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1.
J Colloid Interface Sci ; 607(Pt 1): 163-170, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34506998

RESUMO

HYPOTHESIS: Dynamic imine surfactants (DIS) can be constructed by the formation of dynamic imine bonds (Dibs) between aromatic aldehydes and aliphatic amines in water. Because of the nature of Dibs in water, a thermodynamic equilibrium state was achieved between the DIS and aldehyde and amine precursors to form a dynamic combinatorial library (DCL). When the DIS served as sole emulsifier to form oil-H2O emulsions, the precursors migrated between the H2O phase and the oil phase, which altered the DCL equilibrium. The DIS concentration and emulsion stability also changed. EXPERIMENTS: By mixing 4-(2-sulfobetaine-ethoxy)-benzaldehyde (SBBA) and aliphatic amines of CnH2n+1NH2 (n = 4, BA; n = 6, HA; n = 8, OA; n = 10, DA) in water, four amphoteric DIS (SBBA-BA/HA/OA/DA) were prepared. Dib formation was characterized using 1H NMR. The DIS surface activity was studied by surface tension and fluorescence probe methods. The reversible switching of DIS and its wormlike micelles were explored. FINDINGS: SBBA-OA (or SBBA-DA) DIS was not a suitable emulsifier for stable hydrocarbon (HC)-H2O emulsions. OA and DA were more soluble in the HC phase than the H2O phase. The precursors of OA and DA migrated from the H2O to the HC phase, and the thermodynamic equilibrium state of DCL shifted towards Dib dissociation. The Dib could be regenerated by HC phase removal. A novel strategy where volatile HC (such as pentane) was used as a trigger was developed to switch the DIS reversibly and its self-assemblies (such as wormlike micelles) in water without inorganic salt accumulation. The SBBA-HA (or SBBA-BA) DIS was a suitable emulsifier for stable emulsions because HA and BA were more soluble in the H2O phase.


Assuntos
Iminas , Tensoativos , Emulsões , Micelas , Água
2.
Anal Chim Acta ; 1188: 339191, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34794562

RESUMO

Lanthanide-functionalized porous organic materials have been the promising candidates in the chemical and biological sensing. Considering the superior thermal and solvent stability of covalent organic frameworks (COFs), the development of lanthanide ions-functionalized COFs based sensing platform is meaningful, while remains to be a challenge. In this work, a new imine-linked COF which provides suitable coordination sites for Tb3+ was constructed via the Schiff base reaction between P-phenylenediamine (Pda) and 2,6-Diformylpyridine (Dfp). Benefiting from its high signal-to-noise, the COF@Tb shows excellent ability to determinate ciprofloxacin (CIP) with a detection limit of 3.01 nM. The measurement can maintain good stability in the presence of potential interference or in actual sample. Being washed with ethanol after each measurement, COF@Tb can be recycled for five times. This work provides a novel alternative strategy for efficient construction of lanthanide-grafted COFs and may promote the development of porous organic materials based chemical sensing.


Assuntos
Estruturas Metalorgânicas , Antibacterianos , Iminas , Porosidade , Solventes
3.
J Chromatogr A ; 1659: 462647, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34731758

RESUMO

In this study, spherical imine-linked covalent organic frameworks (COFs) were fabricated from 2,5-dimethoxybenzene-1,4-dialdehyde (DMTP) and 1,3,5-tris (4-aminophenyl) benzene (TAPB) and named as TAPB-DMTP-COFs. The resulting powders were coated onto bare glass bars via physical-adhesion to obtain TAPB-DMTP-COFs coated stir bars. The self-made stir bars exhibited higher extraction efficiency (74-85%) and faster dynamics (50 min) towards non-steroidal anti-inflammatory drugs (NSAIDs) over ethylene glycol-Silicone (42-68%, 180 min) and polydimethylsiloxane (3-61%, 180 min) coated stir bars. Fourier transform infrared (FT-IR) spectra, X-ray photoelectron spectroscopy (XPS), zeta potential and water contact angle were employed to provide a comprehensive understanding of the adsorption mechanism between the coating and analytes. The results displayed that methoxy group worked as an adsorption site helping the adsorption of interest NSAIDs onto the TAPB-DMTP-COFs coating and hydrogen bonds formed between the O atoms and the analytes. Additionally, the adsorption mechanisms possibly also involved π-π interaction and hydrophobic interaction. Moreover, TAPB-DMTP-COFs coated stir bars exhibited good stability and could be reused more than 60 times. Subsequently, a method by combining TAPB-DMTP-COFs coated stir bar sorptive extraction (SBSE) with liquid chromatography (HPLC)-ultraviolet detector (UV) was established for the determination of four NSAIDs in environmental waters. Under the optimized conditions, the established method showed a wide linear range of 0.2/1-500 µg/L for interest NSAIDs, the limits of detection varied from 0.039 to 0.312 µg/L. Yangtze River water, East Lake water and Spring water were subjected to the proposed method, the recoveries in spiked samples were 84.7-104%, 81.2-101% and 82.6-97.6%, respectively.


