RESUMO
Two new strategies for the efficient synthesis of racemic 1,2,3,4-tetrahydroisoquinoline-3-phosphonic acid (TicP) (±)-2 have been developed. The first strategy involves the electron-transfer reduction of the easily obtained α,ß-dehydro phosphonophenylalanine followed by a Pictet-Spengler cyclization. The second strategy involves a radical decarboxylation-phosphorylation reaction on 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic). In both strategies, the highly electrophilic N-acyliminium ion is formed as a key intermediate, and the target compound is obtained in good yield using mild reaction conditions and readily available starting materials, complementing existing methodologies and contributing to the easy accessibility of (±)-2 for further research.
Assuntos
Ácidos Fosforosos/síntese química , Tetra-Hidroisoquinolinas/síntese química , Ciclização , Descarboxilação , Estrutura Molecular , Peptidomiméticos/síntese química , Peptidomiméticos/química , Ácidos Fosforosos/química , Fosforilação , Estereoisomerismo , Tetra-Hidroisoquinolinas/químicaRESUMO
In this study, cellulose was chemically modified through the addition of the phosphorylating agent, metaphosphoric acid in order to obtain a new material (MPCel) with higher adsorptive properties than the starting material. Both materials were characterized by infrared spectroscopy, X-ray diffraction, solid-state phosphorus-31 nuclear magnetic resonance spectroscopy and thermogravimetric analysis. Maximal adsorption capacity, at 45°C for pure cellulose, was 90.5mgg-1, at pH=10 and contact time of 40min, with experimental isotherms better adjusted to the Langmuir model. MPCel at the same temperature conditions showed contact time of 10min, pH=10, and maximal adsorption capacity of 150.0mgg-1, being better adjusted to the Temkin model. The kinetic study of both materials followed the pseudo-second-order model. Modification successfully occurred and both adsorbents were shown able to be capable of removing the brilliant green dye, but MPCel was more efficient for purpose, when compared to the pure cellulose.
Assuntos
Celulose/química , Modelos Químicos , Ácidos Fosforosos/química , Compostos de Amônio Quaternário/química , Adsorção , CinéticaRESUMO
Low molecular weight protein tyrosine phosphatases (LMW-PTP, EC 3.1.3.48) are a family of single-domain enzymes with molecular weight up to 18 kDa, expressed in different tissues and considered attractive pharmacological targets for cancer chemotherapy. Despite this, few LMW-PTP inhibitors have been described to date, and the structural information on LMW-PTP druggable binding sites is scarce. In this study, a small series of phosphonic acids were designed based on a new crystallographic structure of LMW-PTP complexed with benzylsulfonic acid, determined at 2.1Å. In silico docking was used as a tool to interpret the structural and enzyme kinetics data, as well as to design new analogs. From the synthesized series, two compounds were found to act as competitive inhibitors, with inhibition constants of 0.124 and 0.047 mM. We also report the 2.4Å structure of another complex in which LMW-PTP is bound to benzylphosphonic acid, and a structure of apo LMW-PTP determined at 2.3Å resolution. Although no appreciable conformation changes were observed, in the latter structures, amino acid residues from an expression tag were found bound to a hydrophobic region at the protein surface. This regions is neighbored by positively charged residues, adjacent to the active site pocket, suggesting that this region might be not a mere artefact of crystal contacts but an indication of a possible anchoring region for the natural substrate-which is a phosphorylated protein.
Assuntos
Ácidos Fosforosos/química , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Sítios de Ligação , Domínio Catalítico , Cristalografia por Raios X , Humanos , Cinética , Simulação de Acoplamento Molecular , Ácidos Fosforosos/metabolismo , Proteínas Tirosina Fosfatases/química , Proteínas Tirosina Fosfatases/genética , Proteínas Proto-Oncogênicas/química , Proteínas Proto-Oncogênicas/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Especificidade por Substrato , Ácidos Sulfônicos/química , Ácidos Sulfônicos/metabolismoRESUMO
Combined microscopy techniques are used to establish the usability of phosphonic acid layers as promoters of hydroxyapatite (HAp) growth. Using spread coating, octadecylphosphonic acid (OPA) self-assembled bilayers are delivered to the thin natural oxide layer of a titanium film surface with no prior treatment. These bilayers aggregate two major advantages of phosphonic moieties to titanium surfaces: nucleation of hydroxyapatite crystals from ionic solution and affinity for both titanium oxide surface and HAp crystals. The functionalized substrates and bare titanium (control) samples are immersed in an aqueous solution containing calcium and phosphorus ions. Over a 4-week immersion time, OPA-functionalized substrates present numerous large agglomerates of inorganic crystals, in contrast to control samples, with no significant amount of deposits. Initial sample characterization was performed with atomic force microscopy (AFM). Compositional and structural characterization of these agglomerates (using TEM, EDS, and electron diffraction), revealed that they are indeed HAp, the main component of the inorganic bone matrix.
