Preparation of phenylboronic acid functionalized cation-exchange monolithic columns for protein separation and refolding

In this study, we described a simple and effective modification procedure to prepare poly (methacrylate-co-ethylene glycol dimethacrylate) monolithic columns functionalized with 3-aminophenylboronic acid. The column morphology, pore size and specific surface area of the fabricated monolith were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, and mercury intrusion porosimeter, respectively. The frontal analysis was carried out for dynamic loading capacity of the model protein on the modified column. The chromatographic performance of the cation-exchange monolith was evaluated through separating a mixture of five proteins such as lysozyme, cytochrome c, ribonuclease A, trypsin and bovine serum albumin and one-step purification of lysozyme from egg whites, and the expected results were obtained. In addition, the functionalized column was used to refold ribonuclease A and cytochrome c, and this procedure was monitored by circular dichroism and fluorescence spectroscopy. Compared with the conventional dilution refolding method, the ion-exchange chromatography refolding method developed here is more effective for specific bioactivity recovery.     

A modification of the phenol/sulfuric acid assay for total carbohydrates giving more comparable absorbances

The conditions and acid strength of the phenol/sulfuric acid assay were investigated to improve agreement between absorbances obtained from different sugars. It was found that by increasing acid strength and by cooling the tubes in water after a short reaction time, the values obtained for several sugars, including fructose and xylose, agreed, on an equimolar value, with that for glucose.     

Colorimetric detection of glucose using a boronic acid derivative receptor attached to unmodifed AuNPs简

A simple, cheap and non-enzymatic colorimetric strategy for glucose detection has been designed based on the interactions between a phenylboronic acid （PBA） derivative, which is coupled with gold nanoparticles （AuNPs） as the colorimetric reporters, and glucose. The PBA-AuNPs hybrid system proposed here exhibits ordered photochemistry behaviors upon the addition of glucose at different pH values. There are two linear regions of glucose concentration for the glucose sensor at different pH values, i.e., between 0.1 mmol/L and 9.8 mmol/L at pH 6 with the detection limit of 64μmol/L and between 0 and 6.5 mmol/L with the detection limit of 48 μmol/L at pH 9, respectively. To test the practicality of the sensor system, we also applied this assay to detect a glucose sample in the artificial saliva.     

Phenylboronic acid and dopamine as probe set for electrochemical detection of saccharides

A novel electrochemical approach for detection of saccharides via indicator displacement assay was presented. In this system, 2-fluorophenylboronic acid and dopamine (DA) were performed as probe set. The electrochemical properties of DA and the binding to 2-fluorophenylboronic acid in phosphate buffer at different pH values were investigated by cyclic voltammetry. After addition of fructose to the solution, a competition for the binding 2-fluorophenylboronic acid occurred that led to the release of the DA. The regenerate oxidation current of DA increased with increasing fructose concentration. Under optimized experimental conditions, the peak current was linearly related to fructose concentration in the range of 0.3-5.0 mmol/L with a detection limit of 0.1 mmol/L. In addition, the interaction between 2-fluorophenylboronic acid and other cis-diol compounds such as glucose, galactose and mannose was investigated.     

3-Aza-8,10-dioxa-bicyclo[5.2.1]decane (9-exo BTKa) carboxylic acid as a new reverse turn inducer: synthesis and conformational analysis of a model peptide

Dipeptide isostere 5, belonging to the class of 9-exo BTKa, was synthesised starting from R,R-tartaric acid and 4-nitro-1-(3-nitrophenyl)butan-1-one. The nine-membered lactam showed interesting structural features and was inserted in a 5-residue model peptide. The conformational properties of this modified peptide have been studied by NMR and molecular modelling, indicating that compound 5 acted as a reverse turn inducer.     

Hydroxynorleucine as a glycosyl acceptor is an efficient means for introducing amino acid functionality into complex carbohydrates

A new approach to the synthesis of biologically relevant glycosyl amino acids using a non-natural amino acid as the glycosyl acceptor is described. The procedure involves a glycosylation reaction of a suitable carbohydrate donor with Fmoc-l-hydroxynorleucine benzyl ester. This reaction results in the direct incorporation of the amino acid moiety. The acceptor can be used for the preparation of α- or β-O-linked glycosides depending upon the nature of the glycosyl donor. This method has been applied in the synthesis of six different tumor-associated carbohydrate antigens.     

