Hexacyanometalate molecular chemistry: heptanuclear heterobimetallic complexes; control of the ground spin state

Following a bottom-up approach to nanomaterials, we present a rational synthetic route from hexacyanometalates [M(CN)(6)](3-) (M=Cr(III), Co(III)) cores to well-defined heptanuclear complexes. By changing the nature of the metallic cations and using a localised orbital model it is possible to control and to tune the ground state spin value. Thus, with M=Cr(III), d(3), S=3/2, three heptanuclear species were built and characterised by mass spectrometry in solution, by single-crystal X-ray diffraction and by powder magnetic susceptibility measurements, [Cr(III)(CNbondM'L(n))(6)](9+) (M'=Cu(II), Ni(II), Mn(II), L(n)=polydentate ligand), showing spin ground states S(G)=9/2 [Cu(II)], with ferromagnetic interactions J(Cr,Cu)=+45 cm(-1), S(G)=15/2 [Ni(II)] and J(Cr,Ni)=+17.3 cm(-1), S(G)=27/2 [Mn(II)], with an antiferromagnetic interaction J(Cr,Mn)=-9 cm(-1), (interaction Hamiltonian H=-J(Cr,M) [S(Cr)Sigma(i)S(M)(i)], i=1-6). With M=Co(III), d(6), S=0, the heptanuclear analogues [Co(III)(CN-M'L(n))(6)](9+) (M'=Cu(II), Ni(II), Mn(II)) were similarly synthesised and studied. They present a singlet ground state and allow us to evaluate the weak antiferromagnetic coupling constant between two next-nearest neighbours M'-Co-M'.     

A fast and inexpensive procedure for the isolation of synthetic cannabinoids from ‘Spice’ products using a flash chromatography system

In the age of the Internet, the variety of drugs offered online is constantly increasing, and new drugs emerge every month. One group of drugs showing such an enormous increase is that of synthetic cannabinoids. Since their first identification in ‘herbal mixtures’, new structural modifications continue to appear on the market. In order to keep up with this process, toxicological screening methods need to be up to date. This can become extremely difficult if no reference material is available. In this article, a fast and effective way to extract and purify synthetic cannabinoids from ‘herbal mixtures’ is presented. This method opens a new opportunity for a timely reaction by obtaining reference material straight out of the ‘herbal mixtures’ ordered via the Internet. Isolation was carried out on a flash chromatography system with gradient elution on a C18 column using methanol and 0.55 % formic acid as mobile phases. The obtained purity of all compounds exceeded 99 %. In addition to the isolation of single compounds, the method proved to be suitable for the separation of various synthetic cannabinoids in one mixture, including the diastereomers cis- and trans-CP-47,497-C8. This approach for obtaining pure standards of new drugs proved to be effective, inexpensive and much quicker than waiting for the substances to be commercially available as reference material.

Sensitive quantification of clozapine and its main metabolites norclozapine and clozapine-<Emphasis Type="Italic">N</Emphasis>-oxide in serum and urine using LC-MS/MS after simple liquid–liquid extraction work-up

An LC-MS/MS method for the determination of the atypic neuroleptic clozapine and its two main metabolites norclozapine and clozapine-N-oxide has been developed and validated for serum and urine. After addition of d4-clozapine as deuterated internal standard a fast single-step liquid–liquid extraction under alkaline conditions and with ethyl acetate as organic solvent followed. The analytes were chromatographically separated on a Synergi Polar RP column using gradient elution with 1 mM ammonium formate and methanol. Data acquisition was performed on a QTrap 2000 tandem mass spectrometer in multiple reaction monitoring mode with positive electrospray ionization. Two transitions were monitored for each analyte in order to fulfill the established identification criteria. The validation included the determination of the limits of quantification (1.0 ng/mL for all analytes in serum and 2.0 ng/mL for all analytes in urine), assessment of matrix effects (77% to 92% in serum, 21 to 78% in urine) and the determination of extraction efficiencies (52% to 85% for serum, 59% to 88% for urine) and accuracy data. Imprecision was <10%, only the quantification of norclozapine in urine yielded higher relative standard deviations (11.2% and 15.7%). Bias values were below ±10%. Dilution of samples had no impact on the correctness for clozapine and norclozapine in both matrices and for clozapine-N-oxide in serum. For quantification of clozapine-N-oxide in urine a calibration with diluted calibrators has to be used. Calibration curves were measured from the LOQ up to 2,000 ng/mL and proved to be linear over the whole range with regression coefficients higher than 0.98. The method was finally applied to several clinical serum and urine samples and a cerebro-spinal fluid sample of an intoxicated 13-month-old girl.     

