Off-line and real-time monitoring of acetaminophen photodegradation by an electrochemical sensor.

The photochemistry of N-acetyl-para-aminophenol (acetaminophen, APAP) is here investigated by using differential pulse voltammetry (DPV) analysis to monitor APAP photodegradation upon steady-state irradiation. The purpose of this work is to assess the applicability of DPV to monitor the photochemical behaviour of xenobiotics, along with the development of an electrochemical set-up for the real-time monitoring of APAP photodegradation. We here investigated the APAP photoreactivity towards the main photogenerated reactive transients species occurring in sunlit surface waters (hydroxyl radical HO, carbonate radical CO3-, excited triplet state of anthraquinone-2-sulfonate used as proxy of the chromophoric DOM, and singlet oxygen 1O2), and determined relevant kinetic parameters. A standard procedure based on UV detection coupled with liquid chromatography (HPLC-UV) was used under identical experimental conditions to compare and verify the DPV-based results. The latter were in agreement with HPLC data, with the exception of the triplet-sensitized processes. In the other cases, DPV could be used as an alternative to the well-tested but more costly and time-consuming HPLC-UV technique. We have also assessed the reaction rate constant between APAP and HO by real-time DPV, which allowed for the monitoring of APAP photodegradation inside the irradiation chamber. Unfortunately, real-time DPV measurements are likely to be affected by temperature variations of the irradiated samples. Overall, DPV appeared as a fast, cheap and reasonably reliable technique when used for the off-line monitoring of APAP photodegradation. When a suitable real-time procedure is developed, it could become a very straightforward method to study the photochemical behaviour of electroactive xenobiotics.

α-trideuteromethyl[15N]glutamine: A long-lived hyperpolarized perfusion marker.

PURPOSE: We characterized the performance of a novel hyperpolarized perfusion marker, α-trideuteromethyl[15N]glutamine, for direct comparison with a 13C-based hyperpolarized perfusion marker, [13C, 15N2]urea. METHODS: A hardware platform and pulse sequence for in vivo 15N experiments were established. Hyperpolarized solutions of α-trideuteromethyl[15N]glutamine and [13C, 15N2]urea were injected into healthy male Lewis rats. Kidney slice images were acquired using a single-shot spiral readout. Both compounds were compared to determine in vivo signal lifetime and tracer distribution. Mass spectrometry was performed to evaluate excretion of the compound. RESULTS: Compared with 13C-labeled urea, a significantly increased signal lifetime was observed. While the urea signal was gone after 90 s, decay of the glutamine compound was sufficiently slow to obtain a quantifiable signal, even after 5 min. The glutamine derivative showed strong localization in the kidneys with little background signal. Effective T1 of α-trideuteromethyl[15N]glutamine was approximately eight-fold higher than that of urea. Mass spectrometry results confirmed rapid excretion within the time scale of the measurement. CONCLUSION: Hyperpolarized α-trideuteromethyl[15N]glutamine is a highly promising candidate for renal studies because of its long signal lifetime, strong localization and rapid excretion. Magn Reson Med 76:1900-1904, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Properties of the humic-like material arising from the photo-transformation of L-tyrosine.

The UVB photolysis of L-tyrosine yields species with fluorescence and absorption spectra that are very similar to those of humic substances. By potentiometric measurements, chemical modeling and the application of NMR, mass spectrometry and laser flash photolysis, it was possible to get insights into the structural and chemical properties of the compounds derived by the L-tyrosine phototransformation. The photolytic process follows aromatic-ring hydroxylation and dimerization. The latter is presumably linked with the photoinduced generation of tyrosyl (phenoxy-type) radicals, which have a marked tendency to dimerize and possibly oligomerize. Interestingly, photoinduced transformation gives compounds with protogenic and complexation capabilities similar to those of the humic substances that occur naturally in surface waters. This finding substantiates a new and potentially important abiotic (photolytic) pathway for the formation of humic compounds in surface-water environments.

Charge-transfer complexes of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone with amino molecules in polar solvents.

The charge-transfer complexes have scientific relevance because this type of molecular interaction is at the basis of the activity of pharmacological compounds and because the absorption bands of the complexes can be used for the quantification of electron donor molecules. This work aims to assess the stability of the charge-transfer complexes between the electron acceptor 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and two drugs, procaine and atenolol, in acetonitrile and ethanol. The stability of DDQ in solution and the time required to obtain the maximum complex formation were evaluated. The stoichiometry and the stability of the complexes were determined, respectively, by Job's plot method and by the elaboration of UV-vis titrations data. The latter task was carried out by using the non-linear global analysis approach to determine the equilibrium constants. This approach to data elaboration allowed us to overcome the disadvantages of the classical linear-regression method, to obtain reliable values of the association constants and to calculate the entire spectra of the complexes. NMR spectra were recorded to identify the portion of the donor molecule that was involved in the interaction. The data support the participation of the aliphatic amino groups in complex formation and exclude the involvement of the aromatic amine present in the procaine molecule.

