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1.
Physiol Plant ; 176(1): e14206, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356346

RESUMO

Aroma or fragrance in rice is a genetically controlled trait; Its high appreciation by consumers increases the rice market price. Previous studies have revealed that the rice aroma is controlled by a specific gene called BETAINE ALDEHYDE DEHYDROGENASE (OsBADH2), and mutation of this gene leads to the accumulation of an aromatic substance 2-acetyl-1-pyrroline (2-AP). The use of genetic engineering to produce aroma in commercial and cultivated hybrids is a contemporary need for molecular breeding. The current study reports the generation of aroma in the three-line hybrid restorer line Shu-Hui-313 (SH313). We created knock-out (KO) lines of OsBADH2 through the CRISPR/Cas9. The analysis of KO lines revealed a significantly increased content of 2AP in the grains compared with the control. However, other phenotypic traits (plant height, seed setting rate, and 1000-grain weight) were significantly decreased. These KO lines were crossed with a non-aromatic three-line hybrid rice male sterile line (Rong-7-A) to produce Rong-7-You-626 (R7Y626), R7Y627 and R7Y628. The measurement of 2-AP revealed significantly increased contents in these cross combinations. We compared the content of 2-AP in tissues at the booting stage. Data revealed that young spike stalk base contained the highest content of 2-AP and can be used for identification (by simple chewing) of aromatic lines under field conditions. In conclusion, our dataset offers a genetic source and illustrates the generation of aroma in non-aromatic hybrids, and outlines a straightforward identification under field conditions.


Assuntos
Betaína/análogos & derivados , Oryza , Oryza/genética , Sistemas CRISPR-Cas/genética , Odorantes , Genes de Plantas
2.
Int J Biol Macromol ; 260(Pt 1): 129465, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242394

RESUMO

Chitosan exhibits a wide source, non-toxic and biodegradable, and is the optimal functional raw material for preparing food packaging materials. However, the pure chitosan film has some disadvantages such as limited antibacterial activity and weak mechanical properties. In this study, sulfobetaines modified chitosan (CS-SBMA) was synthesized by grafting copolymerized betaine methacrylate sulfonate onto the chain of chitosan to improve the anti-bacterial adhesion and antibacterial properties of chitosan, aiming to develop antibacterial and anti-bacterial adhesion films based on CS-SBMA and polyvinyl alcohol (PVA) by the casting method. The structure of CS-SBMA was characterized by 1H NMR and FTIR. The appropriate proportion of CS-SBMA/PVA was determined to be 1/1 and 1/2, by characterizing the composite films with FTIR, XRD, SEM, mechanical, optical, and water resistance behaviors. In addition, CS-SBMA/PVA films showed excellent antibacterial, anti-bacterial adhesion and biofilm control function. The colonies number of E. coli and S. aureus on the surface of CS-SBMA/PVA 1/1 film decreased 94.15 % and 94.27 %, respectively, and 92.93 % of S. aureus and 94.87 % of E. coli colonies were inactivated within 60 min contact. These results indicate that CS-SBMA/PVA film exhibits potential antibacterial and anti-bacterial adhesion properties, which is suitable for food packaging materials.


Assuntos
Betaína/análogos & derivados , Quitosana , Quitosana/química , Álcool de Polivinil/química , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/química , Embalagem de Alimentos/métodos
3.
Environ Sci Pollut Res Int ; 31(2): 2314-2326, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38057675

