Activatable Small‐Molecule Photoacoustic Probes that Cross the Blood–Brain Barrier for Visualization of Copper(II) in Mice with Alzheimer's Disease

Copper enrichment in the brain is highly related to Alzheimer's disease (AD) pathogenesis, but in vivo tracing of Cu²⁺ in the brain by imaging techniques is still a great challenge. In this work, we developed a series of activatable photoacoustic (PA) probes with low molecular weights (less than 438 Da), RPS1 – RPS4 , which can specifically chelate with Cu²⁺ to form radicals with turn‐on PA signals in the near‐infrared (NIR) region. Introducing the electron‐donating group N,N‐dimethylaniline into the probe was found to significantly enhance the radical stability and PA intensity. The best probe in the series, RPS1 , showed a fast response (within seconds) to Cu²⁺ with high selectivity and a low PA detection limit of 90.9 nm . Owing to the low molecular weight and amphiphilic structure, RPS1 could effectively cross the blood–brain barrier (BBB) and thus allowed us, for the first time, to visualize Cu²⁺ in vivo via PA imaging in the brains of AD mice.     

The production of 103Pd and 109Cd from a proton irradiated tandem natAg/natAg targets

This paper describes a new method for the production of ¹⁰³Pd and ¹⁰⁹Cd using the 66 MeV proton beam of iThemba LABS on a tandem natural silver target (Ag/Ag). The radiochemical separation of the Pd radionuclides (¹⁰³Pd, ¹⁰⁰Pd) from the bulk ^natAg was done using a Chelex-100 chelating resin column. The recovery of ¹⁰³Pd from the irradiated ^natAg target was found to be >98 % without any Ag or Rh impurities detected. The radiochemical separation of ¹⁰⁹Cd from the bulk ^natAg target was done by the precipitation of Ag ions by Cu followed by the separation of ¹⁰⁹Cd, traces of Ag, Cu²⁺ and Rh using a AG1-X10 anion exchange resin column. The recovery yield of ¹⁰⁹Cd was >99 % without any Ag or Rh impurities detected.     

Spectrometric Studies on the Complexation of Pd(II), Fe(III) and Pt(IV) with mandelazo I

Abstract

A spectrometric study of the reaction between Pd(II), Fe(III) and Pt(IV) ions, and Mandelazo I was carried out. The optimum conditions favouring the formation of the complexes are extensively investigated. The stoichiometry of the complexes formed in solution (1:2, 1:1, 1:1), their apparent stability constants (5.45 × 10⁹, 2.39 × 10⁶, 4.12 × 10⁵) and the ranges for obedience to beer's law (0.2 – 6.4, 0.25 – 7.0, 1.5 – 42.0 μg/mL) are reported for Pd(II), Fe(III) and Pt(IV), respectively. The effect of some metal ions including Cu(II), Zn(II), Mn(II), Cd(II), Hg(II), Co(II), Ni(II), Be(II), Al(III), Th(IV) and U(VI), on the maximum absorbance of the formed complexes was also investigated.     

Development of [103Pd]-2-acetylpyridine 4 N-methyl thiosemicarbazone complex for targeted therapy

Summary Due to interesting biological properties of palladium-thiosemicarbazono complexes, production of a ¹⁰³Pd-labeled anti-cancer complex, i.e., [¹⁰³Pd]-2-acetylpyridine ⁴N-methylthiosemicarbazone ([¹⁰³Pd]-APMTS) was developed. Palladium-103 (T_1/2 = 16.96 d) produced via the ¹⁰³Rh(p,n)¹⁰³Pd nuclear reaction using natural rhodium target, was separated from the irradiated target material. Proton energy was 18 MeV with 200 mA irradiation for 15 hours (final activity 700 mCi of ¹⁰³Pd²⁺, RCY>95%, radionuclidic purity>99%). The final activity was eluted in form of Pd(NH₃)₂Cl₂ in order to react with 2-acetylpyridine-⁴N-methylthiosemicarbazone to yield [¹⁰³Pd]-APMTS. Chemical purity of the final product was confirmed to be within the accepted limits by polarography. [¹⁰³Pd]-APMTS was prepared with a radiochemical yield of more than 80% at room temperature after 3 hours. The labeling reaction was optimized for time, temperature and radioactivity and ligand ratio. A mixture of APMTS and Pd activity in ethanol was heated at 90 °C for 3 hours followed by reverse phase SPE purification using C₁₈ plus Sep-Pak. Radiochemical purity of more than 99% using RTLC and specific activity of about 12500 Ci/mol was obtained. The stability of the tracer was checked in the final product and the presence of human serum at 37 °C up to 3 hours. The partition coefficient of the final complex was determined by octanol : saline buffer distribution.     