Regioselective side-chain as well as nuclear monobromination of aromatic substrates with N-bromosuccinimide using phosphotungstic acid supported on zirconia as a heterogeneous catalyst

Regioselective monobromination of aromatic substrates with N-bromosuccinimide has been achieved in excellent isolated yields (84–98%) using phosphotungstic acid supported on zirconia as a novel heterogeneous catalyst. The catalyst has been characterized by means of X-ray diffraction (XRD), scanning electron microscopy (SEM), surface area and acidity measurements. Remarkably, the new catalyst system described brought about the side-chain bromination of aromatics to afford bromomethyl arenes in excellent yields (86–98%) without the need for a radical initiator. Recovery and recylability of the catalyst have been well established.     

A novel hydroxy-bisphosphonic acid prodrug as a candidate for the delivery of ibuprofen to bone

Abstract

Active targeting with controlled delivery of anti-inflammatory drugs to the bone is not sufficiently explored. In this study, concise and novel synthesis of a hydroxy-bisphosphonic acid (HBPA) prodrug containing ibuprofen is described. The key step consisted of preparing the HBPA function from a carboxylic acid precursor, in mild conditions and using appropriate Arbuzov reactions with tris(trimethylsilyl)phosphite. This prodrug would be an excellent candidate for the treatment of bone inflammation diseases such as rheumatoid arthritis.     

A novel fluorescent method for determination of peroxynitrite using folic acid as a probe

A novel method for the determination of peroxynitrite using folic acid as a fluorescent probe is described. The method is based on the oxidation of the reduced, low-fluorescent folic acid by peroxynitrite to produce a high-fluorescent emission product. The fluorescence increase is linearly related to the concentration of peroxynitrite in the range of 3 × 10⁻⁸ to 5.0 × 10⁻⁶ mol L⁻¹ with a correlation coefficient of 0.998, and the detection limit is 1 × 10⁻⁸ mol L⁻¹. Interferences from some metal ions normally seen in biological samples, and also some anions structurally similar to peroxynitrite were studied. The optimal conditions for the detection of peroxynitrite were evaluated.     

A sequential injection system for indirect spectrophotometric determination of lactic acid in yogurt and fermented mash samples

A suitable non-enzymatic method is presented as an alternative to the lactic acid determination in yogurt and fermented mash samples. The oxidative conversion of lactic acid by Ce⁴⁺ to CO₂ was performed in a sequential injection system with a heating coil set at 45 °C. A gas diffusion unit was coupled to the flow system for promoting the permeation of CO₂, which was collected into a bromothymol blue solution (pH 8.4), used as indicator solution for the spectrophotometric determination (619 nm). Simplicity in operation, low reagent consumption, low cost and ruggedness are some remarkable characteristics of the proposed system. Base line drift was < 0.005 h^− 1. A linear range from 20.0 to 100.0 mg L^− 1 lactic acid was obtained (r² = 0.998), and the detection and quantification limits were estimated as 0.158 mg L^− 1 and 1.6 mg L^− 1, respectively. The sampling rate was 22 h^− 1, with a consumption of 0.04 g Ce⁴⁺ per determination. Interferences of matrix components were not detected. Samples of yogurt and sugar cane fermented mash products were analyzed, and no significant difference at 95% confidence level was observed when comparing the proposed method with HPLC analysis.     

A one-pot procedure for trifluoroacetylation of arylamines using trifluoroacetic acid as a trifluoroacetylating reagent

A convenient procedure for the preparation of aryl trifluoroacetamides from aryl amines is described that employs 2-4 M equiv of trifluoroacetic acid in refluxing xylene as a trifluoroacetylating agent. Addition of an amount of pyridine that is equimolar to the amount of trifluoroacetic acid present in the reaction mixture facilitates the trifluoroacetylation of rather basic arylamines.     

A theoretical study on the pyrolysis of perfluorobutanoic acid as a model compound for perfluoroalkyl acids

The potential energy surface is mapped out for all plausible reactions in the self-decomposition of perfluorobutanoic acid (CF₃CF₂CF₂COOH) as a model compound for the notoriously toxic and bio-accumulative perfluoroalkyl acids. Initial decomposition of perfluorobutanoic acid is found to be controlled by HF elimination and the formation of an α-lactone intermediate. The fate of this intermediate is predicted to be dominated by two competing channels, namely formation of pentafluoropropanoyl fluoride (CF₃CF₂COF) and the closed-shell singlet CF₃CF₂CF:. Direct elimination of CO₂ through decarboxylation is found to be retarded by strong hyperconjugation effects induced by fluorine atoms on the carbon chain. The results presented herein provide insightful information towards a comprehensive understanding of the decomposition of perfluoroalkyl acids in thermal systems.     

