A pH switchable hydrophilic fluorescent BODIPY sodium disulfonate for Fe3+ multicolor detection: Experimental and DFT studies.

BODIPY-based chemosensors are widely used owing to merits like good selectivity, high fluorescence quantum yield, and excellent optical stability. As such, a pH-switchable hydrophilic fluorescent probe, BODIPY-PY-(SO3Na)2, was developed for detection of Fe3+ ion in aqueous solutions. BODIPY-PY-(SO3Na)2 revealed strong fluorescence intensity and was responsive to pH value in the range of 6.59-1.96. Additionally, BODIPY-PY-(SO3Na)2 showed good selectivity and sensitivity towards Fe3+. A good linear relationship for Fe3+ detection was obtained from 0.0 µM to 50.0 µM with low detecting limit of 6.34 nM at pH 6.59 and 2.36 nM at pH 4.32, respectively. The response to pH and detection of Fe3+ induced obvious multicolor changes. BODIPY-PY-(SO3Na)2 can also be utilized to quantitatively detect Fe3+ in real water sample. Different mechanisms of Fe3+ detection at investigated pH values were unraveled through relativistic density functional theory (DFT) calculations in BODIPY-PY-(SO3Na)2 and experiments of coexisting cations, anions and molecules. These results enabled us to gain a deeper understanding of the interactions between BODIPY-PY-(SO3Na)2 and Fe3+ and provide valuable fundamental information for design of efficient multicolor chemosensors for Fe3+ as well.

Tunable fiber attenuator for electrically wet-driven micromirrors.

Herein we report an electronically controlled tunable fiber-optic attenuator that leverages the microfluidic electro-wetting effect, which enables a fine-tuning of the solid-liquid interface wetting angle to control the micro-reflector, thus regulating the lens fiber coupling efficiency. Theoretical calculations indicated an optical attenuation regulation effect of 0-45.0 dB in the voltage range of 0-30.0 V. Experimental results align closely with theoretical calculations, demonstrating an attenuation range of 0.59-43.0 dB within a voltage variation range of 0-25.0 V, with control accuracy of 0.56 dB. Our study unveils the potential for designing fiber-optic attenuators with varying tuning accuracy by precisely adjusting the solid-liquid interface wetting angle.

A colorimetric indicator-displacement assay based on stable Cu2+ selective carbon dots for fluorescence turn-on detection of pyrophosphate anions in urine.

Determination of PPi levels in urine represents a measurable factor for diagnostic, treatment, and monitoring of urolithiasis. Owing to the quenching ability of Cu2+ on fluorescent carbon dots (CDs) and strong binding affinity between Cu2+ and PPi, we develop a new off-on assay for PPi detection using newly BPHA CDs (BPHA: N,N-bis(pyridin-2-ylmethyl)hexan-1-amine). The fluorescence intensity of BPHA CDs was significantly quenched by Cu2+ ("off") through forming BPHA CDs/Cu2+ complexes and the fluorescence intensity of BPHA CDs /Cu2+ system was completely resumed by PPi ("on") owing to the release of free Cu2+. The fluorescence turn-off/on approach showed a highly selective response to PPi over the large family of other anions. The detection limits were 0.094 µM for Cu2+ and 0.025 µM for PPi, respectively. A wide linear range for PPi was up to 4400 µM. The indicator displacement assay (IDAs) using pyrocatechol violet (PV) as a colorimetric indicator was carried out to detect PPi with the naked eyes. The "off-on" fluorescent sensor based on BPHA CDs shows many merits, including convenient operation, cost-saving, high sensitivity, selectivity, stability and wide detecting range, which is applied to PPi detection in human urine sample.

Targeting Energy Metabolism by a Platinum(IV) Prodrug as an Alternative Pathway for Cancer Suppression.

Cancer is characterized by abnormal cellular energy metabolism, which preferentially switches to aerobic glycolysis rather than oxidative phosphorylation as a means of glucose metabolism. Many key enzymes involved in the abnormal glycolysis are potential targets of anticancer drugs. Platinum(IV) complexes are potential anticancer prodrugs and kinetically more inert than the platinum(II) counterparts, which offer an opportunity to be modified by functional ligands for activation or targeted delivery. A novel platinum(IV) complex, c, c, t-[Pt(NH3)2Cl2(C10H15N2O3S)(C2HO2Cl2)] (DPB), was designed to explore the effects of axial ligands on the reactivity and bioactivity of the complex as well as on tumor energy metabolism. The complex was characterized by electrospray ionization mass spectrometry and multinuclear (1H, 13C, and 195Pt) NMR spectroscopy. The introduction of dichloroacetate (DCA) markedly increases the lipophilicity, reactivity, and cytotoxicity of the complex and blocks the growth of cancer cells having active glycolysis, and the introduction of biotin (C10H16N2O3S) enhances the tumor-targeting potential of the complex. The cytotoxicity of DPB is increased dramatically in a variety of cancer cell lines as compared with the platinum(IV) complex PB without the DCA group. DPB alters the mitochondrial membrane potential and disrupts the mitochondrial morphology. The levels of mitochondrial and cellular reactive oxygen species are also decreased. Furthermore, the mitochondrial function of tumor cells was impaired by DPB, leading to the inhibition of both glycolysis and glucose oxidation and finally to the death of cancer cells via a mitochondria-mediated apoptotic pathway. These findings demonstrate that DPB suppresses cancer cells mainly through altering metabolic pathways and highlight the importance of dual-targeting for the efficacy of anticancer drugs.

