A comprehensive study of the different classes of cycloaddition reactions ([3+2], [2+2], and [2+1]) of SO2 to acetylene and ethylene has been performed using density functional theory (DFT) and composite wavefunction methods. The [3+2] cycloaddition reaction, that was previously explored in the context of the cycloaddition of thioformaldehyde S-methylide (TSM) to ethylene and acetylene, proceeds in a concerted way to the formation of stable heterocycles. In this paper, we extend our study to the [2+2] and [2+1] cycloadditions of SO2 to acetylene, which would produce 1,1-oxathiete-2-oxide and thiirene-1,1-dioxide, respectively. One of the main conclusions is that cyclic 1,1-oxathiete-2-oxide can open through a relatively easy breaking of the SO single bond and rearrange toward sulfinyl acetaldehyde (SA). The SA molecule can easily undergo several internal rearrangements, which eventually lead to sulfenic acid and sulfoxide derivatives of ethenone, 1,2,3-dioxathiole, and CO plus sulfinylmethane. The most probable path, however, produces 2-thioxoacetic acid, whose derivatives (or those of the corresponding acetate) are usually obtained by Willgerodt-Kindler-type sulfuration of acetates. This product can in turn decompose, leading to the final products CO2 and H2CS. Comparison of this decomposition path with that of 2-amino-2-thioxoacetic acid shows that the process occurs through different H-transfer processes.

In a case study, the acetic anhydride-promoted reaction of a model pyrimidine N-oxide to the corresponding 4-acetoxymethyl-substituted pyrimidine derivative (Boekelheide rearrangement) was investigated in detail by experiment and quantum chemical calculations. The reaction conditions were varied and several side products formed in low to moderate yields were identified. These experiments indicate that a (pyrimidin-4-yl)methyl radical is one of the key species of the rearrangement. This interpretation was supported by the fact that rearrangements performed in solvents which can easily lose hydrogen atoms, afford considerable quantities of products incorporating the solvent. With TEMPO the key radical could be trapped. Other carboxylic acid anhydrides confirm the conclusion that the Boekelheide rearrangement of the model pyrimidine N-oxide proceeds, at least in part, via radical intermediates. The high level closed and open shell quantum chemical calculations show that concerted [3,3]-sigmatropic rearrangements or stepwise processes, either via ion pairs or via radicals, are energetically feasible.

Fe(II)/2-oxoglutarate dependent dioxygenases (ODDs) share a double stranded beta helix (DSBH) fold and utilise a common reactive intermediate, ferryl species, to catalyse oxidative transformations of substrates. Despite the structural similarities, ODDs accept a variety of substrates and facilitate a wide range of reactions, that is hydroxylations, desaturations, (oxa)cyclisations and ring rearrangements. In this review we present and discuss the factors contributing to the observed (regio)selectivities of ODDs. They span from inherent properties of the reactants, that is, substrate molecule and iron cofactor, to the interactions between the substrate and the enzyme\'s binding cavity; the latter can counterbalance the effect of the former. Based on results of both experimental and computational studies dedicated to ODDs, we also line out the properties of the reactants which promote reaction outcomes other than the \"default\" hydroxylation. It turns out that the reaction selectivity depends on a delicate balance of interactions between the components of the investigated system.

Thebaine 6-O-demethylase (T6ODM) is an Fe(II)/2-oxoglutarate-dependent dioxygenase catalysing two oxidative O-demethylation reactions in morphine biosynthesis. Its crystal structure revealed a large active site pocket which is at least two times larger than necessary to accommodate a substrate (thebaine or oripavine) molecule. Since so far no crystal structures have been obtained for enzyme-substrate complex, which is necessary to explain the enzyme regiospecificity towards the C6-bound methoxy group, in this work we used computational methods and multi-parametric surface plasmon resonance measurements to elucidate the most likely structure of this complex and the reaction mechanism starting therefrom. Results of simulations and experiments unanimously indicate that the enzyme-substrate complex of T6ODM has a 1:2 stoichiometry. The key residues responsible for substrate binding are: Val-128, Glu-133, Met-150 and Agr-219 for the substrate in the distal position, and Asp-144, Leu-235 and Leu-353 for the proximal substrate molecule. QM/MM and DFT calculations show that the oxo ligand is bound trans to His-295 and the enzyme catalyzes hydroxylation of the C6-bound methoxy group according to the established rebound mechanism. The final stage of the demethylation reaction, which includes deformylation and enol-keton tautomerization steps, is most likely catalysed by water molecules and takes place in the solvent.

The catalytic mechanism of the decarboxylation of 5-carboxyvanillate by LigW producing vanillic acid has been studied by using QM cluster and hybrid QM/MM methodologies. In the QM cluster model, the environment of a small QM model is treated with a bulky potential while two QM/MM models studies include partial and full protein with and without explicitly treated water solvent. The studied reaction involves two sequential steps: the protonation of the carbon of the 5-carboxy-vanillate substrate and the decarboxylation of the intermediate from which results deprotonated vanillic acid as product. The structures and energetics obtained by using three structural models and two density functionals are quite consistent to each other. This indicates that the small QM cluster model of the presently considered enzymatic reaction is appropriate enough and the reaction is mainly influenced by the active site.

C2 -C70 (CF3 )8 was found to be a very promising substrate in the Bingel and the Bingel-Hirsch reactions combining perfect regioselectivity with much higher reactivity compared to its analogs. The reactions with diethyl malonate yield a single isomer of the monoadduct C70 (CF3 )8 [C(CO2 Et)2 ] and a single C2 -symmetrical bisadduct C70 (CF3 )8 [C(CO2 Et)2 ]2 . The Bingel-Hirsch variation is particularly interesting in that it additionally affords, in a similar regioselective manner, the unexpected alkylated derivatives C70 (CF3 )8 [CH(CO2 Et)2 ]H and C70 (CF3 )8 [C(CO2 Et)2 ][CH(CO2 Et)2 ]H. The novel compounds have been isolated and structurally characterized by means of (1) H and (19) F NMR spectroscopy as well as single-crystal X-ray diffraction. The mechanistic and regiochemical aspects of the reaction are explained with the aid of DFT calculations.