谷氨酸低分子量有机凝胶的药物控制释放行为

低分子量的有机胶凝剂组装形成的有机凝胶可应用于药物缓释体系.本研究中,使用亲水的钙黄绿素和疏水的布洛芬为模型分子,研究其在谷氨酸衍生物有机凝胶体系中的缓释行为.研究表明,与药物分子与有机胶凝剂简单混合的体系相比,亲水或疏水的药物分子在有机凝胶体系中的释放速度显著减缓.SEM的研究发现药物粒子嵌入在有机凝胶的三维网络中,因此,有机凝胶的三维网络结构可认为是实现药物缓慢释放的基质,药物分子从网络中的释放受限导致了其从有机凝胶中的缓释行为.     

A reassessment of mycophenolic acid as a lead compound for the development of inhibitors of chikungunya virus replication

Mycophenolic acid (MPA) has been previously reported as an inhibitor of the chikugunya virus (CHIKV) with an EC₅₀ value of 0.2 μM. We used MPA as a lead compound designing and synthesizing a series of isatins and benzolactones in a typical medicinal chemistry program. The synthesis and testing of 19 derivatives produced compounds with no desired activity which prompted us to retest the lead compound, MPA. We can reveal that MPA shows no anti-CHIKV activity and therefore needs to be reassessed as a lead compound for this target.     

A green protocol for the N-formylation of amines using molybdate sulfuric acid as a reusable solid catalyst

A novel and efficient method for the N-formylation of amines via the reaction of orthoformates and amines is developed. The reactions are mediated by a catalytic amount of molybdate sulfuric acid as a heterogeneous solid acid.     

Trifluoromethanesulfonic acid as a catalyst for the formation of dansylhydrazone derivatives

Trifluoromethanesulfonic acid (TFMSA) is presented as a new, efficient catalyst in the pre-column fluorescent derivatization of the 3-ketosteroid budesonide with dansylhydrazine and compared to the commonly used catalyst trifluoroacetic acid. With TFMSA the derivatization reaction may be carried out at room temperature, with a considerably higher reaction rate compared to previously used acids. The chromatograms also show that TMFSA results in less formation of spurious peaks from the reagent. Derivatization of steroid solutions ranging from 0.5 to 64 μM could be performed using identical reaction conditions.     

A new type of boronic acid fluorescent reporter compound for sugar recognition

Fluorescent boronic acids that change fluorescent properties upon carbohydrate binding are very useful for the preparation of fluorescent sensors for sugars. Herein we report 5-quinolineboronic acid (5-QBA) that shows significant fluorescent property changes through a unique pK_a-switching mechanism upon binding a diol in aqueous solution.     

Computer‐aided design of a novel ligand for retinoic acid receptor in cancer chemotherapy

The isotypes of RAR and RXR are retinoic acid and retinoid X acid receptors, respectively, whose ligand‐binding domain contains the ligand‐dependent activation function, with distinct pharmacological targets for retinoids, involved in the treatment of various cancers and skin diseases. Due to the major challenge which cancer treatment and cure still imposes after many decades to the international scientific community, there is actually considerable interest in new ligands with increased bioactivity. We have focused on the retinoid acid receptor, which is considered an interesting target for drug design. In this work, we carried out density functional geometry optimizations and different docking procedures. We performed screening in a large database (hundreds of thousands of molecules which we optimized at the AM1 level) yielding a set of potential bioactive ligands. A new ligand was selected and optimized at the B3LYP/6‐31G* level. A flexible docking program was used to investigate the interactions between the receptor and the new ligand. The result of this work is compared with several crystallographic ligands of RAR. Our theoretically more bioactive new ligand indicates stronger and more hydrogen bonds as well as hydrophobic interactions with the receptor. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Aqueous phosphoric acid as a mild reagent for deprotection of the t-butoxycarbonyl group

Aqueous phosphoric acid (85 wt%) is an efficient and mild reagent for the deprotection of N-BOC groups. Acid sensitive functionalities including benzyl and methyl esters, TBDMS ether, CBZ and isopropylidene groups are compatible with the reaction conditions. The reactions are high yielding, and the workup is convenient.