Assuntos
Estruturas Metalorgânicas , Preparações Farmacêuticas , Poluentes Químicos da Água , Anti-Inflamatórios não Esteroides , Cromatografia Líquida de Alta Pressão , Iminas , Limite de Detecção , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier , Água , Poluentes Químicos da Água/análise
4.
Int J Mol Sci ; 22(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34639219

RESUMO

A five-step transformation of a spiroketal side chain of tigogenin into an indolizidine system present in solanidane alkaloids such as demissidine and solanidine was elaborated. The key intermediate in the synthesis was spiroimine 3 readily obtained from tigogenin by its RuO4 oxidation to 5,6-dihydrokryptogenin followed by amination with aluminum amide generated in situ from DIBAlH and ammonium chloride. The mild reduction of spiroimine to a 26-hydroxy-dihydropyrrole derivative and subsequent mesylation resulted in the formation of 25-epidemissidinium salt or 23-sulfone depending on reaction conditions.


Assuntos
Diosgenina/química , Iminas/química , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/síntese química , Espirostanos/química
5.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641292

RESUMO

Dapsone (DDS) is an antibacterial drug with well-known antioxidant properties. However, the antioxidant behavior of its derivatives has not been well explored. In the present work, the antioxidant activity of 10 dapsone derivatives 4-substituted was determined by an evaluation in two in vitro models (DPPH radical scavenging assay and ferric reducing antioxidant power). These imine derivatives 1-10 were obtained through condensation between DDS and the corresponding aromatic aldehydes 4-substuited. Three derivatives presented better results than DDS in the determination of DPPH (2, 9, and 10). Likewise, we have three compounds with better reducing activity than dapsone (4, 9, and 10). In order to be more insight, the redox process, a conceptual DFT analysis was carried out. Molecular descriptors such as electronic distribution, the total charge accepting/donating capacity (I/A), and the partial charge accepting/donating capacity (ω+/ω-) were calculated to analyze the relative donor-acceptor capacity through employing a donor acceptor map (DAM). The DFT calculation allowed us to establish a relationship between GAPHOMO-LUMO and DAM with the observed antioxidant effects. According to the results, we concluded that compounds 2 and 3 have the lowest Ra values, representing a good antioxidant behavior observed experimentally in DPPH radical capturing. On the other hand, derivatives 4, 9, and 10 display the best reducing capacity activity with the highest ω- and Rd values. Consequently, we propose these compounds as the best antireductants in our DDS imine derivative series.


Assuntos
Antioxidantes/síntese química , Dapsona/química , Iminas/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Simulação por Computador , Teoria da Densidade Funcional , Iminas/química , Iminas/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade
6.
J Chromatogr A ; 1658: 462610, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34662826

RESUMO

Food safety is a great concern of the general public. Chlorophenols (CPs) as organic pollutant can be found in drinking water and foods, causing serious harm to human health. Herein, imine-linked covalent organic frameworks (COFs), named as TAPT-AN-COF, was synthesized by aniline modulation strategy through condensation of 1,3,5-triformylphoroglucinol and 4,4',4''-(1,3,5-Triazine-2,4,6-triyl)trianiline with aniline as modulator. The prepared TAPT-AN-COF possesses good crystallinity and regular morphology, displaying excellent adsorption capability towards CPs pollutants. Thus, the TAPT-AN-COF was used as novel adsorbent for off-line solid-phase extraction of four CPs (2-CP, 3-CP, 2,3-CPs, 2,4-CPs) from bottled water, tea drink and honey samples before high performance liquid chromatography-ultraviolet detection. Under optimal conditions, wide linear range, low detection limits and satisfactory extraction recovery were gained. The π-stacking and hydrophobic interactions between the TAPT-AN-COF and the analytes played an important role in the adsorption. The established method has a great potential in determining other hydrophobic aromatic compounds.


