Mesocyclic chelating agents such as AAZTA and its derivatives have been recently reported to overcome the relatively low thermodynamic stability of metal complexes of acyclic chelating agents and the slow complexation kinetics of macrocyclic chelating agents. This work reports the preparation of a spirobicyclic hexadentate AAZTA-like chelating agent (TRASUTA) and the investigation of the thermodynamic, kinetic, and structural properties of the corresponding chelates with the PET-relevant Ga and selected metal ions. A combination of analytical techniques allowed identification of a coordination isomerization process, involving the coordinating side arms and the inversion of a nitrogen atom and leading to lower thermodynamic and kinetic inertness with respect to mononuclear mesocyclic analogues.
View Article and Find Full Text PDFImaging in the shortwave infrared (SWIR, 1000-1700 nm) region is gaining traction for biomedical applications, leading to an in-depth search for fluorophores emitting at these wavelengths. The development of SWIR emitters, to be used in vivo in biological media, is mostly hampered by the considerable lipophilicity of the structures, resulting from the highly conjugated scaffold required to shift the emission to this region, that limit their aqueous solubility. In this work, we have modulated a known SWIR emitter, named Flav7, by adding hydrophilic moieties to the flavylium scaffold and we developed a new series of Flav7-derivatives, which proved to be indeed more polar than the parent compound, but still not freely water-soluble.
View Article and Find Full Text PDF[Gd(HP-DO3A)] (gadoteridol) as an active compound of ProHance is a widely employed contrast agent in clinical MRI scans in the last 30 years. Recent concerns about the long-term retention of gadolinium-based contrast agents (GBCAs) led to a deeper investigation of the structural features underlying the integrity of the paramagnetic metal complex. Several human and nonclinical studies have noted marked differences among the macrocyclic GBCAs, with the least retention of Gd traces and most rapid elimination consistently being reported for [Gd(HP-DO3A)].
View Article and Find Full Text PDFCommercially available near-infrared (NIR) dyes, including indocyanine green (ICG), display an end-tail of the fluorescence emission spectrum detectable in the short-wave infrared (SWIR) window. Imaging methods based on the second NIR spectral region (1,000-1,700 nm) are gaining interest within the biomedical imaging community due to minimal autofluorescence and scattering, allowing higher spatial resolution and depth sensitivity. Using a SWIR fluorescence imaging device, the properties of ICG vs.
View Article and Find Full Text PDFAl(III) complexes have been recently investigated for their potential use in imaging with positron emission tomography (PET) by formation of ternary complexes with the radioisotope fluorine-18 (F). Although the derivatives of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) are the most applied chelators for [AlF] labelling and (pre)clinical PET imaging, non-macrocyclic, semi-rigid pentadentate chelators having two N- and three O-donor atoms such as RESCA1 and AMPDA-HB have been proposed with the aim to allow room temperature labelling of temperature-sensitive biomolecules. The paucity of stability data on Al(III) complexes used for PET imaging instigated a complete thermodynamic and kinetic solution study on Al(III) complexes with aminomethylpiperidine (AMP) derivatives AMPTA and AMPDA-HB and the comparison with a RESCA1-like chelator CD3A-Bn (-1,2-diaminocyclohexane--benzyl-,,-triacetic acid).
View Article and Find Full Text PDFThe introduction of a phenolate pendant arm in place of an acetate on AAZTA- and DATA-like ligands resulted in hepta- and hexadentate chelators able to form Ga(III) complexes with thermodynamic stability and kinetic inertness higher than that of other Ga(III) complexes based on the parent 6-amino-6-methylperhydro-1,4-diazepine scaffold. In particular, the heptadentate AAZ3A-endoHB with a phenolate arm on an endocyclic N-atom shows a logK of 27.35 and a remarkable resistance to hydroxide coordination up to basic pH (pH>9).
View Article and Find Full Text PDFIn this study, we report the synthesis and the equilibrium, kinetic, relaxation, and structural properties of two new Gd complexes based on modified 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (HPDO3A) designed to modulate the relaxivity at acidic and basic pH due to intra- and intermolecular proton exchange. The presence of a carboxylic or ester moieties in place of the methyl group of HPDO3A allowed differentiation of a protic and nonprotic functional group, highlighting the importance of the formation of an intramolecular hydrogen bond between the coordinated hydroxyl and the carboxylate groups for proton exchange ( = 1.5 × 10 M s, = 1.
View Article and Find Full Text PDFA current challenge in medical diagnostics is how to obtain high MRI relaxation enhancement using Gd-based contrast agents (CAs) containing the minimum concentration of Gd ions. We report that in GdHPDO3A-like complexes a primary amide group located in close proximity to the coordinated hydroxyl group can provide a strong relaxivity enhancement at slightly acidic pH. A maximum relaxivity of = 9.
View Article and Find Full Text PDFEu(HP-DO3A) is present in solution as a mixture of two diastereoisomers whose alcoholic groups are the source of the mobile protons for the CEST effect. The exchange is base catalyzed. Two novel Eu complexes of HP-DO3A-like ligands containing an amino or a carboxylate functionality in the proximity of the -OH groups showed the occurrence of intramolecular catalysis of the prototropic exchange.
