Pt Nanodot Inlaid Mesoporous NaBiOF Nanoblackberry for Remarkable Signal Amplification Toward Biomarker Detection.

A new ultrasensitive sandwich-type electrochemical immunosensor has been successfully constructed to quantitatively detect carcinoembryonic antigen (CEA) using blackberry-like mesoporous bismuth-based nanospheres NaBiOF (NBOF NSs) inlaid with Pt nanodots (NDs) (BiPt NSs) as the antibody capture and signal-amplifying probe. The growth of Pt NDs inside the holes of NBOF NSs formed the nanozyme inlay outside NBOF NSs, greatly increasing the specific surface area and exposure of the catalytic active sites by minimizing the particle size of the Pt to nanodot scale. Such a blackberry-shaped heterojunction structure of BiPt NSs was well-suited to antibody capture and improved the catalytic performance of BiPt NSs in reducing H2O2, amplifying the signal, and yielding highly sensitive detection of CEA. The use of Au nanoparticle-modified multi-walled carbon nanotubes (Au@MWCNTs) as the electrode substrates significantly enhanced the electron transfer behavior over the electrode surface, further increasing the conductivity and sensitivity of the immunosensor. Remarkably, good compatibility with human body fluid was achieved using the newly developed BiPt-based immunosensor resulting from the favorable biocompatibility and stability of both BiPt NSs and Au@MWCNTs. Benefiting from the double signal amplification strategy and the high biocompatibility, the immunosensor responded linearly to CEA in a wide range from 50 fg/mL to 100 ng/ml with an extremely low detection limit of 3.52 fg/mL (S/N = 3). The excellent detection properties of this new immunosensor were evidenced by the satisfactory selectivity, reproducibility, and stability obtained, as well as the reliable and precise determination  of CEA in actual human blood samples. This work provides a new strategy for the early clinical diagnosis of cancer. Novel blackberry-like mesoporous NaBiOF nanospheres with Pt nanodot inlay were successfully usedto construct a sandwich-type electrochemical immunosensor for the ultra-sensitive detection ofcarcinoembryonic antigen in human blood plasma based on a remarkable signal amplification strategy.

Ti3C2@Bi2O3 nanoaccordion for electrochemical determination of miRNA-21.

Based on a dual signal amplification strategy of novel accordion-like Bi2O3-decorated Ti3C2 (Ti3C2@Bi2O3) nanocomposites and hybridization chain reaction (HCR), an ultra-sensitive electrochemical biosensor was constructed for miRNA-21 detection. By etching Ti3AlC2 with HF, Ti3C2 with an accordion-like structure was first obtained and subsequently covered by Bi2O3 nanoparticles (NPs), forming Ti3C2@Bi2O3. A layer of Au NPs was electrodeposited on the glassy carbon electrode coated with Ti3C2@Bi2O3, which not only significantly improved the electron transport capacity of the electrode but also greatly increased its surface active area. Upon the immobilization of the thiolated capture probe (SH-CP) on the electrode, the target miRNA-21 specifically hybridized with SH-CP and thus opened its hairpin structure, triggering HCR to form a long double strand with the primers H1 and H2. A large number of the electrochemical indicator molecules were thus embedded inside the long double strands to produce the desirable electrochemical signal at a potential of - 0.19 V (vs. Ag/AgCl). Such dual signal amplification strategy successfully endowed the biosensor with ultra-high sensitivity for miRNA-21 detection in a wide linear range from 1 fM to 100 pM with a detection limit as low as 0.16 fM. The excellent detection of miRNA-21 in human blood plasma displayed a broad prospect in clinical diagnosis. An ultra-sensitive electrochemical biosensor was successfully constructed for miRNA-21 detection in human blood plasma based on the dual signal amplification strategy of novel accordion-like Bi2O3 decorated Ti3C2 (Ti3C2@Bi2O3) nanocomposites and hybridization chain reaction.

Rapid electrochemical detection of MiRNA-21 facilitated by the excellent catalytic ability of Pt@CeO2 nanospheres.