Assuntos
Clorofenóis , Estruturas Metalorgânicas , Adsorção , Humanos , Iminas , Limite de Detecção , Extração em Fase Sólida
7.
Anal Chim Acta ; 1181: 338886, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34556223

RESUMO

A facile and rapid strategy for preparation of covalent organic framework (COF) coated fibers at ambient temperature is urgently needed for solid-phase microextraction (SPME) technology. In this work, an in situ room-temperature rapid growth strategy was developed to high-efficiently fabricate imine-linked COF (TPB-DVA) coated fibers in as little as 30 min at room temperature, and the thickness of the coating reached 9 µm. The prepared TPB-DVA coated fiber offer high thermal and chemical stability, and outstanding service lifetime. Moreover, we generalize this strategy to other two imine-linked COF (TPB-DMTP and TFPB-TAPB) coated fibers and the fibers were fabricated at room temperature for 3 h and 12 h, respectively, which demonstrate the applicability of this strategy. Subsequently, a SPME-GC-MS/MS analytical method was developed for trace pyrethroids (PYs) detection, which exhibited high enhancement factors (EFs, 2700-13195), wide linear range (0.08-800 ng L-1), low limits of detection (LODs, 0.02-0.20 ng L-1), and good repeatability (RSD ≤ 8.5%, n = 6). Furthermore, the developed analytical method was applied to tea samples and trace PYs (1.31-4.32 ng L-1) were found with satisfactory recovery (80.2-119.8%). The above results demonstrated that the feasibility of the developed strategy for the facile and rapid fabrication of imine-linked COF coated fibers.


Assuntos
Estruturas Metalorgânicas , Piretrinas , Poluentes Químicos da Água , Iminas , Limite de Detecção , Microextração em Fase Sólida , Espectrometria de Massas em Tandem , Temperatura , Poluentes Químicos da Água/análise
8.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576025

RESUMO

Aziridination reactions represent a powerful tool in aziridine synthesis. Significant progress has been achieved in this field in the last decades, whereas highly functionalized aziridines including 3-arylated aziridine-2-carbonyl compounds play an important role in both medical and synthetic chemistry. For the reasons listed, in the current review we have focused on the ways to obtain 3-arylated aziridines and on the recent advances (mainly since the year 2000) in the methodology of the synthesis of these compounds via aziridination.


Assuntos
Aziridinas/química , Cetonas/química , Aziridinas/síntese química , Ácidos Carboxílicos/química , Iminas/química , Estrutura Molecular , Estereoisomerismo
9.
J Org Chem ; 86(18): 12840-12850, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34469687

RESUMO

Stereoselective synthesis of the C4-C16 polyketide fragment of portimines A and B is reported, enabled by our previously established method for the stereoselective synthesis of syn-α,α'-dihydroxyketones. The preparation of this advanced fragment provides insights useful for the total synthesis of portimines A and B. An asymmetric Evans aldol reaction was used to install the C10-C11 adjacent stereogenic centers before incorporation of indantrione, followed by epoxidation and epoxide opening to forge the challenging syn-α,α'-dihydroxyketone functionality.