View Article and Find Full Text PDFGold nanoparticles carrying fluorinated ligands in their monolayer are, by themselves, contrast agents for F magnetic resonance imaging displaying high sensitivity because of the high density of fluorine nuclei achievable by grafting suitable ligands on the gold core surface. Functionalization of these nanoparticles with Gd(III) chelates allows adding a further functional activity to these systems, developing materials also acting as contrast agents for proton magnetic resonance imaging. These dual mode contrast agents may allow capitalizing on the benefits of H and F magnetic resonance imaging in a single diagnostic session.
View Article and Find Full Text PDFThe kinetic analysis of the place exchange reaction on the neutral Au25(SCH2CH2Ph)18 cluster by using 4-fluorobenzylthiol and a series of substituted arylthiols allowed us to establish, for the first time, that the selectivity for the inner and outer positions of the dimeric staples of the cluster can be modulated by using incoming thiols with different structures.
View Article and Find Full Text PDFTwo structurally different water-soluble homoligand gold nanoparticle systems, one featuring a rigid fluorous monolayer in the proximity of the gold core and the other featuring a flexible fluorinated region in a distal position, were studied as putative hosting systems by determining their binding constants for a series of fluorinated and non-fluorinated radical probes by means of ESR spectroscopy. Comparison of the binding constants obtained with hydrogenated homoligand nanoparticles of similar structure used as the reference evidenced that the binding of both hydrogenated and fluorinated guests is favoured in the presence of fluorinated nanoparticles. In addition, a flexible fluorinated monolayer acts as a better hosting system than the more rigid counterpart.
View Article and Find Full Text PDFThe [Pd(dppp)(OTf)2] complex acts as an efficient transporter of halide anions, in particular the biologically relevant chloride anion, across a phospholipid bilayer.
View Article and Find Full Text PDFGold nanoparticles coated with fluorinated ligands (F-MPCs) present features suitable for (19)F MRI as observed from phantom experiments. Cellular uptake, by HeLa cells, and toxicity of fluorescent dye-decorated F-MPCs are presented together with their ability to bind hydrophobic molecules allowing for a potential combination of targeting, delivery and imaging features.
View Article and Find Full Text PDFThe reaction between 5-(4-pyridyl)dipyrrylmethane and aromatic aldehydes affords meso-arylsubstituted trans-A2B2 di(4-pyridyl)porphyrins which are key building blocks in the metal-mediated self-assembling of supramolecular structures. A careful optimization of the reaction conditions allowed us to obtain 5,15-diphenyl-10,20-di(4-pyridyl)porphyrin (P1), and two analogues bearing on the meso-phenyl substituents two dipropyl- (P4) or dihexyl-alkyl chains (P5), with yields ranging from 53 to 63%. Porphyrin P1 reacts with Re(CO5)Br to give the expected 4 + 4 Re(I)-porphyrin metallacycle which has been fully characterized by means of infrared, NMR and UV-Vis (absorption and emission) spectroscopies and by guest inclusion studies.
View Article and Find Full Text PDFA stable tetraporphyrin metallacycle with Re(I) corners (1) is capable of forming nanopores in a liposomial membrane, provided that the porphyrin units are properly functionalized with peripheral carboxylic acid residues that, by establishing an hydrogen bond network, allow the formation of dimers that span the depth of the membrane.
View Article and Find Full Text PDFIn this work, carbohydrate-based systems designed as artificial ion transporters have been surveyed. Despite the large structural diversity and ease of manipulations of carbohydrates, in principle endowed with a variety of desirable properties for ionophoric activity, only few examples of sugar-containing compounds have been reported in the literature for these purposes. The most remarkable example is the family of modified β-cyclodextrins, resulting in active cation and/or anion transporters when long, flexible n-alkyl or oligo-ethylene or butylene glycol chains are appended at the lower rim of the macrocycle.
View Article and Find Full Text PDFA small library of sugar-modified guanosine derivatives has been prepared, starting from a common intermediate, fully protected on the nucleobase. Insertion of myristoyl chains and of diverse hydrophilic groups, such as an oligoethylene glycol, an amino acid or a disaccharide chain, connected through in vivo reversible ester linkages, or of a charged functional group provided different examples of amphiphilic guanosine analogues, named G1-G7 herein. All of the sugar-modified derivatives were positive in the potassium picrate test, showing an ability to form G-tetrads.
View Article and Find Full Text PDFA novel fluorescently labelled synthetic ionophore, based on a cyclic phosphate-linked disaccharide (CyPLOS) backbone and decorated with four tetraethylene glycol tails carrying dansyl units, has been synthesised in 12 steps in 26% overall yield. The key intermediate in the synthetic strategy is a novel glucoside building block, serving through its 2- and 3-hydroxy groups as the anchor point for flexible tetraethylene glycol tentacles with reactive azido moieties at their ends. To test the versatility of this glucoside scaffold, it was preliminarily functionalised with a set of diverse probes--as fluorescent, redox-active or hydrophobic tags--either by reduction of the azides followed by condensation with activated carboxylic acid derivatives, or by a direct coupling with a terminal alkyne in a Cu(I)-promoted 1,3-dipolar cycloaddition.
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