Host–guest interactions and their role in enantioselective hydrogenation of α-keto esters: An analysis of model systems

The interaction between cinchonidine and methyl pyruvate has been proposed as the key step leading to enantiodifferentiation in the enantioselective hydrogenation of α-ketoesters. In the present work, we employ ab initio MP2/6-31G(d) and MP2/6-31G(d,p) methods to carry out an analysis of the most relevant kind of interactions operating in representative model systems. These interactions are discussed in terms of orbital superposition and dipolar interaction. When approaching H₂CO to NH₃ at distances lower than 3.4 Å, orbital superposition is the predominant interaction, while at distances above 3.4 Å, both orbital superposition and dipolar interactions may contribute to stabilization, with a small prevalence of dipolar interactions. The stabilization energy at large distances (above 4.5 Å) is very small (about 0.5 kcal mol⁻¹), probably not enough to be responsible for the enantiodifferentiation process. Semiempirical calculations on the parent systems were also unable to reveal any special interaction which could be attributed to the enantiodifferentiation process.     

Spectral patterns and ultrafast dynamics in planar acetylene

A diabatic correlation diagram procedure is used to classify energy and intensity patterns in a planar model for coupled stretches and bends of acetylene using an effective spectroscopic fitting Hamiltonian. Analysis with polyad phase spheres accounts for the observed patterns in terms of classical phase space structure and bifurcations of the normal modes. Received 29 August 2000 and Received in final form 14 September 2000     

Complexation of dichlorocarbene by methylanisoles

Dichlorocarbene generated by laser flash photolysis of dichlorodiazirine readily forms UV-vis active π- and O-ylidic complexes with methylanisole derivatives.     

Intramolecular Reactivity of π-Coordinated P-Heterocycles: How to Form Five-Membered Rings out of Phosphaalkynes

Experimental and theoretical evidence is presented for a novel metal-dependent intramolecular reactivity of ~ -bonded, unsaturated P-heterocycles like 1,3-diphosphete and 1,3,5-triphosphinine. The nucleophilic attack of a P lone pair of 1,3-diphosphete toward a neighboring ligand leads to new bicyclic ligands with unique structural features. A metal-initiated intramolecular hydrogen transfer and C--C bond formation are observed for (1,3,5-triphosphinine)(COD)Fe to result in the formation of [(CO) 5 Cr(4,5,6-trihydro-1,3,5-triphosphinine)(trihydropentalene)Fe].     

N-Aryl-N-Hydroxy Urethanes as Peroxidase Substrates

Summary.  N-Aryl-N-hydroxy urethanes (AHUs), which are promising N*OH mediators for oxidoreductase catalysis, are electrochemically active redox compounds with a redox potential of 0.35–0.40 V vs. SCE (0.59–0.64 V vs. NHE). Alkyl substituents in the carbamic acid residue have, as expected, only little influence on the redox potential. The highest potential was noticed for N-hydroxy-N-(4-cyanophenyl)-carbamic acid methyl ester. Recombinant Coprinus cinereus peroxidase (rCiP) catalyzes oxidation of the AHUs with apparent bimolecular constants k _ox of 2.5ċ10⁴–7.5ċ10⁴ M ⁻¹s⁻¹ at pH = 8.5 and 25°C. Structure-function connectivities of the substrates were analysed within the framework of the Marcus cross relationship and by using ab initio quantum chemical calculations. An excellent correlation of the redox potentials and the HOMO energies could be found. However, no correlation of log(k _ox) with redox potential and HOMO energy was indicated as predicted by theory. This was explained by specific docking of the substrates in the active center of rCiP. Received June 26, 2000. Accepted (revised) August 9, 2000     

Synthesis and Characterization of the Trisulfate Pb[S3O10] and Theoretical Analysis of H2S3O10

The reaction of (NH₄)₂PbCl₆ and fuming sulfuric acid (65 % SO₃) in a sealed glass tube at 250 °C led to colorless single crystals of Pb[S₃O₁₀] (orthorhombic, Pbcn, Z = 4, a = 10.9908(4), b = 8.5549(3), c = 8.0130(3) Å, V = 753.42(5) ų). The compound shows a three‐dimensional linkage of the tenfold oxygen coordinated Pb²⁺ ions and exhibits the unusual trisulfate anion, [S₃O₁₀]^2–, that consists of three vertex connected [SO₄] tetrahedra. The distances S–O within the S–O–S bridges of the anion are remarkable asymmetric with distances of 155 and 169 pm, respectively. This structural feature is well reproduced by calculations on a PBE0/cc‐pVTZ and a MP2/cc‐pVTZ level of theory. Similar calculations allow also for an inspection of the yet unknown corresponding acid, H₂S₃O₁₀. Also for this acid non‐symmetric S–O–S bridges are predicted. The thermal behavior of Pb[S₃O₁₀] is characterized by the loss of two equivalents of SO₃ at low temperature and the decomposition of intermediate Pb[SO₄] at higher temperature.     

