Preparation and medical application of magnetic beads conjugated with bioactive molecules

Ferrite nanobeads were synthesized from an aqueous solution utilizing Fe²⁺ to Fe³⁺ oxidation for use as magnetic carriers in bioscreening, bio-molecular recognition and anti-cancer diagnosis and therapy. The beads had a crystal structure that was intermediate between Fe₃O₄ and γ-Fe₂O₃. Functional biomolecules were strongly conjugated onto the surfaces of the ferrite beads via COOH and SH groups. The addition of ferrite seed crystals (3-8 nm in size) together with a disaccharide enabled the synthesis of monodisperse, spherical ferrite beads with average diameters (d¯) between 50 and 150 nm and relative deviation Δd/d¯=9-16%. Hollow ferrite nano-spheres (d¯=150-450 nm, Δd/d¯≈10%) were prepared using silica spheres as templates, which were dissolved in NaOH solution. Ferrite beads 40 nm in size were encapsulated in polymer spheres of styrene and polymerized glycidyl methacrylate (poly-GMA), 184±9 nm in diameter. They were used for high throughput bioscreening system for affinity purification of target proteins which make specific bindings to anti-cancer drugs, porphyrins, environment hormones, etc.     

Bifunctional Heterogeneous Catalysis of Silica–Alumina‐Supported Tertiary Amines with Controlled Acid–Base Interactions for Efficient 1,4‐Addition Reactions

We report the first tunable bifunctional surface of silica–alumina‐supported tertiary amines (SA–NEt₂) active for catalytic 1,4‐addition reactions of nitroalkanes and thiols to electron‐deficient alkenes. The 1,4‐addition reaction of nitroalkanes to electron‐deficient alkenes is one of the most useful carbon–carbon bond‐forming reactions and applicable toward a wide range of organic syntheses. The reaction between nitroethane and methyl vinyl ketone scarcely proceeded with either SA or homogeneous amines, and a mixture of SA and amines showed very low catalytic activity. In addition, undesirable side reactions occurred in the case of a strong base like sodium ethoxide employed as a catalytic reagent. Only the present SA‐supported amine (SA–NEt₂) catalyst enabled selective formation of a double‐alkylated product without promotions of side reactions such as an intramolecular cyclization reaction. The heterogeneous SA–NEt₂ catalyst was easily recovered from the reaction mixture by simple filtration and reusable with retention of its catalytic activity and selectivity. Furthermore, the SA–NEt₂ catalyst system was applicable to the addition reaction of other nitroalkanes and thiols to various electron‐deficient alkenes. The solid‐state magic‐angle spinning (MAS) NMR spectroscopic analyses, including variable‐contact‐time ¹³C cross‐polarization (CP)/MAS NMR spectroscopy, revealed that acid–base interactions between surface acid sites and immobilized amines can be controlled by pretreatment of SA at different temperatures. The catalytic activities for these addition reactions were strongly affected by the surface acid–base interactions.     

Greedy approximation for the source location problem with vertex-connectivity requirements in undirected graphs

Let $G=(V,E)$ be a simple undirected graph with a set V of vertices and a set E of edges. Each vertex $v\in V$ has a demand $d(v)\in Z_{+}$, and a cost $c(v)\in R_{+}$, where $Z_{+}$ and $R_{+}$ denote the set of nonnegative integers and the set of nonnegative reals, respectively. The source location problem with vertex-connectivity requirements in a given graph G asks to find a set S of vertices minimizing ${\sum }_{v\in S}c(v)$ such that there are at least $d(v)$ pairwise vertex-disjoint paths from S to v for each vertex $v\in V?S$. It is known that the problem is not approximable within a ratio of $O(\ln {\sum }_{v\in V}d(v))$, unless NP has an $O(N^{\log \log N})$-time deterministic algorithm. Also, it is known that even if every vertex has a uniform cost and $d^1=4$ holds, then the problem is NP-hard, where $d^1=\max \{d(v)|v\in V\}$.In this paper, we consider the problem in the case where every vertex has uniform cost. We propose a simple greedy algorithm for providing a $\max \{d^1,2d^1?6\}$-approximate solution to the problem in $O(\min \{d^1,\sqrt{|V|}\}{d}^1{|V|}^2)$ time, while we also show that there exists an instance for which it provides no better than a $(d^1?1)$-approximate solution. Especially, in the case of $d^1?4$, we give a tight analysis to show that it achieves an approximation ratio of 3. We also show the APX-hardness of the problem even restricted to $d^1?4$.     

Enantioselective synthesis of a phenylalanine library containing alkyl groups on the aromatic moiety: confirmation of stereostructure by X-ray analysis

Six phenylalanine analogues containing 2'-methyl-, 2',6'-dimethyl-, 2'-ethyl-6'-methyl-, 2'-isopropyl-6'-methyl-, 2',4',6'-trimethyl-, and 3',5'-dimethyl-L-phenylalanine were synthesized enantioselectively through asymmetric hydrogenation of acetamidoacrylate derivatives. Enzymatic digestion and X-ray analysis supported the L-configuration of the phenylalanine derivatives obtained.     