Assuntos
Policetídeos , Compostos de Espiro , Compostos de Epóxi , Iminas
10.
J Org Chem ; 86(18): 12932-12944, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34482692

RESUMO

Although dynamic reactions of imines have been extensively studied, the dynamic behaviors manipulated by chirality remain nearly unexplored. In this work, enantioselective amine exchange reactions were demonstrated as a first example via the reaction of enantiomeric chiral amines such as natural amino acids with a series of innovative axially chiral 1,1'-binaphthyl-2,2'-diamine (BNDA)-based imines that were prepared from the condensation reactions between BNDA and salicylaldehyde (SA) or its derivatives. This enantioselective dynamic behavior can be directly indicated by the degree of the fluorescence response of the R-configuration of imines to the d-enantiomer of chiral amine, because the released BNDA can serve as the fluorescence signal output when the amine exchange reaction occurs, which is far higher than the response to its l-enantiomer under identical experimental conditions. For the S-configuration of chiral imines, the fluorescence response is the opposite. The enantioselective exchange reaction can be tuned by altering the electron-withdrawing or electron-donating capability of the substituent at position 4 or 5 of the SA part of chiral imines. Not only o-OH groups in SA-based imines but also protic solvents used as reaction media were found to be important to the dynamic behavior at high rates.


Assuntos
Aminas , Iminas , Catálise , Diaminas , Estereoisomerismo
11.
J Org Chem ; 86(19): 13454-13464, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34515479

RESUMO

A new type of diazo compounds, namely, CH-diazomethane sulfonamides (generated in situ from readily available α-acetyl-α-diazomethane sulfonamides), was employed in a 1,3-dipolar cycloaddition reaction with imines (also formed in situ from primary amines and aldehydes). The reaction gave hitherto undescribed 1,5-disubstituted 1,2,3-triazoline-4-sulfonamides, which were obtained in good to excellent yields with complete trans diastereoselectivity. These new sulfonamides based on the nonaromatic 1,2,3-triazoline core are rather attractive from a medicinal chemistry standpoint in light of the strong emphasis recently put on the nonflat, more saturated (higher Fsp3) scaffolds for lead-generation libraries. The oxidative aromatization of 1,2,3-triazoline-4-sulfonamides by manganese(IV) oxide gave nearly quantitative yields of 1,2,3-triazole-4-sulfonamides, of which only two examples have been reported in the literature.


Assuntos
Iminas , Sulfonamidas , Aldeídos , Compostos Azo , Estrutura Molecular
12.
J Org Chem ; 86(19): 13693-13701, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34529434

RESUMO

A transition-metal-free postmodification of the Groebke-Blackburn-Bienaymé (GBB) reaction for the synthesis of spiro[chromene-imidazo[1,2-a]pyridin]-3'-imine was discovered. The unusual transformation represents the first example of activation and the reaction of the imidazole carbon atom. In this postcondensational modification, KOt-Bu acts as a base, which, after the isomerization of an alkyne moiety to allene, causes the next unique nucleophilic reaction of the imidazole carbon atom that results in spirocyclic structures. The proposed reaction mechanism was confirmed based on the DFT calculations.


Assuntos
Iminas , Elementos de Transição , Alcinos , Benzopiranos , Ciclização
13.
Acc Chem Res ; 54(19): 3710-3719, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34565142

RESUMO

Redox reactions that take place in enzymes and on the surfaces of heterogeneous catalysts often require active sites that contain multiple metals. By contrast, there are very few homogeneous catalysts with multinuclear active sites, and the field of organometallic chemistry continues to be dominated by the study of single metal systems. Multinuclear catalysts have the potential to display unique properties owing to their ability to cooperatively engage substrates. Furthermore, direct metal-to-metal covalent bonding can give rise to new electronic configurations that dramatically impact substrate binding and reactivity. In order to effectively capitalize on these features, it is necessary to consider strategies to avoid the dissociation of fragile metal-metal bonds in the course of a catalytic cycle. This Account describes one approach to accomplishing this goal using binucleating redox-active ligands.In 2006, Chirik showed that pyridine-diimines (PDI) have sufficiently low-lying π* levels that they can be redox-noninnocent in low-valent iron complexes. Extending this concept, we investigated a series of dinickel complexes supported by naphthyridine-diimine (NDI) ligands. These complexes can promote a broad range of two-electron redox processes in which the NDI ligand manages electron equivalents while the metals remain in a Ni(I)-Ni(I) state.Using (NDI)Ni2 catalysts, we have uncovered cases where having two metals in the active site addresses a problem in catalysis that had not been adequately solved using single-metal systems. For example, mononickel complexes are capable of stoichiometrically dimerizing aryl azides to form azoarenes but do not turn over due to strong product inhibition. By contrast, dinickel complexes are effective catalysts for this reaction and avoid this thermodynamic sink by binding to azoarenes in their higher-energy cis form.Dinickel complexes can also activate strong bonds through the cooperative action of both metals. Norbornadiene has a ring-strain energy that is similar to that of cyclopropane but is not prone to undergoing C-C oxidative addition with monometallic complexes. Using an (NDI)Ni2 complex, norbornadiene undergoes rapid ring opening by the oxidative addition of the vinyl and bridgehead carbons. An inspection of the resulting metallacycle reveals that it is stabilized through a network of secondary Ni-π interactions. This reactivity enabled the development of a catalytic carbonylative rearrangement to form fused bicyclic dienones.These vignettes and others described in this Account highlight some of the implications of metal-metal bonding in promoting a challenging step in a catalytic cycle or adjusting the thermodynamic landscape of key intermediates. Given that our studies have focused nearly exclusively on the (NDI)Ni2 system, we anticipate that many more such cases are left to be discovered as other transition-metal combinations and ligand classes are explored.