Assuntos
Matriz Óssea/química , Materiais Revestidos Biocompatíveis/química , Durapatita/química , Cálcio/química , Cristalização , Durapatita/metabolismo , Microscopia de Força Atômica , Microscopia Eletrônica de Transmissão , Microscopia de Varredura por Sonda , Ácidos Fosforosos/química , Fósforo/química , Propriedades de Superfície , Titânio/químicaRESUMO
OBJECTIVES: To compare the effects of two etching procedures using meta-phosphoric (MPA) or ortho-phosphoric acid (OPA) on dentine demineralisation, resin-dentine bonds durability and interface nanoleakage/ultra-morphology. METHODS: Middle-dentine specimens were etched using 37% OPA (15s) or 40% MPA (60s) and submitted to infrared spectroscopy (FTIR) or ultra-morphology dye-assisted (calcium-staining) confocal microscopy (Ca-CLSM). A three-step etch-and-rinse adhesive was formulated, applied onto dentine and light-cured for 30s before composite build-up. After 24h, the dentine-bonded specimens were cut into 1mm(2) beams; half were immediately submitted to microtensile bond strength (µTBS) and half stored in DW for six months. The µTBS results were analysed with repeated-measures ANOVA and Tukey's test (p<0.05). Further teeth were bonded and prepared for interface nanoleakage/ultra-morphology confocal evaluation. RESULTS: FTIR and Ca-CLSM analyses showed dicalcium phosphate dihydrate (Brushite) precipitation in MPA-etched dentine and on the bottom (front of demineralisation) of the OPA-etched dentine. Statistical analysis showed similar µTBS for both etching procedures after 24h. The µTBS of specimens in OPA-group dropped significantly (p<0.05) after six month; the specimens in the MPA group showed no statistically difference (p>0.05). CLSM depicted no evident sign of nanoleakage within the resin-dentine interface of the MPA-treated specimens, while the specimens in OPA-group presented intense nanoleakage and interface degradation. CONCLUSION: The use of MPA (60s) as an alternative dentine conditioning agent in etch-and-rinse bonding procedures may be a suitable strategy to create more durable resin-dentine bonds.
Assuntos
Condicionamento Ácido do Dente/métodos , Fosfatos de Cálcio/química , Infiltração Dentária/classificação , Adesivos Dentinários/química , Dentina/ultraestrutura , Ácidos Fosfóricos/química , Ácidos Fosforosos/química , Adulto , Precipitação Química , Colagem Dentária , Análise do Estresse Dentário/instrumentação , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Humanos , Cura Luminosa de Adesivos Dentários/métodos , Teste de Materiais , Metacrilatos/química , Microscopia Confocal/métodos , Fenóis , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Estresse Mecânico , Sulfóxidos , Propriedades de Superfície , Resistência à Tração , Adulto JovemRESUMO
Melting and premelting phenomena in self-organized organic systems have been extensively explored in the literature, exploring distinct behaviors of different molecule lengths and morphologies. Nevertheless, the influence of the supramolecular assembly configuration on the occurrence of premelting remains poorly explored. Here we use phosphonic acids as model systems for self-organized molecular assemblies. These molecules exhibit long-range order on different types of substrates. The balance between chain-to-chain and head-to-head interactions leads to distinct types of stackings. Although their structural configurations are well understood, very little is known about their behavior near the melting transition. We show here that premelting occurs in lamellar structures and that its behavior depends directly on the ordered configuration assumed in the studied multilayers. Two molecules with different chain lengths were investigated: octadecyl phosphonic and octyl phosphonic acids. Although almost no dependence on the molecule length was observed, the occurrence of premelting is strongly influenced by their lamellar packing configuration. For tilted packings premelting is unfavored while in straight configurations, where alkyl chain interactions are weakened with respect to head-to-head interactions, strong premelting is observed. We find that the onset of premelting occurs at the domain boundaries with straight lamellar configurations and the domain sizes exhibit power law temperature dependences.
Assuntos
Cristalização/métodos , Modelos Químicos , Modelos Moleculares , Ácidos Fosforosos/química , Simulação por Computador , Transição de FaseRESUMO
Chitosan is a modified, natural carbohydrate polymer derived by deacetylation of chitin. Due to the presence of two functional groups can undergo many chemical modifications. In a previous work we described the synthetic strategy and characterization of a novel soluble derivative: N-propyl-N-methylene phosphonic chitosan (PNMPC). In the study of some physicochemical properties, results showed that this modified chitosan aggregates in several steps when the concentration is increased. By addition of NaOH the initially coiled molecules stretch exposing more phosphonic acid groups to neutralization and finally give a cooperative reaction with OH((). PNMPC has emulsifying properties and gives O/W emulsions with quasi-monodisperse small droplets. Emulsions with 0.18% PNMPC and 30:70 o:w ratio exhibited the best emulsifying properties within the test range. This emulsion ratio showed high stability to long time storage and several successive freeze/thaw and heating/cooling cycles.
Assuntos
Fenômenos Químicos , Quitosana/análogos & derivados , Quitosana/química , Emulsificantes/química , Ácidos Fosforosos/química , Cosméticos , Manipulação de Alimentos , Óleos de Plantas/química , Óleo de GirassolRESUMO
The emergence of a multidrug-resistant HIV-1 strain and the toxicity of anti-HIV-1 compounds approved for clinical use are the most significant problems facing antiretroviral therapies. Therefore, it is crucial to find new agents to overcome these issues. In this study, we synthesized a series of new oxoquinoline acyclonucleoside phosphonate analogues (ethyl 1-[(diisopropoxyphosphoryl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylates 3a-3k), which contained different substituents at the C6 or C7 positions of the oxoquinoline nucleus and an N1-bonded phosphonate group. We subsequently investigated these compounds' in vitro inhibitory effects against HIV-1-infected peripheral blood mononuclear cells (PBMCs). The most active compounds were the fluoro-substituted derivatives 3f and 3g, which presented excellent EC(50) values of 0.4±0.2 µM (3f) and 0.2±0.005 µM (3g) and selectivity index values (SI) of 6240 and 14675, respectively.