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1.
J Enzyme Inhib Med Chem ; 34(1): 1414-1425, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31401901

RESUMO

The emergence of drug-resistant pathogenic bacteria is occurring due to the global overuse and misuse of ß-lactam antibiotics. Infections caused by some bacteria which secrete metallo-ß-lactamases (enzymes that inactivate ß-lactam antibiotics) are increasingly prevalent and have become a major worldwide threat to human health. These bacteria are resistant to ß-lactam antibiotics and MBL-inhibitor/ß-lactam antibiotic combination therapy can be a strategy to overcome this problem. So far, no clinically available inhibitors of metallo-ß-lactamases (MBLs) have been reported. In this study, L-benzyl tyrosine thiol carboxylic acid analogues (2a-2k) were synthesized after the study of computational simulation by adding of methyl, chloro, bromo and nitro groups to the benzyl ring for investigation of SAR analysis. Although the synthesized molecules 2a-k shows the potent inhibitory effects against metallo-ß-lactamase (IMP-1) with the range of Kic values of 1.04-4.77 µM, they are not as potent as the candidate inhibitor.


Assuntos
Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/farmacologia , Compostos de Sulfidrila/química , Tirosina/química , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Ácidos Carboxílicos/química , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/enzimologia , Relação Estrutura-Atividade , Inibidores de beta-Lactamases/química
2.
Anal Chim Acta ; 1078: 200-211, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31358220

RESUMO

The effect of the ionization in the RP-HPLC retention of 66 acid-base compounds, most of them drugs of pharmaceutical interest, is studied. The retention time of the compounds can be related to the pH measured in the mobile phase (pwsH) through the sigmoidal equations derived from distribution of the neutral and ionic forms of the drug into the stationary and mobile phases. Fitting of the obtained retention vs. pH profiles provides the retention times of the ionic and neutral forms and the pKa values of the drugs in the mobile phase (pwsKa). The obtained pwsKa values are linearly correlated to the pKa values in water (pwwKa) with two different correlations, one for neutral acids and another for neutral bases that reflect the different influence of the dielectric constant of the medium in ionization of acids and bases. The retention of the neutral species is well correlated to the octanol-water partition coefficient of the drugs as measure of the lipophilicity of the drug, which affects chromatographic retention. Also, the retention time of the ionized forms is related to the retention time of the neutral forms by two different linear correlations, one for anions and the other for cations. These last correlations point out the different retention behaviour of anions and cations: anions are less retained than cations of the same lipophilicity, as measured by the octanol-water partition coefficient of the neutral form. The different retention behaviour of anionic, cationic and neutral forms is confirmed by the hold-up times obtained from different approaches: pycnometry and retention times of anionic (KBr and KI) and neutral (DMSO) markers. Hold-up times obtained by pycnometric measurements agree with those obtained by retention of neutral markers (0.83-0.85 min), whereas hold-up time for anions is mobile phase pH dependent. At acidic pH it is similar to the hold-up time for neutral markers (0.83 min), but then it decreases with the increase of mobile phase pH to 0.65 min at pH 11. The decrease can be explained by the ionization of the silanols of the column and exclusion of anions by charge repulsion. Although not directly measured, the obtained retention data and correlations indicate hold-up time for cations are similar or slightly lower than hold-up time for neutral compounds (0.77-0.83 min). The model proposed and the correlations obtained can be very useful for its implementation in retention prediction algorithms for optimization of separation purposes.


Assuntos
Aminas/química , Ácidos Carboxílicos/química , Fenóis/química , Piridinas/química , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Modelos Químicos
3.
Food Chem ; 296: 1-8, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31202292

RESUMO

Immobilized lipases are excellent biocatalysts for the enzymatic synthesis of short- and medium-chain fatty esters used as food flavor compounds. Herein a new approach for a magnetic core-shell biocatalyst by immobilization of Candida antarctica B lipase is reported, coating single-core magnetic nanoparticles with an organic shell, preferably poly(benzofurane-co-arylacetic acid), followed by the covalent attachment of the enzyme and embedment of the primary biocatalyst in a silica layer. Although covalent and sol-gel immobilization were efficient on their own, their combination can ensure additional operational stability through multi-point linkages. Moreover, silanes holding glycidoxy groups, which can also form covalent linkages, have been successfully used as precursors for the silica coating layer. The structural, magnetic and morphological characteristics were assessed by TEM, SEM-EDX, X-ray photoelectron spectroscopy and vibrating sample magnetometry. The new biocatalysts demonstrated high catalytic efficiency in the solventless synthesis of isoamyl esters of natural carboxylic acids, also in multiple reaction cycles.