Assuntos
Complexos de Coordenação/química , Iminas/química , Níquel/química , Piridinas/química , Complexos de Coordenação/síntese química , Ligantes , Estrutura Molecular , Oxirredução
14.
Artigo em Inglês | MEDLINE | ID: mdl-34343946

RESUMO

A single laboratory method performance verification is reported for a rapid sensitive UHPLC-MS/MS method for the quantification of eight cyclic imine and two brevetoxin analogues in two bivalve shellfish matrices: mussel (Mytilus edulis) and Pacific oyster (Crassostrea gigas). Targeted cyclic imine analogues were from the spirolide, gymnodimine and pinnatoxin groups, namely 20-Me-SPX-C, 13-desMe-SPX-C, 13,19-didesMe-SPX-C, GYM-A, 12-Me-GYM, PnTx-E, PnTx-F and PnTx-G. Brevetoxin analogues consisted of the shellfish metabolites BTX-B5 and S-desoxy-BTX-B2. A rapid dispersive extraction was used as well as a fast six-minute UHPLC-MS/MS analysis. Mobile phase prepared using ammonium fluoride and methanol was optimised for both chromatographic separation and MS/MS response to suit all analytes. Method performance verification checks for both matrices were carried out. Matrix influence was acceptable for the majority of analogues with the MS response for all analogues being linear across an appropriate range of concentrations. In terms of limits of detection and quantitation the method was shown to be highly sensitive when compared with other methods. Acceptable recoveries were found with most analogues, with laboratory precision in terms of intra- and inter-batch precision deemed appropriate. The method was applied to environmental shellfish samples with results showing low concentrations of cyclic imines to be present. The method is fast and highly sensitive for the detection and quantification of all targeted analogues, in both mussel and oyster matrices. Consequently, the method has been shown to provide a useful tool for simultaneous monitoring for the presence or future emergence of these two toxin groups in shellfish.


Assuntos
Bivalves/química , Cromatografia Líquida de Alta Pressão/métodos , Toxinas Marinhas/análise , Ostreidae/química , Espectrometria de Massas em Tandem/métodos , Animais , Iminas/análise , Iminas/química , Iminas/isolamento & purificação , Limite de Detecção , Modelos Lineares , Extração Líquido-Líquido , Toxinas Marinhas/química , Toxinas Marinhas/isolamento & purificação , Oxocinas/análise , Oxocinas/química , Oxocinas/isolamento & purificação , Reprodutibilidade dos Testes
15.
J Org Chem ; 86(17): 11599-11607, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34351161

