1 state, and more importantly, the excited-state hydrogen bonds of HOF are stronger than those of SHOF and NSHOF. In order to explore the effects of solvent polarity, we analyze the core-valence bifurcation (CVB) index, infrared (IR) vibration spectrum, and the potential energy curves. We find that for HOF, SHOF, and NSHOF, the strength of the excited-state hydrogen bonds increases as the solvent polarity decreases. The solvent polarity dependent ESIPT mechanisms pave the way for further designing novel flavonoid-based solvatofluorochromic probes in future.


Assuntos
Flavonoides , Prótons , Ligação de Hidrogênio , Modelos Moleculares , Solventes
12.
Biosens Bioelectron ; 195: 113662, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34571484

RESUMO

Herein, the sequence-specific short-stranded biomarker DNA (hDNA, 21-nt) is acted as targeting out-primer to implement the loop-mediated isothermal amplification for releasing hydrogen ions (LAMP-H+). Using LAMP-H+ as signaling transducer, we report a highly sensitive electrochemical ratiometric biosensor for hDNA with minimized background signal, which is achieved via magnetic separation using AuNPs-modified Fe3O4 (Au@Fe3O4) as micro-reactor. In Au@Fe3O4, a double-stranded complex of a pH-responsible strand (I*) and a substrate strand (S*) is bound via Au-N bonds, where the treatment with LAMP-H+ leads to I* folding into i-motif conformation and S* dehybridization. The S* further hybridizes a catalytic strand (C*) to assemble Mg2+-DNAzymes that are cleaved by Mg2+, releasing C* for repeated formation and robust nicking of Mg2+-DNAzymes. The resultant output fuel strands (F*) are introduced in a modified electrode to drive the strand displacement of two hairpins individually labeled with two electron mediators. Through F*-mediated recycled amplification, the ratio of their electrochemical currents changed in opposite is highly sensitive to the varied hDNA down to 2.1 fM. By integrating LAMP-H+-stimulated i-motif switching with Mg2+-DNAzyme cleavage, this logic transduction of LAMP-H+(i-motif/Mg2+-DNAzyme)F* efficiently minimizes the inherent background of traditional LAMP-based assays. Resultantly, our electrochemical ratiometric strategy would be applicable to diverse short-stranded DNAs or even RNAs as targeting primers of LAMP.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , DNA , Ouro , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Prótons
13.
Clin Imaging ; 81: 15-23, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34597999

RESUMO

OBJECTIVE: To explore the value of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) for differential diagnosis of fibroadenomas and malignant breast tumors. MATERIALS AND METHODS: This prospective study enrolled 56 patients with suspected breast tumors and performed APTw imaging. Based on the histopathology results, patients were divided into group 1 with malignant breast tumors (n = 41) and group 2 with fibroadenomas (n = 15). The measured image parameters (APTw value, ADC value, type of Time of Intensity Curve, maximum tumor diameter in image) and the maximal diameter of the tumors measured from surgical resection were compared between the two groups, and the diagnostic performance based on these parameters was quantified with ROC curve. Spearman's correlation coefficient was used to analyze the association between APTw or ADC values and ER, PR, HER2, and Ki-67 expressions. RESULTS: The intraclass correlation coefficients (ICC = 0.87 and 0.91) indicated a good inter-observer agreement of the measured APTw values. APTw values of malignant lesions were significantly higher than those of fibroadenomas (3.21 ± 1.04% vs 1.50 ± 0.54%, p < 0.001). Area under the curve (AUC) obtained from APTw imaging, DWI, DCE, APTw imaging+DWI, APTw imaging+DWI, and APTw imaging+DWI + DCE was 0.959, 0.897, 0.976, 0.997, and 1 respectively. The APTw value showed a negative correlation with ER expression (r = -0.357). CONCLUSION: APTw imaging yielded similar diagnosis performance in discriminating fibroadenomas and malignant breast tumors when compared to the DCE and better than DWI imaging, and provided supplement information on tumor cell activity to DWI images. The APTw value showed correlations with some prognostic factors for breast cancer.