RESUMO

Water treatment for most public pools involves disinfection with active chlorine leading to the formation of disinfection by-products (DBPs). Among them, nitrogen-containing compounds (N-DBPs) having increased toxicity and adverse effects on human health are of the greatest concern. Being the major component of various body washers for swimmers, cocamidopropyl betaine (CAPB) represents a potential and still underestimated anthropogenic precursor of N-DBPs in pool water. The purpose of this study was to investigate CAPB transformation pathways and mechanisms under the aqueous chlorination conditions. High-performance liquid and two-dimensional gas chromatography hyphenated with high-resolution mass spectrometry were used for the search and tentative identification of the primary and final CAPB transformation products. A wide range of DBPs containing up to five chlorine atoms including these in combination with hydroxyl and additional carbonyl groups has been revealed in model chlorination experiments for the first time. The proposed mechanism of their formation involves nucleophilic substitution of the secondary amide hydrogen atom at the first stage with subsequent free radical and electrophilic addition reactions resulting in non-selective introduction of halogen atoms and hydroxyl groups in the alkyl chain. The deep transformation products include short-chain chlorinated hydrocarbons and their oxidation products as well as dimethylcarbamoyl chloride possessing high toxicity and carcinogenic properties. Targeted analysis of real swimming pool water samples confirmed the results of model experiments enabling semi-quantitative determination of CAPB (0.8 µg L-1) and 18 primary DBPs, including 10 chlorine-containing compounds with the total concentration of 0.1 µg L-1. Among them, monochloro (50%) and hydroxydichloro (25%) derivatives predominate. The toxicity and health of the main DBPs has been estimated using QSAR/QSTR approach. Thus, the possibility of formation of new classes of potentially toxic chlorine-containing DBPs associated with the widespread use of detergents and cosmetics was shown.


Assuntos
Betaína/análogos & derivados , Compostos Clorados , Desinfetantes , Hidrocarbonetos Clorados , Piscinas , Poluentes Químicos da Água , Purificação da Água , Humanos , Desinfecção , Desinfetantes/química , Cloro/química , Nitrogênio/análise , Hidrocarbonetos Clorados/análise , Compostos Clorados/análise , Halogenação , Compostos de Nitrogênio , Cloretos , Poluentes Químicos da Água/análise
4.
ACS Appl Bio Mater ; 7(1): 144-153, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38150303

RESUMO

Cell migration is an essential dynamic process for most living cells, mainly driven by the reorganization of actin cytoskeleton. To control actin dynamics, a molecular architecture that can serve as a nucleator has been designed by polymerizing sulfobetaine methacrylate. The synthesized zwitterionic polymer, poly(sulfobetaine methacrylate) (PZI), effectively nucleates the polymerization process of G-actin and substantially accelerates the rate of polymerization. Isothermal titration calorimetry (ITC) and bioinformatics analysis indicated binding between PZI and monomeric G-actin. Thus, in vitro actin dynamics was studied by dynamic light scattering (DLS), pyrene-actin polymerization assay, and total internal reflection fluorescence microscopy (TIRFM). Furthermore, a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophore-containing monomeric unit was incorporated into the sulfobetaine zwitterionic architecture to visualize the effect of polymer in the cellular environment. The BODIPY-containing zwitterionic sulfobetaine polymer (PZI-F) successfully penetrated the cell and remained in the lysosome with minimal cytotoxicity. Confocal microscopy revealed the influence of this polymer on the cellular actin cytoskeleton dynamics. The PZI-F polymer was successfully able to inhibit the collective migration of the human cervical cancer cell line (HeLa cell) and breast cancer cell line (MDA-MB-231 cell), as confirmed by a wound healing assay. Therefore, polyzwitterionic sulfobetaine could be explored as an inhibitor of cancer cell migration.


Assuntos
Actinas , Betaína/análogos & derivados , Compostos de Boro , Neoplasias , Humanos , Actinas/metabolismo , Células HeLa , Citoesqueleto de Actina/metabolismo , Movimento Celular
5.
J Mater Chem B ; 10(39): 7979-7994, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-36093922

RESUMO

Antibacterial wound dressing is essential for inflammation control and accelerated wound healing. This study investigates polyzwitterion-functionalized silver nanoparticles (AgNPs) with enhanced antibacterial performance in an injectable wound dressing hydrogel. A mussel-inspired poly(sulfobetaine methacrylate-co-dopamine methacrylamide) (PSBDA) copolymer consisting of sulfobetaine and catechol moieties is developed and used in the stabilizing strategy for a facile one-step synthesis of AgNPs. The catechol moieties in PSBDA reduce AgNO3 in an alkaline solution and anchor PSBDA onto the surface of AgNPs. The zwitterionic AgNPs exhibit a uniform size profile and significantly improved stability, which are critical for maintaining antibacterial efficiency in a physiological environment. An injectable wound dressing hydrogel is developed by incorporating zwitterionic AgNPs into the mixed precursors of gelatin methacryloyl (GelMA) and poly(vinyl alcohol) (PVA). The hydrogel precursors exhibit good injectability and rapidly respond to UV-induced in situ gelation. The zwitterionic AgNP-incorporating hydrogel demonstrates significantly improved antibacterial efficiency compared to the non-zwitterionic counterpart both in vitro and in vivo. The zwitterionic modification also provides enhanced hemocompatibility and biocompatibility. The as-developed hydrogel dressing facilitates the resolution of inflammation and results in a rapid re-epithelization for the accelerated wound healing process in a rat full-thickness wound model.


