Danijela Barić

Basicity of exceedingly strong non-ionic organic bases in acetonitrile —Verkade's superbase and some related phosphazenes

The basicity of Verkades superbase (12) in MeCN solution is considered by a quite accurate theoretical model. It is shown that the corresponding pKa value is 29.0. Hence, its basicity is comparable or higher than that of some other P1 phosphazenes, but it is lower than the basicity of P2 phosphazenes. Structural characteristics of Verkades superbase and its conjugate acid, as well as the origin of its pronounced basicity, are briefly discussed. Extended Verkades superbase 13 and some Janus-type phosphazenes are examined too. It is shown that they are very good candidates for even stronger neutral organic superbases. A very useful by-product of the present study are quite accurate estimates of the gas phase proton affinities of some P1, P2, P3 and P4 polyaminophosphazenes obtained by the B3LYP/6-311+G(2df,p)//B3LYP/6-31G* scheme. The latter was successfully tested against G2 results on small molecules. This is of importance, because the experimentally measured gas phase values for phosphazenes are not available, implying that the theoretical data fill this gap with reliable information.

The additivity of the π-electron correlation energy in planar heteroatomic molecules

Abstract We have shown that the π-electron correlation energy of planar chain and branched polyenes containing various heteroatoms follows simple additivity rules. It is a multilinear function of a number of atoms of each element entering into a given compound. The same holds for the nondynamical E (ND) π and dynamical E (D) π components of the total correlation energy. It is found that the former is insensitive to the quality of the employed basis set. In contrast, the dynamical correlation is strongly dependent on the intricacy of utilized basis sets. These findings are rationalized by taking into account a difference in their definitions, the different nature of E (ND) π and E (D) π correlation energies, and the way of their calculation. An extension of the completely active subspace considerably changes E (ND) π and E (D) π values and to some extent introduces changes in the total π-electron correlation. However, the additivity rule persistently holds, indicating that it is a robust property. Finally, it is shown that the E (ND) π energy can serve as a good indicator of the intrinsic (anti)aromaticity of cyclic compounds.

On the correlation energy features in planar heteroatomic molecular systems

The correlation energy in planar heteroatomic open chain polyene systems involving N, O, and F atoms is considered by the CASSCF and CASPT2 methods employing a number of the cc-pVmZ (VDZ, VTZ, etc.) correlation consistent basis sets. A thorough study of the smallest molecules shows that the nondynamical correlation energy is virtually independent of the quality of the basis set. In contrast, the dynamical correlation energy is very sensitive to the basis set and, in estimating reliable dynamical correlation effects for larger systems, one has to rely on adequate extrapolation formulas to obtain the infinite basis set limit. We find that a method recently proposed by Truhlar offers economical yet reasonable estimates of the complete basis set results. Investigation of the sensitivity of the results to the choice of active space and the comparison to single reference MP2 calculations indicate that such extrapolations offer a good general method for saturating the basis set in multireference calculations. Th...

On the Reaction of Glycerol Dehydratase with But-3-ene-1,2-diol

High-level conventional ab initio and density functional theory (DFT) calculations have been performed to examine the fate of the native substrate glycerol (1) and its analogue but-3-ene-1,2-diol (7) in the coenzyme B(12)-dependent enzyme glycerol dehydratase (GDH). Experimental studies find that 7 irreversibly inactivates GDH, though the mechanism for the inactivation remains unknown. Interestingly, the EPR data suggest that the spin density for an observed radical is located in the vicinity of the C1 atom, which has been interpreted to indicate termination of the pathway at the substrate-derived radical 8. Our calculations show that if analogue 7 were to follow a similar mechanistic pathway to that followed by 1, then the reaction would be unlikely to stop at 8 but would rather proceed to the highly stabilized product-related radical 9. However, the EPR characteristics of 9 would not be consistent with the observed EPR data. Calculations involving an initial H-atom abstraction from the C2 position of 7 identify alternative radicals that might account for the EPR data, though they are of relatively high energy. A proposal that could explain the experimental observations is that the enzyme binds 7 in such a manner as to prevent the efficient transformation of 8. Recent work with the related enzyme diol dehydratase suggests that a common, but as yet unexplained, inactivation mechanism may be operative for both enzymes. Finally, we note the good overall performance of the MPWB1K, BMK, M05-2X, and B2-PLYP DFT procedures for these reactions, with the BMK method producing the best results.

Non-enzymatic ribonucleotide reduction in the prebiotic context.

Model studies of prebiotic chemistry have revealed compelling routes for the formation of the building blocks of proteins and RNA, but not DNA. Today, deoxynucleotides required for the construction of DNA are produced by reduction of nucleotides catalysed by ribonucleotide reductases, which are radical enzymes. This study considers potential non-enzymatic routes via intermediate radicals for the ancient formation of deoxynucleotides. In this context, several mechanisms for ribonucleotide reduction, in a putative H2 S/HS(.) environment, are characterized using computational chemistry. A bio-inspired mechanistic cycle involving a keto intermediate and HSSH production is found to be potentially viable. An alternative pathway, proceeding through an enol intermediate is found to exhibit similar energetic requirements. Non-cyclical pathways, in which HSS(.) is generated in the final step instead of HS(.) , show a markedly increased thermodynamic driving force (ca. 70 kJ mol(-1) ) and thus warrant serious consideration in the context of the prebiotic ribonucleotide reduction.

Computational Tale of Two Enzymes: Glycerol Dehydration With or Without B12

We present a series of QM/MM calculations aimed at understanding the mechanism of the biological dehydration of glycerol. Strikingly and unusually, this process is catalyzed by two different radical enzymes, one of which is a coenzyme-B12-dependent enzyme and the other which is a coenzyme-B12-independent enzyme. We show that glycerol dehydration in the presence of the coenzyme-B12-dependent enzyme proceeds via a 1,2-OH shift, which benefits from a significant catalytic reduction in the barrier. In contrast, the same reaction in the presence of the coenzyme-B12-independent enzyme is unlikely to involve the 1,2-OH shift; instead, a strong preference for direct loss of water from a radical intermediate is indicated. We show that this preference, and ultimately the evolution of such enzymes, is strongly linked with the reactivities of the species responsible for abstracting a hydrogen atom from the substrate. It appears that the hydrogen-reabstraction step involving the product-related radical is fundamental to the mechanistic preference. The unconventional 1,2-OH shift seems to be required to generate a product-related radical of sufficient reactivity to cleave the relatively inactive C-H bond arising from the B12 cofactor. In the absence of B12, it is the relatively weak S-H bond of a cysteine residue that must be homolyzed. Such a transformation is much less demanding, and its inclusion apparently enables a simpler overall dehydration mechanism.