Assuntos
Neoplasias da Mama , Fibroadenoma , Amidas , Neoplasias da Mama/diagnóstico por imagem , Diferenciação Celular , Imagem de Difusão por Ressonância Magnética , Feminino , Fibroadenoma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Estudos Prospectivos , Prótons
14.
Phys Chem Chem Phys ; 24(2): 875-882, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34908064

RESUMO

Selenium nucleic acids possess unique properties and have been demonstrated to have a wide range of applications such as in DNA X-ray crystallography and novel medical therapies. However, as a heavy atom, selenium substitution may easily alter the photophysical properties of a nucleic acid by red-shifting the absorption spectra and introducing effective intersystem crossing to triplet excited states. In present work, the excited state dynamics of a naturally occurring selenium substituted uracil (2-selenuracil, 2SeU) is studied by using femtosecond transient absorption spectroscopy as well as quantum chemistry calculations. Ultrafast intersystem crossing to the lowest triplet state (T1) and effective non-radiative decay of this state to the ground state (S0) are demonstrated in the neutral form 2SeU. However, the triplet lifetime of the deprotonated form 2SeU is found to be almost one order of magnitude longer than that in the neutral one. Quantum chemistry calculations indicate that the short triplet lifetime in 2SeU is due to excited state population decay through a crossing point between T1 and S0. In the deprotonated form, shortening the N1-C2 bond length makes the structural distortion more difficult and brings a larger energy barrier on the pathway to the T1/S0 crossing point, resulting in one order of magnitude increase of the triplet state lifetime. Our study reveals one key factor to regulate the triplet lifetime of 2SeU and sets the stage to further investigate the photophysical and photochemical properties of 2SeU-containing DNA/RNA duplexes.


Assuntos
Selênio/química , Uracila/química , Teoria da Densidade Funcional , Simulação de Dinâmica Molecular , Prótons
15.
J Colloid Interface Sci ; 605: 701-709, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34365306

RESUMO

The attachment and dissociation of a proton from a water molecule and the proton transfers at solid-liquid interfaces play vital roles in numerous biological, chemical processes and for the development of sustainable functional materials for energy harvesting and conversion applications. Using first-principles computational methodologies, we investigated the protonated forms of polyhedral oligomeric silsesquioxane (POSS-H+) interacting with water clusters (Wn, where n = 1-6) as a model to quantify the proton conducting and localization ability at solid-liquid interfaces. Successive addition of explicit water molecules to POSS-H+ shows that the assistance of at least three water molecules is required to dissociate the proton from POSS with the formation of an Eigen cation (H9O4+), whereas the presence of a fourth water molecule highly favors the formation of a Zundel ion (H5O2+). Reaction pathway and energy barrier analysis reveal that the formation of the Eigen cation requires significantly higher energy than the Zundel features. This confirms that the Zundel ion is destabilized and promptly converts in to Eigen ion at this interface. Moreover, we identified a Grotthuss-type mechanism for the proton transfer through a water chain close to the interface, where symmetrical and unsymmetrical arrangements of water molecules around H+ of protonated POSS-H+ are involved in the conduction of proton through water wires where successive Eigen-to-Zundel and Zundel-to-Eigen transformations are observed in quick succession.