Assuntos
Nanopartículas Metálicas , Prata , Animais , Antibacterianos/farmacologia , Betaína/análogos & derivados , Catecóis , Dopamina/farmacologia , Gelatina , Hidrogéis/farmacologia , Inflamação , Metacrilatos/farmacologia , Álcool de Polivinil/farmacologia , Ratos , Prata/farmacologia , Cicatrização
6.
Phys Chem Chem Phys ; 24(37): 22679-22690, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36106535

RESUMO

Mixtures of sulfobetaine based lipids with phosphocholine phospholipids are of interest in order to study the interactions between zwitterionic surfactants and the phospholipids present in cell membranes. In this study we have investigated the structure of mixed monolayers of sulfobetaines and phosphocholine phospholipids. The sulfobetaine used has a single 18-carbon tail, and is referred to as SB3-18, and the phospholipid used is DMPC. Surface pressure-area isotherms of the samples were used to determine whether any phase transitions were present during the compression of the monolayers. Neutron and X-ray reflectometry were then used to investigate the structure of these monolayers perpendicular to the interface. We found that the average headgroup and tail layer thickness was reasonably consistent across all mixtures, with a variation of less than 3 Å reported in the total thickness of the monolayers at each surface pressure. However, by selective deuteration of the two components of the monolayers, it was found that the two components have different tail layer thicknesses. For the mixture with equal compositions of DMPC and SB3-18 or with a higher composition of DMPC the tail tilts were found to be constant, resulting in a greater tail layer thickness for SB3-18 due to its longer tail. For the mixture higher in SB3-18 this was not the case, the tail tilt angle for the two components was found to be different and DMPC was found to have a greater tail layer thickness than SB3-18 as a result.


Assuntos
Fosfolipídeos , Água , Betaína/análogos & derivados , Carbono , Dimiristoilfosfatidilcolina/química , Fosfolipídeos/química , Fosforilcolina , Propriedades de Superfície , Tensoativos , Água/química
7.
Biomacromolecules ; 23(10): 4349-4356, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36049071

RESUMO

Inspired by the melanogenesis occurring in nature, we report tyrosinase-mediated antifouling surface coating by synthesizing a tyrosine-conjugated sulfobetaine derivative (Tyr-SB). Synthetic Tyr-SB contains zwitterionic sulfobetaine and tyrosine, whose phenolic amine group acts as a dormant coating precursor. In contrast to catecholamine derivatives, tyrosine derivatives are stable against auto-oxidation and are enzymatically oxidized only in the presence of tyrosinase to initiate melanin-like oxidation. When the surface of interest was applied during the course of Tyr-SB oxidation, a superhydrophilic poly(Tyr-SB) film was coated on the surfaces, thereby showing antifouling performance against proteins or adherent cells. Because the oxidation of Tyr-SB occurred under mild aqueous conditions (pH 6-7) without the use of any chemical oxidants, such as sodium periodate or ammonium persulfate, we anticipate that the coating method described herein will serve as a biocompatible tool in the field of biosensors, cell surface engineering, and medical devices, whose interfaces differ in chemistry.


