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OBJECTIVE: This research investigates how particle parameters, such as zeta potential, size, functional group, material composition, and hydrophobicity affect their affinity and deposition of particles onto hair. METHODS: Streaming potential was used as the technique for analysis. The streaming potential data obtained was then converted to surface coverage data. Scanning electron microscopy (SEM) was also done to visualize particle localization on the hair surface. RESULTS: This study found stronger particle affinity on healthy than on damaged (oxidatively bleached) hair, due to diminished interaction sites from the removal of the hair shaft's external lipid layer. SEM imaging supported these findings and offered insights into particle localization. Hydrophilic silica particles accumulated along the exposed hydrophilic cuticle edges of healthy hair, due to hydrogen bonding with the exposed endocuticle. This localization is hypothesized to be due to the limited hydrophilic binding sites on the hydrophobic healthy hair cuticle surface. In damaged hair, an abundance of hydrophilic sites across the cuticle surface results in more dispersed binding. Hydrogen bonding and electrostatic attraction were shown to be the predominant forces influencing deposition, with hydrophobic interactions playing a less influential role. The affinity studies also proved that electrostatic attractions work over a longer range and are more effective at lower particle conditions compared with hydrogen bonding which only start to play a bigger role at higher particle concentrations. Steric hindrance of bulky side groups acted as a significant repulsive force. Results also revealed that larger particles deposit poorly on both healthy and damaged hair compared with smaller ones. Compared with neutrally charged silica nanoparticles (SN-2), positively charged PMMA particles (PN+16) have a stronger affinity to healthy hair, with highly charged particles (PN+49) depositing most rapidly. CONCLUSION: This study provides a fundamental understanding of how particle-surface parameters influence their affinity to hair and how damaging hair affects deposition.
OBJECTIF: Cette étude examine comment les paramètres des particules, tels que le potentiel zêta, la taille, le groupe fonctionnel, la composition du matériau et l'hydrophobie, affectent l'affinité et le dépôt des particules sur les cheveux. MÉTHODES: Le potentiel d'écoulement a été utilisé comme technique d'analyse. Les données de potentiel d'écoulement obtenues ont ensuite été converties en données de couverture de surface. Une microscopie électronique à balayage (MEB) a également été réalisée pour visualiser la localisation des particules à la surface des cheveux. RÉSULTATS: Cette étude a mis en évidence une affinité plus forte des particules sur des cheveux sains que sur des cheveux abîmés (décolorés par oxydation), en raison de la diminution des sites d'interaction due à l'élimination de la couche lipidique externe de la tige du cheveu. L'imagerie MEB a confirmé ces résultats et a permis d'obtenir des informations sur la localisation des particules. Des particules de silice hydrophile se sont accumulées en bordure des cuticules hydrophiles exposées des cheveux sains, en raison de la liaison de l'hydrogène avec l'endocuticule exposée. Il est supposé que cette localisation est due au nombre réduit de sites de liaison hydrophiles à la surface hydrophobe saine de la cuticule capillaire. Sur des cheveux abîmés, l'abondance de sites hydrophiles sur la surface des cuticules entraîne une liaison plus dispersée. La liaison de l'hydrogène et l'attraction électrostatique se sont avérées être les forces prédominantes qui influencent le dépôt, les interactions hydrophobes jouant un rôle moins influent. Les études d'affinité ont également démontré que les attractions électrostatiques fonctionnent sur une plus longue plage et sont plus efficaces dans des conditions de concentration de particules inférieures par rapport à la liaison de l'hydrogène qui ne commence à jouer un rôle plus important qu'à des concentrations de particules plus élevées. L'entrave stérique des groupes latéraux volumineux a agi comme une force répulsive significative. Les résultats ont également révélé que les particules plus grosses se déposent faiblement sur des cheveux sains et des cheveux abîmés par rapport aux particules plus petites. Par rapport aux nanoparticules de silice à charge neutre (SN2), les particules de PMMA à charge positive (PN+16) ont une affinité plus forte avec les cheveux sains, les particules fortement chargées (PN+49) se déposant le plus rapidement. CONCLUSION: Cette étude apporte une compréhension fondamentale de la façon dont les paramètres de la surface et des particules influencent leur affinité avec les cheveux et dans quelle mesure les cheveux abîmés affectent les dépôts.
