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1.
J Chem Phys ; 151(14): 144504, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615223

RESUMO

In this work, a R1SM approach was applied for the calculation of ideal-gas thermodynamic properties of five amino acids with aliphatic side chains: glycine, alanine, valine, leucine, and isoleucine. The first step of the calculation was an extensive conformational analysis that located several conformers not reported previously. A new systematic and user-friendly nomenclature of the conformers was introduced, and the stable conformers were clearly assigned with the previously used labeling where possible. Stability and calculated relative energies of the conformers were compared between various levels of theory and with several experimental studies, demonstrating a good performance of the selected B3LYP-D3/6-311+G(2df,p) level of theory. As a second step, the theoretically calculated vibrational frequencies were compared to the previously reported experimental spectra to verify the performance of the applied double-linear scaling factor. Finally, ideal-gas heat capacities, enthalpies, and absolute entropies were calculated, accounting for all stable conformers using the R1SM model. The resulting thermodynamic data are presented for the first time, since they cannot be determined experimentally and their rigorous calculation requires a complex thermodynamic model.


Assuntos
Aminoácidos/química , Termodinâmica , Teoria da Densidade Funcional , Gases/química , Modelos Químicos , Conformação Molecular , Estatística como Assunto
2.
J Chem Phys ; 151(14): 144901, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615257

RESUMO

We demonstrate that nascent polymer crystals (i.e., nuclei) are anisotropic entities with neither spherical nor cylindrical geometry, in contrast to previous assumptions. In fact, cylindrical, spherical, and other high symmetry geometries are thermodynamically unfavorable. Moreover, postcritical transitions are necessary to achieve the lamellae that ultimately arise during the crystallization of semicrystalline polymers. We also highlight how inaccurate treatments of polymer nucleation can lead to substantial errors (e.g., orders of magnitude discrepancies in predicted nucleation rates). These insights are based on quantitative analysis of over four million crystal clusters from the crystallization of prototypical entangled polyethylene melts. New comprehensive bottom-up models are needed to capture polymer nucleation.


Assuntos
Polietileno/química , Cristalização , Conformação Molecular , Simulação de Dinâmica Molecular , Termodinâmica
3.
Phys Chem Chem Phys ; 21(41): 22857-22868, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31599896

RESUMO

Three low-energy isomers of 9-methylguanine, the amino-oxo (AO) form and two amino-hydroxy (AH1 and AH2) conformers, were trapped from the gas phase into low-temperature argon matrices. The AH1 and AH2 isomers, differing in the orientation of the OH group, were found to transform into each other upon excitation with near-IR light. The population of the AO form of the compound was not changed upon any near-IR irradiation of the matrix samples. Using monochromatic near-IR light, generated by a frequency-tunable laser source, it was possible to selectively induce the AH1 → AH2 or AH2 → AH1 conversion. Photoreversibility of this conformational transformation was then demonstrated. Exposure of matrix-isolated monomers of 9-methylguanine to broadband near-IR light also led to conformational conversions within the amino-hydroxy tautomeric form; the final stage of this process was always the same photostationary state independent of the initial ratio of AH1 and AH2 populations. Spontaneous conformational conversion, transforming the higher-energy AH2 form into the lower-energy AH1 isomer, was observed for matrix-isolated monomers of 9-methylguanine kept in the dark. The mechanism of this process must rely on quantum tunneling of the light hydrogen atom. Irradiation of matrix-isolated 9-methylguanine with UV laser light at λ = 288 or 285 nm led to a substantial consumption of the two AH forms, while the amount of AO isomer remained unchanged. On the other hand, a decrease in the population of the AO isomer occurred upon excitations at shorter wavelengths, λ = 280 or 275 nm. The spectral changes observed after UV-irradiation suggest the generation (and stabilization in the matrix) of a radical species, resulting from the photocleavage of the O-H or N1-H bonds, in the AH or AO isomer, respectively.