Assuntos
Incrustação Biológica , Monofenol Mono-Oxigenase , Betaína/análogos & derivados , Incrustação Biológica/prevenção & controle , Catecolaminas , Melaninas , Oxidantes , Tirosina
8.
J Alzheimers Dis ; 89(4): 1439-1452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36057823

RESUMO

BACKGROUND: Animal studies suggest that gut microbiome metabolites such as trimethylamine N-oxide (TMAO) may influence cognitive function and dementia risk. However potential health effects of TMAO and related metabolites remain unclear. OBJECTIVE: We examined prospective associations of TMAO, γ-butyrobetaine, crotonobetaine, carnitine, choline, and betaine with risk of cognitive impairment and dementia among older adults aged 65 years and older in the Cardiovascular Health Study (CHS). METHODS: TMAO and metabolites were measured in stored plasma specimens collected at baseline. Incident cognitive impairment was assessed using the 100-point Modified Mini-Mental State Examination administered serially up to 7 times. Clinical dementia was identified using neuropsychological tests adjudicated by CHS Cognition Study investigators, and by ICD-9 codes from linked Medicare data. Associations of each metabolite with cognitive outcomes were assessed using Cox proportional hazards models. RESULTS: Over a median of 13 years of follow-up, 529 cases of cognitive impairment, and 522 of dementia were identified. After multivariable adjustment for relevant risk factors, no associations were seen with TMAO, carnitine, choline, or betaine. In contrast, higher crotonobetaine was associated with 20-32% higher risk of cognitive impairment and dementia per interquintile range (IQR), while γ-butyrobetaine was associated with ∼25% lower risk of the same cognitive outcomes per IQR.∥Conclusion:These findings suggest that γ-butyrobetaine, crotonobetaine, two gut microbe and host metabolites, are associated with risk of cognitive impairment and dementia. Our results indicate a need for mechanistic studies evaluating potential effects of these metabolites, and their interconversion on brain health, especially later in life.


Assuntos
Disfunção Cognitiva , Demência , Animais , Betaína/análogos & derivados , Betaína/metabolismo , Carnitina/metabolismo , Colina , Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Medicare , Metilaminas/metabolismo , Estados Unidos/epidemiologia
9.
J Chromatogr A ; 1681: 463442, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36058078

RESUMO

We have coated a typical C18 column with the pH cationic charge controllable zwitterionic synthetic surfactant, cocamidopropyl betaine (CAPB), in order to generate a mixed mode reversed phase weak ion exchange column. As determined by the Thomas model, the column has an adsorbed surfactant capacity of 0.557 mmoles. The addition of 8.8 × 10-4 M CAPB to the totally aqueous mobile phase ensured stability of the surfactant on the column and permitted separation of the four component sulfonamide mixture with micellar liquid chromatography (MLC) in under 11 min. Comparatively, with a dilute H2SO4 mobile phase with no CAPB, the separation time for the sulfonamide mixture reached an excessive run time of an hour on the bare C18 chains. With CAPB in the mobile phase (no organic solvent present), a seven component sulfonamide mixture could be separated in less than 45 min. A five component short chain carboxylic acid mixture, separated in 20 min, was used to examine the ion exchange character of the column in pH environments of 2.3 and 4.6. Three phase MLC equilibrium analysis was also done in these pH environments with the sulfa drug and carboxylic acid mixtures to determine partition coefficients. Finally, a quite high molecular weight (70,000) anionic polystyrene sulfonate polymer was characterized by MLC with only CAPB and variable pH mobile phases; the optimal pH was determined to be 5.6. A totally aqueous mobile phase without CAPB was not suitable for profiling this polymer.


Assuntos
Micelas , Tensoativos , Betaína/análogos & derivados , Ácidos Carboxílicos , Cromatografia Líquida , Polímeros , Solventes/química , Sulfonamidas , Tensoativos/química , Água/química
10.
Soft Matter ; 18(35): 6618-6628, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36000279

