Current Research Projects

Reaction mechanisms

A knowledge of the mechanism associated with a chemical reaction, going from reactants to products, is of paramount importance in understanding chemical behavior. Computationally, it is desired to determine the lowest energy path along the reaction coordinate for the rearrangement of atoms when going from the reactants to the products. This is commonly referred to as the reaction minimum energy path (RMEP). The RMEP can consist of many maxima and minima. The maxima are first-order saddle points or transition states while the minima are stable intermediates (long- or short-lived) along the reaction coordinate. From this information, one can calculate the thermodynamic and kinetic data associated with the chemical reaction.

The determination of the RMEP for a chemical reaction can be a daunting computational problem even for the simplest of reactions. The Nudged Elastic Band (NEB) method provides a convenient computational tool for calculating the RMEP connecting a set of reactants and products. The NEB method is a two ended method requiring a reactant and product supermolecule. In calculating the RMEP, the NEB minimization process only requires the calculation of gradients (first derivatives of the energy with respect to displacement of the nuclei) making it a computationally inexpensive approach. We have interfaced the NEB code [published by Alfonso and Jordan, J Comp Chem 24 (2003) 990-996] to the quantum mechanical software packages Gaussian 2009, ACES II, ACES III, CFOUR and DMol3. We further modified the code to include variable spring constants, climbing image and the FIRE optimizer [Bitzek, Koskinen, Gahler, Moseler and Gumbsch, Phys Rev Letters 97 (2006) 170201(1-4)] in the NEB software package. The FIRE optimizer is well suited for minimizing the NEB forces. The Simplified Generalized Simulated Annealing (SGSA) procedure [Dall'Inga Junior, Silva, Mundim and Dardenne, Genetics and Molec. Biol., 27, (2004) 616-622] is used to search for the global minimum of the reactant and product supermolecules. We have interfaced the GSA with DMol3, Mopac93, Mopac2009 and Gaussian 2009. In our implementation of the GSA, the optimization search can be restricted to defined torsion angles, internal coordinates and Cartesian coordinates. The transition states are refined with the modified dimer method [Heyden, Bell and Keil, J Chem Phys 123 (2005) 224101(1-14)], which we have also interfaced to the above QM codes. The bonding characteristics of the generated molecular structures are studied using the atoms in molecules software InteGriTy [Katan, Rabiller, Guezo, Oison and Souhassou, J Appl Crsyt 36 (2003) 65-73] to generate molecular graphs. All graphics and animations involving molecules was rendered using PyMOL, courtesy of DeLano Scientific LLC, Palo Alto, California.

We plan to use the NEB method to study reactions of chemical interest. As an example, toluene is a major pollutant of the atmosphere. The following animation shows the NEB calculated reaction mechanism for the reaction of the oxygen molecule with the toluene-hydroxyl radical (which is consistent with published work).

All calculations were performed with the DMol3 implementation of the NEB and the improved dimer methods on the SGI Origin 350 and SGI Altix 4700 at East Carolina University.

L.J Bartolotti and E.O. Edney

Acrolein-Guanine reaction

Acrolein is a irritating toxic chemical that is derived from a variety of sources. It occurs as a product of incomplete combustion of organic matter, a contaminate of food and water, and a metabolite of various compounds. It is a product of tobacco combustion and has been implicated in DNA damage of the gene for the tumor-suppressor p53 and causes mutations which mimics those found in lung cancer patients. Acrolein binds with guanine of the cytosine-guanine base pair of DNA. Thus is most important to understand the mechanism for the reaction of acrolein with DNA. We begin by looking at the reaction of acrolein with guanine to form 8-hydroxy-1,N2-propanodexoyguaosine. The DMol3 implementation of NEB was again used to calculate the reaction minimum energy path. The animation of the calculated mechanism is

There are several energy maxima along the RMEP, with the highest being 46.34 kCal/mol. This is a rather high activation energy and suggests that the above is not the correct mechanism. Acrolein readily undergoes hydrolysis, thus it is instructive to investigate whether water may play a role in lowering the energy barrier. We looked at acrolein reacting with water. It too had a large barrier (48.0 kCal/mol). We then investigated a mechanism that included two waters.

The barrier is now 36.3 kCal/mol, a significant lowering of the activation energy. Here, the second water acts as a catalysts. We are now looking at a mechanism(s) that involves three waters.

All calculations were performed with the DMol3 implementation of the NEB and the improved dimer methods on the SGI Origin 350 and SGI Altix 4700 at East Carolina University.

