Classification and application of metal-based nanoantioxidants in medicine and healthcare.

Antioxidants play an important role in the prevention of oxidative stress and have been widely used in medicine and healthcare. However, natural antioxidants have several limitations such as low stability, difficult long-term storage, and high cost of large-scale production. Along with significant advances in nanotechnology, nanomaterials have emerged as a promising solution to improve the limitations of natural antioxidants because of their high stability, easy storage, time effectiveness, and low cost. Among various types of nanomaterials exhibiting antioxidant activity, metal-based nanoantioxidants show excellent reactivity because of the presence of an unpaired electron in their atomic structure. In this review, we summarize some novel metal-based nanoantioxidants and classify them into two main categories, namely chain-breaking and preventive antioxidant nanomaterials. In addition, the applications of antioxidant nanomaterials in medicine and healthcare are also discussed. This review provides a deeper understanding of the mechanisms of metal-based nanoantioxidants and a guideline for using these nanomaterials in medicine and healthcare.

Enhanced Sensitivity and Detection of Near-Infrared Refractive Index Sensor with Plasmonic Multilayers.

In this work, the multilayer of the surface plasmon resonance (SPR) sensor was optimized to achieve the maximum sensor sensitivity. By optimizing the thickness of the silver layer (Ag) and dielectric films (TiO2 and AlAs), the optimum sensitivity of the SPR sensor could be obtained. The performance of the SPR sensor proposed was compared with control simulations utilizing zinc oxide (ZnO) and molybdenum oxide (MoO3). The numerical results indicate that the figure-of-merits (FOM) of the SPR sensor was achieved around 150/RIU, corresponding to the sensor sensitivity of 162.79°/RIU with the optimized thicknesses of the TiO2, Ag, and AlAs layers of 140 nm, 60 nm, and 25 nm, respectively. This refractive index sensor shows the FOM to have high detection accuracy and high sensitivity that lead to finding potential application in bio-chemical detection with a small volume of liquid used in biological diagnosis.

Adsorptive Removal of Iron Using SiO2 Nanoparticles Extracted from Rice Husk Ash.

In this work, SiO2 nanoparticles were prepared by the sol-gel method after sodium silicate was extracted from rice husk ash (RHA) under various experimental conditions such as types of acids, NaOH concentration, dissolved time, and temperature and used for removal of Fe2+ ions from aqueous solutions. The extracted SiO2 was morphologically and chemically characterized and showed a surface area of 78 m2/g and uniform pores of 2.71 nm, offering high adsorption capacity for Fe2+ ions. The influence of pH, contact time, and amount of adsorbent was studied in order to establish the best conditions for the Fe2+ adsorption and removal. Furthermore, the adsorption data were fitted with an exponential shape curve for all the three variable parameters that affect the adsorption process. The best results were obtained for pH 5, 20 min contact time, and 0.5 g adsorbent dose. The loading adsorption capacity was 9 mg of Fe2+ ions/g SiO2 in the concentration range 0.1-1.0 mgL-1. In addition, the synthesized SiO2 with the size of around 50 nm can be used for specific heavy metal removal and drug delivery, after modification of the SiO2 surface with various functional groups.

Blood-based immunoassay of tau proteins for early diagnosis of Alzheimer's disease using surface plasmon resonance fiber sensors.

We present the immunoassay of tau proteins (total tau and phosphorylated tau) in human sera using surface plasmon resonance (SPR) fiber sensors. This assay aimed at harvesting the advantages of using both SPR fiber sensors and a blood-based assay to demonstrate label-free point-of-care-testing (POCT) patient-friendly assay in a compact format for the early diagnosis of Alzheimer's disease (AD). For conducting the assay, we used human sera of 40 subjects divided into halves, which were grouped into AD patients and control groups according to a number of neuropsychological tests. We found that on an average, the concentrations of both total tau and phosphorylated tau proteins (all known to be higher in cerebrospinal fluid (CSF) and the brain) turned out to be higher in human sera of AD patients than in controls. The limits of detection of total tau and phosphorylated tau proteins were 2.4 pg mL-1 and 1.6 pg mL-1, respectively. In particular, it was found that the AD group exhibited average concentration of total tau proteins 6-fold higher than the control group, while concentration of phosphorylated tau proteins was 3-fold higher than that of the control. We can attribute this inhomogeneity between both types of tau proteins (in terms of increase of control-to-AD in average concentration) to un-phosphorylated tau proteins being more likely to be produced in blood than phosphorylated tau proteins, which possibly is one of the potential key elements playing an important role in AD progress.