RESUMO

The ubiquitous nature of microorganisms, especially of biofilm-forming bacteria, makes biofouling a prevalent challenge in many settings, including medical and industrial environments immersed in liquid and subjected to shear forces. Recent studies have shown that zwitterionic groups are effective in suppressing bacteria and protein adhesion as well as biofilm growth. However, the effect of zwitterionic groups on the removal of surface-bound bacteria has not been extensively studied. Here we present a microfluidic approach to evaluate the effectiveness in facilitating bacteria detachment by shear of an antifouling surface treatment using (3-(dimethyl;(3-trimethoxysilyl)propyl)ammonia propane-1-sulfonate), a sulfobetaine silane (SBS). Control studies show that SBS-functionalized surfaces greatly increase protein (bovine serum albumin) removal upon rinsing. On the same surfaces, enhanced bacteria (Pseudomonas aeruginosa) removal is observed under shear. To quantify this enhancement a microfluidic shear device is employed to investigate how SBS-functionalized surfaces promote bacteria detachment under shear. By using a microfluidic channel with five shear zones, we compare the removal of bacteria from zwitterionic and glass surfaces under different shear rates. At times of 15 min, 30 min, and 60 min, bacteria adhesion on SBS-functionalized surfaces is reduced relative to the control surface (glass) under quiescent conditions. However, surface-associated bacteria on the SBS-functionalized glass and control show similar percentages of live cells, suggesting minimal intrinsic biocidal effect from the SBS-functionalized surface. Notably, when exposed to shear rates ranging from 104 to 105 s-1, significantly fewer bacteria remain on the SBS-functionalized surfaces. These results demonstrate the potential of zwitterionic sulfobetaine as effective antifouling coatings that facilitate the removal of bacteria under shear.


Assuntos
Aderência Bacteriana , Incrustação Biológica , Bactérias , Betaína/análogos & derivados , Betaína/química , Betaína/farmacologia , Incrustação Biológica/prevenção & controle , Propriedades de Superfície
11.
Acta Biomater ; 151: 290-303, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35995406

RESUMO

Zwitterionic polymers have shown promising results in non-fouling and preventing thrombosis. However, the lack of controlled surface coverage hinders their application for biomedical devices. Inspired by the natural biological surfaces, a facile zwitterionic microgel-based coating strategy is developed by the co-deposition of poly (sulfobetaine methacrylate-co-2-aminoethyl methacrylate) microgel (SAM), polydopamine (PDA), and sulfobetaine-modified polyethyleneimine (PES). The SAMs were used to construct controllable morphology by using the PDA combined with PES (PDAS) as the intermediate layer, which can be easily modulated via adjusting the crosslinking degree and contents of SAMs. The obtained SAM/PDAS coatings exhibit high anti-protein adhesive properties and can effectively inhibit the adhesion of cells, bacteria, and platelet through the synergy of high deposition density and controllable morphology. In addition, the stability of SAM/PDAS coating is improved owing to the anchoring effects of PDAS to substrate and SAMs. Importantly, the ex vivo blood circulation test in rabbits suggests that the SAM/PDAS coating can effectively decrease thrombosis without anticoagulants. This study provides a versatile coating method to address the integration of zwitterionic microgel-based coatings with high deposition density and controllable morphology onto various substrates for wide biomedical device applications. STATEMENT OF SIGNIFICANCE: Thrombosis is a major cause of medical device implantation failure, which results in significant morbidity and mortality. In this study, inspired by natural biological surfaces (fish skin and vascular endothelial layer) and the anchoring ability of mussels, we report a convenient and efficient method to firmly anchor zwitterionic microgels using an oxidative co-deposition strategy. The prepared coating has excellent antifouling and antithrombotic properties through the synergistic effect of physical morphology and chemical composition. This biomimetic surface engineering strategy is expected to provide new insights into the clinical problems of blood-contacting devices related to thrombosis.


Assuntos
Microgéis , Animais , Anticoagulantes , Betaína/análogos & derivados , Fibrinolíticos , Metacrilatos , Polietilenoimina/farmacologia , Polímeros/química , Coelhos , Propriedades de Superfície
12.
Int J Biol Macromol ; 218: 992-1001, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35878673

RESUMO

Chitosan (CS) derivatives with improved water solubility, antibacterial activity and adequate biocompatibility are attracting increasingly interest in medical application. Herein, we have successfully synthesized isocyanate terminated quaternary ammonium salt (IQAS) and sulfopropylbetaine (ISB) to be readily covalently bounded to CS skeleton by selective reaction with amino and hydroxyl groups. And their molecular structures and crystallinity were confirmed by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, and X-ray diffraction. The effect of the substitution degree, carbon chain length, content ratio of IQAS/ISB on their water solubility, antibacterial activity and cytotoxicity were systematically investigated, which shows that those properties of the CS derivatives can be tailored by adjusting the grafted antibacterial agents and their additive amount. The structure-property relationship of these CS derivatives may provide a solid guidance on the development of CS derivatives for more efficient practical applications.