L.J. Bartolotti, R.C. Morrison, K. Flurchick and P. Fletcher

Published results

Interaction of Peroxyformic Acid with Water Molecules: A First-Principles Study

Mono- or di-substituted derivatives (ROOR'of hydrogen peroxide, by virtue of a wide range of reactions brought about by them, are of great interest in synthetic organic chemistry. Among this class of compounds, peracids, i.e., acids in which the acidic -OH group is replaced by an -OOH group (from peroxide), form by themselves a class of reactants in synthetic organic chemistry. Peracids play a vital role in several chemically important reactions such as oxidizing agents in the epoxidation type of reactions where a carbon-carbon double bond in alkenes undergoes oxidation to generate epoxides (oxiranes), as a reagent in Baeyer-Villiger oxidation type of reactions, and so forth. Some of these acids are peroxycarboxylic acids, such as peroxyformic acid (also called performic acid) and m-chloroperoxybenzoic acid (mCPBA). Performic acid (PFA), a planar molecule (HC(:O)OOH), manifests itself in cis and trans forms (as discussed in section II). For an isolated PFA molecule, the cis form (electrical dipole moment (experimental) ) 1.39 D), exhibits a greater stability than its trans counterpart and is endowed with a low activation barrier for undergoing a reaction. Moreover, the cis form shows a striking feature of an intramolecular hydrogen bond. Recent literature reveals several studies on chemical reactions involving peracids as one of the reactants. In particular, the hydrogen-bonded complexes of peracids constitute a fascinating area that is studied extensively employing experimental and theoretical techniques, as highlighted below.

This published work comprises a theoretical study of structures and energetics of the lowest energy conformers of peroxyformic acid (PFA) viz. restricted Hartree-Fock (RHF) and the second-order Moller-Plesset (MP2) perturbation theory with the basis sets 6-31G(d,p) and 6-311++G-(2d,2p). Modifications in the structure as well as vibrational frequencies of PFA brought about by successive addition of H2O molecules are also discussed. Cooperativity of hydrogen bonding in these clusters can be gauged through a detailed many body interaction energy analysis.

A.D. Kulkarni, D.Rai, L.J. Bartolotti and R.K. Pathak, J. Phys. Chem. 110 (2006) 11855-11861

An example where orbital relaxation is an important contribution to the Fukui function

The paddlewheel molecule W2(hpp)4 has the lowest ionization potential known for any stable neutral molecule. Here the bridging ligand, hpp, is the anion of 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-1]pyrimidine. This exceptionally low ionization potential makes these molecules extremely good Lewis bases. We employ the Fukui function, calculated with density functional theory, to elucidate that the direction of attack by electrophilic reagents. Besides the obvious importance of this complex, we are motivated by the fact that, on the basis of molecular orbital diagram previously presented for this molecule, frontier molecular orbital theory (incorrectly) predicts that electrophiles would attack the metal-metal bond. The Fukui function, mapped upon an isosurface of the electron density corresponding to the Van der Waals surface, correctly predicts the end on attack, depicted by the red area in the image below.

All calculations were performed using the DMol3 software package installed on the SGI Origin 350 at East Carolina University.

L.J. Bartolotti and P.W. Ayers, J. Phys. Chem. 109 (2005) 1146-1151

Density Functional Theory-Based Prediction of Some Aqueous-Phase Chemistry of Superheavy Element 111. Roentgenium(I) Is the 'Softest' Metal Ion

A previous approach (Hancock, R. D.; Bartolotti, L. J. Inorg. Chem. 2005, 44, 7175) using DFT calculations to predict log K1 (formation constant) values for complexes of NH3 in aqueous solution was used to examine the solution chemistry of Rg(I) (element 111), which is a congener of Cu(I), Ag(I), and Au(I) in Group 1B. Rg(I) has as its most stable presently known isotope a t1/2 of 3.6 s, so that its solution chemistry is not easily accessible. LFER (Linear free energy relationships) were established between DE(g) calculated by DFT for the formation of monoamine complexes from the aquo ions in the gas phase, and DG(aq) for the formation of the corresponding complexes in aqueous solution. For M2+, M3+, and M4+ ions, the gas-phase reaction was [M(H2O)6]n+(g) + NH3(g)) = [M(H2O)5NH3]n+(g) + H2O(g) (1), while for M+ ions, the reaction was [M(H2O)2]+(g) + NH3(g) ) = [M(H2O)NH3]+(g) + H2O(g) (2). A value for DG(aq) and for DE for the formation of M = Cu2+, not obtained previously, was calculated by DFT and shown to correlate well with the LFER obtained previously for other M2+ ions, supporting the LFER approach used here. The simpler use of DE values instead of DG(aq) values calculated by DFT for formation of monoamine complexes in the gas phase leads to LFER as good as the DG-based correlations. Values of DE were calculated by DFT to construct LFER with M = H+, and the Group 1B metal ions Cu+, Ag+, Au+, and Rg+, and with L = NH3, H2S, and PH3: [M(H2O)2]+(g) + L(g) = [M(H2O)L]+(g) + H2O(g) (3).  Correlations involving DE calculated by DMol3 for H+, Cu+, Ag+, and Au+ could reliably be used to construct LFER and estimate unknown log K1 values for Rg(I) complexes of NH3, PH3, and H2S calculated using the ADF (Amsterdam density Functional) code. Log K1 values for Rg(I) complexes are predicted that suggest the Rg(I) ion to be a very strong Lewis acid that is extremely 'soft' in the Pearson hard and soft acids and bases sense.

All calculations were performed using the DMol3 software package installed on the SGI Origin 350 at East Carolina University.

N. Kaltsoyannis, L.J. Bartolotti, and R.D. Hancock, Inorg. Chem. 45 (2006) 10780-10785