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This paper describes the method for obtaining a new derivative of the closo-decaborate anion with diethylenetriaminepentaacetic acid (DTPA) as a pendant group attached to the boron cluster through an alkoxyl spacer chain. This derivative is formed by the interaction of 1,4-dioxane derivative of the anion [B10H10]2- with DTPA potassium salt in an aqueous medium. As a result of the reaction, an exo-polyhedral cyclic substituent is opened, and then the addition of a polyfunctional group through an oxygen atom occurs. The synthesized compound is in fact an effective polydentate ligand capable of coordinating to the complexing agent both due to the donor atoms of the attached DTPA fragment and through the formation of three-center two-electron bonds. The obtained compound interacts with gadolinium(III) carbonate forming a complex of the composition [Gd2B10H9O2C4H8(dtpa)]·3H2O. The synthesized substances were studied by IR spectroscopy, polynuclear (11B, 13C and 1H) NMR spectroscopy, ESI mass spectrometry, elemental and thermographic analysis. closo-Decaborate with the pendant DTPA group is of interest in 10B neutron capture therapy of malignant tumors due to the high content of boron atoms and a convenient way of their transport to the affected cells. The obtained boron-containing derivatives of gadolinium(III) can act as drugs of combined action, because they can perform, in addition to the above described therapeutic function, the diagnostic function due to the presence of gadolinium atoms int hem.

The number of scientific reports on the field of imaging in biomedical sciences is rising massively, with the emergence of “noninvasive” in vivo imaging technologies, of which Magnetic Resonance Imaging (MRI) is considered to be among the top techniques in modern Medical Imaging. These techniques manage to detect events at molecular and cellular levels, providing a faster diagnostic evaluation to oncology patients and consequently hastening drug development processes. Of the many contrast agents developed by Organic Chemists during the last decades, tetrapyrrolic macrocycles like porphyrins and related compounds, like phthalocyanines, represent some of the oldest, most widely studied chemical structures in biomedical applications. These macrocyclic structures display intrinsic affinity for tumor localization, and their well-described photosensitizing and photophysical features allured many scientists toward their potential use as contrast agents in a variety of in vivo imaging technologies, namely in the MRI technique. Furthermore, a special emphasis is put on the development of multimodal contrast agents, which may be the future of Medical Imaging. This review intends to give an insight on developments on MRI technologies involving tetrapyrrolic-based contrast agents for cancer detection. It is a Chemist’s view, regarding the synthesis of the crucial contrast agents, selecting influential milestones over the last few decades on this field, along with pertinent reflections pointing to future guidelines. [ABSTRACT FROM AUTHOR]

Three DTPA-amide cyclophanes – including conformational isomers – have been isolated by optimizing the conditions of a reaction between diethylenetriaminepentaacetic (DTPA) dianhydride and p -xylenediamine: a 2 + 2-cyclization product, abbreviated as (cy2)H 6 , that integrates two phenylene groups in the macrocyclic frame and bears six pendant –CH 2 CO 2 H arms, and two isomeric 1 + 1-macrocyles, (cy1)H 3 , carrying three arms. A crucial factor for controlling the ring size is the concentration in the reaction. For (cy2)H 6 , whose binuclear Gd 3+ complex is a potential paramagnetic protein sensor, the synthetic method has been established in 70% yield. The isomerism of (cy1)H 3 is due to the conformation of the rigid macrocyclic frame; the 1 H NMR and geometry optimization show that the conformation is of quasi-C 2 symmetry in one (cy1)H 3 isomer, and of quasi-mirror symmetry in the other. Their distinct conformations define the chemical properties and coordination capability toward Gd 3+ : in the C 2 -symmetric isomer, the amino nitrogen is less basic and the N–H bond is more covalent than in the mirror-symmetric isomer; the former forms a mononuclear Gd 3+ complex whereas the latter does not show sign of complexation with Gd 3+ . [ABSTRACT FROM AUTHOR]

Three isotypic rare earth complexes, catena-poly[[aquabis(but-2-enoato-κ2 O, O′)yttrium(III)]-bis(μ-but-2-enoato)-κ3 O, O′: O;κ3 O: O, O′-[aquabis(but-2-enoato-κ2 O, O′)yttrium(III)]-μ-4,4′-(ethane-1,2-diyl)dipyridine-κ2 N: N′], [Y2(C4H5O2)6(C12H12N2)(H2O)2], the gadolinium(III) analogue, [Gd2(C4H5O2)6(C12H12N2)(H2O)2], and the gadolinium(III) analogue with a 4,4′-(ethene-1,2-diyl)dipyridine bridging ligand, [Gd2(C4H5O2)6(C12H10N2)(H2O)2], are one-dimensional coordination polymers made up of centrosymmetric dinuclear [ M(but-2-enoato)3(H2O)]2 units ( M = rare earth), further bridged by centrosymmetric 4,4′-(ethane-1,2-diyl)dipyridine or 4,4′-(ethene-1,2-diyl)dipyridine spacers into sets of chains parallel to the [20] direction. There are intra-chain and inter-chain hydrogen bonds in the structures, the former providing cohesion of the linear arrays and the latter promoting the formation of broad planes parallel to (010). [ABSTRACT FROM AUTHOR]

