Matthew R. Siebert

The need for enzymatic steering in abietic acid biosynthesis: gas-phase chemical dynamics simulations of carbocation rearrangements on a bifurcating potential energy surface.

Abietic acid, a constituent of pine resin, is naturally derived from abietadiene --a process that requires four enzymes: one (abietadiene synthase) for conversion of the acyclic, achiral geranylgeranyl diphosphate to the polycyclic, chiral abietadiene (a complex process involving the copalyl diphosphate intermediate) and then three to oxidize a single methyl group of abietadiene to the corresponding carboxylic acid. In previous work (Nature Chem.2009, 1, 384), electronic structure calculations on carbocation rearrangements leading to abietadienyl cation revealed an interesting potential energy surface with a bifurcating reaction pathway (two transition-state structures connected directly with no intervening minimum), which links two products--one natural and one not yet isolated from Nature. Herein we describe direct dynamics simulations of the key step in the formation of abietadiene (in the gas phase and in the absence of the enzyme). The simulations reveal that abietadiene synthase must intervene in order to produce abietadiene selectively, in essence steering this reaction to avoid the generation of byproducts with different molecular architectures.

Differentiating Mechanistic Possibilities for the Thermal, Intramolecular [2 + 2] Cycloaddition of Allene−Ynes

Intramolecular [2 + 2] cycloaddition reactions of allene-ynes offer a quick and efficient route to fused bicyclic ring structures. Insights into the mechanism and regiochemical preferences of this reaction are provided herein on the basis of the results of quantum chemical calculations (B3LYP/6-31+G(d,p)) and select experiments; both indicate that the reaction likely proceeds through a stepwise diradical pathway where one radical center is stabilized through allylic delocalization. The influences of the length of the tether connecting the alkyne and allene and substituent effects are also discussed.

Gas-Phase Chemical Dynamics Simulations on the Bifurcating Pathway of the Pimaradienyl Cation Rearrangement: Role of Enzymatic Steering in Abietic Acid Biosynthesis.

The biosynthesis of abietadiene is the first biosynthetically relevant process shown to involve a potential energy surface with a bifurcating reaction pathway. Herein, we use gas-phase, enzyme-free direct dynamics simulations to study the behavior of the key reaction (bifurcating) step, which is conversion of the C20 pimaradienyl cation to the abietadienyl cation. In a previous study (J. Am. Chem. Soc.2011, 133, 8335), a truncated C10 model was used to investigate this reaction. The current work finds that the complete C20 pimaradienyl cation gives reaction dynamics similar to that reported for the truncated C10 model. We find that in the absence of the enzyme, the C20 abietadienyl cation is generated in almost equal quantity (1.3:1) as an unobserved (in nature) seven-membered ring product. These simulations allude to a need for abietadiene synthase to steer the reaction to avoid generation of the seven-membered ring product. The methodology of post-transition state chemical dynamics simulations is also considered. The trajectories are initiated at the rate-controlling transition state (TS) separating the pimaradienyl and abietadienyl cations. Accurate results are expected for the short-time direct motion from this TS toward the abietadienyl cation. However, the dynamics may be less accurate for describing the unimolecular reactions that occur in moving toward the pimaradienyl cation, due to the unphysical flow of zero-point energy.

Reaction dynamics of temperature-variable anion water clusters studied with crossed beams and by direct dynamics

We present a study of the different product channels in the reactions of OH and OH-(H2O) with methyl iodide over a range of collision energies. Direct dynamics classical trajectory simulations are employed to obtain an atomistic comparison with the experimental results. For the experiments we have combined a crossed beam ion imaging setup with a multipole rf ion trap. The trap allows us to prepare the molecular and cluster ions with a controlled internal temperature and thus provides well-defined initial conditions for reaction experiments at low collision energy. Changing the internal temperature of the cluster ions was found to have a profound effect on their reactivity.

Evaluating the Accuracy of Hessian Approximations for Direct Dynamics Simulations.

Direct dynamics simulations are a very useful and general approach for studying the atomistic properties of complex chemical systems, since an electronic structure theory representation of a systems potential energy surface is possible without the need for fitting an analytic potential energy function. In this paper, recently introduced compact finite difference (CFD) schemes for approximating the Hessian [J. Chem. Phys.2010, 133, 074101] are tested by employing the monodromy matrix equations of motion. Several systems, including carbon dioxide and benzene, are simulated, using both analytic potential energy surfaces and on-the-fly direct dynamics. The results show, depending on the molecular system, that electronic structure theory Hessian direct dynamics can be accelerated up to 2 orders of magnitude. The CFD approximation is found to be robust enough to deal with chaotic motion, concomitant with floppy and stiff mode dynamics, Fermi resonances, and other kinds of molecular couplings. Finally, the CFD approximations allow parametrical tuning of different CFD parameters to attain the best possible accuracy for different molecular systems. Thus, a direct dynamics simulation requiring the Hessian at every integration step may be replaced with an approximate Hessian updating by tuning the appropriate accuracy.

