Reynier Suardíaz

Influence of Density Functionals and Basis Sets on One-Bond Carbon-Carbon NMR Spin-Spin Coupling Constants.

The basis set and the functional dependence of one-bond carbon-carbon NMR spin-spin coupling constants (SSCC) have been analyzed using density functional theory. Four basis sets (6-311G**, TZVP, EPR-III, and aug-cc-pVTZ-J) and four functionals (PBE, PW91, B3LYP, and B3P86) are tested by comparison with 70 experimental values corresponding to 49 molecules that represent multiple types of hybridization of the carbon atoms. The two hybrid functionals B3P86 and B3LYP combined either EPR-III or aug-cc-pVTZ-J basis sets lead to the best accuracy of calculated SSCC. However, a simple linear regression allows for the obtaining of scaled coupling constants that fit much better with the experimental data and where the differences between the different basis sets and/or functional results are significantly reduced. For large molecules the TZVP basis set can be an appropriate election presenting a good compromise between quality of results and computational cost.

Approximating correlation effects in multiconfigurational self-consistent field calculations of spin-spin coupling constants

The multiconfigurational self-consistent field (MCSCF) method in their approximations restricted and complete active spaces (RAS and CAS) provides a theoretically accurate description of the coupling constants of a wide range of molecules. To obtain accurate results, however, very large basis sets and large configuration spaces must be used. Nuclear magnetic resonance coupling constants for the equilibrium geometry have been calculated for a series of small molecules using approximated correlation contributions. The four contributions to the coupling constants (Fermi contact, spin dipolar, orbital paramagnetic, and orbital diamagnetic) have been calculated at the CAS and RAS MCSCF and second-order polarization propagator approximation levels using a large basis set. An additive model that considers the effect on the coupling constants from excitation of more than two electrons and from core-electron correlation is used to estimate the coupling constants. Compared with the experimental couplings, the best calculated values, which correspond to the MCSCF results, present a mean absolute error of 3.6 Hz and a maximum absolute deviation of 13.4 Hz. A detailed analysis of the different contributions and of the effects of the additive contributions on the coupling constants is carried out.

An insight into the regiospecificity of linoleic acid peroxidation catalyzed by mammalian 15-lipoxygenases.

15-Lipoxygenases (15-LOs) catalyze the peroxidation reaction of linoleic acid (LA) in mammals producing almost exclusively 13-(S)-hydroperoxyoctadecadienoic acid (13-(S)-HPODE). Although several hypotheses have been formulated, the molecular basis of such enzymatic regiospecificity is unclear. We have here combined quantum mechanics/molecular mechanics (QM/MM) calculations with molecular dynamics simulations to analyze the peroxidation mechanism using a complete rabbit 15-LO-1/LA solvated model. C9 and C13 being equivalent for planarity and spin density, the QM/MM potential energy profiles of the O2 addition to those two atoms were calculated. The difference in the potential energy barrier heights is clear enough to justify that O2 selectively attacks C13 giving 13-(S)-HPODE. Oxygenation at C9 is hindered by two steric-shielding residues (Leu597 and Gln548). The calculated free energy profile at 300 K for the O2 addition to C13 confirms that the peroxidation on C13 is a reversible viable process in agreement with experiments. Thus, the subsequent reduction of the peroxyl radical to give the final hydroperoxidated product is expected to give the irreversibility character to the overall process.

On the unusual 2J C 2H f coupling dependence on syn/anti CHO conformation in 5‐X‐furan‐2‐carboxaldehydes

A remarkable difference for 2J  C 2H f coupling constant in syn and anti conformers of 5‐X‐furan‐2‐carboxaldehydes (X = CH3, Ph, NO2, Br) and a rationalization of this difference are reported. On the basis of the current knowledge of the Fermi‐contact term transmission, a rather unusual dual‐coupling pathway in the syn conformer is presented. The additional coupling pathway resembles somewhat that of the JHH in homoallylic couplings, which are transmitted by hyperconjugative interactions involving the πCC electronic system. The homoallylic coupling pathway can be labeled as σ*CH ← πCC → σ*CH. In the present case, this additional coupling pathway, using an analogous notation, can be labeled as σ*  C 2C C ← LP1(O1)··· LP2(OC) →σ*  C CH f (σ*  C 2C C ) where O1 and OC stand for the ring and carbonyl O atoms, respectively. This additional coupling pathway is not activated in the anti conformers since both oxygen lone pairs do not overlap. Copyright

Studies on the regioselectivity of the baeyer-villiger reaction of 3-keto steroids : Conformational effects determine the migration aptitude

A detailed study of the Baeyer-Villiger reaction of 3-ketosteroids has been performed by using m-chloroperoxybenzoic and trifluoroperoxyacetic acids as oxidants. The process was fully regiospecific for 3-keto-5alpha-steroids with the employ of both peracids, and only partially regioselective for 3-keto-5beta-steroids by using trifluoroperoxyacetic acid. Interestingly, the reaction resulted completely unselective for 3-keto-5beta-steroids by using m-chloroperoxybenzoic acid. Theoretical studies were performed to explain the regiochemistry of this process, which is suggested to be controlled by conformational effects in the transition state of the Criegee rearrangement.