Assuntos
Prótons , Água
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120296, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454130

RESUMO

ESIPT behavior has attracted a lot of eyes of researchers in recent years because of its unique optical properties. Due to its large Stokes shift and double emission fluorescence, white light can be generated in the fluorophore based on the excited state intramolecular proton transfer (ESIPT) principle. The excited state proton transfer behavior of hydroxylated benzoxazole (BO-OH), benzothiazole (BS-OH) and benzoselenazole (BSe-OH) have been investigated in heptane, chloroform and DMF solvents. By comparing the infrared vibration spectra and the variation of bond parameters from the S0 to S1 states, and analyzing the frontier molecular orbitals, the influence of hydrogen bond dynamics, the solvent polarity, charge redistribution and the effects of different proton acceptors on proton transfer were observed. The only structural difference among the three substituted hydroxyfluorenes is the heteroatom in the azole ring (oxygen, sulfur and selenium, respectively). We have scanned the potential energy curve of the ESIPT process, and compared the potential barrier, it is found that the heavier chalcogen atoms are more favorable for proton transfer. At the same time, the potential application of changing heteroatoms in the azole ring by walking down the chalcogenic group in crystal luminescence color regulation is also discussed.


Assuntos
Calcogênios , Prótons , Azóis , Ligação de Hidrogênio , Modelos Moleculares
17.
Methods Mol Biol ; 2363: 51-62, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34545485

RESUMO

The integrity of isolated mitochondria can be estimated functionally using enzymatic activities or the permeability of mitochondrial membranes to molecules of different sizes. Thus, the permeability of the outer membrane to the protein cytochrome c, the permeability of the inner membrane to protons, and the permeability of the inner membrane to NAD+, NADH and organic acids using soluble matrix dehydrogenases as markers have all been used. These assays all have limitations to how the data can be converted into a measure of integrity, are differently sensitive to artifacts and require widely variable amounts of material. Therefore, each method has a restricted utility for estimating integrity, depending on the type of mitochondria analysed. Here, we review the advantages and disadvantages of different integrity assays and present protocols for integrity assays that require relatively small amounts of mitochondria. They are based on the permeability of the outer membrane to cytochrome c, and the inner membrane to protons or NAD(H). The latter has the advantage of utilizing a membrane-bound activity (complex I) and the pore-forming peptide alamethicin to gain access to the matrix space. These methods together provide a toolbox for the determination of functionality and quality of isolated mitochondria.


Assuntos
Mitocôndrias , Citocromos c/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias Hepáticas/metabolismo , NAD/metabolismo , Prótons
18.
Food Chem ; 373(Pt A): 131422, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-34710693

RESUMO

Solids-water interactions of corn and quinoa flours were evaluated through 1H NMR, DSC, and water sorption isotherms. Glass transition temperature (Tg), observed by DSC, was better distinguished through FID signals, and correlated to water content through the Gordon and Taylor model. Enthalpy relaxations, identified by thermal analysis at 50-70 °C were studied through transverse relaxation times (T2) measured after Hahn spin-echo sequence, which revealed a rearrangement of the biopolymers structures that cause immobilization of polymer chains and reduced mobility of water molecules with weak interactions with solids (lower T22). The higher lipid content of quinoa flour was manifested after the CPMG sequence (T2 ≈ 100 ms) and caused reduced hygroscopicity and Tg values compared with corn flour systems. 1H NMR resulted efficient for assigning proton populations and understanding the changes in their distribution with temperature, analyzing glass transition and interpreting the implications of enthalpy relaxations processes in corn and quinoa flours.


Assuntos
Chenopodium quinoa , Água , Farinha , Espectroscopia de Prótons por Ressonância Magnética , Prótons , Vitrificação , Zea mays
19.
Acc Chem Res ; 54(24): 4462-4473, 2021 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-34894649