Abstract: The mononuclear high-spin iron(III) complexes [Fe(3-MeOsalpn)Cl(H2O)] (1) and [Fe(3-MeOsalpn)(NCS)(H2O)]·0.5CH3CN (2) and the tetranuclear oxo-bridged compound [{Fe(3-MeOsalpn)Gd(NO3)3}2(μ-O)]·CH3CN (3) [3-MeOsalpn2− = N,N′-propylenebis(3-methoxysalicylideneiminate)] have been prepared and magneto-structurally characterised. The iron(III) ion in 1 and 2 is six-coordinated in a somewhat distorted octahedral surrounding with the two phenolate-oxygens and two imine-nitrogens from the Schiff-base building the equatorial plane and a water (1 and 2) and a chloro (1)/thiocyanate-nitrogen (2) in the axial positions. The neutral mononuclear units of 1 and 2 are assembled into centrosymmetric dinuclear motifs through hydrogen bonds between the axially coordinated water molecule of one iron centre and methoxy-oxygen atoms from the Schiff-base of the adjacent iron atom. The values of the intradimer metal–metal distance within the supramolecular dimers are 4.930 (1) and 4.878Å (2). The tetranuclear of 3 can be described as two {FeIII(3-MeOsalpn)} units connected through an oxo-bridge, each one hosting a [GdIII(NO3)3] entity in the outer cavity defined by the two phenolate- and two methoxy-oxygen atoms. The values of the intramolecular Fe⋯Fe and Fe⋯Gd distances in 3 are 3.502 and 3.606Å, respectively. The analysis of the magnetic data of 1–3 in the temperature range 1.9–300K shows the occurrence of weak intermolecular antiferromagnetic interactions in 1 and 2 [J =−0.76 (1) and −0.75cm−1 (2) with the Hamiltonian defined as H =−JS Fe1·S Fe1] whereas two intramolecular antiferromagnetic interactions coexist in 3, one very strong between the two iron(III) ions (J 1) through the oxo bridge and the other much weaker between the iron(III) and the Gd(III) ions (J 2) across the double phenoxo oxygens [J 1 =−275cm−1 and J 2 =−3.25cm−1, the Hamiltonian being defined as ]. These values are analysed in the light of the structural data and compared with those of related systems. [Copyright &y& Elsevier]

The magnetic coupling interactions of the nitronyl nitroxide radicals bound to diamagnetic (YIII) and paramagnetic (GdIII) rare earth ions in two model magnetic systems based on novel rare earth organic radical complexes Ln(hfac)3(NITPhOCH3)2 (Ln = YIII 1, GdIII 2; hafc = hexafluoroacetylacetonate; NITPhOCH3 = 4′-methoxyo-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) have been investigated by density functional theory (DFT). The magnetic coupling mechanisms were also explored from the viewpoint of molecular orbital and spin density populations. DFT calculations show that the empty 4 d-orbitals of YIII and 5 d-orbitals of GdIII play an important role in the antiferromagnetic coupling between the two nitronyl nitroxide radical ligands, and that the ferromagnetic coupling between the GdIII ion and the radical magnetic centers can be attributed to the nearly complete localization of the isotropic 4 f-shell and singly occupied magnetic orbital (Π*) of the nitronyl nitroxide. [ABSTRACT FROM AUTHOR]

[Display omitted] • Capability of Gd(III) complex-based contrast agents in magnetic resonance imaging (MRI) was introduced. • Mechanisms for the design of responsive Gd(III) complex-based probes were highlighted. • Progress in the development of Gd(III) complex-based probes for magnetic resonance (MR) detection and imaging of various target analytes was reviewed. • Gd(III) complex-based bimodal probes for target analytes detection and MRI were briefly summarized. • Challenges and research perspectives for the development of Gd(III) complex-based probes were discussed. Magnetic resonance imaging (MRI) is a molecular imaging technology that has been widely adopted in biomedical and clinical diagnostics fields owing to its capability of deep tissue imaging with high spatiotemporal resolution. Responsive small molecule MRI contrast agents, known as MRI probes, are of particular interest for the detection and visualisation of target analytes in vitro and in vivo , thus expanding MRI's capability into the molecular imaging regime. Each of the responsive MRI probe selectively responds to corresponding target analyte and then gives the magnetic resonance (MR) signal change for this analyte detection. In this work, advances in developing responsive MRI probes based on gadolinium(III) (Gd(III)) complexes are systematically summarized. Specifically, we first introduce the strategies in developing Gd(III) complex probes through different response mechanisms, and then discuss the progresses in developing Gd(III) complex-based resposnvie MRI probes for different target analytes, including biologically relevant cations, anions, pH, biomolecules and redox homeostasis. Responsive bimodal probes, such as MRI-fluorescence probes, MRI-PET probes, and MRI-SPECT probes are then briefly outlined. The applications of Gd(III) complex-based responsive probes in in vivo and in vitro MRI are also included. Current limitations and future research directions in developing Gd(III) complex probes for MR analysis and imaging are also proposed. It is anticipated that this work will promote the ongoing research on developing Gd(III) complex-based MRI probes and their applications in understanding the bioactive analytes' pathophysiological processes. [ABSTRACT FROM AUTHOR]

