Structures and Electron Affinities of Aluminum Hydride Clusters AlnH (n = 3-13).

Low-energy structures and electron affinities (EAs) for aluminum hydride clusters AlnH (n = 3-13) have been calculated using ab initio and density functional calculations. Geometries were optimized at the PBE0/def-2-TZVPP level of theory, which has been shown to match the currently accepted lowest-energy structures for the all-aluminum clusters Aln and their anions. Neutral hydride clusters with n = 4, 7, and 9-12 are predicted to adopt terminal structures with the hydrogen atom bound to only one aluminum atom and with only minor alterations of the aluminum atom arrangement from that of the all-aluminum cluster. Clusters with n = 3 and 13 are predicted to adopt "face-centered" geometries, and the n = 6 cluster is predicted to prefer an isomer with the hydrogen atom bridging two aluminum atoms, also with little or no distortion to the aluminum atom arrangement from the all-aluminum cluster. Addition of a hydrogen atom to clusters with n = 5 and 8 is predicted to distort the aluminum atom arrangement significantly from that of the corresponding all-aluminum cluster. In the anionic clusters, terminal clusters are preferred for all cluster sizes except for n = 6 that prefers a face-centered arrangement. Minor distortions in the aluminum scaffolding for Al11 and Al12 were found, while all other anionic clusters adopt structures with little or no deviation in the aluminum atom arrangement from the corresponding all-aluminum cluster. Raw adiabatic electron affinities were computed using CCSD(T)/aug-cc-pVTZ single-point energies for the anionic and neutral hydride clusters at their respective DFT geometries. Isodesmic electron affinities for the hydride clusters were computed relative to their all-aluminum counterparts and show an even-odd alternation with cluster size. Derived EAs alternate in magnitude between even- and odd-numbered clusters, with the even-numbered clusters having relatively larger EAs.

The nature of persistent interactions in two model ß-grasp proteins reveals the advantage of symmetry in stability.

Two proteins within the ß-grasp superfamily, the B1-domain of protein G and the small archaeal modifier protein 1, were investigated to elucidate the key determinants of structural stability at the level of individual interactions. These symmetrical proteins both contain two ß-hairpins which form a sheet flanked by a central α-helix. They were subjected to high temperature molecular dynamics simulations and the detailed behavior of each long-range interaction was characterized. The results revealed that in GB1 the most stable region was the C-terminal hairpin and in SAMP1 it was the opposite, the N-terminal hairpin. Experimental results for GB1 support this finding. In conclusion, it appears that the difference in the location and number of hydrophobic interactions dictate the differential stability which is accommodated due to structural symmetry of the ß-grasp fold. Thus, the hairpins are interchangeable and in nature this lends itself to adaptability and flexibility.

Catalytic Oxidation of CO by N2O Enabled by Al2O2/3+: Temperature Dependent Kinetics and Statistical Modeling.

The reactions of Al2O2+ + N2O and Al2O3+ + CO, forming a catalytic cycle oxidizing CO by N2O, have been investigated from 300 to 600 K in a variable ion source, temperature adjustable, selected-ion flow tube (VISTA-SIFT). Reaction coordinates have been calculated using density functional theory and statistical modeling of those surfaces compared to experimental kinetics data for mechanistic insight. The reaction of Al2O2+ + N2O proceeds at the Su-Chesnavich collisional limit at all temperatures studied, yielding only Al2O3+, with the exception of a small (<5%) amount of association product, Al2O2(N2O)+ at 300 K. The reaction of Al2O3+ with CO produces Al2O2+ with a rate constant of 4.7 ± 1.2 × 10-10 cm3 s-1 at 300 K, decreasing with temperature as T-0.5±0.2. In addition, a significant amount of association product, Al2O3(CO)+, was observed with rate constants for formation ranging from 10-11 to 10-10 cm3 s-1 dependent upon He buffer gas concentration and temperature. Implications of these kinetic measurements with regard to the reactive surface are discussed.

Nonbonded, attractive cation-pi interactions in azide-mediated asymmetric ring expansion reactions.

The influence of attractive, nonbonded interactions on the reactions of 1,2- and 1,3-hydroxyalkyl azides with ketones has been investigated through experimental and computational means. A series of 1,3-hydroxyalkyl azides bearing electronically tuned aromatic groups at the 2 position were prepared and reacted along with several derivatives designed to conformationally restrict the rotational orientation of the aromatic substituent. These studies showed that a cation-pi interaction between an aryl moiety and an N2(+) leaving group plays a role in determining the stereoselectivity of these reactions. A series of ab initio calculations supported this hypothesis. A computational and experimental analysis suggested a primarily steric model for the analogous reactions of substituted 2-azido-1-ethanol analogues.

Reactions of cyclopropanone acetals with alkyl azides: carbonyl addition versus ring-opening pathways.