The express simultaneous neutron activation determination of gold,palladium and platinum

The method of express neutron-activation (NA) determination of Au, Pd and Pt has been developed. The method is based on the quantitative isolation of¹⁹⁸Au+¹⁹⁹Au and¹⁰⁹Pd activities by extraction with organic sulfides. The radiation of¹⁰⁹Pd is measured on a thin NaI(Tl) crystal and that of¹⁹⁸Au and¹⁹⁹Au on a Ge(Li) detector. The calculations of interferences from gold have been performed for various neutron fluxes and various cadmium ratios. Some interferences introduced by other competitive nuclear reactions into the determination of Pt by its daughter isotope¹⁹⁹Au are discussed.     

Macroporous anion exchanger purolite A-500 loaded with ferron for palladium(II) recovery

A systematic study on interaction of Pd(II) with 7-iodo-8-hydroxyquinoline-5 sulfonic acid (Ferron) and the strongly basic anion exchange resin Purolite A-500 in its chloride form was carried out. It was found that for Ferron/resin ratio ranging from 0.15 to 0.70 mmol g-1, the retention of chelating reagent on the investigated ion exchanger is practically quantitative. The sorption increase of Pd(II) on Ferron-loaded resin was observed for higher values of parameters like: pH solution, initial concentration and temperature. It was observed that the equilibrium distribution of Pd(II) between sorbent and solution could adequately be described by the Langmuir model with two parameters. The thermodynamic quantities characteristic of Pd(II) sorption process (ΔG = -18.4 kJ mol^-1; ΔH = 11.7 kJ mol^-1; ΔS = 104.4 J mol^-1 K^-1) suggest a strong affinity between Ferron-loaded resin and the tested cation.     

Preparation,characterization of some transition metal complexes of hydrazone derivatives and their antibacterial and antioxidant activities

A new series of metal complexes of Pd(II), Cd(II) and Cu(II, I) of polydentate Schiff base ligand (H₂L), namely ((Z)-2-(phenylamino)-N'-(thiophen-2-ylmethylene) acetohydrazide) have been prepared. The ligand and its metal complexes have been characterized based on various physicochemical studies as elemental analyses, molar conductance, spectral (UV–Vis, MS, IR, ¹H NMR, ¹³C NMR and XRD), magnetic moment measurements and thermal studies (TG, DTG). In the view of previous studies, the ligand (H₂L) acts as polydentate one and coordinates with metal ions to form all metal complexes. The kinetic and thermodynamic parameters of decomposition process (ΔG, ΔH, ΔS) were calculated. The possible structures of the metal complexes have been computed using the molecular mechanic calculations using the hyper chem. 8.03 molecular modeling program. The calculations are performed to obtain the optimized molecular geometry. The antibacterial study of the selected compounds was assayed against two pathogenic bacteria. Moreover, the complexes (Cu II, I), Cd(II), Pd(II)) and the ligand revealed excellent antioxidant properties and could be useful in fighting the free radicals which occur in close connection with cancerous cells. It was remarkable that the two complexes (Cu II, I) demonstrated stronger antioxidant effects than their parent compounds. It is clear that the new complexes are good active compounds for use in a variety of applications.     

“Palladiazo” a new selective metallochromic reagent for palladium: Part I the main characteristics of the pure reagent and its reaction with palladium(II)

The synthesis and purification of 2,7-bis(4-azophenylarsono)-1,8-dihydroxy-naphthalene 3,6-disulphonic acid is reported. Because of its selectivity for palladium-(II), the name palladiazo is suggested for the reagent. Aqueous solutions of palladiazo are very stable and exhibit 2 absorption maxima located at 540 and 625 nm, the molar absorptivities being 3.3 · 10⁴ and 1.7 · 10⁴, respectively. Palladiazo changes color stepwise and reversibly with increase in hydrochloric acid concentration from 0 to 13 M. A negatively charged complex of type M₂L₃ is formed with Pd(II) at pH 2.5–3.5, and shows an absorption maximum at 640 nm with a molar absorptivity of (5.7 ± 0.1) ·10⁴; the complex can be readily extracted with diphenylguanidine chloride or quaternary ammonium salts dissolved in n-butanol or higher alcohols. The complex obeys Beer's law at 675 nm in the concentration range 10–250 μg Pd(II)/50 ml. Pb(II), Bi(III), Ce(III) and the rare-earth elements are the only expected cationic interferences.     