Assuntos
Argônio/química , Temperatura Baixa , Guanina/análogos & derivados , Raios Infravermelhos , Raios Ultravioleta , Guanina/química , Isomerismo , Conformação Molecular/efeitos da radiação
4.
Phys Chem Chem Phys ; 21(41): 23169-23178, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31612182

RESUMO

The lateral diffusion of lipids and of small molecules inside a membrane is strictly related to the arrangement of acyl chains and to their mobility. In this study, we use FTIR and time resolved 2D-IR spectroscopic techniques to characterize the structure and dynamics of the hydrophobic region of palmitoyl-oleylphosphatidylcholine/cholesterol vesicles dispersed in water/dimethylsulfoxide solutions. By means of a non-polar probe, hexacarbonyl tungsten, we monitor the distribution of free volumes inside the bilayer and the conformational dynamics of hydrophobic tails in relation to the different compositions of the membrane or the different compositions of the solvent. Despite the important structural changes induced by the presence of DMSO in the solvating medium, the picosecond dynamics of the membrane is preserved under the different conditions.


Assuntos
Colesterol/química , Dimetil Sulfóxido/química , Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Água/química , Difusão , Interações Hidrofóbicas e Hidrofílicas , Conformação Molecular , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de Fourier
5.
Chem Pharm Bull (Tokyo) ; 67(9): 935-939, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474732

RESUMO

Chafuroside A and chafuroside B are flavone C-glycosides isolated from oolong tea leaves. They have a number of beneficial pharmacological activities related to antiinflammation at various concentrations. However, no crystallographic study of chafurosides has yet been reported. In the present study, the crystal structures of chafuroside A and chafuroside B were investigated using single-crystal X-ray diffraction. The asymmetric unit of the chafuroside A crystal consists of one chafuroside A and two water molecules, and that of chafuroside B contains one chafuroside B and one water molecule. The flavone moiety of chafuroside A is curved, i.e., the angle between the best-fit planes of the chromene and phenyl rings is 18.9°, whereas the chafuroside B flavone moiety is relatively flat. A comparison of the curvatures of the flavone moieties of various C-glycosides showed that the curvature of chafuroside A is significantly larger than those of the others. This structural feature might contribute to the differences between the strengths of the pharmacological activities of chafurosides A and B.


Assuntos
Flavonas/química , Glicosídeos/química , Compostos Heterocíclicos de 4 ou mais Anéis/química , Chá/química , Camellia sinensis/química , Camellia sinensis/metabolismo , Cristalografia por Raios X , Conformação Molecular , Folhas de Planta/química , Folhas de Planta/metabolismo
6.
Chem Pharm Bull (Tokyo) ; 67(9): 953-958, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474735

RESUMO

Asymmetric total syntheses of dihydropyran containing natural products, (+)-eurotiumide F and (+)-eurotiumide G have been described. These total syntheses revealed the absolute configuration of eurotiumide F and G, and confirmed the reported structure of eurotiumide F and revised the reported structure of eurotiumide G. Highlight of these syntheses is thermal rearrangement with 4-methoxyisochroman-1-one derivative having propargyl ether on phenolic ether under thermal condition to construct dihydropyran ring. X-Ray crystallographic analysis of (+)-eurotiumide G clarified the stereochemistry at the C1-position.


Assuntos
Produtos Biológicos/química , Piranos/química , Produtos Biológicos/síntese química , Cristalografia por Raios X , Conformação Molecular , Piranos/síntese química , Solventes/química , Estereoisomerismo
7.
Phys Chem Chem Phys ; 21(37): 20727-20742, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31509121

RESUMO

The left-handed polyproline II (PPII) type helical structures are thought to play a very important role in many essential biological processes, particularly in recognition mechanisms. However, reliable characterisation of PPII conformation in solution can be experimentally challenging. Computational simulation of these structures offers an attractive alternative, but the accuracy of the results is dependent on the accuracy of the force field employed. In this report, we present the results of simulation of the structural and dynamical properties of a proline-rich viral fusion peptide for which a solution NMR study reported a substantial stretch of PPII conformation in the central region. The suggested mode of action of the p15 fusion peptide depended on the exposure of the flanking N-terminal hydrophobic residues to solvent thereby facilitating their interaction with the target membrane. Our simulations with a set of four force field and water model combinations consisting of (AMBER ff99SB*-ILDNP + TIP3P), (OPLS-AA + SPC/E), (AMBER ff03ws + TIP4P/2005 water with scaled protein-water interactions) and (CHARMM36m + TIP3P) showed a general agreement with the NMR results for all the four force field and water model combinations. The central region encompassing positions 9-15 showed a large PPII propensity, reduced flexibility and lower conformational entropy. The PPII conformations were stable and satisfied the Burgi-Dunitz criteria without the participation of any significant water bridging interaction. However, comparison of the experimentally observed chemical shifts with the distribution of shifts predicted from the simulated ensembles showed a much better agreement for the CHARMM36m + TIP3P and AMBER ff03ws + TIP4P/2005 combinations. The models based on these two force fields also generated conformations which were in much better agreement with the NMR model than the much more compact structures predicted by the AMBER ff99SB*-ILDNP and OPLS-AA force fields and predicted a substantially larger solvent accessible surface area in accordance with the suggested mechanism of action of the peptide.


