1H and 17O NMR relaxometric study in aqueous solution of Gd(III) complexes of EGTA-like derivatives bearing methylenephosphonic groups

The Gd(III) complexes of three new octadentate chelators, prepared by substitution of four, two, and one carboxylate groups of EGTA with phosphonate groups, have been investigated by 1H and 17O NMR relaxometric techniques in aqueous solutions. The analysis of the solvent proton relaxivity data as a function of pH, temperature, and magnetic field strength (nuclear magnetic relaxation dispersion (NMRD) profiles) in combination with the 17O transverse relaxation rate data at variable temperature allowed assessing the hydration state of the complexes, the occurrence of pH-dependent oligomerization processes for the tetraphosphonate derivative, the presence of a well-defined second sphere of hydration that markedly contributes to the relaxivity, and the values of the structural and dynamic relaxation parameters. In addition, in the case of the monophosphonate derivative the presence of a coordinated water molecule has allowed evaluation of the kinetic parameters of the exchange process, highly relevant for the possible use of this Gd(III) complex as an MRI probe. The rate of exchange of the water molecule, (298)k(ex) = 4.2 x 10(8)s(-1), is one of the highest measured so far for a nonacoordinate Gd(III) chelate and optimal for developing contrast-enhancing probes of high efficacy at high magnetic fields.     

High relaxivity gadolinium hydroxypyridonate-viral capsid conjugates: nanosized MRI contrast agents

High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a 5-fold increase in relaxivity, leading to a peak relaxivity (per Gd3+ ion) of 41.6 mM(-1) s(-1) at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (i) there is facile diffusion of water to the interior of capsids and (ii) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2), and the NMRD fittings highlight the differences in the local motion for the internal (tauRl = 440 ps) and external (tauRl = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups.     

pH-Dependent Hydration Change in a Gd-Based MRI Contrast Agent with a Phosphonated Ligand

The heptadentate ligand L was shown to form an extremely stable Gd complex at neutral pH with a pGd value of 18.4 at pH 7.4. The X-ray crystal structures of the complexes formed with Gd and Tb displayed two very different coordination behaviors being, respectively, octa- and nonacoordinated. The relaxometric properties of the Gd complex were studied by field-dependent relaxivity measurements at various temperatures and by ¹⁷O NMR spectroscopy. The pH-dependence of the longitudinal relaxivity profile indicated large changes around neutral pH leading to a very large value of 10.1 mm ⁻¹⋅s⁻¹ (60 MHz, 298 K) at pH 4.7. The changes were attributed to an increase of the hydration number from one water molecule in basic conditions to two at acidic pH. A similar trend was observed for the luminescence of the Eu complex, confirming the change in hydration state. DOSY experiments were performed on the Lu analogue, pointing to the absence of dimers in solution in the considered pH range. A breathing mode of the complex was postulated, which was further supported by ¹H and ³¹P NMR spectroscopy of the Yb complex at varying pH and was finally modeled by DFT calculations.     

Fracture behavior and mechanical,thermal, and rheological properties of biodegradable films extruded by flat die and calender

The development of biodegradable materials for tailored applications, particularly in the field of polymeric films and sheets, is a challenging technological goal as well as a contribution to help protect the environment. Poly(lactic) acid (PLA) is a promising substitute for several oil-based polymers; however, to overcome its thermal and mechanical drawbacks, researchers have developed solutions such as blending PLA with polybutylene adipate terephthalate (PBAT), which is capable of increasing the ductility of the final material. In this study, PLA/PBAT binary blends, with minimum possible content of nonrenewable materials, were examined from processing, thermal, morphological, and rheological perspective. An optimized PLA/PBAT ratio was chosen as the polymeric basis to obtain a biodegradable formulation by adding a biobased plasticizer and appropriate fillers to produce a micrometer film with tailored flexibility and tear resistance. The processing technology involved flat-die extrusion, followed by calendering. The tearing resistance of the produced film was investigated, and the results were compared with literature data. A study on the essential work of fracture was implemented to explore the mode III out-of-plane fracture resistance starting from a trouser tear test.     

Effect of adding new phosphazene compounds to poly(butylene terephthalate)/polyamide blends. II: Effect of different polyamides on the properties of extruded samples

Poly(butylene terephthalate) (PBT) and a sample of polyamide have been melt processed in the presence of two new phosphazene compounds, namely 2,2-dichloro-4,4,6,6-bis[spyro(2′,2″-dioxy-1′,1″-biphenyl)]cyclotriphosphazene (2Cl-CP) and 2,2-bis(2-methoxy-4-methyleneoxy-phenoxy)-4,4,6,6-bis[spyro(2′,2″-dioxy-1′,1″-biphenyl)]cyclophosphazene (CP-2EPOX).The blends were prepared by using polyamide 6 (PA6) and polyamide 6,6 (PA66) in 25/75 and 75/25 w/w compositions by using a co-rotating twin-screw extruder.The materials have been completely characterized from a mechanical, rheological, and morphological point of view. The results indicate that the additives used cause an increase of the rupture properties and of the viscosity, especially in the PA6 rich blends containing CP-2EPOX. This result can be not only attributed to a chain extension effect on the PA phase but also to in situ formation of PA/PBT copolymers promoted by the presence of the CP compound as confirmed by NMR and MALDI-TOF analyses. The compatibilization effect fades in blends containing PA66, probably due to a thermal deactivation of the additives at higher temperature required to process this polymer.     