Assuntos
Ésteres/metabolismo , Proteínas Fúngicas/metabolismo , Lipase/metabolismo , Nanopartículas de Magnetita/química , Biocatálise , Ácidos Carboxílicos/química , Ácidos Carboxílicos/metabolismo , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Ésteres/análise , Proteínas Fúngicas/química , Cromatografia Gasosa-Espectrometria de Massas , Lipase/química , Dióxido de Silício/química
4.
J Photochem Photobiol B ; 197: 111516, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31170508

RESUMO

In the search for new therapeutic agents we have synthesized 13 new organotin(IV) carboxylate derivatives of (E)-4-((4-methoxy-2-nitrophenyl)amino)-4-oxobut-2-enoic acid. The synthesized complexes were characterized by several spectroscopic techniques. A chelating or bridging bidentate nature of the carboxylate ligand was suggested from the solid state FT-IR results. Solution state multinuclear NMR (1H, 13C and 119Sn) results reveal that the geometry around the Sn atom in triorganotin(IV) complexes is trigonal bipyramidal and in diorganotin(IV) complexes is octahedral. The ligand, (E)-4-((4-methoxy-2-nitrophenyl)amino)-4-oxobut-2-enoic acid, complex 1 and complex 2 were also analyzed by single crystal X-ray technique and the results fully supports the spectroscopic data. For 1 and 2 the geometry optimized by the single crystal X-ray analyses is distorted trigonal bipyramidal. The interaction of the studied compounds with SS-DNA was investigated by UV-Vis. Spectroscopy and Molecular docking showing an intercalative mode of binding. The evaluation of the screened compounds for cancer treatment displays even higher than that of the vincristine used as a standard drug. Similarly the performance of the tested compounds as an antileishmanial agent considers them very close in activity to the standard drug, amphotericin B. The antibacterial results show that the most of the compounds have a moderate sensitivity against the studied bacterial pathogens.


Assuntos
Complexos de Coordenação/química , Compostos Orgânicos de Estanho/química , Sítios de Ligação , Ácidos Carboxílicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Cristalografia por Raios X , DNA/química , DNA/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Leishmania tropica/efeitos dos fármacos , Ligantes , Espectroscopia de Ressonância Magnética , Conformação Molecular , Simulação de Acoplamento Molecular , Conformação de Ácido Nucleico , Espectroscopia de Infravermelho com Transformada de Fourier
5.
Environ Pollut ; 246: 999-1007, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159149

RESUMO

The binding of metal ions with humic acid (HA) plays an important role in the aggregation of HA and the migration of metal ions in the environments. The effects of common cations (Na+, Mg2+, Ca2+ and Al3+) and heavy metal ions (Ag+, Cd2+, Cu2+, Cr3+ and Eu3+) on the aggregation of HA were investigated systematically by aggregation kinetics, spectroscopic techniques and molecular dynamic (MD) simulations. The critical coagulation concentration (CCC) of mono-, di- and trivalent cations could be predicted by the Schulze-Hardy rule. The aggregation of HA in the presence of Na+ and Ag+ was mainly due to the reduction of repulsive force and the hydrogen bonds between HA molecules. While the complexation of di- and trivalent cations with carboxylic/phenolic groups, or the cation-π interactions enhanced the intra- or inter-molecular bridges in HA and then contributed greatly to the aggregation of HA. Heavy metal ions could easily pass through the electric double-layer of HA compared with common cations. MD simulations further signified the strong aggregation ability of HA molecules in solutions containing high valence metal ions. These findings are important for understanding not only how the influence of metal ions on the aggregation of HA, but also the conditions which ions more efficient for aggregation.