Radioiodination and biodistribution of isolated lawsone compound from Lawsonia inermis (henna) leaves extract

Lawsonia inermis (henna) is one of the most effective medicinal plants and it has been using for treatment of wounds and burns for centuries. The using of Henna leaves is very popular for cosmetic as well as medicine in many countries. Henna leaves contain lots of different compounds and lawsone (LW) is the main one. In current study, extraction with bidistillated water of henna leaves was performed and LW was isolated by using high performance liquid chromatography system. Chemical structure of LW was evaluated by nuclear magnetic resonance method. LW was radiolabeled with iodine-131 (¹³¹I) radionuclide which is well known for nuclear imaging and therapy in nuclear medicine by utilizing iodogen method. The yield of radiolabeling of LW (¹³¹I-LW) was calculated as 92.70 ± 4.312 % (n = 10) by thin layer radio chromatography. Its in vivo biological activity was investigated by biodistribution studies which were performed by using healthy female and male Balb/C mice. According to results of biodistribution, uptake of ¹³¹I labeled LW compound in uterus, breast and ovary for female mice and prostate in male mice was higher than other organs in the body.     

Synthesis,characterization and in vitro cytotoxicity of palladium(II) complexes with mixed ligands. X‐ray diffraction study of C31H36ClNPPdS2

Pd(II) complexes with organophosphines and dithiocarbamates derivatives of α‐amino acids were synthesized by reacting N,N‐dicyclohexyldithiocarbamate (DCHDTC, compounds 1 – 3 ) and N‐methylcyclohexyldithiocarbamate (MCHDTC, compounds 4 – 6 ) with (R₃P)₂PdCl₂ (R = Ph, o‐tolyl, Ph₂Cl) in a 1:1 molar ratio. The complexes were characterized by elemental analyses, FT‐IR, multinuclear (¹H, ¹³C and ³¹P) NMR and single X‐ray crystallography, showing that the dithiocarbamate acts as a bidentate ligand and binds to Pd(II) via two sulfur atoms, resulting in a square planar geometry around Pd(II). The cytotoxicity of compounds 2, 3 and 4 was determined in vitro against six human tumour cell lines, MCF7, EVSA‐T, WIDR, IGROV, M19 MEL, A498 and H226. Compounds 3 and 4 showed a moderate to low cytotoxicity, whereas compound 2 exhibited a very low cytotoxicity. The results of antifungal assays showed that compounds 1 – 6 possess antifungal activity against Fusarium moniliformes, Fusarium saolani, Mucor sp., Aspergillus niger and Aspergillus fumigatus. The anti‐inflammatory screening results of 1–6 are quite similar to those observed for the standard drug Declofenac at 10 mg kg^?1, which inhibited the odema by 74% after 4 h. Copyright © 2007 John Wiley & Sons, Ltd.     

A Study of the Metabolic Degradation of an insect juvenile hormone analog using different radiolabeling

The fate of an insect juvenile hormone analog applied to the insect body of the flesh fly (Sarcophaga bullata) or the tsetse fly (Glossina palpalis), respectively, was studied using three different radiolabeled positions in the parent biologically active compound 1 . Several metabolites were found and analyzed. A mechanism of degradation of the applied molecule was designed using a combination of several radioanalytical methods. A unique monitoring of the applied compound and its metabolites was provided, based on the different radiolabeling of the structure (cf. 1a – 1c ), and established their fate in an insect body during a 10-day experiment. A ¹⁴C and ³H radiolabeling, respectively, was employed to synthesize three different radiolabeled forms 1a – 1c derived from the parent non-labeled 1 . A combination of three different ways of radiolabeling resulted in an advantage in tracing the metabolic pathway of degradation of the employed compound 1 in its radiolabeled forms 1a – 1c .     

