•Functional ion and ligands were used directly to design and customize sensor for H+ by MOF platform.•These functional components were made into responsive nanoparticles.•Well-designed combination led to a highly specific fluorescent response to H+ via preset mechanism.•Tb3+-luminescent nanoparticles are impervious to autofluorescence of biosystems.Newly emerged metal organic frameworks (MOFs) have aroused the great interest in designing functional materials by means of its flexible structure and component. In this study, we used lanthanide Tb3+ ions and small molecular ligands to design and assemble a kind of pH-sensitive MOF nanoparticle based on intramolecular-charge-transfer effect. This kind of made-to-order MOF nanoparticle for H+ is highly specific and sensitive and could be used to fluorescently indicate pH value of strong acidic solution via preset mechanism through luminescence of Tb3+. The long luminescence lifetime of Tb3+ allows eliminating concomitant non-specific fluorescence by time-revised fluorescence techniques, processing an advantage in sensing H+ in biological media with strong autofluorescence. Our method showed a great potential of MOF structures in designing and constructing sensitive sensing materials for specific analytes directly via the assembly of functional ions/ligands.

•A luminescent Tb-MOF nanoenzyme was designed and made for the catalytic reaction of H2O2.•This nanoenzyme is highly catalytic and can real-time indicate the concentration of H2O2 luminescently.•A new assay of H2O2 to replace a common combined use of natural enzymes and chromogenic reagents.•Tb3+-based luminescent nanoenzyme is impervious to autofluorescence of biosystems.Metal organic frameworks (MOFs) with flexible structures and components have aroused great interest in designing functional materials. In this work, we designed and made a kind of PA-Tb-Cu MOF nanoenzyme capable of emitting fluorescence for the catalytic reaction of hydrogen peroxide (H2O2). Luminescent Tb3+, catalytic Cu2+ and bridging ligand were assembled and integrated into a single material nanoenzyme. This PA-Tb-Cu MOF nanoenzyme not only possessed excellent catalytic activity comparable to horseradish peroxidase but also can real-time fluorescently indicate the concentration of H2O2 as low as 0.2 µM during catalysis. Luminescent PA-Tb-Cu MOF nanoenzyme did not need a common combined use of natural/artificial enzymes and chromogenic reactions for the quantification of H2O2 in widely-used enzyme-catalytic reactions. The present strategy assembled directly from functional ions/molecules provides a new way for the design and development of smart, multifunctional artificial enzymes for wide applications in biocatalysis, bioassays and nano-biomedicine.Download high-res image (120KB)Download full-size image

•Metal organic framework structure was used to design and organize smart nanosensors.•Multiple functional components were made into nanoparticles for sensing and scavenging of NO2−NO2−.•Well-designed combination led to specific detection of NO2−NO2− via preset mechanism.•Tb3+-luminescent nanoparticles are impervious to autofluorescence of biosamples.Newly emerged metal organic coordination polymers have aroused the great interest in designing tailored functional materials. In this study, multiple functional components, luminescent Tb3+ ion, nucleobase and antenna molecule, were integrated in a single material and prepared into a responsive nanoparticle for nitrite. The terbium coordination polymer nanoparticles made of this kind of material have the dual functions of recognition and transduction and obey a preset sensing mechanism without a post-functionalization of common materials. As the result of the tailored, the terbium coordination polymer nanoparticles are highly sensitive and selective to nitrite by means of Dexter energy transfer between Tb3+ ion and nitrite, and can be used for the scavenger for nitrite in aqueous solution. The detection limit, dynamic range and removal capacity of U–Tb–OBBA CPNPs for nitrite are 0.3 µM, 0.3–470 µM and 4.44 mg per gram of particles, respectively. Metal organic coordination polymers show an attractive potential in constructing smart sensing materials.

