Ernst Anders

Optimization and application of lithium parameters for PM3

Lithium parameters have been optimized for Stewarts standard PM3 method. The average deviation of the heats of formation calculated for 18 reference compounds is 6.2 kcal/mol from the experimental or high‐level ab initio data; the average deviation with Li/MNDO is 18.9 kcal/mol. The average error in bond lengths is also reduced by a factor of two to three. Ionization potentials and dipole moments are reproduced with comparable accuracy than Li/MNDO. However, the mean deviation for the heats of formation of both methods increases when being applied to other systems, especially to small inorgnic molecules. The applicability of the new parameter set is demonstrated further for various compounds not included in the reference set, for the calculation of the activation barriers of several lithiation reactions, as well as for the estimation of oligomerization energies of methyl lithium (including the tetramer). Li/PM3 gives reliable results even for large dimeric complexes, like [{4‐(CH3CR)C5H4N}Li]2, containing TMEDA or THF as coligands and reproduces the haptotropic interaction between Li+ and π‐systems (e.g., in benzyl lithium) as well as the relative energies and structural features of compounds with “hypervalent” atoms (e.g., in lithiated sulfones).

Formation of a unique zinc carbamate by CO2 fixation: implications for the reactivity of tetra-azamacrocycle ligated Zn(II) complexes.

The macrocyclic ligand [13]aneN 4 ( L1, 1,4,7,10-tetra-azacyclotridecane) was reacted with Zn(II) perchlorate and CO 2 in an alkaline methanol solution. It was found that, by means of subtle changes in reaction conditions, two types of complexes can be obtained: (a) the mu 3 carbonate complex 1, {[Zn( L1)] 3(mu 3-CO 3)}(ClO 4) 4, rhombohedral crystals, space group R3 c, with pentacoordinate zinc in a trigonal bipyramidal enviroment, and (b) an unprecedenced dimeric Zn(II) carbamate structure, 2, [Zn( L2)] 2(ClO 4) 2, monoclinic crystals, space group P2 1/ n. The ligand L2 (4-carboxyl-1,4,7,10-tetra-azacyclotridecane) is a carbamate derivative of L1, obtained by transformation of a hydrogen atom of one of the NH moieties into carbamate by means of CO 2 uptake. In compound 2, the distorted tetrahedral Zn(II) coordinates to the carbamate moiety in a monodentate manner. Most notably, carbamate formation can occur upon reaction of CO 2 with the [Zn L1] (2+) complex, which implicates that a Zn-N linkage is cleaved upon attack of CO 2. Since complexes of tetra-azamacrocycles and Zn(II) are routinely applied for enzyme model studies, this finding implies that the Zn-azamacrocycle moiety generally should no longer be considered to play always only an innocent role in reactions. Rather, its reactivity has to be taken into account in respective investigations. In the presence of water, 2 is transformed readily into carbonate 1. Both compounds have been additionally characterized by solid-state NMR and infrared spectroscopy. A thorough comparison of 1 with related azamacrocycle ligated zinc(II) carbonates as well as a discussion of plausible reaction paths for the formation of 2 are given. Furthermore, the infrared absorptions of the carbamate moiety have been assigned by calculating the vibrational modes of the carbamate complex using DFT methods and the vibrational spectroscopy calculation program package SNF.

New Insights into the Mechanistic Details of the Carbonic Anhydrase Cycle as Derived from the Model System [(NH3)3Zn(OH)]+/CO2: How does the H2O/HCO3− Replacement Step Occur?