Synthesis,structure, and characterization of picolyl- and benzyl-linked biphenyl palladium N-heterocyclic carbene complexes and their catalytic activity in acylative cross-coupling reactions

N-heterocyclic carbene ligands with picolyl (L¹H₂Br₂, L³H₂Br₂) and benzyl (L²H₂Br₂, L⁴H₂Br₂) linked biphenyl backbone were synthesized and characterized. Their palladium(II) complexes [PdL¹]Br₂ ( 1 ), [PdL²Br₂] ( 2 ), [PdL³]Br₂ ( 3 ), and [PdL⁴Br₂] ( 4 ) were synthesized by direct method using Pd(OAc)₂. All complexes ( 1 – 4 ) were characterized by CHN analysis, electrospray ionization-MS, nuclear magnetic resonance, and single-crystal X-ray diffraction. Molecular structures confirm the distorted square planar geometry around the Pd(II) center. All of them showed good catalytic activity in acylative Suzuki cross coupling of phenyl boronic acid with benzoyl chloride to afford benzophenone in good yields.     

Abtrennung von Palladiumspuren aus Reinstplatin nach Neutronenaktivierung unter Berücksichtigung weiterer Spurenverunreinigungen

As first step the separation of¹⁰⁹Pd (T1/2=13.5 h) after neutron activation from the highly radioactive platinum is performed after addition of Pd carrier as chloro-complex on strong basic anion-exchangers. The simultaneous separation of some further short living radionuclides of trace element stakes place. After a purification step with dimethylglyoxime decontamination factors up to 10⁶ are attainable. Using an Ge(Li)-detector and evaluating theγ-irradiation of the¹⁰⁹Pd daughter^109mAg 0.4 μg of Pd could be determined with a standard deviation of 6.5%.     

X-ray photoelectron study of electron density distribution in palladium(II) β-diketonate complexes

This work is devoted to experimental (X-ray photoelectron) and theoretical investigations of electron density distribution in Pd(II) β-diketonate complexes. Data about the electronic structure (effective charges, core level energies) of the compounds are compared with their thermodynamic parameters (thermal stability, vaporization enthalpy). In molecular crystals of Pd(II) β-diketonates, the volatility of the complexes and vaporization enthalpy ΔH _T ⁰ depend not only on van der Waals interactions, but also on electrostatic interactions of molecules in crystal.     

Planare Pt(II)- und Pd(II)-Komplexe aus dreizähnigen Azo- und Azomethinliganden: Ein Beitrag zur Frage der Nα/Nβ-Isomerie

Planar Pt(II)- and Pd(II)-Complexes with Terdentate Azo- and Azomethine Ligands: A Contribution to the Question of Nα/Nβ-Isomerism. The preparation and properties of novel Pt(II)- and Pd(II)-complexes with terdentate azo- and azomethine ligands and with an amine in the fourth coordination position of the metals are described. In certain cases the formation of isomeric complexes is observed, which are interpretated as Nα/Nβ-isomers according to their ¹H-NMR.-signals. The postulated isomerism will be proved by ¹⁵N-NMR.-spectroscopy – in the following publication [5] using ¹⁵N-enriched compounds whose syntheses are described in this publication.     

Phosphazene/Lewis Acids as Highly Efficient Cooperative Catalyst for Synthesis of High-Molecular-Weight Polyesters by Ring-Opening Alternating Copolymerization of Epoxide and Anhydride

The synthesis of high-molecular-weight polyesters via the ring-opening alternating copolymerization (ROAC) of cyclic anhydrides and epoxides using organocatalysts remains a major challenge. In this context, the organic cyclic trimeric phosphazene base ( CTPB ) was used as an efficient catalyst for the ROAC of phthalic anhydride (PA) with epoxides. It was found that the activity and PA conversion dramatically increased with the addition of triethyl borane (TEB) as a cocatalyst, even a small amount of TEB, for example, 5 mol % relative to CTPB . The molecular structures of obtained polyesters were characterized by nuclear magnetic resonance (¹H NMR, ¹³C NMR) and matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF), which demonstrated the formation of perfectly alternating polyesters with unimodal and narrow molecular weight distributions. Different molecular weight polyesters (up to 118.5 kg mol⁻¹) were facilely prepared by reducing the loading of CTPB and TEB, while the polymerizations were fast (turnover frequency, TOF up to 500 h⁻¹). Thermal analysis of the resulting polymers indicated that the alternating polyesters were amorphous, and their T_gs increased with the increment of molecular weights. © 2020 Wiley Periodicals, Inc. J. Polym. Sci. 2020 , 58, 803–810     

