Unravelling the Time Scale of Conformational Plasticity and Allostery in Glycan Recognition by Human Galectin-1

The interaction of human galectin-1 with a variety of oligosaccharides, from di-(N-acetyllactosamine) to tetra-saccharides (blood B type-II antigen) has been scrutinized by using a combined approach of different NMR experiments, molecular dynamics (MD) simulations, and isothermal titration calorimetry. Ligand- and receptor-based NMR experiments assisted by computational methods allowed proposing three-dimensional structures for the different complexes, which explained the lack of enthalpy gain when increasing the chemical complexity of the glycan. Interestingly, and independently of the glycan ligand, the entropy term does not oppose the binding event, a rather unusual feature for protein-sugar interactions. CLEANEX-PM and relaxation dispersion experiments revealed that sugar binding affected residues far from the binding site and described significant changes in the dynamics of the protein. In particular, motions in the microsecond-millisecond timescale in residues at the protein dimer interface were identified in the presence of high affinity ligands. The dynamic process was further explored by extensive MD simulations, which provided additional support for the existence of allostery in glycan recognition by human galectin-1.     

A Preorganized Hydrogen-Bonding Motif for the Molecular Recognition of Carbohydrates

The choice between adaptive and preorganized architectures, or of the most effective hydrogen bonding groups to be selected, are dilemmas that supramolecular chemists must address in designing synthetic receptors for such a challenging guest as carbohydrates. In this paper, structurally related architectures featuring two alternative hydrogen bonding motifs were compared to ascertain the structural and functional origin of their binding differences and the advantages that can be expected in monosaccharide recognition. A set of structurally related macrocyclic receptors were prepared, and their binding properties were measured by NMR and ITC techniques in chloroform vs a common saccharidic target, namely, the β-octyl glycoside of D-glucose. Results showed that the diaminocarbazolic motif, recently reported as the constituting unit of highly effective receptors for saccharides in water, is a superior hydrogen bonding motif compared to the previously described diaminopyrrolic motif, which was successfully employed in molecular recognition of carbohydrates in polar organic solvents, due to intrinsic structural and functional factors, rather than to hydrophobic contributions. In addition, the occurrence of a rare example of a thermodynamic template effect exerted by the beta-glucoside has been ascertained, enhancing the synthesis outcome of the otherwise low yielding preparation of the described macrocyclic receptors.     

Conformational and electronic study of dopamine interacting with the D2 dopamine receptor

We report an exhaustive conformational and electronic study on dopamine (DA) interacting with the D₂ dopamine receptor (D₂DR). For the first time, the complete surface of the conformational potential energy of the complex DA/D₂DR is reported. Such a surface was obtained through the use of QM/MM calculations. A detailed study of the molecular interactions that stabilize and destabilize the different molecular complexes was carried out using two techniques: Quantum Theory of Atoms in Molecules computations and nuclear magnetic shielding constants calculations. A comparative study of the behavior of DA in the gas phase, aqueous solution, and in the active site of D₂DR has allowed us to evaluate the degree of deformation suffered by the ligand and, therefore, analyze how rustic are the lock-key model and the induced fit theory in this case. Our results allow us to propose one of the conformations obtained as the “biologically relevant” conformation of DA when it is interacting with the D₂DR.     

Furanoside thioether-phosphinite ligands for Pd-catalyzed asymmetric allylic substitution reactions: Scope and limitations

A series of readily available thioether-phosphinite ligands has been tested in the Pd-catalyzed allylic substitution reactions of several acyclic and cyclic allylic substrates (S1-S7). This series of ligands have been designed to uncover their important structural features and to determine the scope of the thioether-phosphinite ligands in these catalytic reactions. Systematic variation of the electronic and steric properties at the thioether moiety provide useful information about the ligand parameters that control the enantiodiscrimination. By carefully selecting the ligand parameters, good enantioselectivities with high activities were obtained for hindered linear substrates S1 and S2 (ee’s up to 95%) and for unhindered cyclic substrates S4 and S5 (ee’s up to 91%).     