Pt@CeO2 nanospheres (NSs) were first synthesized by simply mixing Ce(NO3)3 and K2PtCl4 under the protection of pure argon at 70 °C for 1 h, which exhibited excellent catalytic ability toward hydrogen peroxide (H2O2). An electrochemical biosensor was successfully developed using Pt@CeO2 NSs as a capture probe for the ultra-sensitive and fast detection of miRNA-21, a new type of biomarker for disease diagnostics, especially for cancer. During the step-by-step construction process of the RNA sensor, Pt@CeO2 NSs were functionalized with streptavidin (SA) to obtain SA-Pt@CeO2 NSs through amide bonds. Gold nanoparticles (Au NPs) were electrodeposited on the surface of the glassy carbon electrode to improve the transmission capacity of electrons and provided Au atoms for fixing the thiolated capture probe (SH-CP) with a hairpin structure on the electrode via forming Au-S bonds. The target miRNA-21 specifically hybridized with SH-CP and opened the hairpin structure to form a rigid duplex so as to activate the biotin at the end of the capture probe. SA-Pt@CeO2 NSs were thus specially attached to the electrode surface through the biotin-streptavidin affinity interaction, finally leading to the significant signal amplification. The ultra-sensitive and rapid detection of miRNA-21 was finally realized as expected benefiting from the excellent catalytic ability of Pt@CeO2 NSs toward H2O2 in a wide linear concentration range from 10 fM to 1 nM with the detection limit as low as 1.41 fM. The results achieved with this new RNA sensor were quite satisfactory during the blood sample analysis.

Exploring the interaction of mercury(II) by N(2)S(2) and NS(3) anthracene-containing macrocyclic ligands: photophysical, analytical, and structural studies.

The complexation properties toward Hg(II) of six macrocyclic ligands, 3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L1), 7-(9-anthracenylmethyl)-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L2), 7-(10-methyl-9-anthracenylmethyl)-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L3), 7,7'-[9,10-anthracenediylbis(methylene)]bis-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L4), 1,4,7-trithia-11-azacyclotetradecane (L5), and 11,-(anthracen-9-ylmethyl)-1,4,7-trithia-11-azacyclotetradecane (L6), were studied. The stoichiometries of the formed species were determined from absorption and fluorescence titrations. In these anthracene-containing macrocycles, a fluorescent quenching of the emission was found upon Hg(II) addition. The X-ray crystal structure of [HgCl2(L2)] x 1/2CH2Cl2 was determined. The asymmetric unit contains two independent [HgCl2(L2)] molecules and one dichloromethane molecule. Each Hg(II) ion is coordinated by the pyridine nitrogen, the two sulfur atoms of one L2 molecule, and two chloride ions. Analytical studies using solvent extraction separation of Hg(II) from aqueous solutions were performed to determine the Hg(II) extraction capability of ligands L1, L2, and L5.

Structural and EPR studies on single-crystal and polycrystalline samples of copper(II) and cobalt(II) complexes with N2S2-based macrocyclic ligands.

The properties of Cu(II) and Co(II) complexes with oxygen- or nitrogen-containing macrocycles have been extensively studied; however, less attention has been paid to the study of complexes containing sulfur atoms in the first coordination sphere. Herein we present the interaction between these two metal ions and two macrocyclic ligands with N2S2 donor sets. Cu(II) and Co(II) complexes with the pyridine-containing 14-membered macrocycles 3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L) and 7-(9-anthracenylmethyl)-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L1) have been synthesized. The X-ray structural analysis of {[Co(ClO4)(H2O)(L)][Co(H2O)2(L)]}(ClO4)3 shows two different metal sites in octahedral coordination. The EPR spectra of powdered samples of this compound are typical of distorted six-coordinated Co(II) ions in a high-spin (S=3/2) configuration, with the ground state being S=1/2 (g1=5.20, g2=3.20, g3=1.95). The EPR spectrum of [Cu(ClO4)(L)](ClO4) was simulated assuming an axial g tensor (g1=g2=2.043, g3=2.145), while that of [Cu(ClO4)(L1)](ClO4) slightly differs from an axial symmetry (g1=2.025, g2=2.060, g3=2.155). These results are compatible with a Cu(II) ion in square-pyramidal coordination with N2S2 as basal ligands. Single-crystal EPR experiment performed on [Cu(ClO4)(L1)](ClO4) allowed determining the eigenvalues of the molecular g tensor associated with the copper site, as well as the two possible orientations for the tensor. On the basis of symmetry arguments, an assignment in which the eigenvectors are nearly along the Cu(II)-ligand bonds is chosen.

Basicity and coordination properties of a new phenanthroline-based bis-macrocyclic receptor.