Assuntos
Modelos Moleculares , Prolina/química , Proteínas Recombinantes de Fusão/química , Simulação por Computador , Espectroscopia de Ressonância Magnética , Conformação Molecular , Água/química
8.
Curr Top Med Chem ; 19(14): 1201-1225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509099

RESUMO

The significant spread of helminth and protozoan infections, the uncontrolled intake of the known drugs by a large population, the emergence of resistant forms of pathogens have prompted people to search for alternative drugs. In this review, we have focused attention on structures and synthesis of peroxides active against parasites causing neglected tropical diseases and toxoplasmosis. To date, promising active natural, semi-synthetic and synthetic peroxides compounds have been found.


Assuntos
Produtos Biológicos/farmacologia , Brugia Malayi/efeitos dos fármacos , Helmintos/efeitos dos fármacos , Doenças Negligenciadas/tratamento farmacológico , Peróxidos/farmacologia , Toxoplasmose/tratamento farmacológico , Animais , Produtos Biológicos/síntese química , Produtos Biológicos/química , Conformação Molecular , Testes de Sensibilidade Parasitária , Peróxidos/síntese química , Peróxidos/química
9.
Chemosphere ; 235: 1180-1188, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561309

RESUMO

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are a class of highly persistent contaminants with high bioaccumulation and toxicity. Our previous studies showed that perfluorooctanoic acid (PFOA) can be completely defluorinated under UV irradiation in organo-montmorillonite/indole acetic acid (IAA) system. However, there is still lack of information for the degradation mechanism and the test for wastewater treatment. Here, we systematically investigated the defluorination reaction in the presence of different organo-montmorillonites and found that the degradation process was apparently controlled by the configuration of surfactants. In hexadecyltrimethyl ammonium (HDTMA)-modified montmorillonite, HDTMA exists as a tilt conformation and isolated clay interlayer from the aqueous solution, protecting hydrated electrons generated by photo-irradiation of IAA from quenching by oxygen. Defluorination hydrogenation process was the dominant degradation pathway. While in poly-4-vinylpyridine-co-styrene (PVPcoS)-modified montmorillonite, due to the multiple charges of PVPcoS, a flat conformation parallel to clay surface was expected. Hydroxyl radicals, which were generated by the reaction of hydrated electrons with oxygen molecules diffused into clay interlayer, are also involved in the degradation process. Our results further demonstrate that mixture modified montmorillonite could combine the advantages of both modifications, thus showing superior reactivity even for actual industrial wastewater without any pretreatment. This technique would have great potential for treatment of actual wastewater.


Assuntos
Bentonita/química , Caprilatos/química , Argila/química , Elétrons , Fluorcarbonetos/química , Tensoativos/química , Adsorção , Radical Hidroxila/química , Conformação Molecular , Purificação da Água/métodos
10.
Chem Commun (Camb) ; 55(77): 11511-11514, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31490471

RESUMO

A short metallofullere-peapod of Y2@C79N⊂[4]CHBC was constructed. The strong confinement effect from the large π-extended [4]CHBC nanoring induces molecular orientation of the wrapped Y2@C79N, which can be sensed by a Y2@C79N spin probe. The low susceptibility of the spin phase memory time (Tm) for the Y2@C79N spin was also found in a confined space.