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The retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt), which is a promising therapeutic target for immune diseases, is a major transcription factor of genes related to psoriasis pathogenesis, such as interleukin (IL)-17A, IL-22, and IL-23R. Inspired by the co-crystal structure of RORγt, a 6-oxo-4-phenyl-hexanoic acid derivative 6a was designed, synthesized, and identified as a ligand of RORγt. The structure-activity relationship (SAR) studies in 6a, which focus on the improvement of its membrane permeability profile by introducing chlorine atoms, led to finding 12a, which has a potent RORγt inhibitory activity and a favorable pharmacokinetic profile.
Assuntos
Caproatos/farmacologia , Descoberta de Drogas , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/agonistas , Animais , Caproatos/química , Caproatos/metabolismo , Relação Dose-Resposta a Droga , Humanos , Camundongos , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Relação Estrutura-AtividadeRESUMO
Aqueous organic redox flow batteries (AORFBs) have received considerable attention for large-scale energy storage. Quinone derivatives, such as 9,10-anthraquinone-2,7-disulphonic acid (2,7-AQDS), have been explored intensively owing to potentially low cost and swift reaction kinetics. However, the low solubility in pH-neutral electrolytes restricts their application to corrosive acidic or caustic systems. Herein, the single molecule redox-targeting reactions of 2,7-AQDS anolyte are presented to circumvent its solubility limit in pH-neutral electrolytes. Polyimide was employed as a low-cost high-capacity solid material to boost the capacity of 2,7-AQDS electrolyte to 97â Ah L-1 . Through inâ situ FTIR spectroscopy, a hydrogen-bonding mediated reaction mechanism was disclosed. In conjunction with NaI as catholyte and nickel hexacyanoferrate as the catholyte capacity booster, a single-molecule redox-targeting reaction-based full cell with energy density up to 39â Wh L-1 was demonstrated.
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Don't cross me! 2-Alkynyl indoles were prepared efficiently by the AgOTf-catalyzed tandem heterocyclization/alkynylation of 1-(2-tosylamino)aryl)but-2-yne-1,4-diols under mild conditions (see scheme). The attractiveness of this approach lies in the fact that both the indole ring and alkyne side chain of the N-heterocycle are sequentially formed from low cost, readily available, and ecologically benign starting materials. It also provides the first route to this synthetically valuable class of compounds that is not based on a cross-coupling strategy.
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Álcoois/química , Alcinos/química , Indóis/síntese química , Mesilatos/química , Catálise , Ciclização , Indóis/química , Estrutura MolecularRESUMO
A Brønsted acid-catalyzed method to prepare tri- and tetrasubstituted furans efficiently from cycloisomerization of but-2-yne-1,4-diols with or without 1,3-dicarbonyl compounds is described. By taking advantage of the orthogonal modes of reactivity of the alcoholic substrate through slight modification of the reaction conditions, a divergence in product selectivity was observed. At room temperature, p-TsOH·H(2)O-mediated tandem alkylation/cycloisomerization of the propargylic 1,4-diol with the ß-dicarbonyl compound was found to selectively occur to provide the tetrasubstituted furan product. On the other hand, increasing the reaction temperature to 80 °C was discovered to result in preferential p-TsOH·H(2)O-catalyzed dehydrative rearrangement of the unsaturated alcohol and formation of the 2,3,5-trisubstituted furan adduct.