The full reaction path for the conversion of carbon dioxide to hydrogencarbonate has been computed at the B3LYP/6‐311+G** level, employing a [(NH3)3Zn(OH)]+ model catalyst to mimic the active center of the enzyme. We paid special attention to the question of how the catalytic cycle might be closed by retrieval of the catalyst. The nucleophilic attack of the catalyst on CO2 has a barrier of 5.7 kcal mol−1 with inclusion of thermodynamic corrections and solvent effects and is probably the rate‐determining step. This barrier corresponds well with prior experiments. The intermediate result is a Lindskog‐type structure that prefers to stabilize itself via a rotation‐like transition state to give a Lipscomb‐type product, which is a monodentate hydrogencarbonate complex. By addition of a water molecule, a pentacoordinated adduct with pseudo‐trigonal‐bipyramidal geometry is formed. The water molecule occupies an equatorial position, whereas the hydrogencarbonate ion is axial. In this complex, proton transfer from the Zn‐bound water molecule to the hydrogencarbonate ion is extremely facile (barrier 0.8 kcal mol−1), and yields the trans,trans‐conformer of carbonic acid rather than hydrogencarbonate as the leaving group. The carbonic acid molecule is bound by a short O⋅⋅⋅H−O hydrogen bond to the catalyst [(NH3)3Zn(OH)]+, in which the OH group is already replaced by that of an entering water molecule. After deprotonation of the carbonic acid through a proton relay to histidine 64, modeled here by ammonia, hydrogencarbonate might undergo an ion pair return to the catalyst prior to its final dissociation from the complex into the surrounding medium.

Evaluation of the accuracy of PM3, AM1 and MNDO/d as applied to zinc compounds

Abstract The applicability of the semiempirical methods PM3, AM1 and MNDO/d for the calculation of zinc complexes and organometallic compounds containing Zn2+ was evaluated. In Part I we compared calculational results with X-ray structural data. The majority of a randomly chosen set of structures could be satisfactorily reproduced by all three methods. MNDO/d appears to be the most adequate method for the description of bio-organic complexes containing Zn2+ but reveals deficiencies in the description of Zn–S interactions. PM3 fails to satisfactorily describe Zn–O interactions in sterically crowded molecules but proves to be the best method for the description of Zn–N complexes. AM1 shows a behaviour similar to PM3. However, the errors found for AM1 are ca. 30% larger than for PM3. In Part II, optimal geometries and dissociation energies were calculated for model compounds and than compared with high level DFT (B3LYP/6-311+G(3df,3pd)) and ab initio (CCSD(T)/6-311+G∗) calculations in order to find the source of the errors determined in Part I. PM3 and AM1 underestimate the energy of the Zn–O interaction to a significant extent in accordance with the findings of Part I. Finally, a case study was performed in that essential steps of the carbonic anhydrase catalytic cycle were calculated using a simple model. Despite the acceptable results presented in Part I, MNDO/d failed the case study due to errors based on the original MNDO parametrisation.

Novel syntheses of heterocycles with N-(1-Haloalkyl)azinium Halides. Part 2. Preparation of N-Unsubstituted 1,4-Dihydropyridines☆

Abstract N-(1-Chloroalkyl)pyridinium chlorides, prepared from thionyl chloride, pyridine, and aldehydes, readily react with enaminocarbonyl derivatives to yield 1,4-dihydropyridines under mild and neutral conditions.

The missing link in COS metabolism: a model study on the reactivation of carbonic anhydrase from its hydrosulfide analogue.

Carbonic anhydrase (CA) is known to react with carbonyl sulfide, an atmospheric trace gas, whereby H2S is formed. It has been shown that, in the course of this reaction, the active catalyst, the His3ZnOH structural motif, is converted to its hydrosulfide form: His3ZnOH+COS→His3ZnSH+CO2. In this study, we elucidate the mechanism of reactivation of carbonic anhydrase (CA) from its hydrosulfide analogue by using density functional calculations, a model reaction and in vivo experimental investigation. The desulfuration occurs according to the overall equation His3ZnSH+H2O ⇌ His3ZnOH+H2S. The initial step is a protonation equilibrium at the zinc‐bound hydrosulfide. The hydrogen sulfide ligand thus formed is then replaced by a water molecule, which is subsequently deprotonated to yield the reactivated catalytic centre of CA. Such a mechanism is thought to enable a plant cell to expel H2S or rapidly metabolise it to cysteine via the cysteine synthase complex. The proposed mechanism of desulfuration of the hydrosulfide analogue of CA can thus be regarded as the missing link between COS consumption of plants and their sulfur metabolism.