Assuntos
Complexos de Coordenação/química , Fulerenos/química , Hidrocarbonetos Cíclicos/química , Marcadores de Spin , Ítrio/química , Compostos Aza/química , Teoria da Densidade Funcional , Conformação Molecular , Transição de Fase , Temperatura Ambiente , Termodinâmica
11.
Chem Biol Interact ; 311: 108798, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31433962

RESUMO

Natural products are a valuable source of anticancer agents, with many naturally derived compounds currently used in clinical and preclinical treatments. This study aims to investigate the antiproliferative activity and potential mechanism of action of the xanthoquinodin JBIR-99, isolated from fungi Parengyodontium album MEXU 30,054 and identified by single-crystal X-ray crystallography. Cytotoxicity of xanthoquinodin was evaluated in a panel of human cancer cells lines and CCD-112-CoN normal colon cells, using the sulforhodamine B assay. PC-3 prostate cancer cells were used in biochemical assays including cell cycle, mitochondrial transmembrane potential (MTP), reactive oxygen species (ROS) and caspase activity. Expression levels of apoptosis-pathway-related proteins were analyzed by Western blot. The in vivo toxicity of xanthoquinodin was determined using a zebrafish model. Xanthoquinodin showed cytotoxicity in all cancer cell lines but demonstrated relative selective potency against PC-3 cells with an IC50 1.7 µM. In CCD-112-CoN cells, xanthoquinodin was non-cytotoxic at 100 µM. In PC-3 cells, the compound induced loss of MTP, production of ROS, and cell cycle arrest in S phase. The expression and activity of caspase-3 was increased, which correlates with the upregulation of Cyt c, Bax, nuclear factor kappa-B (NF-κB) (p65) and IKKß, and downregulation of poly ADP ribose polymerase (PARP-1) and Bcl-2. Lastly, xanthoquinodin did not cause any visible developmental toxicity in zebrafish at 50 µM. These results demonstrate xanthoquinodin induces apoptosis in PC-3 prostate cancer cells by activation of both intrinsic and extrinsic apoptotic pathways. In addition, the non-toxic effect in vivo indicates that xanthoquinodin could be a useful lead in the development of a novel, anti-cancer agent that is selective for prostate cancer.


Assuntos
Apoptose/efeitos dos fármacos , Ascomicetos/química , Cromonas/farmacologia , Ascomicetos/metabolismo , Linhagem Celular Tumoral , Cromonas/química , Cristalografia por Raios X , Citocromos c/metabolismo , Humanos , Quinase I-kappa B/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Conformação Molecular , Poli(ADP-Ribose) Polimerase-1/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
12.
J Enzyme Inhib Med Chem ; 34(1): 1498-1505, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31423863

RESUMO

Recent studies identified the benzoxaborole moiety as a new zinc-binding group able to interact with carbonic anhydrase (CA) active site. Here, we report a structural analysis of benzoxaboroles containing urea/thiourea groups, showing that these molecules are very versatile since they can bind the enzyme assuming different binding conformations and coordination geometries of the catalytic zinc ion. In addition, theoretical calculations of binding free energy were performed highlighting the key role of specific residues for protein-inhibitor recognition. Overall, these data are very useful for the development of new inhibitors with higher selectivity and efficacy for various CAs.


Assuntos
Compostos de Boro/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Compostos de Boro/síntese química , Compostos de Boro/química , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade
13.
Inorg Chem ; 58(16): 10611-10615, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31380629

RESUMO

Luminescent lanthanides provide a promising alternative to organic chromophores for cellular bioimaging and bioassay applications; efficacy is closely governed by their respective quantum yields. Conventionally utilized quantum-yield measurements for lanthanides are laborious and not amenable to rapid relative comparison of compound performance. Here, we introduce a high-throughput optical imaging method to determine and directly compare relative quantum yield using Cherenkov-radiation-mediated excitation of luminescent lanthanide complexes.


Assuntos
Complexos de Coordenação/química , Ensaios de Triagem em Larga Escala , Elementos da Série dos Lantanídeos/química , Teoria Quântica , Luminescência , Conformação Molecular
14.
Chem Pharm Bull (Tokyo) ; 67(8): 839-848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366833

RESUMO

Panacis Japonici Rhizoma (PJR) contains various kinds of saponins, which possesses extensive pharmacological activities, but studies of comprehensive analysis of its saponins were limited. Thus, ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (UFLC-Triple TOF-MS/MS) and ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UFLC-QTRAP-MS/MS) methods were established for the qualitative and quantitative analysis of the saponins in PJR, separately. Fifty three saponins in PJR were identified by UFLC-Triple TOF-MS/MS method, 23 saponins of which were unequivocally identified by reference substances. In addition, fragmentation pathways of different types of saponins were preliminarily deduced by fragmentation behavior of 53 saponins. Furthermore, the simultaneous determination of the contents of 13 saponins in PJR samples harvested at different times were analyzed by UFLC-QTRAP-MS/MS method. Furthermore, the quality of the samples was evaluated by grey relational analysis. This study might be beneficial to the quality assessment and control of PJR. Meanwhile, it might provide the basic information for confirming its optimal harvested period.