The Lamb-dip spectrum of the J = 1 ← 0 transition of DF: Crossing resonances and hyperfine components

The Lamb-dip technique has been applied to the observation of the J = 1 ← 0 transition of DF: for the first time, the hyperfine structure due to D and F have been resolved by using microwave spectroscopy. The high accuracy of this technique allows us to provide hyperfine parameters that are in very good agreement with those obtained from molecular beam experiment. In addition, our frequencies together with the unresolved ones up to J″ value of 47 allow us to provide the most accurate ground state rotational constants of DF known at the moment. Furthermore, due to the presence of a relevant number of strong crossing resonances, the J = 1 ← 0 transition of DF can be considered an illustrative case to show how they modify the shape of Lamb-dip spectra.     

Electron-pair densities of group 2 atoms in their and terms

Electron-pair intracule (relative motion) and extracule (center-of-mass motion) densities are studied in both position and momentum spaces for the ¹ P and ³ P terms of the group 2 atoms Be (atomic number Z =4), Mg (Z =12), Ca (Z =20), Sr (Z =38), Ba (Z =56), and Ra (Z =88). In position space, the ¹ P - ³ P difference in the intracule densities shows that the probability of a small interelectronic distance is larger in the triplet for all the six atoms, as reported for the lightest Be atom in the literature. The position-space extracule density clarifies that the triplet electrons are more likely to be at opposite positions with respect to the nucleus than the singlet electrons for all the atoms. In momentum space, the singlet generally has a larger probability of a small relative momentum between two electrons as a na?ve manifestation of the Fermi hole in the triplet. The extracule density in momentum space shows that the ¹ P term has a distribution larger in a large center-of-mass momentum region than the ³ P term. Received: 26 August 1998 / Received in final form: 1 February 1999     

Quantitation of low concentrations of polysorbates in high protein concentration formulations by solid phase extraction and cobalt-thiocyanate derivatization

A spectrophotometric method was developed to quantify low polysorbate (PS) levels in biopharmaceutical formulations containing high protein concentrations. In the method, Oasis HLB solid phase extraction (SPE) cartridge was used to extract PS from high protein concentration formulations. After loading a sample, the cartridge was washed with 4 M guanidine HCl and 10% (v/v) methanol, and the retained PS was eluted by acetonitrile. Following the evaporation of acetonitrile, aqueous cobalt-thiocyanate reagent was added to react with the polyoxyethylene oxide chain of polysorbates to form a blue colored PS–cobaltothiocyante complex. This colored complex was then extracted into methylene chloride and measured spectrophotometrically at 620 nm. The method performance was evaluated on three products containing 30–40 mg L⁻¹ PS-20 and PS-80 in ≤70 g L⁻¹ protein formulations. The method was specific (no matrix interference identified in three types of protein formulations), sensitive (quantitation limit of 10 mg L⁻¹ PS) and robust with good precision (relative standard deviation ≤6.4%) and accuracy (spike recoveries from 95% to 101%). The linear range of the method for both PS-20 and PS-80 was 10 to 80 mg L⁻¹ PS. By diluting samples with 6 M guanidine HCl and/or using different methylene chloride volumes to extract the colored complexes of standards and samples, the method could accurately and precisely quantify 40 mg L⁻¹ PS in up to 300 g L⁻¹ protein formulations.     

How Small Amounts of Impurities Are Sufficient to Catalyze the Interconversion of Carbonyl Compounds and Iminium Ions,or Is There a Metathesis through 1,3‐Oxazetidinium Ions? Experiments,Speculations, and Calculations

Under the ‘best anhydrous’ conditions, we were able to achieve, the bicyclic oxazolidinones derived from proline and pivalaldehyde (or cyclohexanone) equilibrate with added carbonyl compounds in (D₆)DMSO and in (D₆)benzene. With (¹⁸O)cyclohexanone, no incorporation of the label into the 1,3‐oxazolidinone ring was observed (in‐situ NMR investigations; Figs. 1, 3, and 4). Since an iminium‐carboxylate zwitterion might be involved in this process, we also studied the reaction of N‐isopropylidene‐pyrrolidinium perchlorate with cyclohexanone in anhydrous CDCl₃ (Fig. 5). We speculated that an interconversion between iminium and carbonyl species might occur in the absence of H₂O or other impurities, i.e., formally a metathesis through 1,3‐oxazetidinium ions (Schemes 2 and 3). A theoretical investigation with various DFT methods, ranging all the way to CCSD(T)/aug‐cc‐pVTZ//MP2/def2‐QZVPP, shows (Figs. 8–11) that oxazetidinium ions are stable species (more or less equi‐energetic with the reactants iminium ion+carbonyl system), but that the transition states leading to these cations are too high in energy for a reaction taking place in the gas phase at room temperature. Further investigations are proposed to study the iminium? carbonyl interconversion mechanism.