Assuntos
Quitosana , Antibacterianos/química , Antibacterianos/farmacologia , Betaína/análogos & derivados , Quitosana/química , Escherichia coli , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus , Água/farmacologia
13.
Contact Dermatitis ; 87(5): 439-446, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35736503

RESUMO

BACKGROUND: The European baseline series (EBS) of contact allergens is subject to change. An allergen is considered for inclusion when routine patch testing of patients with suspected contact dermatitis results in ≥0.5% prevalence rate. OBJECTIVES: We aimed to determine the frequency of sensitizations to 30 EBS allergens and 10 locally added allergens. Additionally, we assessed the strength and evolution of reactions to all tested allergens and co-reactivity of additional allergens. METHODS: Patch testing with our baseline series of 40 allergens was done in 748 consecutive adults. Tests were applied to the upper back and removed by patients after 48 h. Readings were done on Day 3 (D3) and D6 or D7 (D6/7). Positive reactions fulfilled the criteria of at least one plus (+) reaction. A retrospective analysis was done. RESULTS: Eight allergens not listed in the EBS had ≥0.5% prevalence rate (i.e., cocamidopropyl betaine, thiomersal, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, propylene glycol, Compositae mix II and dexamethasone-21-phosphate), and 16.6% of positive reactions would have been missed without D6/7 readings. CONCLUSION: We propose further studies to evaluate whether cocamidopropyl betaine, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea and Compositae mix II need to be added to the EBS.


Assuntos
Alérgenos , Dermatite Alérgica de Contato , Adulto , Alérgenos/efeitos adversos , Betaína/análogos & derivados , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Dexametasona , Humanos , Nitroparafinas , Testes do Emplastro/métodos , Fosfatos , Propano/análogos & derivados , Propilenoglicóis , Estudos Retrospectivos , Timerosal , Ureia/análogos & derivados
14.
ACS Biomater Sci Eng ; 8(6): 2463-2476, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35536230

RESUMO

ß-Cyclodextrins (ß-CDs) and ß-CD-containing polymers have attracted considerable attention as potential candidates for the treatment of cholesterol-related metabolic and intractable diseases. We have advocated the use of ß-CD-threaded acid-degradable polyrotaxanes (PRXs) as intracellular delivery carriers for ß-CDs. As unmodified PRXs are insoluble in aqueous solutions, chemical modification of PRXs is an essential process to improve their solubility and impart novel functionalities. In this study, we investigated the effect of the modification of zwitterionic sulfobetaines on PRXs due to their excellent solubility, biocompatibility, and bioinert properties. Sulfobetaine-modified PRXs were synthesized by converting the tertiary amino groups of precursor 2-(N,N-dimethylamino)ethyl carbamate-modified PRXs (DMAE-PRXs) using 1,3-propanesultone. The resulting sulfobetaine-modified PRXs showed high solubility in aqueous solutions and no cytotoxicity, while their intracellular uptake levels were low. To further improve this system, we designed PRXs cografted with zwitterionic sulfobetaine and cationic DMAE groups via partial betainization of the DMAE groups. Consequently, the interaction with proteins, intracellular uptake levels, and liver accumulation of partly betainized PRXs were found to be higher than those of completely betainized PRXs. Additionally, partly betainized PRXs showed no toxicity in vitro or in vivo despite the presence of residual cationic DMAE groups. Furthermore, partly betainized PRXs ameliorated the abnormal free cholesterol accumulation in Niemann-Pick type C disease patient-derived cells at lower concentrations than ß-CD derivatives and previously designed PRXs. Overall, the cografting of sulfobetaines and amines on PRXs is a promising chemical modification for therapeutic applications due to the high cholesterol-reducing ability and biocompatibility of such modified PRXs. In addition, modification with both zwitterionic and cationic groups can be used for the design of various polymeric materials exhibiting both bioinert and bioactive characteristics.