DFT analysis: Fe4 cluster and Fe(110) surface interaction studies with pyrrole,furan, thiophene,and selenophene molecules

DFT studies of both the Fe₄ cluster and the Fe(110) surface interaction with pyrrole, furan, thiophene, and selenophene showed that selenophene forms a stabler adsorbate iron complex than the other heterocyclic molecules; this is consistent with the binding energy data that were calculated between the Fe cluster and the Fe(110) surface with the heterocycles. Furthermore, when the adsorption of the compounds with the iron cluster was analyzed by molecular orbital studies, the orbitals of selenophene overlapped more strongly with the Fe atom than that of the other molecules. In TD-DFT, the π → π* peak observed for the molecules disappeared when they formed complexes, and there appeared a charge transfer band (ligand to metal), thus confirming the coordination of these molecules with the cluster. The data suggest that the chemisorption is an exothermic process.     

Well‐Defined Palladium Nanoparticles Supported on Siliceous Mesocellular Foam as Heterogeneous Catalysts for the Oxidation of Water

Herein, we describe the use of Pd nanoparticles immobilized on an amino‐functionalized siliceous mesocellular foam for the catalytic oxidation of H₂O. The Pd nanocatalyst proved to be capable of mediating the four‐electron oxidation of H₂O to O₂, both chemically and photochemically. The Pd nanocatalyst is easy to prepare and shows high chemical stability, low leaching, and recyclability. Together with its promising catalytic activity, these features make the Pd nanocatalyst of potential interest for future sustainable solar‐fuel production.     

Monitoring of the metal displacement from the recombinant mouse liver metallothionein Zn(7)-complex by capillary zone electrophoresis with electrospray MS detection

A solution of a Zn-complex of recombinant mouse MT-1 isoform (Zn(7)-MT-1) was prepared and titrated with Cd(2+) ions. A method based on the coupling of capillary zone electrophoresis (CZE) with electrospray MS detection was developed for the analysis of the stoichiometry of the species formed during the titration. The method offered the possibility of the on-line removal of up to 100 mM Tris or phosphate buffer solutions that would otherwise suppress the electrospray signal. By allowing the determination of the metal stoichiometry of the complex species present in solution the method was shown to be complementary to circular dichroism and UV-VIS spectrophotometry conventionally used for similar studies. The titration of the Zn(7)-MT complex with Cd(II) showed the sequential displacement of the Zn by Cd. The unusually high stability of the Cd(6)Zn(1)-MT species was observed which suggests a structural role of the remaining Zn(II) ion.     

Structural and Spectroscopic Characterization of Bis(thiosaccharinato)‐trispyridine‐cadmium(II)

The crystal structure of the title complex, [Cd(tsac)₂(py)₃], has been determined by single crystal X‐ray diffractometry. It crystallizes in the monoclinic space group C2/c with Z = 8.The Cd ²⁺ cation is at the center of a square‐ bipyramidal environment, equatorially coordinated to two thiosaccharinate anions through their sulfur atoms and the nitrogen atom of one of them acting as a bidentate ligand. Nitrogen atoms of pyridine molecules occupy the fourth equatorial position and the two axial ones. The infrared and electronic spectra of the complex were briefly discussed. Its thermal stability was investigated by thermogravimetric and differential thermal analysis.     

Chemoenzymatic dynamic kinetic resolution of beta-halo alcohols. An efficient route to chiral epoxides

Enzymatic resolution of beta-chloro alcohols in combination with ruthenium-catalyzed alcohol isomerization led to a successful dynamic kinetic resolution (conversion up to 99% and ee up to 97%). The efficiency of the DKR is dramatically reduced when beta-bromo alcohols are used. The presence of the bromo substituent causes decomposition of the ruthenium catalysts, which triggers the progressive deactivation of the enzyme. The synthetic utility of this procedure has been illustrated by the practical synthesis of different chiral epoxides.