The Lewis acid-mediated reactions of substituted cyclopropanone acetals with alkyl azides were found to strongly depend on the structure of the ketone component. When cyclopropanone acetal was treated with alkyl azides, N-substituted 2-azetidinones and ethyl carbamate products were obtained, arising from azide addition to the carbonyl, followed by ring expansion or rearrangement, respectively. When 2,2-dimethylcyclopropanone acetals were reacted with azides in the presence of BF3.OEt2, the products obtained were alpha-amino-alpha'-diazomethyl ketones, which arose from C2-C3 bond cleavage of the corresponding cyclopropanone, giving oxyallyl cations that were captured by azides. Aryl-substituted cyclopropanone acetals, when subjected to these conditions, afforded [1,2,3]oxaborazoles exclusively, which were also the result of C2-C3 bond rupture, azide capture, and then loss of nitrogen. In the reactions of n-hexyl-substituted cyclopropanone acetals with alkyl azides, a mixture of 2-azetidinones and regioisomeric [1,2,3]oxaborazoles was obtained. The reasons for the different behavior of the various systems are discussed.

Theoretical and experimental investigation of the energetics of cis-trans proline isomerization in peptide models.

The energetics of cis-trans proline isomerization in small peptide models have been investigated using the hybrid density functional theory method B3LYP with a 6-31+G* basis set. The molecules studied are models for the phospho-Ser/Thr-Pro substrate for Pin-1, a peptidyl-prolyl isomerase (PPIase) involved in cell division. Pin-1 requires phosphorylation of a Ser or Thr residue adjacent to a Pro residue in the substrate and catalyzes cis-trans isomerization about the proline amide bond. The dihedral angle that would correspond to the reaction coordinate for isomerization of the omega peptide bond was investigated for several small models. Relaxed potential energy scans for this dihedral angle in N-methylacetamide, 1, N,N-dimethylacetamide, 2, acetylpyrrolidine, 3 and acetylproline, 4, were carried out in 20 degrees steps using the B3LYP/6-31+G* level of theory. In addition, similar scans were carried out for 1-4 protonated on the acetylamide carbonyl oxygen. Optimized structures for 1-4 protonated on the amide nitrogen were also obtained at B3LYP/6-31+G*. Relative proton affinities were determined for each site at various angles along the reaction coordinate for isomerization. The relative proton affinities were anchored to experimental gas phase proton affinities, which were taken from the literature for 1 and 2, or determined in an electrospray ionization-quadrupole ion trap instrument using the extended kinetic method for 3 and 4. Proton affinities of 925 +/- 10 and 911 +/- 12 kJ/mol were determined for 3 and 4, respectively. These studies suggest that the nitrogen atom in these amides becomes the most basic site in the molecule at a dihedral angle of ca. 130 degrees . In addition, the nitrogen atoms in 2-4 are predicted to attain basicities in the range 920-950 kJ/mol, making them basic enough to be the preferred site for hydrogen bonding in the Pin-1 active site, in support of the proposed mechanism for PPIases.

Study of the dative bond in 2-aminoethoxydiphenyl borate at various levels of theory: another poor performance of the B3LYP method for B-N dative bonds.

Aminoethoxydiphenyl borate (2-APB), 1, is a potent inhibitor of store-operated calcium entry channels (SOCCs). Other SOCC inhibitors are being investigated as promising pharmacological agents for a variety of conditions. Though toxic, 2-APB could be useful in the development of additional inhibitors, but its preferred binding structure must first be determined. Thus, we performed ab initio calculations to study the conformers and the strength of the dative bond of 2-APB. As a first step, we performed a series of computations at various levels of theory. We obtained vastly different dissociation energies for the dative bond depending on whether we used MP2 or B3LYP (7-10 kcal/mol different). This discrepancy has previously been observed for other B-N dative bonds by Gilbert, who found that the MP2 values were in much better agreement with experimental values (Gilbert, T. M. J. Phys. Chem. A 2004, 108, 2550-2554). Since we lacked experimental data for comparison, we performed CCSD(T) calculations and found them to have similar results to those from MP2. Thus, we conclude that MP2 is more accurate for 2-APB. The dissociation free energy at the MP2 level is 7 kcal/mol and indicates that the dative bond conformer will be the predominant structure in the gas phase. The dissociation energy is comparatively low due to the electron donation from the oxygen atom to the boron atom and due to the ring strain in the dative bond conformer.

The preference for anti over Gauche migration in the Baeyer-Villiger reaction.

Explanations for stereoselectivity in the Baeyer-Villiger reaction have relied on the assumption that the antiperiplanar (app) group migrates. However, the magnitude of the preference for app-migration over gauche migration is unknown. To investigate this, the energy differences between the two were estimated from ab initio calculations. App-migration was found to be the preferred pathway since no transition structure could be located for gauche migration. Barriers for gauche migration were estimated by performing constrained optimizations. App-migration was found to be strongly favored with a barrier that is at least 3.8 kcal/mol and as much as 58.0 kcal/mol lower in energy than the gauche migration barrier.

Ab initio approach to understanding the stereoselectivity of reactions between hydroxyalkyl azides and ketones.

A new stereoselective version of the Schmidt reaction has been discovered by Aubé and co-workers (J. Am. Chem. Soc. 2003, 125, 7914-7922). Quantum chemical calculations reported in this paper were carried out to examine the observed diastereoselectivities. The azide attack step is found to be reversible, but a thermodynamic preference for the equatorial attack product is observed. The final stereoselectivity of the reaction is determined by the axial/equatorial ratio of the chiral substituent in the resulting intermediate. In the case of 2-R-hydroxypropyl azides, interesting axial/equatorial preferences are observed. In particular, the phenyl substituent shows a preference for the axial position resulting from a novel interaction with a N(2) cationic group.