Assuntos
Rotaxanos , beta-Ciclodextrinas , Aminas , Betaína/análogos & derivados , Cátions , Colesterol/metabolismo , Humanos , Rotaxanos/química , Rotaxanos/metabolismo , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia
15.
Org Biomol Chem ; 20(22): 4640-4649, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35612088

RESUMO

This article describes the synthetic efforts towards the solubilization of organic fluorescent emitters based on a 2-(2'-hydroxybenzofuranyl)benzazole (HBBX) scaffold in aqueous media under physiological conditions (PBS, pH 7.4). These dyes are well-known to display the excited-state intramolecular proton transfer (ESIPT) process which leads to a Stokes-shifted fluorescence with enhanced photostability and strong environment dependent features. Organic dyes are hydrophobic by nature and their vectorization into aqueous media usually necessitates amphiphilic polymers. In this study, we show that the incorporation of one or two sulfobetaine fragments, a highly biocompatible zwitterionic unit leads to the vectorization in buffer solution at pH 7.4 while keeping a reasonable ESIPT fluorescence emission. The photophysical properties of all dyes were studied in multiple solvents and showed that, depending on structure and environment, different excited-state species are observed: normal or tautomeric species, as well as a competitive anionic fluorescent derivative. This study shows that it is not only possible to solubilize fluorescent ESIPT dyes in water using sulfobetaine(s) but also that the optical properties can be finely tuned depending on small structural inputs.


Assuntos
Corantes Fluorescentes , Prótons , Betaína/análogos & derivados , Corantes Fluorescentes/química , Espectrometria de Fluorescência , Água
16.
Molecules ; 27(4)2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35209152

RESUMO

Regulating the structure of macrocyclic host molecules and supramolecular assemblies is crucial because the structure-activity relationship often plays a role in governing the properties of these systems. Herein, we propose and develop an approach to the synthesis of the family of sulfobetaine functionalized thiacalix[4]arenes with regulation of the self-assembly and cytotoxic effect against cancer cell lines. The dynamic light scattering method showed that the synthesized macrocycles in cone, partial cone and 1,3-alternate conformations form submicron-sized particles with Ag+ in water, but the particle size and polydispersity of the systems studied depend on the macrocycle conformation. Based on the results obtained by 1H and 1H-1H NOESY NMR spectroscopy and transmission electron microscopy for the macrocycles and their aggregates with Ag+, a coordination scheme for the Ag+ and different conformations of p-tert-butylthiacalix[4]arene functionalized with sulfobetaine fragments was proposed. The type of coordination determines the different shapes of the associates. Cytotoxic properties are shown to be controlled by the shape of associates, with the highest activity demonstrated by thiacalix[4]arenes in partial cone conformation. This complex partial cone/Ag+ is two times higher than the reference drug imatinib mesylate. High selectivity against cervical carcinoma cell line indicates the prospect of their using as components of new anticancer system.


Assuntos
Betaína/análogos & derivados , Fenóis/química , Fenóis/farmacologia , Sulfetos/química , Sulfetos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Betaína/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Humanos , Espectroscopia de Ressonância Magnética , Metais , Estrutura Molecular , Solubilidade , Relação Estrutura-Atividade
17.
J Mater Chem B ; 10(14): 2649-2660, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35024722

RESUMO

Multicellular tumor spheroids (MCTSs) are attractive for drug screening before animal tests because they emulate an in vivo microenvironment. The permeability of the MCTSs and tumor tissues towards the candidate drugs is not sufficient even though the drugs can penetrate monolayer cultured cells; therefore, nanocarriers are required to enhance permeability and deliver drugs. In this study, we prepared zwitterionic polymers of sulfobetaine methacrylates and (meth)acrylamides with or without hydroxy groups between the zwitterions to serve as highly permeable nanocarriers. In the sulfobetaine polymers, poly(2-hydroxy-3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate), P(OH-MAAmSB), the hydroxy group containing methacrylamide polymer exhibited little cytotoxicity and membrane translocation ability against monolayer cultured cells. Moreover, the excellent permeability of the hepatocyte MCTS enabled P(OH-MAAmSB) to permeate it and reach the center region (∼325 µm in diameter) at approximately 150 s, although poly(trimethyl-2-methacroyloxyethylammonium), a cationic polymer, penetrated just 1 to 2 layers from the periphery. The superior permeability of P(OH-MAAmSB) might be due to its good solubility and side chain conformation. P(OH-MAAmSB) is a promising nanocarrier with membrane translocation and permeability.