RESUMO

The mechanisms for the three- and four-component variants of the Castagnoli-Cushman reaction (CCR) have been investigated. A series of crossover experiments were conducted to probe the structure and reactivity of known amide-acid intermediates for the three- and four-component variants of the CCR (3CR and 4CR, respectively). Control experiments paired with in situ reaction monitoring with infrared spectroscopy for the 4CR align with a mechanism in which amide-acids derived from maleic anhydride can reversibly form free amine and cyclic anhydride. Although this equilibrium is unfavorable, the aldehyde present can trap the primary amine through imine formation and react with the enol form of the anhydride through a Mannich-like mechanism. This detailed mechanistic investigation coupled with additional crossover experiments supports an analogous mechanism for the 3CR and has led to the elucidation of new 3CR conditions with homophthalic anhydride, amines, and aldehydes for the formation of dihydroisoquinolones in good yields and excellent diastereoselectivity. This work represents the culmination of more than a decade of mechanistic speculation for the 3- and 4CR, enabling the design of new multicomponent reactions that exploit this novel mechanism.


Assuntos
Aldeídos , Aminas , Amidas , Anidridos , Iminas
16.
Biomolecules ; 11(8)2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34439823

RESUMO

Alveolar osteitis (AO) is a common complication following the extraction of the teeth, particularly the lower third molars. It starts within a few days after the extraction and manifests mainly as pain in the extraction site. Several strategies of treatment are available in order to relieve pain and heal the extraction wound. Recently, a novel medical device combining hyaluronic acid (HA) and octenidine (OCT) was introduced for the treatment of AO. This series of case reports aims to summarize the initial clinical experiences with this new device and to highlight factors possibly interfering with this treatment. The medical documentation of five patients with similar initial situations treated for AO with HA + OCT device was analyzed in detail. Smoking and previous treatment with Alveogyl (Septodont, Saint-Maur-des-Fossés, France) were identified as factors interfering with the AO treatment with the HA + OCT device. In three patients without these risk factors, the treatment led to recovery within two or three days. The patient pretreated with Alveogyl and the smoker required six and seven applications of the HA + OCT device, respectively. According to these initial observations, it seems smoking and previous treatment with Alveogyl prolong the treatment of AO using the HA + OCT device that, in turn, shows a rapid effect if these risk factors are not present.


Assuntos
Alvéolo Seco/tratamento farmacológico , Ácido Hialurônico/uso terapêutico , Iminas/uso terapêutico , Dor/tratamento farmacológico , Piridinas/uso terapêutico , Cicatrização/efeitos dos fármacos , Adolescente , Adulto , Creosoto/efeitos adversos , Combinação de Medicamentos , Alvéolo Seco/etiologia , Alvéolo Seco/fisiopatologia , Alvéolo Seco/cirurgia , Equipamentos e Provisões , Feminino , Humanos , Hidrocarbonetos Iodados/efeitos adversos , Pessoa de Meia-Idade , Dente Molar/cirurgia , Dor/etiologia , Dor/fisiopatologia , Dor/cirurgia , Fatores de Risco , Fumar/efeitos adversos , Extração Dentária/efeitos adversos , Resultado do Tratamento , Cicatrização/fisiologia
17.
Mater Sci Eng C Mater Biol Appl ; 127: 112210, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225862

RESUMO

Thymopentin (TP5) is widely used in the treatment of autoimmune diseases, but the short in vivo half-life of TP5 strongly restricts its clinical applications. A series of blank and TP5 loaded hydrogels were synthesized via reversible dual imine bonding by mixing water soluble O-carboxymethyl chitosan (CMCS) with a dynamer (Dy) prepared from Jeffamine and benzene-1,3,5-tricarbaldehyde. TP5 release from hydrogels was studied at 37 °C under in vitro conditions. The molar mass of CMCS, drug loading conditions and drug content were varied to elucidate their effects on hydrogel properties and drug release behaviors. Density functional theory was applied to theoretically confirm the chemical connections between TP5 or CMCS with Dy. All hydrogels exhibited interpenetrating porous architecture with average pore size from 59 to 83 µm, and pH-sensitive swelling up to 10,000% at pH 8. TP5 encapsulation affected the rheological properties of hydrogels as TP5 was partially attached to the network via imine bonding. Higher TP5 loading led to higher release rates. Faster release was observed at pH 5.5 than at pH 7.4 due to lower stability of imine bonds in acidic media. Fitting of release data using Higuchi model showed that initial TP5 release was essentially diffusion controlled. All these findings proved that the dynamic hydrogels are promising carriers for controlled delivery of hydrophilic drugs, and shed new light on the design of drug release systems by both physical mixing and reversible covalent bonding.


