Minimizing the entropy penalty for ligand binding: lessons from the molecular recognition of the histo blood-group antigens by human galectin-3

6 p.-5 fig.-2 tab.Ligand conformational entropy plays an important role in carbohydrate recognition events. Glycans are characterized by intrinsic flexibility around the glycosidic linkages, thus in most cases, loss of conformational entropy of the sugar upon complex formation strongly affects the entropy of the binding process. By employing a multidisciplinary approach combining structural, conformational, binding energy, and kinetic information, we investigated the role of conformational entropy in the recognition of the histo blood‐group antigens A and B by human galectin‐3, a lectin of biomedical interest. We show that these rigid natural antigens are pre‐organized ligands for hGal‐3, and that restriction of the conformational flexibility by the branched fucose (Fuc) residue modulates the thermodynamics and kinetics of the binding process. These results highlight the importance of glycan flexibility and provide inspiration for the design of high‐affinity ligands as antagonists for lectins.We thank Agencia Estatal de Investigacion and ISCIII of Spain and the European Research Council for financial support.Peer reviewe

Catálisis homogénea con oro: desde los primeros pasos hasta la fiebre del oro

Gold has been a latecomer in organic synthesis, mainly because of the wrong perception of its lack of reactivity in homogeneous catalysis. Here, we present a brief account of the key discoveries that have fi nally led to a true gold rush in the last ten years.El oro ha tardado en incorporarse a la síntesis orgánica, principalmente debido a la errónea percepción de su falta de reactividad en catálisis homogénea. Aquí presentamos un breve relato de los descubrimientos clave que han desencadenado una auténtica “fi ebre del oro” en los últimos diez años

Gold(I)-Catalyzed Inter- and Intramolecular Additions of Carbonyl Compounds to Allenenes

The gold(I)-catalyzed intramolecular reaction of allenes with oxoalkenes leads to bicyclo[6.3.0]undecane ring systems, although in the case of terminally disubstituted allenes, seven-membered rings are formed. The related intermolecular addition of aldehydes to allenenes also gives seven-membered rings

Ni-Catalyzed Borylation of Aryl Fluorides via C–F Cleavage

A Ni-catalyzed borylation via C–F activation is described. This protocol is distinguished by a wide scope, including unactivated fluoroarenes, without compromising its efficiency and scalability, thus representing a significant step-forward toward the implementation of C–F activation protocols

Reactions of cationic hydrido complexes [Ru(CO)H(MeCN)2(PPh3)2]A (A ClO4, PF6) with alkynes. The crystal structure of [Ru(CO) (MeOOCCCHCOOMe) (MeCN)2(PPh3)2]ClO4

Reactions of [Ru(CO)H(MeCN)2(PPh3)2]A with mono- and di-substituted acetylenes give the alkenyl derivatives [Ru(CO)(RCCHR′)(MeCN)2(PPh3)2]A (A ClO4, R H; R′ C3H7, CMe3, Ph, COOMe; R R′ COOMe; A PF6, R R′ Ph) resulting from a cis-insertion of the alkyne into the RuH bond. The reaction of the perchlorate complex with diphenylacetylene yields alkenyl chlororuthenium derivatives resulting from the unexpected reduction of the perchlorate anion to chloride. The crystal structure of [Ru(CO)(MeOOCCCHCOOMe)(MeCN)2(PPh3)2]ClO4 has been determined by X-ray crystallography (orthorhombic, P212121, a 14.498(1), b 15.080(1), c 22.677(2) Å). In this cationic complex both phosphine and acetonitrile molecules and, consequently, the carbonyl and alkenyl ligands are mutually trans, whereas in the other complexes only the phosphine ligands are in trans disposition, as inferred from 1H NMR spectroscopic data. © 1989.We gratefully acknowledge financial support of this work by the DGICYT (PB 020102) and the CSICPeer Reviewe

Synthesis of new ruthenium(II) carbonyl hydrido, alkenyl, and alkynyl complexes with chelating diphosphines