Assuntos
Álcoois/química , Furanos/síntese química , Cetonas/química , Catálise , Ciclização , Temperatura Alta , Estrutura Molecular , EstereoisomerismoRESUMO
Degradable poly(acrylic acid) has been prepared via free radical ring-opening copolymerization of tert-butyl acrylate and 2-methylene-1,3-dioxepane followed by tert-butyl deprotection, under acidic conditions. The resulting degradable poly(acrylic acid) analogue possesses ester groups within the backbone, which facilitate environmental hydrolysis into short chain oligomers, which subsequently undergo biodegradation. The degradable poly(acrylic acid) reported displays a significant degree of biodegradability (27.50% in 28 days) under environmental conditions, when compared to a conventional all carbon backbone non-degradable version, which shows no biodegradability.
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Resinas Acrílicas , Polímeros , Radicais Livres , Polimerização , Polímeros/metabolismoRESUMO
Environmental accumulation of non-degradable polystyrene (PS) microparticles from plastic waste poses potential adverse impact on marine life and human health. Herein, microparticles from a degradable PS analogue (dePS) are formulated and their immuno-modulatory characteristics are comprehensively evaluated. Both dePS copolymer and microparticles are chemically degradable under accelerated hydrolytic condition. In vitro studies show that dePS microparticles are non-toxic to three immortalized cell lines. While dePS microparticles do not induce macrophage polarization in vitro, dePS microparticles induce in vivo upregulation of both pro-inflammatory and anti-inflammatory biomarkers in immuno-competent mice, suggesting the coexistence of mixed phenotypes of macrophages in the host immune response to these microparticles. Interestingly, on day 7 following subcutaneous in mice, dePS microparticles induce a lower level of several immuno-modulatory biomarkers (matrix metallo-proteinases (MMPs), tumor necrosis factor (TNF-α), and arginase activity) compared to that of reference poly(lactic-co-glycolic acid) microparticles. Remarkably, compared to PS microparticles, dePS microparticles exhibit similar in vitro and in vivo bioactivity while acquiring additional chemical degradability. Overall, this study gains new insights into the host immune response to dePS microparticles and suggests that this dePS analogue might be explored as an alternative material choice for biomedical and consumer care applications.
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Macrófagos , Poliestirenos , Animais , Humanos , Imunidade , Macrófagos/metabolismo , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Poliestirenos/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A one-pot, two-step method to prepare 3-halohydrofurans efficiently by TfOH-catalyzed hydroxylation/halocyclization of cyclopropyl methanols with H(2)O and N-halosuccinimide (NXS, X=1, Br, Cl) or Selectfluor is described. The reactions proceed rapidly under mild and operationally straightforward conditions with a catalyst loading as low as 1 mol % and afford the 3-halohydrofuran products in moderate to excellent yields and, in most cases, with preferential cis diastereoselectivity. The method was shown to be applicable to cyclopropyl methanols containing electron-withdrawing, electron-donating, and sterically demanding functional groups and electrophilic halide sources. The mechanism is suggested to involve protonation of the alcohol substrate by the Brønsted acid catalyst and ionization of the starting material. This results in ring-opening of the cyclopropane moiety and in situ formation of a homoallylic alcohol intermediate, which undergoes subsequent intramolecular halocyclization on treating with the electrophilic halide source to give the halohydrofuran. The observed cis product selectivity is thought to be determined by the reaction proceeding through an in situ generated unsaturated alcohol intermediate that contains a (Z)-alkene moiety under the kinetically controlled conditions.
Assuntos
Produtos Biológicos/síntese química , Ciclopropanos/química , Furanos/síntese química , Halogênios/química , Metanol/análogos & derivados , Álcoois/química , Alcenos/química , Catálise , Elétrons , Hidroxilação , Metanol/química , Prótons , Estereoisomerismo , Succinimidas/química , ÁguaRESUMO
A method to prepare 1H-indole-2-carbaldehydes and (E)-2-(iodomethylene)indolin-3-ols by gold(I)-catalyzed cycloisomerization of 1-(2-(tosylamino)phenyl)prop-2-yn-1-ols with N-iodosuccinimide (NIS) is reported. The reactions were shown to be operationally simplistic and proceed efficiently for a wide variety of substrates, affording the corresponding products in good to excellent yields (70-99%). The mechanism is suggested to involve activation of the alkyne moiety of the substrate by the gold(I) catalyst. This triggers intramolecular addition of the tethered aniline moiety to give a vinyl gold intermediate, which undergoes iododeauration with NIS to give the (E)-2-(iodomethylene)indolin-3-ol adduct. Subsequent 1,3-allylic alcohol isomerization (1,3-AAI) followed by formylation of this vinyl iodide intermediate then gives the 1H-indole-2-carbaldehyde.