Abstract: Magnetic resonance imaging (MRI) contrast agents that contain the gadolinium ion are widely used in biomedical research and diagnosis. The relaxation mechanism of these T1-agents highlights their sensitivity towards the proximal environment. Greater knowledge of the structurally related relaxation mechanism, particularly factors that govern relaxivity, leads to scrutinized chelate designs that improve contrast enhancement. Cyclic and acyclic polyaminocarboxylate gadolinium complexes, especially those have favourable water exchange and tumbling rate for relaxation, have been reported to improve relaxivity and specificity. The criteria for a large relaxivity gain upon protein binding, such as the human serum albumin (HSA), are elucidated through the relaxometric study of the protein–chelate adduct. This adduct is an important model for the development of contrast agents, which may allow the in vivo visualization of proteins. The strength of HSA binding and the observed relaxivity are related to the pharmacokinetic profile of the contrast agents and give insight in the sensitivity of the agents after intravenous administration. By using animal models, an understanding of the physiology of contrast agents, including their biodistribution, excretion, and possible site of interaction, is acquired. The in vitro studies of contrast agents have demonstrated the feasibility of imaging various disease-related proteins, cell types, and gene delivery and expression. Imaging at the molecular level can be achieved through this integrative approach and the incorporation of nanotechnology in drug delivery. [Copyright &y& Elsevier]

Two new homobinuclear 4f–4f complexes, [LnIII(L)3]2, (Ln=Pr 1; Gd 2) have been synthesized (L−=2,6-diformyl-4-methylphenolato). The crystallographic investigation of 1 reveals centrosymmetric binuclear entities with the metallic centers connected by two of the anionic ligands. The praseodymium ions are bridged by the phenoxo oxygen atoms. One carbonyl group of a bridging molecule is coordinated to one Pr(III) ion, while the other one is coordinated to the second Pr(III) ion. The other four L− ions act as terminal chelated ligands, through the phenoxo oxygen atom and one carbonyl group. The distance between the Pr(III) ions within the binuclear entity is 4.0711(4) A˚. The supramolecular solid-state architecture is sustained by a system of π–π interactions. The cryomagnetic study of 2 reveals a very weak antiferromagnetic interaction between the Gd(III) ions (J=−0.053 cm−1, H=−JSGd1SGd2). [Copyright &y& Elsevier]

-pentaacetic acid) bearing different substituents for binding to human serum albumin (HSA) are compared. In spite of the structural differences of the recognition synthon and of the residual electric charge, the two chelates display an analogous binding affinity for the serum protein. Upon formation of the adducts with HSA, the exchange rates of the coordinated water appear slowed down by an amount corresponding to ca. 50% of the rates found for the free complexes. The relaxivity of [Gd(BOM)3DTPA (H2O)]2 − is significantly higher than that of MS-325 either in the free complex or in the macromolecular adduct. Finally, the effect of pH on the stability of the HSA adducts and on the values of their relaxivities has been investigated. [ABSTRACT FROM AUTHOR]

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The Gd(III) complex of 4-pentylbicyclo[2.2.2]octane-1-carboxyl-di- l-aspartyl-lysine-derived DTPA, [GdL(H2O)]2–, binds to serum albumin in vivo, through hydrophobic interaction. A variable temperature 17O NMR, EPR, and Nuclear Magnetic Relaxation Dispersion (NMRD) study resulted in a water exchange rate of k298 ex=4.2×106 s–1, and let us conclude that the GdL complex is identical to [Gd(DTPA)(H2O)]2– in respect to water exchange and electronic relaxation. The effect of albumin binding on the water exchange rate has been directly evaluated by 17O NMR. Contrary to expectations, the water exchange rate on GdL does not decrease considerably when bound to bovine serum albumin (BSA); the lowest limit can be given as kex, GdL-BSA= kex, GdL / 2. In the knowledge of the water exchange rate for the BSA-bound GdL complex, the analysis of its NMRD profile at 35 °C yielded a rotational correlation time of 1.0 ns, one order of magnitude shorter than that of the whole protein. This value is supported by the longitudinal 17O relaxation rates. This indicates a remarkable internal flexibility, probably due to the relatively large distance between the protein- and metal-binding moieties of the ligand. [ABSTRACT FROM AUTHOR]