Gabriel Demo

Platinum-Modified Adenines: Unprecedented Protonation Behavior Revealed by NMR Spectroscopy and Relativistic Density-Functional Theory Calculations

Two novel Pt(IV) complexes of aromatic cytokinins with possible antitumor properties were prepared by reaction of selected aminopurines with K(2)PtCl(6). The structures of both complexes, 9-[6-(benzylamino)purine] pentachloroplatinate (IV) and 9-[6-(furfurylamino)purine] pentachloroplatinate (IV), were characterized in detail by using two-dimensional NMR spectroscopy ((1)H, (13)C, (15)N, and (195)Pt) in solution and CP/MAS NMR techniques in the solid state. We report for the first time the X-ray structure of a nucleobase adenine derivative coordinated to Pt(IV) via the N9 atom. The protonation equilibria for the complexes in solution were characterized by using NMR spectroscopy (isotropic chemical shifts and indirect nuclear spin-spin coupling constants) and the structural conclusions drawn from the NMR analysis are supported by relativistic density-functional theory (DFT) calculations. Because of the presence of the Pt atom, hybrid GGA functionals and scalar-relativistic and spin-orbit corrections were employed for both the DFT calculations of the molecular structure and particularly for the NMR chemical shifts. In particular, the populations of the N7-protonated and neutral forms of the complexes in solution were characterized by correlating the experimental and the DFT-calculated NMR chemical shifts. In contrast to the chemical exchange process involving the N7-H group, the hydrogen atom at N3 was determined to be unexpectedly rigid, probably because of the presence of the stabilizing intramolecular interaction N3-H···Cl. The described methodology combining the NMR spectroscopy and relativistic DFT calculations can be employed for characterizing the tautomeric and protonation equilibria in a large family of transition-metal-modified purine bases.

Synthesis and X-Ray Structures of Zinc(II) and Cadmium(II) Heteroleptic Complexes Involving 1,1-Dithiolate and N-Donor Ligands

GRAPHICAL ABSTRACT Abstract A series of zinc(II) and cadmium(II) complexes, involving a combination of S–donor (xanthates and dithiophosphates) and N-donor (1,10-phen = 1,10-phenanthroline, 2,2′–bipy = 2,2′-bipyridine) ligands, of the composition [Cd(S2COnPr)2(2,2′-bipy)] (1), [Cd(S2COnPr)2(1,10-phen)] (2), [Cd(S2P(OEt)2)2(2,2′-bipy)] (3), [Cd(S2P(OEt)2)2(1,10-phen)] (4), [Zn(S2COnPr)2(2,2′-bipy)] (5), [Zn(S2COnPr)2(1,10-phen)] (6), [Zn(S2P(OEt)2)2(2,2′-bipy)] (7), and [Zn(S2P(OEt)2)2(1,10-phen)] (8) was prepared. The complexes (1–8) were characterized by elemental analysis and single-crystal X-ray analysis. X-ray structures revealed that the coordination geometries vary from octahedral (complexes 1–4), through square-pyramidal (complexes 5 and 6) to tetrahedral (complexes 7 and 8), depending on a combination of the central metal atoms and the corresponding S-donor and N-donor ligands. Similarities and discrepancies among the individual molecular structures as well as noncovalent contacts stabilizing crystal structures are discussed in more detail.

A Novel Fucose-binding Lectin from Photorhabdus luminescens (PLL) with an Unusual Heptabladed β-Propeller Tetrameric Structure.

Photorhabdus luminescens is known for its symbiosis with the entomopathogenic nematode Heterorhabditis bacteriophora and its pathogenicity toward insect larvae. A hypothetical protein from P. luminescens was identified, purified from the native source, and characterized as an l-fucose-binding lectin, named P. luminescens lectin (PLL). Glycan array and biochemical characterization data revealed PLL to be specific toward l-fucose and the disaccharide glycan 3,6-O-Me2-Glcβ1–4(2,3-O-Me2)Rhaα-O-(p-C6H4)-OCH2CH2NH2. PLL was discovered to be a homotetramer with an intersubunit disulfide bridge. The crystal structures of native and recombinant PLL revealed a seven-bladed β-propeller fold creating seven putative fucose-binding sites per monomer. The crystal structure of the recombinant PLL·l-fucose complex confirmed that at least three sites were fucose-binding. Moreover, the crystal structures indicated that some of the other sites are masked either by the tetrameric nature of the lectin or by incorporation of the C terminus of the lectin into one of these sites. PLL exhibited an ability to bind to insect hemocytes and the cuticular surface of a nematode, H. bacteriophora.

