Lucio Randaccio

Organocobalt B12 models: axial ligand effects on the structural and coordination chemistry of cobaloximes

Article de synthese presentant les structures cristallines et moleculaires de molecules contenant la moitie Co(DH) 2 , ou DH est le monoanion de la dimethylglyoxime. Les structures RX sont comparees aux structures en solution. Discussion des implications pour la biochimie de la vitamine B 12

MOLECULAR TRIANGLE FROM ENPTII AND 2,2'-BIPYRAZINE

Twisting of the two pyrazine halves of the 2,2′-bipyrazine ligands appears to be responsible for the facile formation of a enPtII triangle (shown schematically on the right; en=ethylenediamine, omitted from the sketch for clarity).

Vitamin B12: unique metalorganic compounds and the most complex vitamins.

The chemistry and biochemistry of the vitamin B12 compounds (cobalamins, XCbl) are described, with particular emphasis on their structural aspects and their relationships with properties and function. A brief history of B12, reveals how much the effort of chemists, biochemists and crystallographers have contributed in the past to understand the basic properties of this very complex vitamin. The properties of the two cobalamins, the two important B12 cofactors Ado- and MeCbl are described, with particular emphasis on how the Co-C bond cleavage is involved in the enzymatic mechanisms. The main structural features of cobalamins are described, with particular reference to the axial fragment. The structure/property relationships in cobalamins are summarized. The recent studies on base-off/base-on equilibrium are emphasized for their relevance to the mode of binding of the cofactor to the protein scaffold. The absorption, transport and cellular uptake of cobalamins and the structure of the B12 transport proteins, IF and TC, in mammals are reviewed. The B12 transport in bacteria and the structure of the so far determined proteins are briefly described. The currently accepted mechanisms for the catalytic cycles of the AdoCbl and MeCbl enzymes are reported. The structure and function of B12 enzymes, particularly the important mammalian enzymes methyltransferase (MetH) and methyl-malonyl-coenzymeA mutase (MMCM), are described and briefly discussed. Since fast proliferating cells require higher amount of vitamin B12 than that required by normal cells, the study of B12 conjugates as targeting agents has recently gained importance. Bioconjugates have been studied as potential agents for delivering radioisotopes and NMR probes or as various cytotoxic agents towards cancer cells in humans and the most recent studies are described. Specifically, functionalized bioconjugates are used as “Trojan horses” to carry into the cell the appropriate antitumour or diagnostic label. Possible future developments of B12 work are summarized.

Structure determination of the 2:1 derivatives of copper(I) bromide and iodide with bis(diphenylphosphino)methane. A simple structural scheme for the formation of (CuX)nLm species

Abstract The structures of the complexes (CuX)2DPM (X = Br, I; DMP = bis(diphenylphosphino)methane) were determined from three dimensional X-ray data collected by counter methods. The iodine derivative crystallizes in the space group Pbca with eight units in a cell defined by a = 17.128(9), b = 18.306(9) c, = 16.508 (8) A. The structure was refined by the least-squares method to a final R factor of 0.054 for 1336 non-zero independent reflections. The bromine derivative crystallizes in the space group P21/c with eight units in a cell defined by a = 23.707(1), b = 17.805(9), c = 16.991(1) A, β = 136.10(5)°. The final least-squares refinement, based on 2489 non-zero independent reflections, gave an R factor of 0.074. Both the compounds have similar structures with a centrosymmetric (CuX)4 core, in which two copper atoms have a tetrahedral geometry, while the other two are trigonal. The above structures are compared with those already reported for other compounds (CuX)nLm and a single scheme is proposed to rationalize the different geometries of the (CuX)n core on the basis of steric and electronic effects.

Vitamin B12 Coenzyme Models: Perspectives on Recent Developments in the Chemistry of the Cobaloximes and Related Models

Abstract Discoveries on B12 models made since 1989 are assessed in the light of the advances in structural and spectroscopic methodologies. Further studies emanating in part from these advances have confirmed, often definitively, previously identified principles describing the properties of the classic simple models (cobaloximes and iminocobaloximes) and have established some new principles defining the properties of the axial Co-C and Co-N bonds; the latter are clearly relevant to enzymatic processes. Some new simple models have been proposed and studied in relation to the classic ones and to the more complicated natural cobalamins. In several cases, the influence of the steric and electronic factors have been established, sometimes in semi-quantitative terms, also with the help of studies on the rhodium analogues of cobaloximes. New spectroscopic techniques have been introduced, which have been found useful in the study of the natural cobalamins. Recent structural analyses of the binding site in some B1...

