UM Chemistry/Research/Webster Research Group

Our research involves several areas of theoretical and computational chemistry, including areas of biological catalysis, bond activation, and structure and bonding. Model analogues (as well as complete "smaller" systems) may be studied with either density functional or ab initio methods with a high degree of success.

Current Group Members

• Duncan Breland, Ph.D. Student
• Kristie Ruddick, Ph.D. Student
• Jeff Swan, Ph.D. Student
• Yegor Zyrianov, Post Doc

Presentations page
Publications page

β-Phosphoglucomutase
Photochromic Organometallic Compounds
Ethylene Exchange in a Grubb's Catalyst
Other Studies
Selected Recent Publications

Lahiri et al. reported the crystal structure of β-phosphoglucomutase (PGM); it was refined as a five-coordinate phosphorus (with five oxygen ligands, which the authors suggested was a "high-energy reaction intermediate" for phosphoryl transfer in the isomerization of β-glucose 1-phosphate to β-glucose 6-phosphate. The active site of PGM was reported to contain a five-coordinate atom (Y=P) and a pseudo-octahedral Mg, coordinated by four terminal ligands (two waters, one carboxylate oxygen from ASP170, and one backbone carboxyate oxygen from ASP10) and two bridging ligands (one of the carboxylate oxygens from ASP8 and an atom, X_b, bridging to the five-coordinate species, Y, see Scheme). Blackburn et al. later suggested that this structure was actually a transition-state analogue with a five-coordinate magnesium (Y=Mg) with two oxygen and three fluorine ligands.

We utilized two-layered ONIOM(MO:MO) B3LYP density functional theory and semi-empirical PM3 calculations to address the nature of the PGM enzyme active site structure and shed light on the identity of the five coordinate atom, Y, and its ligation (see Scheme).

We concluded that 1) the observed crystal structure was more consistent with a five-coordinate magnesium (a stable transition-state analogue), not a five-coordinate phosphorus (a phosphorane) and 2) the transfer of the phosphoryl group proceeds through a concerted five-coordinate phosphorus transition state that is directly coupled to a proton transfer from the oxygen of bound glucose to the carboxylic group of aspartate 10.

To the left is the animation of the imaginary mode that corresponds to the transition state for phosphoryl tranfer with concomitant proton tranfer from the hydroxyl sugar to ASP10 oxygen.

• Lahiri, Zhang, Dunaway-Mariano, and Allen Science 2003, 299, 2067-2071.
• Allen and Dunaway-Mariano Science 2003, 301, 1184d.
• Blackburn, Williams, Gamblin, and Smerdon Science 2003, 301, 1184c.
• Webster J. Am. Chem. Soc. 2004, 126, 6840-6841.

In collaboration with Ted Burkey's group, we have the studied the linkage isomerization mechanism for the photochromic derivatives of (C₅H₄R)Mn(CO)₃ with chelatable R-functional groups. UV irradiation of the tricarbonyl complex causes CO dissociation. Both pyridyl (2) and carbonyl (1) chelates are observed following irradiation.

Based upon the results from PBE density functional theory calculations, the lowest-energy isomerization pathway from 1 (the carbonyl chelate) to 2 (the pyridine chelate) proceeds via three steps: 1 (the lower-energy oxygen-bound linkage isomer with a carbonyl to pyridine s-trans conformation) to 3 (an η² π-bound carbonyl intermediate), 3 to 4 (an η² π -bound pyridyl intermediate), and 4 to 2 (the nitrogen-bound linkage isomer). The computed activation enthalpy is 20.8 kcal/mol (1 to TS-3-4). Confirmation of the calculations were obtained from kinetic experiments where the rates of decay of proton NMR peaks for 1 and recovery of those for 2 were found to be equal and first order in 1. The corresponding experimental activation enthalpies obtained from Eyring plots were in good agreement with the computed activation enthalpy (22.0 ± 0.5 and 20.8 ± 0.2 kcal/mol, respectively). Furthermore, the computational ΔH^‡ and ΔG^‡ are very similar in value indicating that TΔS^‡ is small (-1.0 kcal/mol at 25 °C). This value is also in good agreement with the small experimental TΔS^‡ (1.0 kcal/mol) which was obtained from the experimental activation entropy of 3.5 ± 0.1 eu (calculated using the average experimental activation enthalpy of 21.4 ± 0.8 kcal/mol). A low activation entropy is consistent with a pathway where the side chain never dissociates from the metal as proposed for 1→3→4→2. The computational results for intermediates 3 with an η² metal-carbonyl interaction and likewise 4 with an η² metal-pyridine interaction that does not involve the nitrogen suggest a mechanism where the metal walks along the π bonds of the side chain from one functional group to another instead of complete dissociation from the side chain followed by addition of the pyridyl group. Computational results indicate that dissociation of the side-chain functional group to form a coordinatively-unsaturated 16-electron complex followed by rotation and coordination by the second functional group is higher in energy than the π-bound pathway. A two-step pathway from 1 to 2 was also found: from 1 to 5 (the higher-energy s-cis conformer of the oxygen-bound linkage isomer) and from 5 to 2. However, this two-step pathway (1→5→2) is higher in energy by more than 6 kcal/mol compared to the π-bound pathway.