15N-permethylated amino acids as efficient probes for MRI-DNP applications.

The synthesis, NMR properties and preliminary polarization tests on protonated and perdeuterated forms of α-trimethylglutamine (NMe3Gln), α-trimethylglutamate (NMe3Glu) and ε-trimethyllysine (NMe3Lys) are reported. The (15)N-permethylated, perdeuterated amino acids display very long (15)N-T1 values, ranging between 190 and 330 s, are well polarized by the dynamic nuclear polarization (DNP) procedure, yielding good polarization levels (10%), and appear to be well tolerated by cells and mice. The obtained results make perdeuterated amino acids excellent candidates for innovative DNP (15)N-MRI applications such as perfusion or targeting studies.

Earth's magnetic field enabled scalar coupling relaxation of 13C nuclei bound to fast-relaxing quadrupolar 14N in amide groups.

Scalar coupling relaxation, which is usually only associated with closely resonant nuclei (e.g., (79)Br-(13)C), can be a very effective relaxation mechanism. While working on hyperpolarized [5-(13)C]glutamine, fast liquid-state polarization decay during transfer to the MRI scanner was observed. This behavior could hypothetically be explained by substantial T(1) shortening due to a scalar coupling contribution (type II) to the relaxation caused by the fast-relaxing quadrupolar (14)N adjacent to the (13)C nucleus in the amide group. This contribution is only effective in low magnetic fields (i.e., less than 800 µT) and prevents the use of molecules bearing the (13)C-amide group as hyperpolarized MRS/MRI probes. In the present work, this hypothesis is explored both theoretically and experimentally. The results show that high hyperpolarization levels can be retained using either a (15)N-labeled amide or by applying a magnetic field during transfer of the sample from the polarizer to the MRI scanner.

In†Vivo Magnetic Resonance Imaging Detection of Paramagnetic Liposomes Loaded with Amphiphilic Gadolinium(III) Complexes: Impact of Molecular Structure on Relaxivity and Excretion Efficiency.

The magnetic resonance imaging (MRI) performance of two liposome formulations incorporating amphiphilic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-like GdIII complexes has been investigated both in vitro and in vivo. The complexes differ in one donor group of the coordination cage (carboxylate versus carboxoamide), and in the length (C12 versus C18 ) and the point of attachment of the aliphatic chains to the chelators. The in vitro 1 H relaxometric characterisation of the systems, performed with a newly developed relaxation model that takes into account the contributions of the GdIII chelates pointing in- and outwards of the liposome, indicates that their efficacy is optimal in the range 0.5-1.5 T. The tetracarboxylic C12 -containing liposomes (LIPO-GdDOTA(GAC12 )2 ; GA=glutaric acid) are four-fold more efficient than the monoamide C18 -based analogue (LIPO-GdDOTAMA(C18 )2 ). Such a difference is also found in vivo at 1 T in a melanoma tumour model on mice. A few hours after intravenous injection, the T1 contrast enhancement in the organs where the nanovesicles typically distribute (liver, spleen, kidneys and tumour) is much higher for LIPO-GdDOTA(GAC12 )2 . Interestingly, after about 7 h post-injection the contrast enhancement observed for the more efficient liposomes decreases rapidly and becomes lower than for LIPO-GdDOTAMA(C18 )2 . The relaxometric data and the quantification of the GdIII complexes in the organs, determined ex vivo by inductively coupled plasma mass spectrometry, indicate that: 1) the differences in the contrast enhancement can be attributed to the different rate of water exchange and rotational dynamics of the Gd complexes, and 2) the rapid contrast decrease is caused by a faster clearance of GdDOTA(GAC12 )2 from the organs. This is also confirmed by using a newly synthesised amphiphilic cyanine-based fluorescent probe (Cy5-(C16 )2 ). As one of the main limitations for the clinical translation of liposomes incorporating amphiphilic imaging agents is related to their very long persistence in the body, the results reported herein suggest that the clearance of the probes can be accelerated, without compromising their role, by a proper selection of the lipophilic portion of the incorporated compound as well as of the ligand site at which the aliphatic tails are linked. Then, GdDOTA(GAC12 )2 complex may represent a good candidate for the development of improved MRI protocols based on paramagnetically labelled lipidic nanoparticles.