STRUCTURAL ASPECTS OF PT COMPLEXES CONTAINING MODEL NUCLEOBASES

Abstract Compounds of Pt(II) and Pt(IV)-containing nucleobases as ligands (also including a few related ligands) are summarized and described, according to the nuclearity of the complexes. The large amount of available crystallographic data allows geometrical parameters such as bond lengths and angles, angular distortions, torsional angles related to the nucleobase plane orientations etc., to be derived with relatively high accuracy. Simple relationships between some of these parameters are reported and discussed. On mononuclear Pt complexes containing one or more nucleobase ligands a simple descriptive statistical analysis has been performed. The structural properties of polynuclear, often heteronuclear species have also been reviewed where the nucleobases, particularly pyrimidines, act as polydentate-often bridging-ligands. A simple MO theoretical analysis of the metal-metal interaction in homo- and heterodinuclear species allows the degree of the intermetallic bond formation to be rationalized and the correlation of the qualitative results with the experimental metal-metal distances. Cyclic polynuclear species, which appear to be a new expanding field in the chemistry of Pt-nucleobase complexes, are also described.

Enantioselective hydrogen transfer reactions from propan-2-ol to ketones catalyzed by pentacoordinate iridium(I) complexes with chiral Schiff bases

Abstract Some diastereoisomeric pentacoordinate complexes of the type [Ir(COD)-(NNR ★ )I] (COD = cis , cis -1,5-cyclooctadiene; NNR ★ = 2-pyridinal-1-phenylethylimine (PPEI) (I), 2-acetylpyridine-1-phenylethylimine (APPEI) (II)) have been synthesized. The complexes are active and selective catalysts for asymmetric hydrogen transfer from propan-2-ol to prochiral ketones. Optical yields of up to 84% have been obtained in the reduction of t-butyl phenyl ketone. The structure and absolute configuration of complexes I and II were determined by X-ray diffraction.

Nanoporous crystals of calixarene/porphyrin supramolecular complex functionalized by diffusion and coordination of metal ions

A highly nanoporous material has been obtained by self-assembly of calixarene and porphyrin building blocks. This supramolecular zeolite-like structure was successively functionalized by diffusion and coordination of metal ions to form a new bifunctionalized nanoporous material containing a porphyrinic pigment together with a metal center.

A novel bimetallic alternating chain: synthesis, crystal structure and magnetic study

A novel one dimensional (1D) bimetallic polymeric complex [ catena -bis(μ- N -(aminoethyl)-3-aminopropanolato)-di-copper(II)-tetracyanonickelate(II)dihydrate] has been synthesized by the reaction of 1:1 mixture of CuCl 2 ·2H 2 O and the hydoxyamine ligand, [ N -(3-hydroxypropyl)ethane-1,2-diamine] with half equivalent of [Ni(CN) 4 ] −2 in aqueous solution. X-ray quality single crystals were obtained by slow evaporation of the ammoniacal solution of the complex. The single crystal structure reveals that it is an alkoxo bridged Cu(II) dimer linked through [Ni(CN) 4 ] 2− in trans -fashion resulting in a 1D chain. The properties of the complex have been studied by variable temperature magnetic susceptibility measurements. The susceptibility data fit well with the Cu(lI) dimer equation to give 2 J =−622 cm −1 , g =2.05. The very high coupling parameter value clearly indicates the presence of very strong antiferromagnetic interaction between the Cu(II) ions.

Structural study on ligand specificity of human vitamin B12 transporters.

Studies comparing the binding of genuine cobalamin (vitamin B12) to that of its natural or synthetic analogues have long established increasing ligand specificity in the order haptocorrin, transcobalamin and intrinsic factor, the high-affinity binding proteins involved in cobalamin transport in mammals. In the present study, ligand specificity was investigated from a structural point of view, for which comparative models of intrinsic factor and haptocorrin are produced based on the crystal structure of the homologous transcobalamin and validated by results of published binding assays. Many interactions between cobalamin and its binding site in the interface of the two domains are conserved among the transporters. A structural comparison suggests that the determinant of specificity regarding cobalamin ligands with modified nucleotide moiety resides in the beta-hairpin motif beta3-turn-beta4 of the smaller C-terminal domain. In haptocorrin, it provides hydrophobic contacts to the benzimidazole moiety through the apolar regions of Arg357, Trp359 and Tyr362. Together, these large side chains may compensate for the missing nucleotide upon cobinamide binding. Intrinsic factor possesses only the tryptophan residue and transcobalamin only the tyrosine residue, consistent with their low affinity for cobinamide. Relative affinity constants for other analogues are rationalized similarly by analysis of steric and electrostatic interactions with the three transporters. The structures also indicate that the C-terminal domain is the first site of cobalamin-binding since part of the beta-hairpin motif is trapped between the nucleotide moiety and the N-terminal domain in the final holo-proteins.