Assuntos
Rizoma/química , Saponinas/análise , Cromatografia Líquida , Conformação Molecular , Espectrometria de Massas em Tandem , Fatores de Tempo
15.
Acta Crystallogr C Struct Chem ; 75(Pt 8): 1031-1035, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31380784

RESUMO

Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one-quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2-[4-(cyclohexylmethyl)piperazin-1-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one, C20H23F3N4O3S} is a promising new drug for treating drug-sensitive and drug-resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by 1H NMR, 13C NMR, HRMS, IR, and X-ray crystallography. The cyclohexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3-benzothiazin-4-one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp2-hybridization of the nitro N atom, which donates into the electron-deficient 1,3-benzothiazin-4-one group.


Assuntos
Antituberculosos/química , Antituberculosos/síntese química , Cristalografia por Raios X , Farmacorresistência Bacteriana , Ligações de Hidrogênio , Conformação Molecular , Tuberculose Pulmonar/tratamento farmacológico
16.
Chemistry ; 25(49): 11574-11580, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31407847

RESUMO

The so-called Securinega alkaloids constitute a class of tetracyclic biologically active specialised metabolites isolated principally from subtropical plants belonging to the Phyllanthaceae family. Following a strategy based on alternative hypotheses for their biosynthesis, an easy and time-efficient divergent synthesis enabled access to twelve of those alkaloids featuring (neo)(nor)securinane skeletons. Moreover, this work permitted to reassign the absolute configurations of (+)-virosine B and (-)-episecurinol A.


Assuntos
Alcaloides/biossíntese , Alcaloides/química , Euphorbiaceae/química , Euphorbiaceae/metabolismo , Mesilatos/química , Conformação Molecular , Estereoisomerismo
17.
Phys Chem Chem Phys ; 21(34): 18699-18705, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31423504

RESUMO

Fully hydrated bilayers of monounsaturated palmitoyloleoylphosphatidylcholine (POPC) and diunsaturated dioleoylphosphatidylcholine (DOPC) lipids have low main phase transition temperatures (271 K for POPC and 253 K for DOPC). Two-pulse echo detected spectra, combined with continuous wave electron paramagnetic resonance spectroscopy, are employed to study the low-temperature lamellar phases of the POPC and DOPC unsaturated bilayers that are usually studied in the fluid state. Phosphatidylcholine spin-labeled at C-5 and C-16 carbon atom positions along the acyl chain were used and the temperature varied over the range 77-270 K. Segmental chain librational oscillations of small amplitude and with correlation time in the subnanosecond to nanosecond range are found in both membranes. The mean-square angular amplitude, α2, of librations increases with temperature, is larger close to the bilayer midplane than close to the first acyl chain segments, and is larger in diunsaturated than in monounsaturated bilayers. In the inner hydrocarbon region of both lipid matrices, α2 increases first slowly and linearly with temperature and then more rapidly, and a dynamical transition is detected in the range 190-210 K. Compared to dipalmitoylphosphatidylcholine bilayers of fully saturated symmetric chain lipids, the presence of double bonds in the acyl chain enhances the intensity of librational motion which is characterized by larger angular variations at the terminal methyl ends. These findings highlight biophysical properties of unsaturated bilayers in the frozen state, including a detailed characterization of segmental chain dynamics and the evidence of a dynamical transition that appears to be a generic feature in hydrated macromolecular systems. These results can also be relevant in regulating membrane physical properties and function at higher physiological temperatures.