Assuntos
Cátions/química , Substâncias Húmicas , Simulação de Dinâmica Molecular , Ácidos Carboxílicos/química , Ligações de Hidrogênio , Cinética , Metais Pesados/química , Fenóis/química , Análise Espectral , Poluentes Químicos da Água/química
6.
Anal Chim Acta ; 1072: 46-53, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31146864

RESUMO

In clinical practice, the excess concentration of bilirubin can trigger diseases such as neonatal jaundice, hepatic failure, septicemia, and so on. The concentration of bilirubin is one of important clinical indexes to evaluate patients with hepatic function disease in clinical practice. Therefore, it is very necessary to develop a rapid detection technique detecting the bilirubin in body fluids. Here, a new electrochemical sensor based on Au nanoparticles/tetrathiafulvalene-carboxylate functionalized reduced grapheneoxide 0D-2D heterojunction(AuNPs/TTF-COOH/RGO) was fabricated for the discrimination of bilirubin in real human blood. The TTF-COOH could effectively repair electron conductivity of RGO nanosheets, decrease interface resistance, and also enhance the dispersity of TTF-COOH/RGO nanosheets in water. What's more, the S atoms of TTF-COOH can bonding the gold nano-particles (AuNPs) to fabricate a 0D-2D heterojunction with excellent biocompatibility and enhanced specific surface area. After bilirubin oxidases were self-assembled on the surface of AuNPs, a specific recognition interface was formed as a sensor for the detection of bilirubin. The heterojunction showed enhanced interface electron transfer rate, excellent biocompatibility, and also prominent electrocatalytic activity for the high efficiency catalysis of bilirubin. The sensor shows a linear response for bilirubin from 2.66 to 83  µmol L-1 and a low detection limit of 0.74 µmol L-1 at 3σ. This work provides one novel approach to detection of bilirubin by functional RGO nanosheets, and broadens the application area of RGO nanosheets in selective catalysis and detection of biomolecule in biological specimens, such as blood, urine.


Assuntos
Bilirrubina/sangue , Ácidos Carboxílicos/química , Técnicas Eletroquímicas , Ouro/química , Grafite/química , Compostos Heterocíclicos/química , Nanopartículas Metálicas/química , Eletrodos , Humanos , Prata/química
7.
J Chromatogr A ; 1600: 80-86, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31047663

RESUMO

Lysozyme is widely used in medical, food and industrial fields due to its bacteriolytic effect and thus it is significant to design and develop a specific adsorbent with high adsorption capacity and selectivity for lysozyme. Inspired by the high uptake capacity of tetrafluoroterephthalonitrile-crosslinked porous ß-cyclodextrin polymers (P-CDPs) and the noncovalent interaction between lysozyme and carboxyl groups, the carboxyl-functionalized P-CDPs (P-CDP-COO-) were synthesized by base-catalysed hydrolysis of nitrile group in P-CDPs to carboxyl. Porous structure, large extent of carboxylic functional groups, cyclodextrin's preventing aggregation, and negatively charged make P-CDP-COO- possess an outstanding adsorption capability for lysozyme. The maximum saturated adsorption capacity reaches 1520 mg g-1, which is much better than the parent polymer and other reported materials. The as-prepared material was successfully utilized for the selective extraction of lysozyme from egg white.


Assuntos
Técnicas de Química Analítica/métodos , Clara de Ovo/química , Muramidase/isolamento & purificação , beta-Ciclodextrinas/química , Adsorção , Ácidos Carboxílicos/química , Ciclodextrinas/química , Muramidase/química , Porosidade
8.
Sci Total Environ ; 678: 197-206, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31075586