Restraining Cancer Cells by Dual Metabolic Inhibition with a Mitochondrion-Targeted Platinum(II) Complex.

Cancer cells usually adapt metabolic phenotypes to chemotherapeutics. A defensive strategy against this flexibility is to modulate signaling pathways relevant to cancer bioenergetics. A triphenylphosphonium-modified terpyridine platinum(II) complex (TTP) was designed to inhibit thioredoxin reductase (TrxR) and multiple metabolisms of cancer cells. TTP exhibited enhanced cytotoxicity against cisplatin-insensitive human ovarian cancer cells in a caspase-3-independent manner and showed preferential inhibition to mitochondrial TrxR. The morphology and function of mitochondria were severely damaged, and the levels of mitochondrial and cellular reactive oxygen species were decreased. As a result, TTP exerted strong inhibition to both mitochondrial and glycolytic bioenergetics, thus inducing cancer cells to enter a hypometabolic state.

Impact of Mitochondrion-Targeting Group on the Reactivity and Cytostatic Pathway of Platinum(IV) Complexes.

Platinum(IV) complexes are prodrugs of cisplatin with multiple potential advantages over platinum(II) drugs. Mitochondria play pivotal roles in producing energy and inducing death of cancer cells. Two platinum(IV) complexes, namely, c,c,t-[Pt(NH3)2Cl2(OH)(OCOCH2CH2CH2CH2PPh3)]Br and c,c,t-[Pt(NH3)2Cl2(OCOCH2CH2CH2CH2PPh3)2]Br2, were designed to explore the effect of mitochondrion-targeting group(s) on the bioactivity and cytotoxicity of platinum(IV) complexes. The complexes were characterized by electrospray ionization mass spectrometry, reverse-phase high-performance liquid chromatography, and multinuclear (1H, 13C, 31P, and 195Pt) NMR spectroscopy. The introduction of triphenylphosphonium targeting group(s) markedly influences the reactivity and cytotoxicity of the Pt(IV) complexes. The targeted complex displays more potent disruptive effect on mitochondria but less inhibitory effect on cancer cells than cisplatin. The lipophilicity of the Pt(IV) complexes is enhanced by the targeting group(s), while their reactivity to DNA is decreased. As a result, the mitochondrial morphology and adenosine triphosphate producing ability are impaired, which constitutes an alternative pathway to inhibit cancer cells. This study shows that both the reactivity of platinum(IV) center and the property of axial targeting ligand exert influences on the cytotoxicity of targeted Pt(IV) complexes. For targeting groups with pharmacological activities, their intrinsic function could enrich the anticancer mechanism of Pt(IV) complexes.

A Potential Bone-Targeting Hypotoxic Platinum(II) Complex with an Unusual Cytostatic Mechanism toward Osteosarcoma Cells.

Osteosarcoma (OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH3)2Cl]NO3 {BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography. The cytotoxicity of BPP toward OS cell lines U2OS and MG-63 was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. BPP exhibits moderate inhibition against U2OS cells through a mechanism involving both DNA binding and a mevalonate pathway. The acute toxicity of BPP to mice is 7-fold lower than that of cisplatin. The relative low systemic toxicity may result from the steric hindrance of the ligand, which blocks BPP approaching the bases of DNA. The results suggest that incorporating bisphosphonates into a platinum complex not only enhances its bone-targeting property but also minimizes its reactivity toward DNA and thereby lowers the systematic toxicity of the complex. The diminished cytotoxicity of BPP could be compensated for by increasing the therapeutic dose with marginal harm. This strategy provides a new possibility for overcoming the ineffectiveness and systemic toxicity of platinum drugs in the treatment of OS.

Dinuclear Platinum(II) Complexes with Bone-Targeting Groups as Potential Anti-Osteosarcoma Agents.