•3,4-Diaminobenzoyl-based FXa inhibitors were designed and synthesized.•Most of them possess good anticoagulant potency.•Thereinto, 7b is an in vivo highly antithrombotic, selective FXa inhibitor.The coagulation factor Xa (FXa) plays a central role in the blood coagulation cascade. Recent studies have shown that FXa is a particularly attractive target for the development of oral antithrombotic agents. In view of the excellent pharmaceutical properties of 1,2-phenylenediamine-based FXa inhibitors and the reported structure–activity relationship (SAR) analysis of FXa inhibitors, we designed and synthesized a series of 3,4-diaminobenzoyl-based FXa inhibitors. Intensive SAR studies on this new series led to the discovery of 3,4-dimethoxyl substituted compound 7b. 7b is a highly potent, selective, direct FXa inhibitor with excellent in vivo antithrombotic activity.A series of 3,4-diaminobenzoyl compounds have been designed and synthesized as novel antithrombotic agents. Thereinto, compound 7b is a highly potent, selective FXa inhibitor with excellent in vivo antithrombotic activity.

A series of isoxazolo[5,4-d]pyrimidin-4(5H)-one derivatives have been designed and synthesized as novel antithrombotic agents. The 4-acetoxyl substituted derivative (6g) displays very strong FXa inhibitory activity (IC50 = 0.013 μM), excellent anticoagulant effect in human plasma (2 × PT = 2.12 μM) and high selectivity to thrombin and trypsin. Docking investigation of 6g with FXa protein revealed that the pyrimidone ring of 6g formed a π–π interaction with the phenyl ring of Tyr99, and the carbonyl group in the P1 moiety formed multiple hydrogen bonds to Ser214 and Trp215. These results showed that isoxazolo[5,4-d]pyrimidin-4(5H)-one is an attractive scaffold for designing novel factor Xa inhibitors and 4-carbonyl substituted phenyl ring could be used as novel S1 binding element.Isoxazolo[5,4-d]pyrimidin-4(5H)-one derivatives are designed as novel antithrombotic agents by selectively inhibiting coagulation factor Xa.

Metal organic coordination polymers have emerged as a new class of functional nanomaterials because of their flexible components and diverse architecture. Here, we report the synthesis of a luminescent sensing nucleotide/Tb3+ coordination polymer by the self-assembly of a biomolecule nucleotide, a lanthanide ion and a functional ligand 1,10-phenanthroline. Due to the incorporation of 1,10-phenanthroline as both a sensitizer and a recognition unit, the luminescence of this coordination polymer was enhanced 32 times, and exhibited excellent selectivity and sensitivity to the iron(II) ions. This coordination polymer containing Tb3+ ions has a long luminescence lifetime of up to a millisecond, and was applied to detect Fe2+ ions in human serum by time-resolved fluorimetry. The detection limit is as low as 30 nM. The results demonstrate that metal organic coordination polymers have great potential in constructing specific nanosensors through their components and structural flexibility, and could provide new chemical sensing methods for ions/molecules.

Metal organic coordination polymers have received great attention because of their flexible compositions and architecture. Here, we report the design and synthesis of a responsive lanthanide coordination polymer (LCP) for hydrogen sulfide (H2S), utilizing self-assembling of biomolecule nucleotide with luminescent terbium ion (Tb3+) and sensitizing silver ion (Ag+) in aqueous solution. LCP is highly fluorescent due to the inclusion of Ag+ ions, which sensitized the fluorescence of Tb3+ ions. H2S can strongly quench the fluorescence of LCP through its high affinity for Ag+ ions. Such configurated LCP material from initial building blocks showed high sensitivity and selectivity for H2S and was applied to the determination of H2S in human serum. LCP with Tb3+ ions also has a long fluorescence lifetime, which allows for time-resolved fluorescence assays, possessing particular advantages to probing H2S in biological systems with autofluorescence.