Assuntos
Quitosana , Timopentina , Aldeídos , Preparações de Ação Retardada , Portadores de Fármacos , Hidrogéis , Concentração de Íons de Hidrogênio , Iminas
18.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281290

RESUMO

Plasmodium falciparum's resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development.


Assuntos
Antimaláricos/farmacologia , Inibidores Enzimáticos/farmacologia , Iminas/farmacologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/antagonistas & inibidores , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Proteínas de Protozoários/antagonistas & inibidores , Pirimidinas/farmacologia , Animais , Antimaláricos/química , Antimaláricos/toxicidade , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/toxicidade , Humanos , Iminas/química , Iminas/toxicidade , Plasmodium falciparum/crescimento & desenvolvimento , Pirimidinas/química , Pirimidinas/toxicidade , Proteínas Recombinantes/efeitos dos fármacos , Relação Estrutura-Atividade , Triazóis/farmacologia
19.
Biophys J ; 120(16): 3392-3408, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34214528

RESUMO

The increasing problem of antibiotic resistance in bacteria requires the development of new antimicrobial candidates. There are several well-known substances with commercial use, but their molecular mode of action is not fully understood. In this work, we focus on two commonly used antimicrobial agents from the detergent family-octenidine dichloride (OCT) and chlorhexidine digluconate (CHX). Both of them are reported to be agents selectively attacking the cell membrane through interaction inducing membrane disruption by emulsification. They are believed to present electrostatic selectivity toward charged lipids. In this study, we tested this hypothesis and revised previously proposed molecular mechanisms of action. Employing a variety of techniques such as molecular dynamics, ζ potential with dynamic light scattering, vesicle fluctuation spectroscopy, carboxyfluorescein leakage measurement, and fluorescence trimethylammonium-diphenylhexatriene- and diphenylhexatriene-based studies for determination of OCT and CHX membrane location, we performed experimental studies using two model membrane systems-zwitterionic PC and negatively charged PG (18:1/18:1):PC (16:0/18:1) 3:7, respectively. These studies were extended by molecular dynamics simulations performed on a three-component bacterial membrane model system to further test interactions with another negatively charged lipid, cardiolipin. In summary, our study demonstrated that detergent selectivity is far more complicated than supposed simple electrostatic interactions. Although OCT does disrupt the membrane, our results suggest that its primary selectivity was more linked to mechanical properties of the membrane. On the other hand, CHX did not disrupt membranes as a primary activity, nor did it show any sign of electrostatic selectivity toward negatively charged membranes at any stage of interactions, which suggests membrane disruption by influencing more discrete membrane properties.


Assuntos
Clorexidina , Piridinas , Membrana Celular , Iminas , Bicamadas Lipídicas , Eletricidade Estática
20.
J Phys Chem B ; 125(30): 8588-8600, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34313112

RESUMO

Three polyazomethines and their corresponding model compounds were protonated with trifluoroacetic acid, and its effect on their optical (UV-vis absorption and photoluminescence) properties and electrochemical behavior has been studied, in the context of the presence and elongation of alkoxy side groups. Moreover, the effect of environment dielectric constants (i.e., polarity of the solvent) was considered on the doping process. It has been proven that the presence of alkoxy side groups is necessary for protonation to occur, while unsubstituted compounds undergo hydrolysis to constitutive units. Acid doping of imines consisting of alkoxy side chains has resulted in a distinct bathochromic shift (>200 nm) of the low-energy absorption band. Even the length of alkyl chains has not affected the position of shifted bands; it has been observed that azomethines with smaller, methoxy side groups undergo the protonation process much faster than their octyloxy-substituted analogues, due to the absence of steric hindrance. The electrochemical studies of these alkoxy-substituted imines have indicated a better p-type behavior after protonation induced by the capability of the protonated form to easily oxidize in acetonitrile and to generate the native molecules. The environmental polarity has also had impact on the doping process, which took place only in low-polar media.


Assuntos
Bases de Schiff , Tiofenos , Álcoois , Iminas , Solventes
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