Osteosarcoma is the most common malignant bone tumor primarily affecting adolescents. Targeted platinum(II) complexes are promising candidates for overcoming the general toxicity of conventional platinum anticancer drugs. In this study four dinuclear platinum(II) complexes, {[cis-Pt(NH3 )2 Cl]2 (PD)} (NO3 )2 (1), {[cis-Pt(NH3 )2 Cl]2 (PDBP)} (NO3 )2 (2), {[cis-Pt(DACH)Cl]2 (PD)} (NO3 )2 (3), and {[cis-Pt(DACH)Cl]2 (PDBP)} (NO3 )2 (4) [PD=5,5'-carbonylbis(2-(2-(pyridin-2-yl)ethyl)isoindoline-1,3-dione), PDBP=tetraethyl (((bis(1,3-dioxo-2-(2-(pyridin-2-yl)ethyl)isoindolin-5-yl)methylene)amino) methylene)bis(phosphonate), DACH=1,2-diaminocyclohexane)], were designed and synthesized. The complexes were fully characterized by 1 H, 13 C, 195 Pt or 31 P NMR spectroscopy and HR-MS. ICP-MS studies showed that considerable amounts of Pt accumulate in U2OS osteosarcoma cells. The interactions of the complexes with calf thymus DNA and plasmid pUC19 DNA were investigated using CD and gel electrophoresis, which indicated that the complexes can react with DNA. The in vitro cytotoxicity showed that 2 is the most potent complex towards U2OS cells. The cellular inhibition mode was examined by flow cytometry. Complex 2 kills U2OS cells predominately through an apoptotic pathway and arrests the cell cycle mainly in the G2 or M phase. The results demonstrate that dinuclear platinum(II) complexes with bone-targeting groups could be anticancer agents for osteosarcoma.

Simultaneous electrochemical detection of ascorbic acid, dopamine and uric acid based on graphene anchored with Pd-Pt nanoparticles.

Pd-Pt bimetallic nanoparticles anchored on functionalized reduced graphene oxide (RGO) nanomaterials were synthesized via a one-step in situ reduction process, in which Pt and Pd ions were first attached to poly(diallyldimethylammonium chloride) (PDDA) functionalized graphene oxide (GO) sheets, and then the encased metal ions and GO were subjected to simultaneous reduction by ethylene glycol. The as-prepared Pd3Pt1/PDDA-RGO nanocomposites were characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and electrochemical methods. In addition, an electrochemical sensor based on the graphene nanocomposites was fabricated for the simultaneous detection of ascorbic acid (AA), dopamine (DA) and uric acid (UA) in their ternary mixture. Three well-separated voltammetric peaks along with remarkable increasing electro-oxidation currents were obtained in differential pulse voltammetry (DPV) measurements. Under the optimized conditions, there were linear relationships between the peak currents and the concentrations in the range of 40-1200 µM for AA, 4-200 µM for DA and 4-400 µM for UA, with the limit of detection (LOD) (based on S/N=3) of 0.61, 0.04 and 0.10 µM for AA, DA and UA, respectively. This improved electrochemical performance can be attributed to the synergistic effect of metallic nanoparticles and RGO and the combination of the bimetallic nanoparticles. Furthermore, the practical electroanalytical utility of the sensor was demonstrated by the determination of AA, DA and together with UA in human urine and blood serum samples with satisfactory results.

4-(4-Pyrid-yl)pyridinium penta-aqua(pyridazine-4,5-dicarboxyl-ato)praseodymate(III).

In the title complex, (C(10)H(9)N(2))[Pr(C(6)H(2)N(2)O(4))(2)(H(2)O)(5)], the Pr atom is nine-coordinated by nine O atoms from two pyridazine-4,5-dicarboxyl-ate anions and five water mol-ecules. It is noteworthy that there is a protonated bipyridine mol-ecule in the structure. Inter-molecular O-H⋯O, O-H⋯N and N-H⋯N hydrogen bonds are present, resulting in a three-dimensional network.

Dichlorido(N,N'-diisopropyl-piperidine-1-carboximidamidato-κN,N')titanium(IV).

In the mononuclear title complex, [Ti(C(12)H(24)N(3))(2)Cl(2)], the Ti(IV) ion, located on a crystallographic inversion center, is six-coordinated by four N atoms from two N',N''-diisopropyl-N-carboxamidine anions and two chloride atoms in a distorted octahedral geometry. The dihedral angles between the piperidine groups and the NCN chelate rings are 51.5 (1) and 52.3 (1)°.

Synthesis, reactivity, and characterization of sodium and rare-earth metal complexes bearing a dianionic N-aryloxo-functionalized beta-ketoiminate ligand.

