Mechanistic studies on the formation and reactivity of dioxygen adducts of diiron complexes supported by sterically hindered carboxylates

Dioxygen activation by enzymes such as methane monooxygenase, ribonucleotide reductase, and fatty acid desaturases occurs at a nonheme diiron active site supported by two histidines and four carboxylates, typically involving a (peroxo)diiron(III,III) intermediate in an early step of the catalytic cycle. Biomimetic tetracarboxylatodiiron(II,II) complexes with the familiar "paddlewheel" topology comprising sterically bulky o-dixylylbenzoate ligands with pyridine, 1-methylimidazole, or THF at apical sites readily react with O(2) to afford thermally labile peroxo intermediates that can be trapped and characterized spectroscopically at low temperatures (193 K). Cryogenic stopped-flow kinetic analysis of O(2) adduct formation carried out for the three complexes reveals that dioxygen binds to the diiron(II,II) center with concentration dependences and activation parameters indicative of a direct associative pathway. The pyridine and 1-methylimidazole intermediates decay by self-decomposition. However, the THF intermediate decays much faster by oxygen transfer to added PPh(3), the kinetics of which has been studied with double mixing experiments in a cryogenic stopped-flow apparatus. The results show that the decay of the THF intermediate is kinetically controlled by the dissociation of a THF ligand, a conclusion supported by the observation of saturation kinetic behavior with respect to PPh(3), inhibition by added THF, and invariant saturation rate constants for the oxidation of various phosphines. It is proposed that the proximity of the reducing substrate to the peroxide ligand on the diiron coordination sphere facilitates the oxygen-atom transfer. This unique investigation of the reaction of an O(2) adduct of a biomimetic tetracarboxylatodiiron(II,II) complex provides a synthetic precedent for understanding the electrophilic reactivity of like adducts in the active sties of nonheme diiron enzymes.     

The diastereoselective synthesis of functionalised isoxazolidines using a Cope elimination/intramolecular nitrone cycloaddition strategy

Functionalised hydroxylamine derivatives of (S)-prolinol prepared by a Cope elimination have been found to undergo oxidation to the nitrone either in the presence of air or a catalytic quantity of TPAP. These undergo intramolecular cycloaddition to give tricyclic isoxazolidines with high diastereoselectivity.     

Diastereoselective Electrophilic Amination of Chiral 1‐Benzoyl‐2,3,5,6‐tetrahydro‐3‐methyl‐2‐(1‐methylethyl)pyrimidin‐4(1H)‐one for the Asymmetric Syntheses of α‐Substituted α,β‐Diaminopropanoic Acids

The chiral compounds (R)‐ and (S)‐1‐benzoyl‐2,3,5,6‐tetrahydro‐3‐methyl‐2‐(1‐methylethyl)pyrimidin‐4(1H)‐one ((R)‐ and (S)‐ 1 ), derived from (R)‐ and (S)‐asparagine, respectively, were used as convenient starting materials for the preparation of the enantiomerically pure α‐alkylated (alkyl=Me, Et, Bn) α,β‐diamino acids (R)‐ and (S)‐ 11 – 13 . The chiral lithium enolates of (R)‐ and (S)‐ 1 were first alkylated, and the resulting diasteroisomeric products 5 – 7 were aminated with ‘di(tert‐butyl) azodicarboxylate’ (DBAD), giving rise to the diastereoisomerically pure (≥98%) compounds 8 – 10 . The target compounds (R)‐ and (S)‐ 11 – 13 could then be obtained in good yields and high purities by a hydrolysis/hydrogenolysis/hydrolysis sequence.     

Approaches to the Synthesis of Perfluoroalkyl-Modified Carbohydrates and Derivatives: Thiosugars,Iminosugars, and Tetrahydro(thio)pyrans

Fluoroalkyl-substituted carbohydrates play relevant roles in diverse areas such as supramolecular chemistry, glycoconjugation, liquid crystals, and surfactants, with direct applications as wetting, antifreeze, and coating agents. In light of these promising applications, new methodologies for the late-stage incorporation of fluoroalkyl R_F groups into carbohydrates and derivatives are herein presented as they are relevant to the synthetic carbohydrate community. Previously reviewed protocols for the installation of R_F groups onto carbohydrates and derivatives will be succinctly summarized in the light of the new achievements. Fluoroalkyl-substituted iminosugars, on the other hand, are also interesting glycomimetic derivatives with prominent roles as glycosidases and glycosyltransferases inhibitors, as has recently been demonstrated. Also, they positively contribute to the study of sugar–protein interactions and enzyme mechanisms. New advances in the syntheses of fluoroalkyl-substituted iminosugars will also be presented here.     