Synthesis and characterisation of dimeric eight-coordinate lanthanide(III) complexes of a macrocyclic tribenzylphosphinate ligand

The macrocyclic ligand 1,4,7,10-tetraazacyclododecane-1,4,7-triyl(methylenebenzyl-phosphinic acid) H3L3, has been prepared and its complexes with Eu, Gd and Tb(III) studied by NMR, relaxometry, luminescence and single crystal X-ray crystallography. In solution and in the crystal, the complexes have eight-coordinate metal centres with bridging phosphinate groups linking the two twisted square antiprismatic coordination polyhedra. A single stereoisomer crystallises from solution with an RRR and SSS configuration at the P centres in each sub-unit. The relaxivity of [GdL3]2 is low (1.9 mM-1 s-1, 298 K, 20 MHz), consistent with the absence of any proximate water molecules. The terbium dimer possesses a relatively long excited state lifetime (2.47 ms, 298 K).     

Efficient crystallization induced emissive materials based on a simple push-pull molecular structure

Solid state luminescent materials are the subject of ever growing interest both from a scientific and a technological point of view. Aggregation caused quenching (ACQ) processes however represent an obstacle to the development of most luminogens in the condensed phase. This is why particularly fascinating are those materials showing higher emission intensity in the solid state than in solution. Here we report on three 4-dialkylamino-2-benzylidene malonic acid dialkyl esters, very simple push-pull molecules, which are hardly emissive in solution and in the amorphous phase but become good emitters in the crystalline phase according to what has been indicated as crystallization induced emission (CIE). Thanks to combined emission and NMR spectroscopies at different temperatures on the prototype compound 4-dimethylamino-2-benzylidene malonic acid dimethyl ester in solution, we give full evidence that a restricted intramolecular rotation (RIR) phenomenon, in particular the hindered rotation around the aryl main axis of the compound, is at the origin of this behaviour. In addition, solid state photophysical and X-ray diffraction structural characterization allow us to identify J-dimeric interactions as responsible for the particularly intense emission of two of the three compounds. Moreover, by exploiting the compounds' acidochromic properties, applications in sensors and optoelectronics are envisaged.     

Aryl‐Phosphonate Lanthanide Complexes and Their Fluorinated Derivatives: Investigation of Their Unusual Relaxometric Behavior and Potential Application as Dual Frequency 1H/19F MRI Probes

A series of low molecular weight lanthanide complexes were developed that have high ¹H longitudinal relaxivities (r₁) and the potential to be used as dual frequency ¹H and ¹⁹F MR probes. Their behavior was investigated in more detail through relaxometry, pH‐potentiometry, luminescence, and multinuclear NMR spectroscopy. Fitting of the ¹H NMRD and ¹⁷O NMR profiles demonstrated a very short water residence lifetime (<10 ns) and an appreciable second sphere effect. At lower field strengths (20 MHz), two of the complexes displayed a peak in r₁ (21.7 and 16.3 mM ^?1 s^?1) caused by an agglomeration, that can be disrupted through the addition of phosphate anions. NMR spectroscopy revealed that at least two species are present in solution interconverting through an intramolecular binding process. Two complexes provided a suitable signal in ¹⁹F NMR spectroscopy and through the selection of optimized imaging parameters, phantom images were obtained in a MRI scanner at concentrations as low as 1 mM . The developed probes could be visualized through both ¹H and ¹⁹F MRI, showing their capability to function as dual frequency MRI contrast agents.     

Amphiphilic Ditopic Bis‐Aqua Gd‐AAZTA‐like Complexes Enhance Relaxivity of Lipidic MRI Nanoprobes

Two amphiphilic mono‐ and dimeric GdAAZTA‐like chelates composed of stable bis‐aquo Gd^III complexes (q=2) linked to one (for the monomer) or two dodecyl aliphatic chains (for the dimer) were synthesized. Both chelates showed high relaxivity when incorporated into the lipid bilayer of liposomes or after interaction with human serum albumin (HSA). The ditopic complex shows a significantly decreased internal motion relative to the monomeric complex, associated with an enhanced relaxivity (r₁≈60 mm ^?1 s^?1, at 30 MHz and 310 K). The presence of two metal‐bound water molecules in fast exchange and the restricted rotational freedom make the relaxivity of this system the highest measured for paramagnetic liposomes.