Isobaric yields and radiochemistry of near-target residues in the interaction of 12C and 16O with 103Rh at an incident energy of 400 MeV

Production cross sections of residues with mass near to that of the target were measured in ¹²C and ¹⁶O induced reactions on Rh at an incident energy of 400 MeV. An ion-exchange method has been developed for the separation of Rh, Pd and Ag nuclides from all other produced activities. Rh and Ag nuclides were separated from elements such as Pd, Ru, and Tc, amongst others, on an AG1-X8 anion exchange resin in 6M HCl. The Ag nuclides were then removed from the effluent using a precipitation technique so that only Rh remained in the final solution. The Pd was afterwards separated from Ru and Tc by eluting it from the resin with 5% ammonia solution. This procedure made it possible to accurately measure production cross sections for ^103mRh and ¹⁰³Pd. Cross sections for the production of various other observed residues are also presented. The results are consistent with an enhanced isobaric yield in the near-target mass region. The radiochemical separation technique is also suitable for the routine production of Pd and Rh nuclides, e.g., ¹⁰³Pd and ^101mRh, in proton-induced reactions on Rh targets     

64Cu radiolabeled nanomaterials for positron emission tomography (PET) imaging

The prevalence of positron emission tomography (PET) imaging has advanced biomedical applications for its ultrahigh sensitivity, deep tissue penetration and quantitative visualization of diseases in vivo. ⁶⁴Cu with ideal half-life and decay characteristics has been designed as radioactive probes for disease diagnosis. The currently reported ⁶⁴Cu-labeled nanomaterials have the advantages of long circulation time in serum, good biocompatibility and mature preparation methods, and have been used in vivo PET imaging, biodistribution and pharmacokinetic monitoring, and imaging guided therapy. At the same time, suitable carrier characteristics and radiolabeling strategies are particularly important in the ⁶⁴Cu PET imaging process. In this review, we summarize different imaging probe designs and ⁶⁴Cu radiolabeling strategies, as well as their eventual applications in biomedicine. The potential challenges and prospects of ⁶⁴Cu labeled nanomaterials are also described, which provides broad prospects for radiolabeling strategies and further applications.     

Sorption behavior of hydroxyapatite for 109Cd(II) as a function of environmental conditions

In this work, hydroxyapatite (HAP) was prepared by aqueous precipitation technique and was characterized by using FT-IR to determine its chemical functional groups. A series of batch experiments were carried out to investigate the effect of various environmental factors such as contact time, pH, ionic strength, foreign ions, fulvic acid (FA) and temperature on the sorption behavior of HAP towards radionuclide ¹⁰⁹Cd(II). The results indicated that the sorption of ¹⁰⁹Cd(II) on HAP was strongly dependent on pH and ionic strength. A positive effect of FA on ¹⁰⁹Cd(II) sorption was found at pH <7.0, whereas a negative effect was observed at pH >7.0. The Langmuir, Freundlich and D-R models were used to simulate the sorption isotherms at three different temperatures of 298.15, 323.15 and 343.15 K. The thermodynamic parameters (ΔH⁰, ΔS⁰ and ΔG⁰) calculated from the temperature dependent sorption isotherms indicated that the sorption process of ¹⁰⁹Cd(II) on HAP was spontaneous and endothermic. At low pH, the sorption of ¹⁰⁹Cd(II) was dominated by outer-sphere surface complexation and ion exchange on HAP surfaces, whereas inner-sphere surface complexation was the main sorption mechanism at high pH. From the experimental results, it is possible to conclude that HAP has good potentialities for cost-effective treatments of ¹⁰⁹Cd(II)-contaminated wastewaters.     

Evaluation of Traumatic Spinal Cord Injury in a Rat Model Using 99mTc-GA-5 as a Potential In Vivo Tracer

Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether ^99mTc-GA-5, a radiotracer targeting Glial Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the ^99mTc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of ^99mTc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5’s recognition/specificity ability were observed after the radiolabeling. The GA-5’s radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.