Assuntos
Bicamadas Lipídicas/química , 1,2-Dipalmitoilfosfatidilcolina/química , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Cinética , Conformação Molecular , Movimento (Física) , Transição de Fase , Fosfatidilcolinas/química , Marcadores de Spin , Temperatura Ambiente , Termodinâmica
18.
Phys Chem Chem Phys ; 21(34): 18741-18752, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31424464

RESUMO

Medical application of nanotechnology implies the development of nanomaterials capable of being functional in different biological environments. In this sense, elongated nanoparticles (e-MNPs) with high-aspect ratio have demonstrated more effective particle cellular internalization, which is favoured by the increased surface area. This paper makes use of an environmentally friendly hydrothermal method to produce magnetic iron oxide e-MNPs, starting from goethite precursors. At high temperatures (Td) goethite transforms into hematite, which subsequently reduces to magnetite when exposed to a hydrogen atmosphere for a certain time. It is shown that by adjusting Td it is possible to obtain Fe3O4 e-MNPs with partially controlled specific surface area and magnetic properties, attributed to different porosity of the samples. The particles' efficiencies for diagnostic and therapeutic purposes (in magnetic resonance imaging and magnetic fluid hyperthermia, respectively) are very good in terms of clinical standards, some samples showing transversal proton nuclear relaxivity r2 (B0 = 1.33 T) = 340 s-1 mM-1 and specific absorption rate SAR > 370 W g-1 at high field amplitudes (B0 = 55 mT). Direct correlations between the SAR, relaxivity, magnetic properties and porosity of the samples are found, and the physico-chemical processes underneath these correlations are investigated. Our results open the possibility of using very efficient high-aspect ratio elongated nanoparticles with optimized chemico-physical properties for biomedical applications.


Assuntos
Nanopartículas de Magnetita/química , Temperatura Alta , Hidrogênio/química , Magnetismo , Conformação Molecular , Fenômenos Físicos , Dióxido de Silício/química , Propriedades de Superfície
19.
Phys Chem Chem Phys ; 21(41): 22711-22721, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31454001

RESUMO

Peptide appended pillar[5]arene (PAP) is an artificial water channel resembling biological water channel proteins, which has shown a significant potential for designing bioinspired water purification systems. Given that PAP channels need to be incorporated at a high density in membrane matrices, it is critical to examine the role of channel-channel and channel-membrane interactions in governing the structural and functional characteristics of channels. To resolve the atomic-scale details of these interactions, we have carried out atomistic molecular dynamics (MD) simulations of multiple PAP channels inserted in a lipid or a block-copolymer (BCP) membrane matrix. Classical MD simulations on a sub-microsecond timescale showed clustering of channels only in the lipid membrane, but enhanced sampling MD simulations showed thermodynamically-favorable dimerized states of channels in both lipid and BCP membranes. The dimerized configurations of channels, with an extensive buried surface area, were stabilized via interactions between the aromatic groups in the peptide arms of neighboring channels. The conformational metrics characterizing the orientational and structural changes in channels revealed a higher flexibility in the lipid membrane as opposed to the BCP membrane although hydrogen bonds between the channel and the membrane molecules were not a major contributor to the stability of channels in the BCP membrane. We also found that the channels undergo wetting/dewetting transitions in both lipid and BCP membranes with a marginally higher probability of undergoing a dewetting transition in the BCP membrane. Collectively, these results highlight the role of channel dynamics in governing channel-channel and channel-membrane interfacial interactions, and provide atomic-scale insights needed to design stable and functional biomimetic membranes for efficient separations.


Assuntos
Aquaporinas/química , Calixarenos/química , Membrana Celular/química , Aquaporinas/metabolismo , Biomimética , Membrana Celular/metabolismo , Modelos Moleculares , Conformação Molecular , Simulação de Dinâmica Molecular
20.
Chem Pharm Bull (Tokyo) ; 67(10): 1082-1087, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31391385

RESUMO

Camptothecin (CPT), a natural alkaloid, possesses potent anticancer activity. However, its application was terminated due to its low bioavailability and high toxicity. This work evaluated the potential of deoxycholic acid-CPT conjugate (G2) to improve the oral absorption of CPT. Deoxycholic acid significantly reduced cytotoxicity and inhibited the uptake of G2, in vitro. And G2 showed sodium-dependent uptake. In addition, in vivo study in rats indicated that the oral bioavailability of G2 was 2.06-fold higher than that of CPT. The present study suggested that using bile acid as the conjugated moiety is a hopeful strategy to improve the oral bioavailability of CPT.


Assuntos
Ácidos e Sais Biliares/administração & dosagem , Ácidos e Sais Biliares/química , Camptotecina/administração & dosagem , Camptotecina/química , Absorção Fisiológica , Administração Oral , Animais , Ácidos e Sais Biliares/farmacologia , Células CACO-2 , Camptotecina/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Masculino , Conformação Molecular , Ratos , Ratos Sprague-Dawley
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