RESUMO

An innovative biofiltration-ozonation-biofiltration process was established and applied for the treatment of oil sands process water (OSPW). With an equivalent hydraulic retention time (HRT) of 8 h, the biofiltration pretreatment removed 24.4% of classical naphthenic acids (NAs) and 3.3% of oxidized NAs from raw OSPW with removal rate of 0.4 mg/L/h and 0.1 mg/L. Oxidized NAs showed higher resistance to the biofiltration process than classical NAs. The mild ozonation process (with utilized ozone dose of 30 mg/L) removed 84.8% of classical NAs and 11.5% of oxidized NAs from the biofiltrated OSPW with a degradation efficiency of 0.3 mg classical NAs/mg O3 and 0.1 mg oxidized NAs/mg O3. However, by using the same utilized ozone dose, the degradation of classical NAs and oxidized NAs from raw OSPW was 32.1% and 3.9% with ozonation efficiency of 0.1 mg classical NAs/mg O3 and 0.0 mg oxidized NAs/mg O3, respectively. Compared with the biofiltration pretreatment, the post biofiltration process (with HRT of 8 h) showed higher degradation effect on oxidized NAs with removal ratio of 22.9% and removal rate of 0.4 mg/L/h, but showed lower degradation effect on classical NAs with removal ratio of 6.7% and removal rate of 0.0 mg/L/h. After biofiltration-ozonation-biofiltration treatment, the microbial community structure in the biofilter was investigated by next generation sequencing. Proteobacteria and Rhodococcus were dominant bacterial phyla and genus in the biofilter, the abundance of which were 47.21% and 9.50% which were different from those in raw OSPW (62.88% and 0.72%). The change of microbial community structure could be resulted from the interaction between microbial community and the circulating OSPW. The ozonation integrated biodegradation process removed 89.3% and 34.0% of classical and oxidized NAs from OSPW which shows high potential to be applied by the oil and gas industry.


Assuntos
Ácidos Carboxílicos/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Ácidos Carboxílicos/química , Hidrocarbonetos , Campos de Petróleo e Gás , Ozônio/química , Poluição por Petróleo , Poluentes Químicos da Água/química
9.
Environ Sci Pollut Res Int ; 26(20): 20742-20752, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104242

RESUMO

Although the increased production of nanoparticles (NPs) has raised extensive concerns about the potential toxic effects on aquatic organisms, as well as the increasing evidences which documented the impact of ocean acidification (OA) on the physiology and fitness of marine invertebrates, limited number of studies reported their combined toxic effects. For these reasons, in the present study, we investigated the physiological and biochemical responses of one of the most economically important bivalve species in the World, the Manila clam Ruditapes philippinarum, after the exposure to an environmnetally relevant concentration of carboxylated carbon nanotubes and predicted OA conditions. The results showed that the organisms were not only susceptible to NPs but also to seawater acidification. Different responses between low pH and NPs for most tested biomarkers were observed, both in terms of physiological (respiration rate) and biochemical responses (metabolic capacity, oxitative status and neurotoxicity). Acidified pH significantly decreased the respiration rate and metabolism and increased the energy reserves consumption. Moreover, increase of the oxidative damage was also detected under this condition confirming that the mechanism of enhanced toxicity in the organisms should be attributed to lower aggregation state with more suspended NPs in acidified seawater, indicating that seawater acidification significantly influenced the impact of the used NPs in the exposed organisms.


Assuntos
Bivalves/fisiologia , Ácidos Carboxílicos/toxicidade , Nanotubos de Carbono/toxicidade , Água do Mar/química , Poluentes Químicos da Água/toxicidade , Animais , Disponibilidade Biológica , Biomarcadores/metabolismo , Bivalves/efeitos dos fármacos , Bivalves/metabolismo , Ácidos Carboxílicos/química , Concentração de Íons de Hidrogênio , Nanotubos de Carbono/química , Estresse Oxidativo , Poluentes Químicos da Água/química
10.
Chem Commun (Camb) ; 55(44): 6297-6300, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31089587

RESUMO

Optical chirality sensing of unprotected amino acids, hydroxy acids, amino alcohols, amines and carboxylic acids based on a practical mix-and-measure protocol with readily available copper, iron, palladium, manganese, cerium or rhodium salts is demonstrated. The generation of strong cotton effects allows quantitative ee analysis of small sample amounts with high speed. In contrast to previously reported assays the use of chromophoric reporter ligands and the control of metal coordination kinetics and redox chemistry are not necessary which greatly simplifies the sensing procedure with the benefit of reduced waste production and cost.