The synthesis and characterisation of the new macrocyclic ligand 6-methyl-2,6,10-triaza-[11]-12,25-phenathrolinophane (L1), which contains a triamine aliphatic chain linking the 2,9 positions of 1,10-phenanthroline and of its derivative L2, composed by two L1 moieties connected by an ethylenic bridge, are reported. Their basicity and coordination properties toward Cu(II), Zn(II), Cd(II), Pb(II) and Hg(II) have been studied by means of potentiometric and spectroscopic (UV-Vis, fluorescence emission) measurements in aqueous solutions. L1 forms 1:1 metal complexes in aqueous solutions, while L2 can give both mono- and dinuclear complexes. In the mononuclear L2 complexes the metal is sandwiched between the two cyclic moieties. The metal complexes with L1 and L2 do not display fluorescence emission, due to the presence of amine groups not involved in metal coordination. These amine groups can quench the excited fluorophore through an electron transfer process. The ability of the Zn(II) complexes with L1 and L2 to cleave the phosphate ester bond in the presence has been investigated by using bis(p-nitrophenyl)phosphate (BNPP) as substrate. The dinuclear complex with L2 shows a remarkable hydrolytic activity, due to the simultaneous presence within this complex of two metals and two hydrophobic units. In fact, the two Zn(II) act cooperatively in substrate binding, probably through a bridging interaction of the phosphate ester; the interaction is further reinforced by pi-stacking pairing and hydrophobic interactions between the phenanthroline unit(s) and the p-nitrophenyl groups of BNPP.

Structural and magnetic properties of a complete halide series of Ni(II) complexes with a pyridine-containing 14-membered macrocycle.

The complete halide series of Ni(II) complexes containing the tetradentate macrocyclic ligand 3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L), was fully characterized by X-ray diffraction. The fluoro, chloro, and bromo complexes are dinuclear species with formula [{Ni(L)}2(mu-X)2]2+ (X = halide), whereas only mononuclear species with formula [Ni(Y)(solv)(L)]n+ (Y = halide or solvent molecule), were obtained with I. To date, the fluoro derivative is the first nonorganometallic coordination compound containing the Ni(mu-F)2Ni core. The magnetic properties of these halo complexes have been studied. Intramolecular interactions were observed in the three dinuclear complexes, being antiferromagnetic in the fluoro derivative and ferromagnetic in both the chloro and bromo ones. The two iodo derivatives are paramagnetic species, as would be expected for mononuclear octahedral Ni(II) complexes. Density functional theory calculations led us to relate the magnetic behaviors of these compounds to the values of the corresponding Ni-X-Ni(i) angle. The analysis of the singly occupied molecular orbitals gave a clear comprehension of the different magnetic exchange interactions found in these Ni(II) complexes.

Color tuning of a nickel complex with a novel N2S2 pyridine-containing macrocyclic ligand.

The novel pyridine-containing 14-membered macrocycle 3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L), which contains an N2S2 donor set, was synthesized, and its protonation behavior was studied by absorption titration with CH3SO3H. The reaction of L with Pd(II) was studied spectroscopically, and the square-planar complex [Pd(L)](BF4) was isolated and characterized. The reactions between L and NiX2 x 6 H2O (X = BF4, ClO4) in ethanol or acetonitrile afforded the octahedral complexes [Ni(CH3CN)(H2O)(L)](X)2 and [Ni(H2O)2(L)](X)2, respectively. The square-planar complexes [Ni(L)](X)2 were obtained by heating these octahedral complexes. Spectrophotometric titrations of [Ni(L)](BF4)2 were performed with neutral and negatively charged ligands. The color of nitromethane solutions of this square-planar complex turns from red to cyan, purple, blue, yellow-green, and pink following addition of halides, acetonitrile, water, pyridine, and 2,2'-bipyridine, respectively. X-ray structural analyses were carried out on the {[Ni(ClO4)(H2O)(L)][Ni(H2O)2(L)]}(ClO4)3, [Ni(CH3CN)(H2O)(L)](ClO4)2, [{Ni(L)}2(mu-Cl)2](ClO4)2, and [{Ni(L)}2(mu-Br)2]Br2 x 2 CH3NO2 complexes.

New fluorescence PET systems based on N2S2 pyridine-anthracene-containing macrocyclic ligands. spectrophotometric, spectrofluorimetric, and metal ion binding studies.

Three new fluorescent devices for protons and metal ions have been synthesized and characterized, and their photophysical properties have been explored; these are the macrocycles 7-(9-anthracenylmethyl)-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L1) and 7-(10-methyl-9-anthracenylmethyl)-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L2) and the bis macrocycle 7,7'-[9,10-anthracenediylbis(methylene)]bis-3,11-dithia-7,17-diazabicyclo[11.3.1]heptadeca-1(17),13,15-triene (L3). All these systems have a pyridil-thioether-containing macrocycles as a binding site and an anthracene moiety as a signaling agent. The coordination properties of these ligands toward Cu(II), Co(II), Ni(II), Zn(II), and Pd(II) have been studied in solution and in the solid state. The addition of these metal ions to dichloromethane solutions of L1, L2, and L3 produce strong changes in the absorption and emission spectra of these ligands. The stoichiometry of the species, formed at 298 K, have been determined from absorption and fluorescence titrations. The Co(II) and Cu(II) complexes of L1 have been studied by EPR spectroscopy. This last complex and its free ligand have also been characterized by X-ray crystallography.