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.     

Formation and stability of phytate complexes in solution

1,2,3,4,5,6 hexakis (di-hydrogen phosphate) myo-inositol, best known as phytic acid, is a very important molecule from a biological, environmental and technological point of view. For a thorough understanding of phytate properties and the mechanisms involving this ligand, a careful study of its acid–base behavior and of the formation and stability of its complexes in solution is necessary. Unfortunately, regarding the thermodynamic data on phytate complexes in solution, some are lacking, while some others exhibit large discrepancies between different authors. This motivated a detailed evaluation of the literature on this topic, aimed at identifying the most accurate data on phytate coordination chemistry in solution. This review presents the results of this, reporting and analyzing the most significant thermodynamic parameters published for both phytate protonation and complex formation with several metal and organometal cations, as well as polyammonium ligands.     

The Role of Ligand Topology in the Decomplexation of Luminescent Lanthanide Complexes by Dipicolinic Acid

In this study, we present the aqueous solution behavior of two luminescent lanthanide antenna complexes (Eu³⁺? 1 , Dy³⁺? 9 ) with different ligand topologies in the presence of dipicolinic acid (DPA, pyridine‐2,6‐dicarboxylic acid). Macrocyclic (1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid, DO3A, 9 ) and acyclic (1,4,7‐triazaheptane‐1,1,7,7‐tetraacetic acid, DTTA, 1 ) ligands have been selected to form a ratiometric pair in which Dy³⁺? 9 acts as a reference and Eu³⁺? 1 acts as a probe for the recognition of DPA. The pair of luminescent complexes in water reveals the capability to work as a DPA luminescent sensor. The change of emission intensity of Eu³⁺ indicates the occurrence of a new sensitization path for the lanthanide cation through excitation of DPA. NMR evidence implies the presence of free 1 and mass spectrometry shows the formation of emitting [EuDPA₂]^? as a result of a ligand exchange reaction.     

On the maximal number of coprime subdegrees in finite primitive permutation groups

We compute the divisor class group of the general hypersurface Y of a complex projective normal variety X of dimension at least four containing a fixed base locus Z. We deduce that completions of normal local complete intersection domains of finite type over C of dimension ≥ 4 are completions of UFDs of finite type over C.     

The scaffold tree--visualization of the scaffold universe by hierarchical scaffold classification

A hierarchical classification of chemical scaffolds (molecular framework, which is obtained by pruning all terminal side chains) has been introduced. The molecular frameworks form the leaf nodes in the hierarchy trees. By an iterative removal of rings, scaffolds forming the higher levels in the hierarchy tree are obtained. Prioritization rules ensure that less characteristic, peripheral rings are removed first. All scaffolds in the hierarchy tree are well-defined chemical entities making the classification chemically intuitive. The classification is deterministic, data-set-independent, and scales linearly with the number of compounds included in the data set. The application of the classification is demonstrated on two data sets extracted from the PubChem database, namely, pyruvate kinase binders and a collection of pesticides. The examples shown demonstrate that the classification procedure handles robustly synthetic structures and natural products.     

Synthesis and characterization of a Gd(III) based contrast agent responsive to thiol containing compounds

A novel Gd(III) complex with a modified DO3A-like chelating cage has been synthesized and characterized as a candidate contrast agent responsive to the concentration of free thiols in tissues (essentially represented by reduced glutathione, GSH). The novel compound (called Gd-DO3AS-Act) bears a flexible linker ending with a 2-pyridyl-dithio group, that can promptly react with free thiols (XSH) to form mixed disulfides of the form Gd-DO3AS-SX. Compound Gd-DO3AS-Act is characterized by a millimolar relaxivity as high as 8.1 mM(-1) s(-1) (at 20 MHz, 25 degrees C and pH 7.4). Upon reaction with GSH, the Gd-DO3AS-SG covalent adduct is formed and the millimolar relaxivity drops to 4.1 mM(-1) s(-1). Such a decrease in relaxivity is explained on the basis of the formation of an intramolecular coordinative bond between one of the glutathionyl carboxyl groups and the Gd(III) centre, lowering the hydration state of the paramagnetic centre. (1)H-NMR dispersion profiles together with (17)O-NMR transverse relaxation time versus temperature profiles confirm that the hydration of the Gd(III) centre is strongly reduced ongoing from Gd-DO3AS-Act to the Gd-DO3AS-SG adduct. The relaxivity difference brought about by the reaction of Gd-DO3AS-Act with GSH can be enhanced up to 60% in the presence of poly-beta-cyclodextrin.     

Influence of the interaction between hydrogen sulfide and ionic liquids on solubility: experimental and theoretical investigation

The solubility of H(2)S in a series of 1-butyl-3-methylimidazolium ([bmim](+)) based ionic liquids (ILs) with different anions, chloride, tetrafluoroborate ([BF(4)](-)), hexafluorophosphate ([PF(6)](-)), triflate ([TfO](-)), and bis(trifluoromethyl)sulfonylimide ([Tf(2)N]-), and in a series of [Tf(2)N] ILs with different cations, i.e., N-alkyl-N'-methylimidazolium, 2-methyl-N-methyl-N'-alkyimidazolium, N-alkylpyridinium, N-butyl-N-methylpyrrolidinium, and N-alkyl-N,N-dimethyl-N-(2-hydroxyethyl)ammonium has been determined using medium-pressure NMR spectroscopy. The observed solubilities are significantly higher than those reported for many other gases in ILs, suggesting the occurrence of specific interactions between H2S and the examined ILs. Quantum chemical calculations have been used to investigate at a molecular level the interaction between H2S and the [bmim](+)-based ILs.