Burkhard Miehlich

Results obtained with the correlation energy density functionals of becke and Lee, Yang and Parr

Abstract Two recently published density functionals (A.D. Becke, J. Chem. Phys. 88 (1988) 1053 and C. Lee, W. Yang and R.G. Parr, Phys. Rev. B 37 (1988) 785) are used to calculate the correlation energies of first-row atoms, ions and molecules. The correlation contributions to ionization energies, electron affinities and dissociation energies thus obtained are of comparable quality to those of other density functionals.

A correlation-energy density functional for multideterminantal wavefunctions

A density functional for dynamical correlation, to be used in connection with wavefunctions of the complete-active-space self-consistent ® eld type, is described, and ® rst applications to the series of two-and four-electron atomic ions as well as to the H2 potential curve are given. 1. Introduction Density functional theory (DFT) has been very successful for both an economic and an accurate description of electronic structure in atomic, molecular and solid-state physics (for example [1]); electron correlation e ects are implicitly included while formally retaining an independent-particle Hartree± Fock (HF)-like picture. The HF picture, on the other hand, is just the starting point for an explicit electron correlation treatment with the wavefunction-based quantum-chemical ab initio methods (for example [2]); in contrast with DFT, a systematic improvement towards the exact results is possible , but at the expense of a heavy computational burden caused by long con® guration interaction (CI) expansions. However, long CI expansions are usually related to dynamical correlation e ects which have to do with the short-range description of the electron correlation hole (electron± electron cusp), while static (long-range) correlation e ects caused by near-degeneracies of ground and low-lying excited states of the same symmetry very often can e ciently be covered by quite short optimized expansions (of the multicon® guration self-consistent ® eld (MCSCF) or complete-active-space self-consistent ® eld (CASSCF) type). Since de® ciencies of DFT, if any, are likely to occur just with the description of near-degeneracies which are special to individual molecules and not easily covered by a universal functional , the idea of a CI± DFT coupling combining the advantages of the two approaches seems to be rewarding.

Structure determinants of substrate specificity of hydroxynitrile lyase from Manihot esculenta

Tryptophan 128 of hydroxynitrile lyase of Manihot esculenta (MeHNL) covers a significant part of a hydrophobic channel that gives access to the active site of the enzyme. This residue was therefore substituted in the mutant MeHNL‐W128A by alanine to study its importance for the substrate specificity of the enzyme. Wild‐type MeHNL and MeHNL‐W128A showed comparable activity on the natural substrate acetone cyanohydrin (53 and 40 U/mg, respectively). However, the specific activities of MeHNL‐W128A for the unnatural substrates mandelonitrile and 4‐hydroxymandelonitrile are increased 9‐fold and ∼450‐fold, respectively, compared with the wild‐type MeHNL. The crystal structure of the MeHNL‐W128A substrate‐free form at 2.1 Å resolution indicates that the W128A substitution has significantly enlarged the active‐site channel entrance, and thereby explains the observed changes in substrate specificity for bulky substrates. Surprisingly, the MeHNL‐W128A–4‐hydroxybenzaldehyde complex structure at 2.1 Å resolution shows the presence of two hydroxybenzaldehyde molecules in a sandwich type arrangement in the active site with an additional hydrogen bridge to the reacting center.

Mechanistic Aspects of Cyanogenesis from Active-Site Mutant Ser80Ala of Hydroxynitrile Lyase from Manihot Esculenta in Complex with Acetone Cyanohydrin.

The structure and function of hydroxynitrile lyase from Manihot esculenta (MeHNL) have been analyzed by X‐ray crystallography and site‐directed mutagenesis. The crystal structure of the MeHNL–S80A mutant enzyme has been refined to an R‐factor of 18.0% against diffraction data to 2.1‐Å resolution. The three‐dimensional structure of the MeHNL–S80A–acetone cyanohydrin complex was determined at 2.2‐Å resolution and refined to an R‐factor of 18.7%. Thr11 and Cys81 involved in substrate binding have been substituted by Ala in site‐directed mutagenesis. The kinetic measurements of these mutant enzymes are presented. Combined with structural data, the results support a mechanism for cyanogenesis in which His236 as a general base abstracts a proton from Ser80, thereby allowing proton transfer from the hydroxyl group of acetone cyanohydrin to Ser80. The His236 imidazolium cation then facilitates the leaving of the nitrile group by proton donating.