Substitution of one or two triphenylphosphine ligands of Ru(CO)ClH(PPh3)3 by bidentate diphosphines Ph2P(CH2)nPPh2 (L-L) (n = 1, dppm; n = 2, dppe; n = 3, dppp; n = 4, dppb) or 1,1′-bis(diphenylphosphino)ferrocene (dppf) led to hydrides Ru(CO)ClH(PPh3)2(L-L) or Ru-(CO)ClH(PPh3)(L-L). The hydrido complexes were characterized spectroscopically and by one X-ray structure. Hydride Ru(CO)ClH(PPh3)(dppf) crystallizes in the monoclinic space group P21/n, with a = 17.768(1) Å, b = 25.252(2) Å, c = 11.213(1) Å, β = 92.83(1)°, Z = 4, and V = 4459.3(6) Å3. Reaction of Ru(CO)ClH(PPh3)3 or [Ru(CO)H(MeCN)2(PPh3)2]+PF6-with 2 equiv of diphosphines L-L led to [Ru(CO)H(L-L)2]+A- (L-L = dppm, dppe, dppp) (A = Cl, PF6). Hydrides Ru(CO)ClH(PPh3)2(L-L) react with 1-alkynes to give alkenyl complexes Ru(CO)Cl(CH=CHR)(PPh3)(L-L) with a chelating diphosphine ligand. Ru(CO)ClH(PPh3)-(L-L) gave σ-alkynyl complexes Ru(CO)Cl(C≡CR)L(L-L) directly in their reactions with 1-alkynes. The hydride with dppb as the ligand showed the highest reactivity. The preparation of hexacoordinated alkenyl derivatives Ru(CO)Cl(CH=CHR)(PPh3)(L-L) with a chelating diphosphine was carried out by treatment of other alkenyl derivatives with the diphosphines. Surprisingly, reaction of alkenyls Ru(CO)Cl(CH=CHR)(Me2Hpz)(PPh3)2 (R = CMe3, P-MeC6H4) with dppf led to complexes Ru(CO)Cl(CH=CHR)(Me2Hpz)(dppf) by substitution of both PPh3 ligands instead of the dimethylpyrazole. Ruthenium alkenyls Ru-(CO)Cl(CH=CHR)L(dppf) (L = Me2Hpz, PPh3) react cleanly with 1-alkynes at room temperature to give alkynyl complexes Ru(CO)Cl(C=CR)L(dppf) in good yield. This reaction was applied to the synthesis of a bimetallic complex Ru(CO)Cl(PPh3)(dppf)(C≡C-p-C6H 4C≡C)-Ru(CO)Cl(PPh)(dppf) as a mixture of meso and dl diastereomers. © 1994 American Chemical Society.We gratefully acknowledge sup- port by the Dirección General de Investigación Cientifica y Técnica (DGICYT) (Project PB91-0612-C03-02). We also acknowledge Drs. R. Jimhnez and A. Gutihrrez (Departamento de Quimica Inorglnica, Universidad Complutense de Madrid) for performing some of the 31P NMR spectra.Peer Reviewe

Reactions of cationic hydrido complexes [Ru(CO)H(MeCN)2(PPh3)2]A (A ClO4, PF6) with alkynes. The crystal structure of [Ru(CO) (MeOOCCCHCOOMe) (MeCN)2(PPh3)2]ClO4

Reactions of [Ru(CO)H(MeCN)2(PPh3)2]A with mono- and di-substituted acetylenes give the alkenyl derivatives [Ru(CO)(RCCHR′)(MeCN)2(PPh3)2]A (A ClO4, R H; R′ C3H7, CMe3, Ph, COOMe; R R′ COOMe; A PF6, R R′ Ph) resulting from a cis-insertion of the alkyne into the RuH bond. The reaction of the perchlorate complex with diphenylacetylene yields alkenyl chlororuthenium derivatives resulting from the unexpected reduction of the perchlorate anion to chloride. The crystal structure of [Ru(CO)(MeOOCCCHCOOMe)(MeCN)2(PPh3)2]ClO4 has been determined by X-ray crystallography (orthorhombic, P212121, a 14.498(1), b 15.080(1), c 22.677(2) Å). In this cationic complex both phosphine and acetonitrile molecules and, consequently, the carbonyl and alkenyl ligands are mutually trans, whereas in the other complexes only the phosphine ligands are in trans disposition, as inferred from 1H NMR spectroscopic data. © 1989.We gratefully acknowledge financial support of this work by the DGICYT (PB 020102) and the CSICPeer Reviewe