RESUMO

Biological energy conversion is catalyzed by membrane-bound proteins that transduce chemical or light energy into energy forms that power endergonic processes in the cell. At a molecular level, these catalytic processes involve elementary electron-, proton-, charge-, and energy-transfer reactions that take place in the intricate molecular machineries of cell respiration and photosynthesis. Recent developments in structural biology, particularly cryo-electron microscopy (cryoEM), have resolved the molecular architecture of several energy transducing proteins, but detailed mechanistic principles of their charge transfer reactions still remain poorly understood and a major challenge for modern biochemical research. To this end, multiscale molecular simulations provide a powerful approach to probe mechanistic principles on a broad range of time scales (femtoseconds to milliseconds) and spatial resolutions (101-106 atoms), although technical challenges also require balancing between the computational accuracy, cost, and approximations introduced within the model. Here we discuss how the combination of atomistic (aMD) and hybrid quantum/classical molecular dynamics (QM/MM MD) simulations with free energy (FE) sampling methods can be used to probe mechanistic principles of enzymes responsible for biological energy conversion. We present mechanistic explorations of long-range proton-coupled electron transfer (PCET) dynamics in the highly intricate respiratory chain enzyme Complex I, which functions as a redox-driven proton pump in bacterial and mitochondrial respiratory chains by catalyzing a 300 Å fully reversible PCET process. This process is initiated by a hydride (H-) transfer between NADH and FMN, followed by long-range (>100 Å) electron transfer along a wire of 8 FeS centers leading to a quinone biding site. The reduction of the quinone to quinol initiates dissociation of the latter to a second membrane-bound binding site, and triggers proton pumping across the membrane domain of complex I, in subunits up to 200 Å away from the active site. Our simulations across different size and time scales suggest that transient charge transfer reactions lead to changes in the internal hydration state of key regions, local electric fields, and the conformation of conserved ion pairs, which in turn modulate the dynamics of functional steps along the reaction cycle. Similar functional principles, which operate on much shorter length scales, are also found in some unrelated proteins, suggesting that enzymes may employ conserved principles in the catalysis of biological energy transduction processes.


Assuntos
Complexo I de Transporte de Elétrons , Prótons , Respiração Celular , Microscopia Crioeletrônica , Transporte de Elétrons , Complexo I de Transporte de Elétrons/metabolismo , Elétrons
20.
Zhonghua Gan Zang Bing Za Zhi ; 29(11): 1077-1082, 2021 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-34933426

RESUMO

Objective: To explore the clinical application value of MRI-PDFF on different liver segments for the evaluation of non-alcoholic fatty liver disease (NAFLD). Methods: 178 volunteers from March 2019 to February 2020 were included. PDFF values ​​of all nine segments of the liver were measured using CSE3.0T MRI scan. The obtained average value was used to represent the average liver fat content. PDFF values of each or combined liver segment were equally compared with the average value to observe the representativeness of fat content. Receiver operating characteristic curve was used to analyze the diagnostic performance of each liver segment, and the Youden index was used to calculate the cutoff value. Paired-sample t-test or non-parametric Kruskal-Wallis test were used to compare measurement data among groups. Results: 178 volunteers average liver fat content ranged from 0.89% to 42.61% with MRI-PDFF, and 71.35% (127/178) of the volunteers had PDFF > 5%. There was no significant difference between SIII, SIVb, SV, and SVIII liver segments when compared with the average value (P > 0.05). PDFF values ​​of SI, SII, and SIV a liver segments were all lower than the average value, while the PDFF values ​​of SVI and SVII liver segments were all higher than the average value (P ​​< 0.05). MRI-PDFF sensitivity value for diagnosing liver steatosis of nine liver segments was 85.8% ~ 94.5%, and the specificity was higher than 96.0%. Among them, the SV liver segment had the highest sensitivity (94.5%), and the corresponding optimal diagnostic threshold value was 5.13%. Compared with single and combined liver segment, the PDFF value of SII, SV, SVI combined liver segment had the highest diagnostic performance for fatty liver, with the sensitivity and specificity of 96.9%, and 100%, respectively, and the corresponding optimal diagnostic threshold value was 5.17%. Conclusion: Compared with single and other combined liver segments, MRI-PDFF values of SII, SV, and SVI combined liver segments have higher sensitivity and specificity for the diagnosis of NAFLD, and it can be used as the first choice for the determination of liver fat content with MRI.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Prótons , Sensibilidade e Especificidade
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