Structure of Hydroxynitrile Lyase from Manihot Esculenta in Complex with Substrates Acetone and Chloroacetone: Implications for the Mechanism of Cyanogenesis

The crystal structures of hydroxynitrile lyase from Manihot esculenta (MeHNL) complexed with the native substrate acetone and substrate analogue chloroacetone have been determined and refined at 2.2 A resolution. The substrates are positioned in the active site by hydrogen-bond interactions of the carbonyl O atom with Thr11 OG, Ser80 OG and, to a lesser extent, Cys81 SG. These studies support a mechanism for cyanogenesis as well as for the stereospecific MeHNL-catalyzed formation of (S)-cyanohydrins, which closely resembles the base-catalyzed chemical reaction of HCN with carbonyl compounds.

The Electronic Ground State of [Fe(CO)3(NO)]−: A Spectroscopic and Theoretical Study

During the past 10 years iron-catalyzed reactions have become established in the field of organic synthesis. For example, the complex anion [Fe(CO)3 (NO)](-) , which was originally described by Hogsed and Hieber, shows catalytic activity in various organic reactions. This anion is commonly regarded as being isoelectronic with [Fe(CO)4 ](2-) , which, however, shows poor catalytic activity. The spectroscopic and quantum chemical investigations presented herein reveal that the complex ferrate [Fe(CO)3 (NO)](-) cannot be regarded as a Fe(-II) species, but rather is predominantly a Fe(0) species, in which the metal is covalently bonded to NO(-) by two π-bonds. A metal-N σ-bond is not observed.

Inversion of stereoselectivity by applying mutants of the hydroxynitrile lyase from Manihot esculenta.

The influence of Trp128‐substituted mutants of the hydroxynitrile lyase from Manihot esculenta (MeHNL) on the stereoselectivity of MeHNL‐catalyzed HCN additions to aldehydes with stereogenic centers, which yield the corresponding cyanohydrins, is described. In rac‐2‐phenylpropionaldehyde (rac‐1) reactions, wild‐type (wtMeHNL) and all MeHNL Trp128 mutants are highly (S)‐selective toward the (R) enantiomer of rac‐1; this results exclusively in (2S,3R)‐cyanohydrin ((2S,3R)‐2) with ≥96 % de. The (S) enantiomer of rac‐1, however, only reacts (S)‐selectively with wtMeHNL to give (2S,3S)‐2 with 80 % de, whereas with Trp128 mutants, (R) selectivity increases with decreasing size of the amino acids exchanged. The MeHNL W128A mutant is exclusively (R)‐selective, resulting in (2R,3S)‐2 with 86 % de. The reaction behavior of rac‐phenylbutyraldehyde (rac‐5) is comparable with rac‐1, which also inverts the stereoselectivity from (S) to (R) when the enzyme is exchanged from wtMeHNL to the W128A mutant. Stereogenic centers not adjacent to the aldehyde group, as in 7 and 9, do not influence the stereoselectivity of MeHNL catalysis, and (S) selectivity is observed in all cases. Stereoselectivity and inversion of stereoselectivity of MeHNL Trp128 mutant‐catalyzed cyanohydrin formation can be explained and rationalized with crystal‐structure‐based molecular modeling.

Ultrafast charge separation in the excited state of pyridinium-substituted anthryl-thiophenes

Abstract The excited-state dynamics of acceptor-substituted anlhryl-thiophenes are investigated by fs-transient absorption and ps-time-resolved fluorescence spectroscopy. Depending on molecular structure and acceptor strength (pyridinium/pyridine) charge separation or conformational relaxation is observed.