Assuntos
Neoplasias , Polímeros , Animais , Betaína/análogos & derivados , Permeabilidade , Polímeros/química , Esferoides Celulares , Microambiente Tumoral
18.
J Biol Chem ; 298(2): 101511, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34929162

RESUMO

Anaerobic microbes in the human gut produce beneficial and harmful compounds, as well as neutral compounds like trimethylamine, which undergoes microbial metabolism or host-catalyzed transformation into proatherogenic trimethylamine-N-oxide. Ellenbogen et al. identified a microbiome-associated demethylase that short-circuits the production of trimethylamine-N-oxide from the metabolite γ-butyrobetaine and instead produces methyltetrahydrofolate, a key intermediate in the microbial production of beneficial small-chain fatty acids. This article highlights an example of how the microbiome is integrally involved in producing metabolites that support our health and in preventing the formation of compounds that promote disease.


Assuntos
Microbioma Gastrointestinal , Microbiota , Betaína/análogos & derivados , Carnitina , Eubacterium , Humanos , Metilaminas/metabolismo , Metiltransferases/metabolismo , Óxidos , Vitamina B 12
19.
J Colloid Interface Sci ; 611: 39-45, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34929437

RESUMO

One of the most intriguing aspects of zwitterionic surfactant micelles is their propensity to exhibit selectivity in the binding of the anions of added salts. In this work we examine the thermodynamics of the interaction of the strongly bound perchlorate ion and the more weakly bound bromide ion with micelles of N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (SB3-14) in aqueous solution employing enthalpies derived from isothermal titration calorimetry combined with Gibbs free energies derived from literature data for the binding equilibria. In both cases, the binding is exothermic and enthalpy driven, but entropically unfavorable, with only modest changes in the Gibbs free energy as a function of the extent of anion binding. Likewise, perchlorate ion binding was found to have little or no effect on the aggregation numbers of SB3-14 micelles determined by time-resolved fluorescence quenching of pyrene by the N-hexadecylpyridinium cation. The results are interpreted within the context of the factors involved in the ion-pairing between the anions and the positive charge center of the zwitterion headgroup and the interplay between electrostatics, solvent reorganization and a net loss of translational degrees of freedom that accompany anion binding.


Assuntos
Micelas , Ânions , Betaína/análogos & derivados , Calorimetria , Termodinâmica
20.
J Colloid Interface Sci ; 608(Pt 2): 1857-1867, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34752975

RESUMO

This study quantified the interfacial forces associated with end-grafted, statistical (AB) co-polymers of sulfobetaine methacrylate (SBMA) and oligoethylene glycol methacrylate (OEGMA) (poly(SBMA-co-OEGMA)). Surface force apparatus measurements compared forces between mica and end-grafted copolymers containing 0, 40, or 80 mol% SBMA. Studies compared forces measured at low grafting density (weakly overlapping chains) and at high density (brushes). At high density, the range of repulsive forces did not change significantly with increasing SBMA content. By contrast, at low density, both the range and the amplitude of the repulsion increased with the percentage of SBMA in the chains. The ionic strength dependence of the film thickness and repulsive forces increased similarly with SBMA content, reflecting the increasing influence of charged monomers and their interactions with ions in solution. The forces could be described by models of simple polymers in good solvent. However, the forces and fitted model parameters change continuously with the SBMA content. The latter behavior suggests that ethyene glycol and sulfobetaine behave as non-interacting, miscible monomers that contribute independently to the interfacial forces. The results suggest that molecular scale properties of statistical poly (SBMA-co-OEGMA) films can be readily tuned by simple variation of the monomer ratios.


Assuntos
Glicóis , Polímeros , Silicatos de Alumínio , Betaína/análogos & derivados , Eletrólitos , Propriedades de Superfície
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