Structural scaffold of 18-crown-6 tetracarboxylic Acid for optical resolution of chiral amino acid: x-ray crystal analyses of complexes of D- and L-isomers of serine and glutamic acid

(+)-18-crown-6 tetracarboxylic acid (18C6H4) has been used as a chiral selector for D/L-amino acids in HPLC, where L-isomer is usually eluted prior to D-isomer, except for the case of serine. To clarify why serine exhibits the reverse order for the elusion, the chiral interactions of D- and L-serines with (+)-18C6H4 were investigated by the X-ray single crystal analyses, together with the case of D- and L-glutamic acids, which exhibit the usual elution order in HPLC. The backbone structures (amino, Calpha-H and carboxyl groups) of these four amino acids showed the nearly same interaction with (+)-18C6H4 despite their different chirality. In contrast, the hydroxyl group of L-serine side chain formed a hydrogen bond with the carboxyl group of (+)-18C6H4, whereas such a interaction was not formed for the side chain of D-serine and D- and L-glutamic acids. Thus, it was shown that the exception of D/L-serine from the first elution rule of L-isomer in HPLC is due to the presence and absence of a hydrogen bond formation of its side chain OH group.     

pi-Allylic C1-substitution in water with nitromethane using amphiphilic resin-supported palladium complexes

Nitromethane was safely applied as a C1 nucleophile for palladium-catalyzed pi-allylic substitution in water with amphiphilic PS-PEG resin-supported phosphine-palladium complexes. Catalytic asymmetric nitromethylation of cycloalkenyl esters was achieved in water as a single reaction medium under heterogeneous conditions using 5 mol % palladium of a PS-PEG resin-supported palladium-imidazoindolephosphine complex to give optically active (cycloalkenyl)nitromethanes with up to 98% ee.     

Synthesis and characterization of bromonium ylides and their unusual ligand transfer reactions with N-heterocycles

Stable aliphatic bromonium ylides (RfSO2)2C--Br+C6H4-p-CF3 (Rf = CF3, CF3(CF2)3) have been synthesized and structurally characterized for the first time. X-ray crystallographic analyses indicated a ylide structure with an sp2 hybridization of the ylide carbanions and with little double-bond character for the ylidic bond. The bromonium ylides selectively undergo transfer of the aryl group to nitrogen heterocycles, such as pyridines, yielding N-arylpyridinium salts. This is in a marked contrast to the reaction of the iodonium ylides, which produces pyridinium ylides through transylidations.     

Cationic amylopectin derivatives as additives for analysis of proteins in capillary electrophoresis

Positively charged amylopectin, which is a major constituent of cationic starch, was used to modify the inner surface of fused-silica capillaries by addition to the running solution, which was subsequently employed in CE. Capillaries filled with cationic amylopectin derivatives were shown to generate a stable reversed EOF in the investigated range of pH 4-8. Among the additives studied, quaternary ammonium amylopectin derivatives with high amino and low hydroxypropyl groups showed fast electroosmotic mobility and very effectively suppressed the adsorption of proteins. The run-to-run and batch-to-batch repeatability of the procedures were satisfactory with RSDs of 0.5% and 2.4%, respectively. A basic protein, alpha-chymotrypsinogen, migrated within 6 min and the theoretical plate number of it reached 560 000 plates/m.     

Cytotoxicity and physico-chemical evaluation of acetylated and pegylated cellulose nanocrystals

The high hydrophilicity of cellulose nanocrystals (CNC) may result in poor dispersion in some matrices and solvents. So in this work, two different methodologies were used to reduce the hydrophilicity of CNC. In the first methodology, CNC were acetylated (CNC-Ac) in a mixture of acetic and hydrochloric acid, and in the second methodology, polyethylene glycol (PEG) was adsorbed onto CNC surface (CNC-PEG) under stirring in aqueous solution. CNC obtained by both methods were characterized by transmission electron microscopy (TEM), infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, and thermogravimetric analysis (TGA). Images of TEM showed that the intrinsic morphology of cellulose was preserved after both treatments. FTIR confirmed acetylation reaction by the presence of a new band at 1732 cm^?1 (acetate groups) and the consumption of OH groups. XRD showed a reduction in the crystallinity index for both applied methodologies. DLS showed reduced stability in water for CNC-Ac and CNC-PEG. Values of zeta potential changed after acetylation, from ??45 mV (CNC) to ??1 mV (CNC-Ac), and after adsorption of PEG, to ??26.7 mV (CNC-PEG). TGA showed a reduction in the thermal stability after both treatments and a change in the main degradation behavior for CNC-PEG. MTT assays showed that both proposed functionalizations induce cell proliferation, being even more evident for acetylation because, in addition to viability increase with time, it increased with the sample concentration.     

DFT calculations for Au adsorption onto a reduced TiO2 (110) surface with the coexistence of Cl

Residual chlorines, which originate from HAuCl₄, enhance the aggregation of gold (Au) nanoparticles and clusters, preventing the generation of highly active supported Au catalysts. However, the detailed mechanism of residual-chlorine-promoted aggregation of Au is unknown. Herein to investigate this mechanism, density functional theory (DFT) calculations of Au and Cl adsorption onto a reduced rutile TiO₂ (110) surface were performed using a generalised gradient approximation Perdew, Burke, and Ernzerhof formula (GGA–PBE) functional and plane-wave basis. Although both Au and Cl atoms prefer to mono-absorb onto oxygen defect sites, Cl atoms have a stronger absorption onto a reduced TiO₂ (110) surface, abbreviated as rTiO₂ (110) in the following, than Au atoms. Additionally, co-adsorption of a Cl atom and a Au atom or Au nanorod onto a rTiO₂ surface was investigated; Cl adsorption onto an oxygen defect site weakens the interaction between a Au atom or Au nanorod and rTiO₂ (110) surface. The calculation results suggest that the depletion of interaction between Au and rTiO₂ surface is due to strong interaction between Cl atoms at oxygen defect sites and neighbouring bridging oxygen (O^B) atoms.