A novel assay of chromium(III) ion based on upconversion fluorescence resonance energy transfer was designed and established. Lysine-capped NaYF4:Yb/Er upconversion nanoparticles (UCNPs) and dimercaptosuccinic acid-capped gold nanoparticles (AuNPs) were used as the energy donor and acceptor, respectively. They were bound together via electrostatic interaction, resulting in the quenching of the fluorescence of UCNPs by AuNPs. Chromium(III) ions can specifically and strongly interact with dimercaptosuccinic acid that was modified on the surface of AuNPs, leading to the separation of AuNPs from UCNPs and the recovery of fluorescence of UCNPs. The fluorescence recovery of UCNPs showed a good linear response to Cr3+ concentration in the range of 2–500 nM with a detection limit of 0.8 nM. This method was further applied to determine the levels of Cr3+ in urine. Compared with other fluorescence methods, current method displayed very high sensitivity and signal-to-noise ratio because of the excitation of near-infrared that can eliminate autofluorescence, providing a promising examination of biological samples for the diagnostic purposes.Graphical abstractHighlights► We report an upconversion fluorescence energy transfer assay for Cr3+ in urine. ► Lysine-capped NaYF4:Yb/Er upconversion particles were used as the energy donor. ► Small molecules was used for the surface conjugation and specific recognition. ► Very high signal-to-noise ratio available in urine. ► Advantageous for the detection of biosamples with autofluorescence.

The Wittig–Horner reaction is a classic method to get alkenes by reaction phosphonates with carbonyl compounds. In this study, it was used for the synthesis of the anticancer drug neratinib. In this method, ethyl diethoxyphosphinylacetate and dimethylaminoacetaldehyde diethylacetal, replacing (E)-4-(dimethylamino)but-2-enoyl acid hydrochloride and oxalyl chloride, were used to synthesize the 6-position side chain of neratinib.

We report on a novel method for visual detection silver(I) ion. It is based on the finding that Ag(I) ions are rapidly reduced by hydroquinone to form a shell of silver on the surface of gold nanoparticles (AuNPs) which act as catalysts for this reaction. This leads to a color change from red to yellow which can be seen with bare eyes. This scheme is sensitive and highly specific for Ag(I) ions. The detection limits are 5 μM for visual inspection and 1 μM for photometric readout, respectively. The method was successfully applied to the determination of Ag(I) ions in spiked lake water and soil.

We have developed a colorimetric method for the determination of Pb(II) ions. It is based on the use of gold nanoparticles and a guanine-rich synthetic oligonucleotide. On addition of Pb(II), the color of the solution turns from red to blue. The ratio of the UV-vis absorption at 630 nm and 525 nm is proportional to the concentration of Pb(II) ions in the range from 10 to 100 nM, and the detection limit is 20 nM. Other metal ions do not interfere if present in up to a 10-fold molar excess. The method was successfully applied to the detection of Pb(II) in lake water and urine. The recovery in case of spiked samples is 92%. The results show that this method is sensitive, simple and fast.

The metal–organic coordination polymers at the nanoscale have emerged as attractive nanomaterials due to their tunable nature. In this work, we for the first time prepared an adenine-based lanthanide coordination polymer nanoparticle (CPNP) with fluorescence sensing function. This kind of CPNP was composed of adenine, terbium ion (Tb3+), and dipicolinic acid (DPA) as an auxiliary linking molecule that can sensitize the fluorescence of Tb3+. The fluorescence of the CPNPs is very weak due to the existence of photoinduced electron transfer (PET) from adenine to DPA, which prevents the intramolecular energy transfer from DPA to Tb3+, leading to the quench of fluorescence of the CPNPs. In the presence of Hg2+, however, significant enhancement in the fluorescence of CPNPs was observed because of the suppression of the PET process by the coordination of Hg2+ with adenine. As a kind of Hg2+ nanosensor, the CPNPs exhibit excellent selectivity and ultrahigh sensitivity up to the 0.2 nM detection limit. The CPNPs also possess an approximately millisecond-scale-long fluorescence lifetime due to the inclusion of Tb3+ ions. We envision that the CPNPs could find great potential applications in ultrasensitive time-resolved fluorometric assays and biomedical imaging in the future owing to their long emission lifetimes, excellent dispersion, and stability in aqueous solution.Keywords: ; coordination polymer nanoparticles; Hg2+; photoinduced electron transfer; sensors