Assuntos
Aminas/química , Aminoácidos/química , Amino Álcoois/química , Ácidos Carboxílicos/química , Hidroxiácidos/química , Metais/química , Sais/química , Ligantes , Estereoisomerismo
11.
Adv Mater ; 31(27): e1901103, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31112631

RESUMO

Ionic liquids (ILs) and deep eutectic solvents have shown great promise in drug delivery applications. Choline-based ILs, in particular choline and geranic acid (CAGE), have been used to enhance the transdermal delivery of several small and large molecules. However, detailed studies outlining the design principles of ILs for transdermal drug delivery are still lacking. Using two model drugs of differing hydrophilicities, acarbose and ruxolitinib and 16 ILs, the dependence of skin penetration on the chemical properties of ILs is examined. First, the impact of ion stoichiometry on skin penetration of drugs is assessed using CAGE, which evidences that a molar ratio of 1:2 of choline to geranic acid yields the highest delivery. Subsequently, variants of CAGE are prepared using anions with structural similarity to geranic acid and cations with structural similarity to choline at a ratio of 1:2. Mechanistic studies reveal that the potency of ILs in enhancing transdermal drug delivery correlates inversely with the inter-ionic interactions as determined by 2D NMR spectroscopy. Using this understanding, a new IL is designed, and it provides the highest delivery of ruxolitinib of all ILs tested here. Overall, these studies provide a generalized framework for optimizing ILs for enhancing skin permeability.


Assuntos
Acarbose/administração & dosagem , Ácidos Carboxílicos/química , Portadores de Fármacos/química , Líquidos Iônicos/química , Pirazóis/administração & dosagem , Administração Cutânea , Animais , Colina/química , Cobaias , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Permeabilidade , Pele/metabolismo , Solventes/química , Terpenos/química
12.
Nat Commun ; 10(1): 1675, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975988

RESUMO

Carboxylic acids are common moieties in medicines. They can be converted to phthalidyl esters as prodrugs. Unfortunately, phthalidyl esters are now mostly prepared in racemic forms. This is not desirable because the two enantiomers of phthalidyl esters likely have different pharmacological effects. Here we address the synthetic challenges in enantioselective modification of carboxylic acids via asymmetric acetalizations. The key reaction step involves asymmetric addition of a carboxylic acid to the catalyst-bound intermediate. This addition step enantioselectively constructs a chiral acetal unit that lead to optically enriched phthalidyl esters. A broad range of carboxylic acids react effectively under mild and transition metal-free conditions. Preliminary bioactivity studies show that the two enantiomers of chlorambucil phthalidyl esters exhibit different anti-cancer activities to inhibit the growth of Hela cells. Our catalytic strategy of asymmetric acetalizations of carboxylic acids shall benefit future development of chiral phthalidyl ester prodrugs and related molecules.


Assuntos
Acetais/química , Antineoplásicos/química , Ácidos Carboxílicos/química , Química Farmacêutica/métodos , Pró-Fármacos/química , Antineoplásicos/farmacologia , Catálise , Proliferação de Células/efeitos dos fármacos , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos , Células HeLa , Humanos , Estrutura Molecular , Ácidos Ftálicos/química , Pró-Fármacos/farmacologia , Estereoisomerismo
13.
Chemosphere ; 227: 381-388, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31005668

RESUMO

The physicochemical properties of biochar determined its sorption of organic contaminations, and the environmental aging process changed the biochar properties. However, the correlation between biochar heterogeneous properties and their sorption characteristics is unclear. In this study, peanut shell biochars were produced at 200-700 °C, and HNO3/H2SO4 was used to oxidize 400 °C biochar for 2-10 h to simulate the enhanced aging process of biochar in the environment. Benzene polycarboxylic acid (BPCA) molecular markers, and bulk characterization were analyzed to describe biochar physicochemical properties and to further predict the sorption characteristics to bisphenol A (BPA). For pristine biochars, the mellitic acid/BPCAs (B6CA/BPCAs) increased with the raise of pyrolysis temperature and the H/C atomic ratio was positively correlated with benzenepentacarboxylic acid/B6CA (B5CA/B6CA) (P < 0.01), which indicated the increased aromatic condensation. After HNO3/H2SO4 treatment, the aromaticity (H/C ratio) decreased while the highly condensed components in biochars were enriched (increased B6CA/BPCAs values). Multiple regression models were adopted to establish a quantitative relationship between biochar heterogeneous properties and their sorption of BPA. Both nonlinearity coefficient N values (N = 0.08 + 0.103 B5CA/B6CA + 0.721 (O + N)/C, R2 = 0.985) and single-point sorption coefficients log Kd (log Kd = 1.236 + 0.006 BPCAs + 1.449 (O + N)/C, R2 = 0.936) could be estimated combining molecular markers and polarity parameters for biochars.