Synthetic hosts for molecular recognition of ureas

Four hosts (7-10) containing 2,6-bisamidopyridine- and 2,5-bisamidopyrrole-bearing pyridyl or 1,8-naphthyridyl groups have been prepared and their structures studied by a combination of multinuclear NMR spectroscopy and X-ray crystallography. Their behavior in molecular recognition of urea derivatives, including (+)-biotin methyl ester, has been approached by molecular modeling (Monte Carlo conformational search, AMBER force field). The minimum energy values for the complexes are correlated with the experimental binding energies determined by means of (1)H NMR titrations.     

Basicity of bisperhalophenyl aurates toward closed-shell metal ions: metallophilicity and additional interactions

The interaction of bisperhalophenyl aurates [AuR₂]^? (R?=?C₆F₅, C₆F₃Cl₂, and C₆Cl₅) with the closed-shell Ag⁺, Cu⁺, and Tl⁺ ions has been studied theoretically and compared with the experimentally known X-ray diffraction crystal structures. Initially, the aurates have been fully optimized at MP2 level of theory in a D _2h symmetry. The analysis of the basicity of the three aurates [AuR₂]^? (R?=?C₆F₅, C₆F₃Cl₂ and C₆Cl₅) against Ag⁺ ions in a C _2v symmetry has been calculated in point-by-point bsse-corrected interaction energy analysis at HF and MP2 levels of theory. Taking into account the experimental observation of additional interactions between the heterometals and C _ipso atoms at the perhalophenyl rings or halogen atoms at the ortho position of the perhalophenyl rings, dinuclear models of the type [AuR₂]^?···Ag⁺ (R?=?C₆Cl₅, and C₆F₅); [AuR₂]^?···Cu⁺ (R?=?C₆F₅, and C₆Cl₅) and [AuR₂]^?···Tl⁺ (R?=?C₆F₅, and C₆Cl₅) with a C _2v , C ₂ , and C _s symmetries have been optimized at DFT-B3LYP level. The interaction energies have been computed through bsse-corrected single point HF and MP2 calculations. The energy stabilization provided and the heterometal preference have been analyzed and compared with the experimental results.     

Modeling the platinum-catalyzed intermolecular hydroamination of ethylene: The nucleophilic addition of HNEt2 to coordinated ethylene in trans-PtBr2(C2H4)(HNEt2)

Compound trans-PtBr₂(C₂H₄)(NHEt₂) (1) has been synthesized by Et₂NH addition to K[PtBr₃(C₂H₄)] and structurally characterized. Its isomer cis-PtBr₂(C₂H₄)(NHEt₂) (3) has been obtained from 1 by photolytic dissociation of ethylene, generating the dinuclear trans-[PtBr₂(NHEt₂)]₂ intermediate (2), followed by thermal re-addition of C₂H₄, but only in low yields. The addition of further Et₂NH to 1 in either dichloromethane or acetone yields the zwitterionic complex trans-Pt⁽⁻⁾Br₂(NHEt₂)(CH₂CH₂N⁽⁺⁾HEt₂) (4) within the time of mixing in an equilibrated process, which shifts toward the product at lower temperatures (ΔH° = −6.8 ± 0.5 kcal/mol, ΔS° = 14.0 ± 2.0 e.u., from a variable temperature IR study). ¹H NMR shows that free Et₂NH exchanges rapidly with H-bonded amine in a 4·NHEt₂ adduct, slowly with the coordinated Et₂NH in 1, and not at all (on the NMR time scale) with Pt-NHEt₂ or -CH₂CH₂N⁽⁺⁾HEt₂ in 4. No evidence was obtained for deprotonation of 4 to yield an aminoethyl derivative trans-[PtBr₂(NHEt₂)(CH₂CH₂NEt₂)]⁻ (5), except as an intermediate in the averaging of the diasteretopic methylene protons of the CH₂CH₂N⁽⁺⁾HEt₂ ligand of 4 in the higher polarity acetone solvent. Computational work by DFT attributes this phenomenon to more facile ion pair dissociation of 5·Et₂NH₂⁺, obtained from 4·Et₂NH, facilitating inversion at the N atom. Complex 4 is the sole observable product initially but slow decomposition occurs in both solvents, though in different ways, without observable generation of NEt₃. Addition of TfOH to equilibrated solutions of 4, 1 and excess Et₂NH leads to partial protonolysis to yield NEt₃ but also regenerates 1 through a shift of the equilibrium via protonation of free Et₂NH. The DFT calculations reveal also a more favourable coordination (stronger Pt-N bond) of Et₂NH relative to PhNH₂ to the Pt^II center, but the barriers of the nucleophilic additions of Et₂NH to the C₂H₄ ligand in 1 and of PhNH₂ to trans-PtBr₂(C₂H₄)(PhNH₂) (1a) are predicted to be essentially identical for the two systems.     