Optical birefringence of liquid crystals for label-free optical biosensing diagnosis.

PURPOSE: We present a polarization-sensitive optical detection platform for label-free quantitative optical biosensing diagnosis using liquid crystals (LCs). This is capable of determining quantitatively the optical birefringence of optical cells containing LCs, whose orientation depends on the immobilized biomolecules. PATIENTS AND METHODS: This technique uses a polarization-dependent double-port detection without any polarizer at a single wavelength and removes the need of aligning optical cells of LCs in the azimuthal direction, with respect to the light path through the optical cell. Thus, this technique enables a stand-alone detection in a relatively compact format without an additional optical instrument, such as a retardation compensator, a Michael-Levy chart, and a spectrophotometer, in order to determine the optical birefringence quantitatively. RESULTS: We demonstrate that bovine serum albumin immobilized on the gold surface of the cell hybrid interfaces that support both homeotropic and planar anchoring of LCs causes optical phase retardation change which can be determined quantitatively. We also provide estimation of the zenithal orientation of LCs near the gold surface of the hybrid interfaces, based on the phase retardation determined. The estimated limit of bovine serum albumin detection is approximately 2.1 µM. CONCLUSION: This optical technique with LCs can serve an optical platform for label-free quantitative diagnosis of proteins in a real time manner.

A regenerative label-free fiber optic sensor using surface plasmon resonance for clinical diagnosis of fibrinogen.

PURPOSE: We present the regenerative label-free fiber optical biosensor that exploits surface plasmon resonance for quantitative detection of fibrinogen (Fbg) extracted from human blood plasma. MATERIALS AND METHODS: The sensor head was made up of a multimode optical fiber with its polymer cladding replaced by metal composite of nanometer thickness made of silver, aluminum, and nickel. The Ni layer coated allowed a direct immobilization of histidine-tagged peptide (HP) on its metal surface without an additional cross-linker in between. On the coated HP layer, immunoglobulin G was then immobilized for specific capturing of Fbg. RESULTS: We demonstrated a real-time quantitative detection of Fbg concentrations with limit of detection of ~10 ng/mL. The fact that the HP layer could be removed by imidazole with acid also permitted us to demonstrate the regeneration of the outermost metal surface of the sensor head for the sensor reusability. CONCLUSION: The sensor detection limit was estimated to be ~10 pM, which was believed to be sensitive enough for detecting Fbg during the clinical diagnosis of cardiovascular diseases, myocardial infarction, strokes, and Alzheimer's diseases.

Bimetal coated optical fiber sensors based on surface plasmon resonance induced change in birefringence and intensity.

We present a surface plasmon resonance (SPR) based multimode fiber sensor with non-golden bimetallic coating. Our detection scheme used, which is capable of measuring the combined effects of SPR-induced birefringence and intensity changes, supported the minimum resolvable refractive index (RI) of 5.8 × 10(-6) RIU with the operating RI range of 0.05 to be experimentally obtained at a single wavelength (632.8 nm) without non-spectroscopic techniques. The asymmetric profile of the thickness of the bimetal coating on the fiber core together with the inherent range of incidence angle for multimode propagation also contributed to the wide operating range. The SPR fiber device with the detection scheme demonstrated will be likely to be developed as a real-time label-free and highly sensitive diagnostic device of a wide operating range for biomedical and biochemical applications in a portable format.

Deprotonative metalation of chloro- and bromopyridines using amido-based bimetallic species and regioselectivity-computed CH acidity relationships.

A series of chloro- and bromopyridines have been deprotometalated by using a range of 2,2,6,6-tetramethylpiperidino-based mixed lithium-metal combinations. Whereas lithium-zinc and lithium-cadmium bases afforded different mono- and diiodides after subsequent interception with iodine, complete regioselectivities were observed with the corresponding lithium-copper combination, as demonstrated by subsequent trapping with benzoyl chlorides. The obtained selectivities have been discussed in light of the CH acidities of the substrates, determined both in the gas phase and as a solution in THF by using the DFT B3LYP method.

Deprotonative metalation of aromatic compounds by using an amino-based lithium cuprate.