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Aldeídos/química , Ouro/química , Indóis/química , Compostos de Tosil/química , Catálise , Ciclização , Isomerismo , TemperaturaRESUMO
Radical ring-opening copolymerization (rROP) between 2-methylene-1,3-dioxepane (MDO) and methacrylic acid N-hydroxysuccinimide ester (NHSMA) furnishes a reactive polyester-based linear copolymer precursor. Subsequent cross-linker mediated chain collapse affords degradable single-chain nanoparticles (DSCNPs). This methodology is an experimentally robust and straightforward route to main-chain degradable polymeric nanoparticles in the sub-30 nm size range.
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The retinoic acid receptor-related orphan nuclear receptor γt (RORγt), a promising therapeutic target, is a major transcription factor of genes related to psoriasis pathogenesis such as interleukin (IL)-17A, IL-22, and IL-23R. On the basis of the X-ray cocrystal structure of RORγt with 1a, an analogue of the known piperazine RORγt inverse agonist 1, triazolopyridine derivatives of 1 were designed and synthesized, and analogue 3a was found to be a potent RORγt inverse agonist. Structure-activity relationship studies on 3a, focusing on the treatment of its metabolically unstable cyclopentyl ring and the central piperazine core, led to a novel analogue, namely, 6-methyl-N-(7-methyl-8-(((2S,4S)-2-methyl-1-(4,4,4-trifluoro-3-(trifluoromethyl)butanoyl)piperidin-4-yl)oxy)[1,2,4]triazolo[1,5-a]pyridin-6-yl)nicotinamide (5a), which exhibited strong RORγt inhibitory activity and a favorable pharmacokinetic profile. Moreover, the in vitro and in vivo evaluation of 5a in a human whole-blood assay and a mouse IL-18/23-induced cytokine expression model revealed its robust and dose-dependent inhibitory effect on IL-17A production.
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A highly efficient triflic acid catalyzed ring opening of a wide variety of 1-cyclopropyl-2-propyn-1-ols with alcohols as an efficient synthetic route to conjugated enynes is reported herein. The reaction was operationally straightforward and accomplished in good to excellent yields (44-100%), high product turnovers (up to 10,000), and with complete regioselectivity under mild conditions with a low catalyst loading of 0.01 mol %. The mechanism is suggested to involve protonation of the alcohol substrate by the TfOH catalyst, followed by ionization of the starting material. This causes ring opening of the cyclopropane moiety and trapping by the alcohol nucleophile to give the conjugated enyne product. The synthetic utility of the present method was also exemplified by the efficient large-scale conversion in gram quantities of one example studied in this work to the corresponding conjugated enyne product in excellent yield and turnover number.
Assuntos
Álcoois/química , Alcenos/química , Alcenos/síntese química , Alcinos/química , Alcinos/síntese química , Ciclopropanos/química , Catálise , Estereoisomerismo , Especificidade por SubstratoRESUMO
An efficient silver triflate-catalyzed tandem hydroamination/hydroarylation cascade generating 1'-allylspiro[indene-1,2'-indolin]-3'-ones from 1-(2-allylamino)phenyl-4-hydroxy-but-2-yn-1-ones is described. The reaction conditions are mild and general in scope and proceed to highly functionalized spiro-targets in high yield. This novel class of molecule possesses both the privileged indene and indolin-3-one scaffold, which may lead to possible pharmacological applications.