High Spin and Anisotropic Molecules Based on Polycyanometalate Chemistry

 This paper points out some recent achievements in the chemistry and physics of high spin and anisotropic molecules based on polycyanometalate complexes. Following a step by step synthetic strategy and using a localized electron orbital model, isotropic high spin molecules were obtained with ground spin states ranging from S = 9/2 to 27/2. In the same way, anisotropic molecules with various nuclearities (bi, tri, tetra, hexa, and hepta-nuclear complexes) have been synthesized. Mixing these two approaches, it has been possible to obtained anisotropic high spin molecules that behave as single molecule magnets. The paper reviews some of the steps that lead to these findings and some of the prospects opened in the field of single molecule magnets. Corresponding author. E-mail: marvaud@ccr.jussieu.fr Received July 19, 2002; accepted July 23, 2002     

Aryl urea substituted fatty acids: a new class of protonophoric mitochondrial uncoupler that utilises a synthetic anion transporter

Respiring mitochondria establish a proton gradient across the mitochondrial inner membrane (MIM) that is used to generate ATP. Protein-independent mitochondrial uncouplers collapse the proton gradient and disrupt ATP production by shuttling protons back across the MIM in a protonophoric cycle. Continued cycling relies on the formation of MIM-permeable anionic species that can return to the intermembrane space after deprotonation in the mitochondrial matrix. Previously described protonophores contain acidic groups that are part of delocalised π-systems that provide large surfaces for charge delocalisation and facilitate anion permeation across the MIM. Here we present a new class of protonophoric uncoupler based on aryl-urea substituted fatty acids in which an acidic group and a π-system are separated by a long alkyl chain. The aryl-urea group in these molecules acts as a synthetic anion receptor that forms intermolecular hydrogen bonds with the fatty acid carboxylate after deprotonation. Dispersal of the negative charge across the aryl-urea system produces lipophilic dimeric complexes that can permeate the MIM and facilitate repeated cycling. Substitution of the aryl-urea group with lipophilic electron withdrawing groups is critical to complex lipophilicity and uncoupling activity. The aryl-urea substituted fatty acids represent the first biological example of mitochondrial uncoupling mediated by the interaction of a fatty acid and an anion receptor moiety, via self-assembly.

A new mitochondrial uncoupler that forms membrane permeable dimers through interactions of remote acidic and anion receptor groups.     

Superabsorbent Hydrogels Based to Polyacrylamide/Cashew Tree Gum for the Controlled Release of Water and Plant Nutrients

Agricultural production is influenced by the water content in the soil and availability of fertilizers. Thus, superabsorbent hydrogels, based on polyacrylamide, natural cashew tree gum (CG) and potassium hydrogen phosphate (PHP), as fertilizer and water releaser were developed. The structure, morphology, thermal stability and chemical composition of samples of polyacrylamide and cashew tree gum hydrogels with the presence of fertilizer (HCGP) and without fertilizer (HCG) were investigated, using X-ray diffractometry (XRD), Fourier Transformed Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Thermogravimetric Analysis (TGA/DTG) and Energy Dispersive Spectroscopy (EDS). Swelling/reswelling tests, textural analysis, effect of pH, release of nutrients and kinetics were determined; the ecotoxicity of the hydrogels was investigated by the Artemia salina test. The results showed that PHP incorporation in the hydrogel favored the crosslinking of chains. This increased the thermal stability in HCGP but decreased the hardness and adhesion properties. The HCGP demonstrated good swelling capacity (~15,000 times) and an excellent potential for reuse after fifty-five consecutive cycles. The swelling was favored in an alkaline pH due to the ionization of hydrophilic groups. The sustained release of phosphorus in HCGP was described by the Korsmeyer–Peppas model, and Fickian diffusion is the main fertilizer release mechanism. Finally, the hydrogels do not demonstrate toxicity, and HCGP has potential for application in agriculture.     