Photometric determination of aqueous cobalt (II), nickel (II), copper (II) and iron (III) with 1-nitroso-2-naphthol-3,6-disulfonic acid disodium salt in gelatin films

Photometric determination of aqueous Co(II), Cu(II), Ni(II) and Fe(III) was performed using indicator films prepared by immobilization of 1-nitroso-2-naphthol-3,6-disulfonic acid disodium salt (NRS) into hardened photographic film. Immobilization was based on electrostatic interaction of reagent and metal complexes with the gelatin. The isoelectric point pH of hardened gelatin (4.46±0.04) was evaluated by viscometry. Co(II), Fe(III), Ni(II) form 1:3 complexes with NRS in gelatin at pH 2 and Cu(II) forms 1:2 complexes. Their log β′ values were: Co-6.7, Fe-8.6, Cu-8.0, and Ni-6.4. The absorption maxima were: 370nm for NRS, and 430nm, 470nm, 495nm and 720nm for complexes of Co(II), Ni(II), Cu(II) and Fe(III). An algorithm for their simultaneous determination using the indicator films was developed. The detection limits were: c_lim(Co²⁺) = 0.45×10⁻⁵ M, c_lim(Fe³⁺) = 0.50×10⁻⁵ M, c_lim(Cu²⁺) = 0.67×10⁻⁵ M, c_lim(Ni²⁺) = 0.75×10⁻⁵ M,; and their sum c_lim(ΣMn⁺) = 0.82×10⁻⁵ M.      

Cyclodextrin-surfactant coassembly depends on the cyclodextrin ability to crystallize

Full equilibrium phase diagrams are presented for two ternary systems composed of the cationic surfactant dodecyltrimethylammonium bromide (DTAB), water (D(2)O), and a cyclodextrin, either β-cyclodextrin (β-CD) or (2-hydroypropyl)-β-cyclodextrin (2HPβCD). (2)H NMR, SAXS, WAXS, and visual examination were used to determine the phase boundaries and characterize the nature of the phases formed. Additionally, diffusion (1)H NMR was used to investigate parts of the diagrams. The water solubility of 2HPβCD is 80% (w/w), whereas it is only 1.85% (w/w) for β-CD. Solubility increases for both species upon complexation with DTAB; while the increase is minute for 2HPβCD, it is dramatic for β-CD. Both systems displayed an isotropic liquid solution (L(1)) one-phase region, the extension of which differs extensively between the two systems. Additionally, the DTAB:2HPβCD:water system also comprised a normal hexagonal (H(1)) area, which was not found for the DTAB:β-CD:water system. In the DTAB:β-CD:water system, on the other hand, we found cocrystallization of DTAB and β-CD. From this work we conclude that DTAB and CD molecules form 1:1 inclusion complexes with high affinities. Moreover, we observed indications of an association of 2HPβCD to DTAB micelles in the isotropic solution phase, which was not the case for β-CD and DTAB micelles. This is, to our knowledge, the first complete phase diagrams of surfactant-CD mixtures; as a novel feature it includes the observation of cocrystallization at high concentrations.