The metal–organic coordination polymer has emerged as a new family of functional nanomaterials. In this work, we prepared a luminescence coordination polymer based on spontaneous self-assembling of nucleotide (AMP) and Eu3+ ions in aqueous solution. After antenna ligand tetracycline (Tc) was introduced to the coordination polymer (AMP/Eu), a strong europium luminescence was observed due to the intramolecular energy transfer from tetracycline to Eu3+. Because of the hydrophobic environment of the polymer interior, the luminescence intensity of AMP/Eu incorporated tetracycline (AMP/Eu–Tc) was 30 times higher than that of AMP/Eu in a solution containing the same amount of tetracycline. AMP/Eu–Tc displays a long emission lifetime, excellent dispersion, and stability in aqueous solution. The coordination polymers based on antenna ligands possess great potential in the applications of ultrasensitive time-resolved fluorometric assays and biological imaging.

The weak fluorescence of lanthanide/nucleotide coordination polymers was greatly enhanced by Ag+ in aqueous solution, which has been used for highly sensitive sensing of Ag+.

A novel, highly sensitive and specific detection method of Hg2+ based on the fluorescence quenching of a terbium chelate probe was presented. The terbium chelate probe is comprised of a quinolone-based dye molecule (cs124) as the light-absorption antenna and a polyaminocarboxylate-based chelator (DTPA) strongly binding metal and lanthanide ions. The cs124–DTPA–Tb is highly luminescent in aqueous solution. The aqueous Hg2+ can efficiently quench the fluorescence of cs124–DTPA–Tb. The fluorescent intensity of cs124–DTPA–Tb displayed a good linear response to Hg2+ concentrations in the range of 4–600 nM with a detection limit of 4 nM. This method was applied successfully to determine the levels of Hg2+ in urine. The quenching mechanism of cs124–DTPA–Tb by Hg2+ is discussed. Compared with other fluorescent assays for Hg2+, a terbium chelate probe has an advantage that the interference of short-lived background fluorescence from sample can be eliminated efficiently by a determination in the mode of time-resolved fluorescence. This method could be used to detect the trace Hg2+ in biological samples and environmental water.

The preparation and detection of highly luminescent aqueous europium nanoparticle labels for the time-resolved fluorometric assays has been demonstrated. The luminescent complexes included in the nanoparticle were composed of a dye sensitizer and a polyaminocarboxylate-based chelator with excellent water-solubility and a high binding constant for lanthanides. The luminescence of europium is greatly enhanced by the sensitization of the dye. The structure design of two functional entities in the single molecule made the lanthanide complex to have both strong luminescence and good aqueous solubility. SiO2 nanoparticles containing europium complexes were prepared by the reverse microemulsion method. One particle of ∼55 nm in diameter has a luminescent intensity corresponding ∼1300 free europium complexes and 0.61 ms fluorescence lifetime. The DNA time-resolved fluorometric assay with this nanoparticle label was carried out by magnetic microbeads as solid phase carrier. The detection sensitivity with the nanoparticles is improved more than 50-fold compared with the conventional dye FITC molecules. This luminescent nanoparticle label based on dye sensitization can be applied in ultrasensitive time-resolved fluorometric assays and imaging.

The weak fluorescence of lanthanide/nucleotide coordination polymers was greatly enhanced by Ag+ in aqueous solution, which has been used for highly sensitive sensing of Ag+.

Metal organic coordination polymers have emerged as a new class of functional nanomaterials because of their flexible components and diverse architecture. Here, we report the synthesis of a luminescent sensing nucleotide/Tb3+ coordination polymer by the self-assembly of a biomolecule nucleotide, a lanthanide ion and a functional ligand 1,10-phenanthroline. Due to the incorporation of 1,10-phenanthroline as both a sensitizer and a recognition unit, the luminescence of this coordination polymer was enhanced 32 times, and exhibited excellent selectivity and sensitivity to the iron(II) ions. This coordination polymer containing Tb3+ ions has a long luminescence lifetime of up to a millisecond, and was applied to detect Fe2+ ions in human serum by time-resolved fluorimetry. The detection limit is as low as 30 nM. The results demonstrate that metal organic coordination polymers have great potential in constructing specific nanosensors through their components and structural flexibility, and could provide new chemical sensing methods for ions/molecules.