Assuntos
Benzeno/química , Carvão Vegetal/química , Modelos Químicos , Adsorção , Benzeno/análise , Compostos Benzidrílicos/química , Ácidos Carboxílicos/química , Fenóis/química , Temperatura Ambiente
14.
Anal Bioanal Chem ; 411(14): 3047-3058, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30931504

RESUMO

To develop bioconjugated materials, it is necessary to understand how the various elements present in a conjugate interact with one another. To gain insights into nanoparticle-capping agent-protein interactions, gold nanoparticles (AuNPs) measuring 30 nm in diameter were coated with different molecules bearing a thiol group: 3-mercaptopropionic acid, 6-mercaptohexanoic acid, and 11-mercaptoundecanoic acid. The covalent conjugation of AuNPs to the protein bovine serum albumin (BSA) via a cross-linker reaction with N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide was systematically investigated under different reaction conditions with variation of the concentrations of the mercaptoalkyl carboxylic acid (MA) and BSA. All the products were analyzed by UV-vis spectroscopy, gel electrophoresis, and Raman spectroscopy in every modification step. From analysis of the UV-vis results, it is possible at low concentrations of MA to see strong coupling among AuNPs, observed when they are aggregated by KCl, which does not happen at higher concentration of MA, indicating an AuNP-to-MA ratio of 1:130,000 is best for bioconjugation purposes. Agarose gel electrophoresis, a classic technique for biomolecule characterization, indicated that BSA is capable of altering the mobility of AuNPs when it modifies completely the surface of AuNPs because of its high molecular mass (around 66 kDa). Principal component analysis of surface-enhanced Raman spectroscopy data was successfully used as a chemometric tool to assist the characterization of the nanoparticle modification with linker molecules in the absence and presence of different BSA concentrations, making it possible to clearly evaluate the gradual substitution/modification of AuNPs (1:13,000 < 1:65,000 < 1:130,000 AuNP-to-MA ratio) and the conjugation with BSA, which is homogenous at a concentration of 0.01 g L-1. Graphical abstract.


Assuntos
Ácidos Carboxílicos/química , Eletroforese em Gel de Ágar/métodos , Ouro/química , Nanopartículas Metálicas/química , Soroalbumina Bovina/química , Espectrofotometria Ultravioleta/métodos , Análise Espectral Raman/métodos , Análise de Componente Principal , Propriedades de Superfície
15.
BMC Res Notes ; 12(1): 197, 2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940193

RESUMO

OBJECTIVE: A synthetic pathway to γ-hydroxy-α-(arylmethyl)carboxylic acids starting from α-angelica lactone and γ-butyrolactone was investigated. These γ-hydroxycarboxylic acids resemble structural motifs of lactic acid and amino acids. The possibility of cocondensation with lactic acid towards functionalized poly(lactic acid)s was analyzed. RESULTS: The functional γ-hydroxycarboxylates sodium 4-hydroxy-2-((N-methylpyrazol-4-yl)methyl)pentanoate and sodium 4-hydroxy-2-(phenylmethyl)butanoate (2-benzyl-4-hydroxybutanoate) were synthesized in good yields as a proof of concept for the proposed reaction pathway. Additionally, sodium (E)-2-((N-methylpyrazol-4-yl)methylene)-4-oxopentanoate presenting an interesting structural motif was isolated. All products have been fully characterized by mass spectrometry, IR spectroscopy and 2D nuclear magnetic resonance (NMR) techniques. In contrast to the carboxylate anions, the corresponding carboxylic acids obtained after acidification were found to be unstable. The instability was analyzed by NMR experiments. With the help of diffusion ordered NMR spectroscopy, the cocondensation with lactic acid was elucidated. The reaction products were characterized as oligomers of pure lactic acid, while intramolecular condensation of the γ-hydroxycarboxylic acids prevents cocondensation with lactide.