The synthesis and reactivity of a series of sodium and rare-earth metal complexes stabilized by a dianionic N-aryloxo-functionalized beta-ketoiminate ligand were presented. The reaction of acetylacetone with 1 equiv of 2-amino-4-methylphenol in absolute ethanol gave the compound 4-(2-hydroxy-5-methylphenyl)imino-2-pentanone (LH2, 1) in high yield. Compound 1 reacted with excess NaH to afford the novel sodium cluster [LNa2(THF)2]4 (2) in good isolated yield. Structure determination revealed that complex 2 has the 22-vertex cage structure. Reactions of complex 2 with anhydrous LnCl3 in a 1:4 molar ratio, after workup, gave the desired lanthanide chlorides [LLnCl(DME)]2 [Ln = Y (3), Yb (4), Tb (5)] as dimers. A further study revealed that complexes 3-5 are inert for chlorine substitution reactions. (ArO)3Ln(THF) (ArO = 2,6-Bu(t)2-4-MeC6H2O) reacted with compound 1 in a 1:1 molar ratio in tetrahydrofuran (THF), after workup, to give the desired rare-earth metal aryloxides as dimers [LLn(OAr)(THF)]2 [Ln = Nd (6), Sm (7), Yb (8), Y (9)] in high isolated yields. All of these complexes are well characterized, and the definitive molecular structures of complexes 2 and 4-6 were determined. It was found that complexes 6-9 can be used as efficient initiators for L-lactide polymerization, and the ionic radii of the central metals have a significant effect on the catalytic activity.

Determination of penehyclidine by gas chromatographic-mass spectrometry and its application to pharmacokinetics in humans, rabbits and mice.

A sensitive and specific gas chromatographic-mass spectrometry with the extracted ion chromatograms (GC-MS/EIC) method has been developed and validated for the identification and quantification of penehyclidine (PH) in human and animal blood. The chromatography was on HP-5 capillary column (12 m x 0.2 mm x 0.3 microm). PH-d(5) was selected as the internal standard (IS). Simultaneous MS detection of PH and IS was performed at m/z 315 (PH) and m/z 320 (PH-d(5)), and the EIC of the two compounds was at 175 and 180. PH and PH-d(5) eluted at approximately 8.2 min and no endogenous materials interfered with their measurement. Linearity was obtained over the concentration range of 0.1-100 ng/ml in the blood. The lower limit of quantification (LLOQ) was reproducible at 50 pg/ml in both human and animal blood. The within-day and between-day precisions were no more than 9.1%. This method was successfully applied to quantification and pharmacokinetic studies of PH in the subjects. The concentration-time profiles of PH in humans, rabbits and mice were all fitted to first order absorption two-compartment open model after i.m. a single dose. The differences in absorption, distribution and elimination of PH among the species were found. The results provided the important information for developing a novel anti-cholinergic drug and for obtaining a more effectual remedy in clinical practice.

Synthesis and structural characterization of beta-diketiminate-lanthanide amides and their catalytic activity for the polymerization of methyl methacrylate and epsilon-caprolactone.

The synthesis and catalytic activity of lanthanide monoamido complexes supported by a beta-diketiminate ligand are described. Donor solvents, such as DME, can cleave the chloro bridges of the dinuclear beta-diketiminate ytterbium dichloride {[(DIPPh)2nacnac]YbCl(mu-Cl)3Yb[(DIPPh)2nacnac](THF)} (1) [(DIPPh)2nacnac = N,N-diisopropylphenyl-2,4-pentanediimine anion] to produce the monomeric complex [(DIPPh)2nacnac]YbCl2(DME) (2) in high isolated yield. Complex 2 is a useful precursor for the synthesis of beta-diketiminate-ytterbium monoamido derivatives. Reaction of complex 2 with 1 equiv of LiNPri2 in THF at room temperature, after crystallization in THF/toluene mixed solvent, gave the anionic beta-diketiminate-ytterbium amido complex [(DIPPh)2nacnac]Yb(NPri2)(mu-Cl)2Li(THF)2 (3), while similar reaction of complex 2 with LiNPh2 produced the neutral complex [(DIPPh)2nacnac]Yb(NPh2)Cl(THF) (4). Recrystallization of complex 3 from toluene solution at elevated temperature led to the neutral beta-diketiminate-lanthanide amido complex [{(DIPPh)2nacnac}Yb(NPri2)(mu-Cl)]2 (5). The reaction medium has a significant effect on the outcome of the reaction. Complex 2 reacted with 1 equiv of LiNPri2 and LiNC5H10 in toluene to produce directly the neutral beta-diketiminate-lanthanide amido complexes 5 and [{(DIPPh)2nacnac}Yb(NC5H10)(THF)(mu-Cl)]2 (6), respectively. These complexes were well characterized, and their crystal structures were determined. Complexes 4-6 exhibited good catalytic activity for the polymerization of methyl methacrylate and epsilon-caprolactone.