Sandwich Compounds of Transition Metals with Cyclopolyenes and Isolobal Boron Analogues

A series of sandwich compounds of transition metals (M=Ni, Fe, Cr) with cyclic hydrocarbon (M(CH)(n)) and borane (M(BH(2))(n)), ligands (including mixed hydrocarbon/borane sandwiches) has been studied using density functional theory (B3LYP/6-311+G(df,p)). Multicenter bonding between the central metal atom and basal cycloborane rings provides stabilization to planar cycloborane species. Large negative NICS values allude to aromatic character in the cycloboranes similar to the analogous cyclic hydrocarbons. The ability of cycloborane sandwiches to stabilize attached carbocations, radicals and carbanions is also assessed.

Mechanism of Thiolate-Disulfide Exchange: Addition–Elimination or Effectively SN2? Effect of a Shallow Intermediate in Gas-Phase Direct Dynamics Simulations

Direct dynamics trajectory simulations were performed for two examples of the thiolate-disulfide exchange reaction, that is, HS(-) + HSSH and CH(3)S(-) + CH(3)SSCH(3). The trajectories were computed for the PBE0/6-31+G(d) potential energy surface using both classical microcanonical sampling at the ion-dipole complex and quasi-classical Boltzmann sampling (T = 300 K) at the central transition state. The potential energy surface for these reactions involves a hypercoordinate sulfur intermediate. Despite the fact that the intermediate resides in a shallow well (less than 5 kcal/mol), very few trajectories follow a direct substitution path (the S(N)2 pathway). Rather, the mechanism is addition-elimination, with several trajectories sampling the intermediate for long times, up to 15 ps or longer.

[3,3]-Sigmatropic Shifts of N-Allylhydrazones: Quantum Chemical Comparison of Concerted and Radical Cation Pathways

N-Allylhydrazones are reported to undergo an elaborate [3,3]-sigmatropic shift/N2 extrusion sequence. Both concerted and radical cation pathways for the [3,3]-sigmatropic shift of several N-allylhydrazones were investigated using B3LYP/6-31+G(d,p) calculations. It was discovered that, assuming facile formation of the N-allylhydrazone radical cation, the rearrangement takes place through a series of low barrier steps energetically preferred to the concerted alternative available to neutral N-allylhydrazones. Subsequent N2 extrusions forming corresponding homoallyl radicals were found to be extremely facile.

Direct dynamics simulation of the activation and dissociation of 1,5-dinitrobiuret (HDNB).

Certain room-temperature ionic liquids exhibit hypergolic activity as liquid bipropellants. Understanding the chemical pathways and reaction mechanisms associated with hypergolic ignition is important for designing new fuels. It has been proposed (J. Phys. Chem. A 2008, 112, 7816) that an important ignition step for the hypergolic ionic liquid bipropellant system of dicyanamide/nitric acid is the activation and dissociation of the 1,5-dinitrobiuret anion DNB(-). For the work reported here, a quasiclassical direct dynamics simulation, at the DFT/M05-2X level of theory, was performed to model H(+) + DNB(-) association and the ensuing unimolecular decomposition of HDNB. This association step is 324 kcal/mol exothermic, and the most probable collision event is for H(+) to directly scatter off of DNB(-), without sufficient energy transfer to DNB(-) for H(+) to associate and form a highly vibrationally excited HDNB molecule. Approximately 1/3 of the trajectories do form HDNB, which decomposes by eight different reaction paths and whose unimolecular dynamics is highly nonstatistical. Some of these paths are the same as those found in a direct dynamics simulation of the high-temperature thermal decomposition of HDNB (J. Phys. Chem. A 2011, 115, 8064), for a similar total energy.

Potential energy surface for dissociation including spin–orbit effects

Previous experiments [J. Phys. Chem. A 116, 2833 (2012)] have studied the dissociation of 1,2-diiodoethane radical cation ( ) and found a one-dimensional distribution of translational energy, an odd finding considering most product relative translational energy distributions are two-dimensional. The goal of this study is to obtain an accurate understanding of the potential energy surface (PES) topology for the unimolecular decomposition reaction  → C2H4I+ + I•. This is done through comparison of many single-reference electronic structure methods, coupled-cluster single-point (energy) calculations, and multi-reference energy calculations used to quantify spin–orbit (SO) coupling effects. We find that the structure of the reactant has a substantial effect on the role of the SO coupling on the reaction energy. Both the BHandH and MP2 theories with an ECP/6-31++G** basis set, and without SO coupling corrections, provide accurate models for the reaction energetics. MP2 theory gives an unsymmetric structure with different C–I bond lengths, resulting in a SO energy for similar to that for the product I-atom and a negligible SO correction to the reaction energy. In contrast, DFT gives a symmetric structure for , similar to that of the neutral C2H4I2 parent, resulting in a substantial SO correction and increasing the reaction energy by 6.0–6.5 kcalmol−1. Also, we find that, for this system, coupled-cluster single-point energy calculations are inaccurate, since a small change in geometry can lead to a large change in energy.