Ru(TAP)3]2+-photosensitized DNA cleavage studied by atomic force microscopy and gel electrophoresis: a comparative study

Topological modifications of plasmid DNA adsorbed on a variety of surfaces were investigated by using atomic force microscopy (AFM). On mica modified with 3-aminopropyltriethoxysilane (APS) or poly-L-lysine, the interaction between the plasmid DNA and the surface "freezes" the plasmid DNA conformation deposited from solution, and the AFM images resemble the projection of the three-dimensional conformation of the plasmid DNA in solution. Modified mica with low concentrations of Mg(2+) leads to a decrease in the interaction strength between plasmid DNA and the substrate, and the AFM images reflect the relaxed or equilibrium conformation of the adsorbed plasmid DNA. Under these optimized deposition conditions, topological modifications of plasmid DNA were produced under irradiation in the presence of [Ru(TAP)(3)](2+) (TAP = 1,4,5,8-tetraazaphenanthrene), which is a non-intercalating complex, and were followed as a function of illumination time. The observed structural changes correlate well with the conversion of the supercoiled covalently closed circular form (ccc form) into the open circular form (oc form), induced by a single-strand photocleavage. The AFM results obtained after fine-tuning of the plasmid DNA-substrate interaction compare well with those observed from gel electrophoresis, indicating that under the appropriate deposition conditions, AFM is a reliable technique to investigate irradiation-induced topological changes in plasmid DNA.     

Simple spectrophotocolorimetric method for quantitative determination of gold in nanoparticles

A simple spectrophotocolorimetric method devoted to the measurement of gold content in nanoparticles (NPs) was developed. It includes two steps: (i) metal gold NPs (Au NPs) are oxidized into the AuCl₄⁻ anion using a 5 × 10⁻² M HCl-1.5 × 10⁻² M NaCl-7 × 10⁻⁴ M Br₂ solution, next (ii) AuCl₄⁻ concentration is measured using a spectrophotometric assay based on the reaction of AuCl₄⁻ with the cationic form of Rhodamine B to give a violet ion pair complex. This latter is extracted with diisopropyl ether and the absorbance of the organic complex is measured at 565 nm. The method is linear in the range 6-29 μM of AuCl₄⁻ with a limit of detection of 4.5 μM.The analytical method was optimized with respect of bromine excess to obtain complete Au NPs oxidation. The method was applied to two types of Au NPs currently under investigation: citrate-stabilized Au NPs and Au NPs capped with dihydrolipoic acid (Au@DHLA). Both the gold content of Au NPs and the concentration of NPs (using NP diameter measured by transmission electron microscopy) have been calculated.     

Untargeted screening of unknown xenobiotics and potential toxins in plasma of poisoned patients using high-resolution mass spectrometry: Generation of xenobiotic fingerprint using background subtraction

A novel analytical workflow was developed and applied for the detection and identification of unknown xenobiotics in biological samples. High-resolution mass spectrometry (HRMS)-based data-independent MS^E acquisition was employed to record full scan MS and fragment spectral datasets of test and control samples. Then, an untargeted data-mining technique, background subtraction, was utilized to find xenobiotics present only in test samples. Structural elucidation of the detected xenobiotics was accomplished by database search, spectral interpretation, and/or comparison with reference standards. Application of the workflow to analysis of unknown xenobiotics in plasma samples collected from four poisoned patients led to generation of xenobiotic profiles, which were regarded as xenobiotic fingerprints of the individual samples. Among 19 xenobiotics detected, 11 xenobiotics existed in a majority of the patients' plasma samples, thus were considered as potential toxins. The follow-up database search led to the tentative identification of azithromycin (X5), α-chaconine (X9) and penfluridol (X12). The identity of X12 was further confirmed with its reference standard. In addition, one xenobiotic component (Y5) was tentatively identified as a penfluridol metabolite. The remaining unidentified xenobiotics listed in the xenobiotic fingerprints can be further characterized or identified in retrospective analyses after their spectral data and/or reference compounds are available. This HRMS-based workflow may have broad applications in the detection and identification of unknown xenobiotics in individual biological samples, such as forensic and toxicological analysis and sport enhancement drug screening.