Carbon dioxide and related heterocumulenes at zinc and lithium cations: bioinspired reactions and principles

This Perspective starts with the discussion of the properties of an interesting metalloenzyme (carbonic anhydrase, CA) that performs extremely successfully the activation of carbon dioxide. Conclusions from that are important for many synthetic procedures and include experimental and theoretical investigation (DFT calculations) of such metal mediated processes in the condensed and in the gas phase in which the zinc cation plays a dominant role. This is extended to the bio-analogue activation of further heterocumulenes such as COS, an important atmospheric trace gas, and CS(2). Novel metal complexes which serve as useful catalysts for the reactions (copolymerisations and cyclisation) of CO(2) and oxiranes are discussed subject to the inclusion of recently published DFT calculations. We continue with the discussion of the very general aspect of the insertion of CO(2) into metal-nitrogen bonds (formation of carbamates). This again is closely related to many biological or bio-analogue processes. We describe the synthesis and mechanistic aspects of characteristic metal carbamates of a wide variety of metals and include a discussion of the mechanistic aspects, especially for the formation of Mg(2+) and Li(+) carbamates and the formation of related cyclic products after addition of the heterocumulenes CO(2), Ph-NCO or CS(2) to novel ligands, the 4H-pyridin-1-ides which finally result in the formation of e.g. 1,3-thiazole-5(2H)-thiones.

Neue methode zur regiospezifischen substitution einiger reaktionsträcer N-heteroaromatischer ringsysteme

Abstract N-Trifluoromethanesulfonyl-heteroarylium salts 1 react with phosphanes 2 to give the C4- or C2-substituted products 4 or 5 . By means of a similar procedure, bisphosphonium salts 6 and 7 are formed. The reaction of sodium azide ( 8 ), and 6 yields the iminophosphorane 10 via the intermediate 9 .

Carboxylation of Acetophenone with Zinc(II) Alkoxides/CO2 Systems: A Mechanistic Study

The crystal structures of the homoleptic dimer zinc(II) 2,6-di-tert-butylphenoxide (1b) and of the corresponding monomer 1b/(DMSO)2 are presented. The structural motif of 1b is a Zn−O−Zn−O four-membered ring. The bulky phenoxide ligands led to a coordination number of only three for the zinc atom. Monomer 1b/(DMSO)2 crystallized as a four-coordinated monomer with a highly distorted tetrahedral geometry around the zinc center. 13C NMR investigations reveal details for the reaction of CO2 with a series of alkoxide zinc(II)/solvent systems [2,6-dimethylphenoxide zinc(II) (1a), zinc(II) 2,6-di-tert-butylphenoxide (1b), zinc(II) 2,6-diphenylphenoxide (1c), zinc(II) 4-tert-butylphenoxide (1d), and zinc(II) 2-pyridylcarbinolato (2)]. The interpretation of the 13C NMR signals agree with ab initio calculations of a model zinc(II) phenoxide/CO2 system. Experimentally, the carboxylation of acetophenone as a representative for CH-acidic substrates was carried out with specific zinc(II) phenoxide/CO2 systems. The reactions resulted in yields of ca. 40% of benzoyl acetic acid. The role of the soluble zinc(II) phenylcarbonate intermediate is discussed with respect to the subsequent CO2 transfer reaction.

An Unusual Aromatization of Hantzsch-type 4-Antipyryl-1,4-dihydropyridines

Under acidic conditions, Hantzsch-type 4-antipyryl-1,4-dihydro-pyri- dines undergo an elimination of the 4-substituent to yield 4-unsubs- tituted pyridines and antipyrine. The mechanism and the scope of the reaction are discussed