Assuntos
Aminoácidos/análise , Vias Biossintéticas , Ácidos Carboxílicos/química , Ácido Láctico/química , Lactonas/química , Espectroscopia de Ressonância Magnética , Poliésteres/química
16.
Biosci Biotechnol Biochem ; 83(7): 1263-1269, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30938230

RESUMO

As a chiral precursor for the important anticoagulant Edoxaban, enantioselective synthesis of (S)-3-cyclohexene-1-carboxylic acid is of great significance. The complicated procedures and generation of massive solid waste discourage its chemical synthesis, and the alternative biocatalysis route calls for an enzyme capable of asymmetric hydrolysis of racemic methyl-3-cyclohexene-1-carboxylate. To this end, we engineered the E. coli esterase BioH for improved S-enantioselectivity via rational design. By combinatorial modulation of steric and aromatic interactions, a positive mutant Mu3 (L24A/W81A/L209A) with relatively high S-selectivity in hydrolyzing racemic methyl-3-cyclohexene-1-carboxylate was obtained, improving the enantiomeric excess from 32.3% (the wild type) to 70.9%. Molecular dynamics simulation was conducted for both (R)- or (S)- complexes of the wild type and Mu3 to provide hints for the mechanism behind the increased S-selectivity. Moreover, the reaction conditions of Mu3 in methyl-3-cyclohexene-1-carboxylate hydrolysis was optimized to improve the conversion rate to 2 folds.


Assuntos
Ácidos Carboxílicos/química , Cicloexenos/química , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Cinética , Simulação de Dinâmica Molecular , Mutação , Estereoisomerismo
17.
Molecules ; 24(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999573

RESUMO

Visible-light-driven photocatalytic supramolecular enantiodifferentiating dimerization of 2-anthracenecarboxylic acid (AC) through triplet-triplet annihilation (TTA), mediated by the Schiff base Pt(II) complex (Pt-1, Pt-2, and Pt-3) was studied. The host concentration and the temperature effects on the stereoselectivity were comprehensively investigated. Increasing the concentration of sensitizers/hosts significantly enhanced the conversion of the photoreaction but led to reduced enantioselectivities of the chiral photodimers 2 and 3 when the photoreaction was triggered by a 532 nm laser, which was in contrast with the results obtained by direct irradiation of AC with a 365 nm light-emitting diode (LED) lamp, due to the aggregation of the sensitizer/host in water. The cyclization of AC through triplet-triplet annihilation displayed significant temperature dependency when Pt-3 was employed as the sensitizer/host. Increasing the temperature from 0 °C to 30 °C with 5% equiv. of Pt-3 led to a great increase of the ee of 2 from 2.1% to 31.6%. However, hardly any temperature dependency was observed when the photodimerization was mediated by other sensitizers and/or hosts, or the photoreaction was triggered directly with a 365 nm LED lamp.


Assuntos
Antracenos/química , Ácidos Carboxílicos/química , Ciclodextrinas/química , Dimerização , Temperatura Alta , Processos Fotoquímicos , Ciclização
18.
Mar Drugs ; 17(4)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987002