Deprotonative cupration of aromatic compounds by using amino-based lithium cuprates was optimized with 2,4-dimethoxypyrimidine and 2-methoxypyridine as the substrates and benzoyl chloride as the electrophile. [(tmp)(2)CuLi] (+2 LiCl) (tmp=2,2,6,6-tetramethylpiperidino) was identified as the best reagent and its use was extended to anisole, 1,4-dimethoxybenzene, other substituted pyridines, furan, thiophene and derivatives, and N-Boc-indole (Boc=tert-butyloxycarbonyl). Of the electrophiles employed to attempt the interception of the generated aryl cuprates, aroyl chlorides, iodomethane, and diphenyl disulfide efficiently reacted. In addition, different oxidative agents were identified to afford symmetrical biaryls. Finally, palladium-catalyzed coupling with aryl halides was optimized and allowed the synthesis of different aryl derivatives in medium to good yields.

Direct metalation of heteroaromatic esters and nitriles using a mixed lithium-cadmium base. Subsequent conversion to dipyridopyrimidinones.

All pyridine nitriles and esters were metalated at the position next to the directing group using (TMP)(3)CdLi in tetrahydrofuran at room temperature. The 2-, 3-, and 4-cyanopyridines were treated with 0.5 equiv of base for 2 h to afford, after subsequent trapping with iodine, the corresponding 3-iodo, 2-iodo, and 3-iodo derivatives, respectively, in yields ranging from 30 to 61%. Cyanopyrazine was similarly functionalized at the 3 position in 43% yield. Ethyl 3-iodopicolinate and -isonicotinate were synthesized from the corresponding pyridine esters in 58 and 65% yield. Less stable ethyl 4-iodonicotinate also formed under the same conditions and was directly converted to ethyl 4-(pyrazol-1-yl)nicotinate in a two-step 38% yield. All three ethyl iodopyridinecarboxylates were involved in a one-pot palladium-catalyzed cross-coupling reaction/cyclization using 2-aminopyridine to afford new dipyrido[1,2-a:3',2'-d]pyrimidin-11-one, dipyrido[1,2-a:4',3'-d]pyrimidin-11-one, and dipyrido[1,2-a:3',4'-d]pyrimidin-5-one in yields ranging from 50 to 62%. A similar cross-coupling/cyclization sequence was applied to methyl 2-chloronicotinate using 2-aminopyridine, 2-amino-5-methylpyridine, and 1-aminoisoquinoline to give the corresponding tricyclic or tetracyclic compounds in 43-79% yield. Dipyrido[1,2-a:4',3'-d]pyrimidin-11-one and dipyrido[1,2-a:3',4'-d]pyrimidin-5-one showed a good bactericidal activity against Pseudomonas aeroginosa . Dipyrido[1,2-a:2',3'-d]pyrimidin-5-one and pyrido[2',3':4,5]pyrimidino[2,1-a]isoquinolin-8-one showed a fungicidal activity against Fusarium and dipyrido[1,2-a:4',3'-d]pyrimidin-11-one against Candida albicans . Ethyl 4-(pyrazol-1-yl)nicotinate and dipyrido[1,2-a:2',3'-d]pyrimidin-5-one have promising cytotoxic activities, the former toward a liver carcinoma cell line (HEPG2) and the latter toward a human breast carcinoma cell line (MCF7).

Deprotonative metalation of functionalized aromatics using mixed lithium-cadmium, lithium-indium, and lithium-zinc species.

In situ mixtures of CdCl(2)TMEDA (0.5 equiv; TMEDA = N,N,N',N'-tetramethylethylenediamine) or InCl(3) (0.33 equiv) with [Li(tmp)] (tmp = 2,2,6,6-tetramethylpiperidino; 1.5 or 1.3 equiv, respectively) were compared with the previously described mixture of ZnCl(2)TMEDA (0.5 equiv) and [Li(tmp)] (1.5 equiv) for their ability to deprotonate anisole, benzothiazole, and pyrimidine. [(tmp)(3)CdLi] proved to be the best base when used in tetrahydrofuran at room temperature, as demonstrated by subsequent trapping with iodine. The Cd-Li base then proved suitable for the metalation of a large range of aromatics including benzenes bearing reactive functional groups (CONEt(2), CO(2)Me, CN, COPh) or heavy halogens (Br, I), and heterocycles (from the furan, thiophene, pyrrole, oxazole, thiazole, pyridine, and diazine series). Five-membered heterocycles benefiting from doubly activated positions were similarly dideprotonated at room temperature. The aromatic lithium cadmates thus obtained were involved in palladium-catalyzed cross-coupling reactions or simply quenched with acid chlorides.