The influence of Mg2+ coordination on 13C and 15N chemical shifts in CKI1RD protein domain from experiment and molecular dynamics/density functional theory calculations

Sequence dependence of 13C and 15N chemical shifts in the receiver domain of CKI1 protein from Arabidopsis thaliana, CKI1RD, and its complexed form, CKI1RD•Mg2+, was studied by means of MD/DFT calculations. MD simulations of a 20–ns production run length were performed. Nine explicitly hydrated structures of increasing complexity were explored, up to a 40‐amino‐acid structure. The size of the model necessary depended on the type of nucleus, the type of amino acid and its sequence neighbors, other spatially close amino acids, and the orientation of amino acid NH groups and their surface/interior position. Using models covering a 10 and a 15 Å environment of Mg2+, a semi‐quantitative agreement has been obtained between experiment and theory for the V67−I73 sequence. The influence of Mg2+ binding was described better by the 15 Å as compared to the 10 Å model. Thirteen chemical shifts were analyzed in terms of the effect of Mg2+ insertion and geometry preparation. The effect of geometry was significant and opposite in sign to the effect of Mg2+ binding. The strongest individual effects were found for 15N of D70, S74, and V68, where the electrostatics dominated; for 13Cβ of D69 and 15N of K76, where the influences were equal, and for 13Cα of F72 and 13Cβ of K76, where the geometry adjustment dominated. A partial correlation between dominant geometry influence and torsion angle shifts upon the coordination has been observed. Proteins 2016; 84:686–699.

X-ray structures of heteroleptic zinc(II) complexes involving combinations of O,O'-dialkyldithiophosphato and bidentate N-donor ligands

Abstract The detailed X-ray structural elucidation of reaction products of a zinc(II) salt with O,O′-dialkyldithiophosphate and nitrogen-containing heterocycles (N–N=1,10-phenanthroline (phen) or 2,2′-bipyridine (bpy)) has been performed. Surprisingly, together with [Zn(S2 P(OR)2)2(N–N)] compounds, also ionic-type complexes having the formula of [Zn(N–N)3](S2 P(OR)2)2 have been obtained using the same molar ratios of the reactants. The prepared complexes have been characterized by elemental analysis and single-crystal X-ray analysis. The crystallographic analysis showed that the bond lengths and bite angles of the prepared complexes are in good agreement with those of similar compounds. The crystal packing of described complexes is formed via π–π stacking interactions and/or C–H···S non-covalent contacts.

Protein engineering study of β-mannosidase to set up a potential chemically efficient biocatalyst

This study is focused on the analysis and mutagenesis of β-mannosidase from Bacteroides thetaiotaomicron with the aim of broadening its substrate specificity to 2-acetamido-2-deoxy-β-d-mannopyranosyl (β-ManNAc) derivatives. Various conformations ((4)C1, (4)H5 and (1)S5) of native and modified ligands were docked to the binding site of the protein to determine the most suitable conformation of sugars for further hydrolysis. Key amino acid residues were mutated in silico focusing on stabilizing the acetamido group of β-ManNAc as well as forming the oxazoline intermediate needed for hydrolysis. The results of large set of 5 ns molecular dynamic simulations showed that the majority of the active site residues are involved in substrate interaction and do not exhibit a higher flexibility except for Asn178. Mutations of Asn178 to alanine and Asp199 to serine could lead to a stabilization of the acetamido group in the binding site. So far, in vitro mutagenesis and the screen of a large variety of biological sources were unable to extend β-mannosidases activity to include β-ManNAc derivatives.

Synthesis and structure of tris(dimethyldithiocarbamato)(1,10-phenanthroline)lanthanide complexes

Abstract Syntheses and structures of three new lanthanide coordination compounds with dithiocarbamate ligands are reported. The complexes [Ln(Me2dtc)3(phen)] (Ln = Pr (1), Nd (2) and Gd (3), Me2dtc = N,N-dimethyldithiocarbamate and phen = 1,10-phenanthroline) were synthetized by a simple metathesis between lanthanide(III) nitrate and sodium dimethyldithiocarbamate followed by addition of 1,10-phenanthroline without the exclusion of moisture. Single crystal X-ray analysis showed that all three complexes are isostructural, crystallizing in the triclinic space group P1̅. The Ln-S and Ln-N bond lengths decrease in agreement with the decrease in ionic radii across the lanthanide series. Similar structures with Et2dtc ligands show no significant effect on the changes of Ln-S bond lengths and also on the S-Ln-S bite angles. The crystal packing of described complexes is formed via π-π stacking interactions and C-H ... S non-covalent contacts.