Equilibrium and Kinetic Properties of the Lanthanoids(III) and Various Divalent Metal Complexes of the Heptadentate Ligand AAZTA

Towards improved kinetic stability : A detailed account of the complexation properties of the ligand 1,4‐bis(hydroxycarbonylmethyl)‐6‐[bis(hydroxycarbonylmethyl)]amino‐6‐methylperhydro‐1,4‐diazepine (AAZTA; see figure) is reported. Its Gd³⁺ complex shows a kinetic stability superior to that of complexes formed by higher denticity ligands and opens the way for a new reference structure for MRI contrast agents.

     

Defining the conditions for the development of the emerging class of FeIII-based MRI contrast agents

Fe(iii) complexes are attracting growing interest in chemists developing diagnostic probes for Magnetic Resonance Imaging because they leverage on an endogenous metal and show superior stability. However, in this case a detailed understanding of the relationship between the chemical structure of the complexes, their magnetic, thermodynamic, kinetic and redox properties and the molecular parameters governing the efficacy (relaxivity) is still far from being available. We have carried out an integrated ¹H and ¹⁷O NMR relaxometric study as a function of temperature and magnetic field, on the aqua ion and three complexes chosen as reference models, together with theoretical calculations, to obtain accurate values of the parameters that control their relaxivity. Moreover, thermodynamic stability and dissociation kinetics of the Fe(iii) chelates, measured in association with the ascorbate reduction behaviour, highlight their role and mutual influence in achieving the stability required for use in vivo.

An integrated ¹H and ¹⁷O NMR relaxometric study on model systems allowed to highlight that the Fe(III) complexes might represent the best alternative to Gd-based MRI contrast agents at the magnetic fields of current and future clinical scanners.     

Pyridino-18-crown-6 ether type chemosensors containing a benzothiazole fluorophore unit: Synthesis and enantiomeric recognition studies

Three new fluorescent enantiopure pyridino-18-crown-6 ethers containing a benzothiazole unit were prepared, and the enantiomeric discrimination of these sensor molecules toward the hydrogen perchlorate salts of 1-phenylethylamine, 1-(1-naphthyl)ethylamine, phenylglycine methyl ester and phenylalanine methyl ester was studied in acetonitrile by fluorescence spectroscopy. The ligands revealed appreciable or moderate selectivity toward the enantiomers of hydrogen perchlorate salts of 1-phenylethylamine, 1-(1-naphthyl)ethylamine and phenylglycine methyl ester.     

Hamiltonian decomposition of lexicographic product

In this paper we prove the conjecture of J.-C. Bermond (Ann. Discrete Math.36 (1978), 21–28): If two graphs are decomposable into Hamiltonian cycles, then their lexicographic product is decomposable, too.     

Development of a Novel Ultrasonic Spectroscopy Method for Estimation of Viscosity Change during Milk Clotting

Ultrasonic testing is an emerging non-destructive testing technology with high repeatability and precision. Milk is a very complex liquid and the change of its viscosity is a highly relevant property throughout conversion into other dairy products. In the following paper, we propose a novel method for the monitoring of viscosity during enzymatic milk clotting by ultrasonic spectroscopy. An ultrasonic transducer–receiver couple with a 250 kHz nominal frequency was submerged in the samples and an enveloped sweep (“chirp”) signal was applied in a through-transmission mode. Simultaneously, the change in viscosity was measured with a rotational viscometer at a constant shearing speed. The data were analyzed with an algorithm developed by the authors for spectral ultrasonic testing. Estimations yielded a high adjusted R² (0.963–0.998) and low cross-validated estimation error (RPD: 4.38–14.22), suggesting that the method is suitable for industrial use given the right instrumentation.     