RESUMO

α-Conotoxins selectively bind to nicotinic acetylcholine receptors (nAChRs), which are therapeutic targets due to their important role in signaling transmission in excitable cells. A previous experimental study has demonstrated that carboxylation of the C-terminal of α-conotoxin LsIA reduces its potency to inhibit human α7 nAChR relative to naturally amidated LsIA. However, little is known about the contribution of conformational changes in the receptor and interactions, induced by C-terminal amidation/carboxylation of conotoxins, to selective binding to nAChRs, since most conotoxins and some disulfide-rich peptides from other conotoxin subfamilies possess a naturally amidated C-terminal. In this study, we employ homology modeling and molecular dynamics (MD) simulations to propose the determinants for differential interactions between amidated and carboxylated LsIAs with α7 nAChR. Our findings indicate an overall increased number of contacts favored by binding of amidated LsIA versus its carboxylated counterpart. Toxin-receptor pairwise interactions, which may play a role in enhancing the potency of the former, include ARG10-TRP77, LEU141 and CYS17-GLN79 via persistent hydrogen bonds and cation-π interactions, which are weakened in the carboxylated form due to a strong intramolecular salt-bridge formed by ARG10 and carboxylated C-terminus. The binding of amidated LsIA also induces enhanced movements in loop C and the juxtamembrane Cys-loop that are closely associated with receptor function. Additionally, the impacts of binding of LsIA on the overall structure and inter-subunit contacts were examined using inter-residue network analysis, suggesting a clockwise tilting of the α7 C and F loops upon binding to carboxylated LsIA, which is absent for amidated LsIA binding. The predicted molecular mechanism of LsIA binding to the α7 receptor may provide new insights into the important role of the C-terminal in the binding potency of conotoxins at neuronal nAChRs for pharmacological purposes.


Assuntos
Aplysia , Conotoxinas/farmacologia , Simulação de Dinâmica Molecular , Antagonistas Nicotínicos/farmacologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Amidas/química , Sequência de Aminoácidos , Animais , Ácidos Carboxílicos/química , Conotoxinas/química , Conotoxinas/genética , Antagonistas Nicotínicos/química , Domínios Proteicos/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Receptor Nicotínico de Acetilcolina alfa7/química
19.
Org Lett ; 21(9): 2968-2972, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31013105

RESUMO

For the first time we have utilized push-pull stilbene as a visible light activated photoremovable protecting group (PRPG) for the uncaging of alcohols and carboxylic acids. The PRPG efficiently release caged molecules with good photochemical quantum yield. It is capable of monitoring the release in real time owing to its fluorescence "turn on" phenomenon upon photorelease in polar medium. The efficient photorelease and real time monitoring abilities of push-pull stilbene were employed for in vitro drug delivery.


Assuntos
Álcoois/química , Ácidos Carboxílicos/química , Corantes Fluorescentes/química , Estilbenos/química , Antineoplásicos/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Clorambucila/administração & dosagem , Ciclização , Portadores de Fármacos , Liberação Controlada de Fármacos , Humanos , Luz , Células MCF-7 , Imagem Óptica/métodos , Fotólise , Espectrometria de Fluorescência/métodos
20.
Artif Cells Nanomed Biotechnol ; 47(1): 1326-1334, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30964347

RESUMO

In the current study, photosensitizer effect of carboxylate multiwalled carbon nanotubes (MWCNTs-COOH) on CT26 fibroblastic cells following near infrared (NIR) irradiation was quantized in photo-thermal therapy (PTT). Moreover, it was tried to achieve optimal dose of MWCNTs-COOH and laser exposure time. Characterizations of MWCNTs-COOH were scrutinized using scanner electron microscope (SEM), spectrophotometer, and particle size analyzer. The seeded CT26 cells were treated with nontoxic concentrations of MWCNTs-COOH and then irradiated. Finally, viability (%) of the CT26 cells was determined using MTT assay. The findings revealed that 10, 50, and 80 µg/mL of MWCNTs-COOH have remarkable photosensitizer effects on CT26 cancerous cell lines against NIR irradiation (2.5 W/cm2). It was shown that using the 80 µg/mL concentration of MWCNTs-COOH against 60, 120, 180, 240, and 300 s of NIR irradiation and also, 10 and 50 µg/mL concentration of MWCNTs-COOH against 180, 240, and 300 s of NIR irradiation can lead to significant decrease in mean cell viability (%) by more than 50%. According to the obtained data, it seems that using the PPT with MWCNTs-COOH, as adjunct therapy in CT26 fibroblastic cells, can help to increase therapeutic ratio of main modalities of cancer treatment such as radiotherapy, chemotherapy, and surgery.


Assuntos
Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Nanotubos de Carbono/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Ácidos Carboxílicos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Fibroblastos/citologia , Humanos , Temperatura Ambiente
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