A Dynamic and Responsive Host in Action: Light‐Controlled Molecular Encapsulation

Abstract The rational design of a flexible molecular box, oAzoBox 4+, incoporating both photochromic and supramolecular recognition motifs is described. We exploit the E↔Z photoisomerization properties of azobenzenes to alter the shape of the cavity of the macrocycle upon absorption of light. Imidazolium motifs are used as hydrogen‐bonding donor components, allowing for sequestration of small molecule guests in acetonitrile. Upon E→Z photoisomerization of oAzoBox 4+ the guest is expelled from the macrocyclic cavity.

Computational NMR coupling constants: Shifting and scaling factors for evaluating 1JCH

Optimized shifting and/or scaling factors for calculating one‐bond carbon–hydrogen spin–spin coupling constants have been determined for 35 combinations of representative functionals (PBE, B3LYP, B3P86, B97‐2 and M06‐L) and basis sets (TZVP, HIII‐su3, EPR‐III, aug‐cc‐pVTZ‐J, ccJ‐pVDZ, ccJ‐pVTZ, ccJ‐pVQZ, pcJ‐2 and pcJ‐3) using 68 organic molecular systems with 88 1JCH couplings including different types of hybridized carbon atoms. Density functional theory assessment for the determination of 1JCH coupling constants is examined, comparing the computed and experimental values. The use of shifting constants for obtaining the calculated coupling improves substantially the results, and most models become qualitatively similar. Thus, for the whole set of couplings and for all approaches excluding those using the M06 functional, the root‐mean‐square deviations lie between 4.7 and 16.4 Hz and are reduced to 4–6.5 Hz when shifting constants are considered. Alternatively, when a specific rovibrational contribution of 5 Hz is subtracted from the experimental values, good results are obtained with PBE, B3P86 and B97‐2 functionals in combination with HIII‐su3, aug‐cc‐pVTZ‐J and pcJ‐2 basis sets. Copyright

Computational NMR coupling constants

Optimized shifting and/or scaling factors for calculating one‐bond carbon–hydrogen spin–spin coupling constants have been determined for 35 combinations of representative functionals (PBE, B3LYP, B3P86, B97‐2 and M06‐L) and basis sets (TZVP, HIII‐su3, EPR‐III, aug‐cc‐pVTZ‐J, ccJ‐pVDZ, ccJ‐pVTZ, ccJ‐pVQZ, pcJ‐2 and pcJ‐3) using 68 organic molecular systems with 88 1JCH couplings including different types of hybridized carbon atoms. Density functional theory assessment for the determination of 1JCH coupling constants is examined, comparing the computed and experimental values. The use of shifting constants for obtaining the calculated coupling improves substantially the results, and most models become qualitatively similar. Thus, for the whole set of couplings and for all approaches excluding those using the M06 functional, the root‐mean‐square deviations lie between 4.7 and 16.4 Hz and are reduced to 4–6.5 Hz when shifting constants are considered. Alternatively, when a specific rovibrational contribution of 5 Hz is subtracted from the experimental values, good results are obtained with PBE, B3P86 and B97‐2 functionals in combination with HIII‐su3, aug‐cc‐pVTZ‐J and pcJ‐2 basis sets. Copyright

A geometrical parametrization of C1'-C5' RNA ribose chemical shifts calculated by density functional theory.

It has been recently shown that NMR chemical shifts can be used to determine the structures of proteins. In order to begin to extend this type of approach to nucleic acids, we present an equation that relates the structural parameters and the (13)C chemical shifts of the ribose group. The parameters in the equation were determined by maximizing the agreement between the DFT-derived chemical shifts and those predicted through the equation for a database of ribose structures. Our results indicate that this type of approach represents a promising way of establishing quantitative and computationally efficient analytical relationships between chemical shifts and structural parameters in nucleic acids.

Karplus Equation for (3)JHH Spin-Spin Couplings with Unusual (3)J(180°) < (3)J(0°) Relationship.

Vicinal (3)JHH coupling constants for monosubstituted ethane molecules present the unusual relationship (3)JHH (180°) < (3)JHH (0°) when the substituent contains bonding and antibonding orbitals with strong hyperconjugative interactions involving bond and antibond orbitals of the ethane fragment. This anomalous behavior is studied as a function of the substituent rotation for three model systems (propanal, thiopropanal, and 1-butene) at the B3LYP/TZVP level. The consistency of this level of theory to study this problem is previously established using different ab initio methods and larger basis sets. The origin of the unusual (3)JHH(180°) - (3)JHH(0°) relationship is attributed to simultaneous σ/π hyperconjugative interactions σCα-Hα → π*Cc═X, and σCα-Cβ → π*Cc═X. These interactions depend on the substituent rotation and their effects are different for (3)JHH(180°) than for (3)JHH(0°). The modelization carried out shows an increase of those effects as the substituent changes from weaker (CH═CH2) to stronger (CH═S) electron acceptor π*C═X.