Semi-Rigid (Aminomethyl) Piperidine-Based Pentadentate Ligands for Mn(II) Complexation

Two pentadentate ligands built on the 2-aminomethylpiperidine structure and bearing two tertiary amino and three oxygen donors (three carboxylates in the case of AMPTA and two carboxylates and one phenolate for AMPDA-HB) were developed for Mn(II) complexation. Equilibrium studies on the ligands and the Mn(II) complexes were carried out using pH potentiometry, ¹H-NMR spectroscopy and UV-vis spectrophotometry. The Mn complexes that were formed by the two ligands were more stable than the Mn complexes of other pentadentate ligands but with a lower pMn than Mn(EDTA) and Mn(CDTA) (pMn for Mn(AMPTA) = 7.89 and for Mn(AMPDA-HB) = 7.07). ¹H and ¹⁷O-NMR relaxometric studies showed that the two Mn-complexes were q = 1 with a relaxivity value of 3.3 mM⁻¹ s⁻¹ for Mn(AMPTA) and 3.4 mM⁻¹ s⁻¹ for Mn(AMPDA-HB) at 20 MHz and 298 K. Finally, the geometries of the two complexes were optimized at the DFT level, finding an octahedral coordination environment around the Mn²⁺ ion, and MD simulations were performed to monitor the distance between the Mn²⁺ ion and the oxygen of the coordinated water molecule to estimate its residence time, which was in good agreement with that determined using the ¹⁷O NMR data.     

Comprehensive Evaluation of the Physicochemical Properties of LnIII Complexes of Aminoethyl‐DO3A as pH‐Responsive T1‐MRI Contrast Agents

N‐Substituted aminoethyl groups were attached to 1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid (DO3A) with the aim to design pH‐responsive Ln^III complexes based on the pH‐dependent on/off ligation of the amine nitrogen to the metal ion. The following ligands were synthesized: AE ‐ DO3A (aminoethyl‐DO3A), MAE ‐ DO3A (N‐methylaminoethyl‐DO3A), DMAE ‐ DO3A (N,N‐dimethylaminoethyl‐DO3A) and MEM ‐ AE ‐ DO3A (N‐methoxyethyl‐N‐methylaminoethyl‐DO3A). The physicochemical properties of the Ln^III complexes were investigated for the evaluation of their potential applicability as magnetic resonance imaging (MRI) contrast agents. In particular, a ¹H and ¹⁷O NMR relaxometric study was carried out for these Gd^III complexes at two different pH values: at basic pH (pendant amino group coordinated to the metal centre) and at acidic pH (protonated amine, not interacting with the metal ion). Eu^III complexes allow one to estimate the number of inner‐sphere water molecules through luminescence lifetime measurements and obtain some structural information through variable‐temperature (VT) high‐resolution ¹H NMR studies. Equilibria between differently hydrated species were found for most of the complexes at both acidic and basic pH. The thermodynamic stability of Ca^II, Zn^II, Cu^II and Ln^III complexes and kinetics of formation and dissociation reactions of Ln^III complexes of AE ‐ DO3A and DMAE ‐ DO3A were investigated showing stabilities comparable to currently approved Gd^III‐based CAs. In detail, higher total basicity (Σlog K_i^H) and higher stability constants of Ln^III complexes were found for AE ‐ DO3A with respect to DMAE ‐ DO3A (i.e., log K_{Gd‐ AE‐DO3A} =22.40 and log K_{Gd‐ DMAE‐DO3A} =20.56). The transmetallation reactions of Gd^III complexes are very slow (Gd‐ AE ‐ DO3A : t_1/2=2.7×10⁴ h; Gd‐ DMAE ‐ DO3A : 1.1×10⁵ h at pH 7.4 and 298 K) and occur through proton‐assisted dissociation.     

Synthesis and fluorescence studies of novel bis(azacrown ether) type chemosensors containing an acridinone unit

Three new bis(azacrown ether)s containing an acridinone fluorescent signalling unit were prepared by reacting 9-chloro-4,5-bis(chloromethyl)acridine with monoazacrown ethers with different cavity sizes followed by a hydrolysis step. Their fluorescent characteristics and the complexation properties of the one containing two monoaza-18-crown-6 ether receptors towards selected metal ions were studied. The operation of the latter ligand is based on the photoinduced electron transfer (PET) process, thus it shows fluorescence enhancement in the presence of metal ions. Since the sensor molecule contains two receptor moieties, it is able to form two types of complex with 1:1 and 1:2 ligand to metal ion ratios, which have different emission spectra. The reason for this spectral difference may be that the 1:1 complex is a sandwich type one in which the acridinone unit can undergo structural changes.