• To, Duke, Junker, O'Brien, Ross, Barnes, Webster, Burkey Organometallics 2008, 27, 289-296.

Olefin metathesis reactions, which exchange the substituents about the double bonds of the alkenes, are important for a variety of chemical syntheses. A metallocyclobutane intermediate has been implicated in the mechanism of the Grubbs-type catalyzed olefin metathesis. Romero and Piers reported an experimental mechanistic study of ethylene exchange with a 14-electron ruthenacyclobutane, (NHC)Cl₂Ru(CH₂CH₂CH₂), where NHC is an N-heterocyclic carbene (1,3-dimesitylimidazolidin-2-ylidene), derived from a second generation Grubbs catalyst, see Scheme. They described 1) intramolecular exchange of C_α and C_β in 1 and 2) intermolecular exchange, the degenerate exchange of free ethylene with 1.

For intramolecular carbon exchange, one could envision a three-step mechanism that would in the first step cleave the metallocyclobutane C-C bond (to form a methylene, ethylene complex), in the second step rotate the coordinated ethylene, and in the third step form the C-C bond (to form the metallocyclobutane, with exchanged α and β carbons). This three-step proposed mechanism is quite reasonable.

For intermolecular ethylene exchange, one could envision a variety of mechanisms. Ethylene could bind to 1 or 2 and a postulated metallocylohexane transition state or intermediate could be involved in the exchange. These structures could have either trans-disposed or cis-disposed chloride analogues (our computational results indicate a multistep mechanism with structures that have trans-disposed, not cis-disposed chlorides).

We applied PBE density functional theory calculations to test various mechanisms and consider dissociative versus associative mechanisms at elevated temperatures at which these olefin metathesis catalysts are also used.

For intramolecular ethylene exchange, our computational results indicate a single-step mechanism (to form a methylene, ethylene complex) starting from the ruthenacyclobutane complex (1) directly producing the ethylene ruthenium carbene complex (2) by a rotational bond-breaking transition state (TS-1-2, see Figure directly above).

For intermolecular ethylene exchange, our computational results indicate a multi-step mechanism starting from 3 (ethylene associated with 1), ethylene binds to the metal (through TS-3-5), which produces the η²-ethylene ruthenacyclobutane complex (5). A rotational bond-breaking transition state (TS-5-6) produces 6 (a bis ethylene methylene complex), from which the ethylene trans to NHC can dissociate (through TS-4-6). A second ruthenacyclobutane complex with associated ethylene (9) is formed through TS-4-9 (similar to TS-1-2). While the proposed pathway is not an energetically symmetric pathway, it does not violate the principle of microscopic reversibility.

An alternative mechanism which involves a ruthenacyclohexane intermediate proceeds from 5, η²-ethylene rotates (through TS-5-7) to form 7. A high-energy ruthenacyclohexane intermediate (8) is formed through TS-7-8. This pathway with a ruthenacyclohexane intermediate is higher in energy than the first described intermolecular ethylene exchange pathway.

Romero and Piers suggested that a competing mechanism involving dissociation of ethylene from 1 at elevated temperatures could become competitive with an associative mechanism. To test that suggestion, the relative free energy of ethylene loss from 1 was computed. A rise of the temperature to 100 °C (from -50 °C) increases the stability of separated ethylene and the methylene fragment by ~11.8 kcal mol^‑1 when compared to 3. Therefore, ethylene dissociation from 1 could become the operative pathway at elevated temperatures.

• Webster, J. Am. Chem. Soc. 2007, 129, 7490-7491.
• Grubbs, Ed. Handbook of Metathesis; Wiley-VCH: New York, 2003.
• Trnka, Grubbs, Acc. Chem. Res. 2001, 34, 18-29.
• Schrock, Hoveyda, Angew. Chem. Int. Ed. 2003, 42, 4592-4633.
• Schrock, Angew. Chem., Int. Ed. 2006, 45, 3748-3759.
• Grubbs, Angew. Chem., Int. Ed. 2006, 45, 3760-3765.
• Romero, Piers, J. Am. Chem. Soc. 2007, 129, 1698-1704.
• Anderson, Hickstein, O’Leary, Grubbs, J. Am. Chem. Soc. 2006, 128, 8386-8387.
• Romero, Piers, J. Am. Chem. Soc. 2005, 127, 5032-5033.

• Other Various Phosphoryl Transfer Enzymes
• Structure and Function of Autocrine Motility Factor Autotoxin (ATX)
• Other Photochromic Organometallic Compounds
• Hydrocarbon Activation and Functionalization
• Nanocatalysis and Nanomaterials
• Tungsto- and Molybdo-enzymes
• Transition Metal Hydride and Dihydrogen Complexes
• Homogeneous Catalysis
• Heterogeneous Catalysis

• R. D. Adams, E. M. Boswell, B. Captain, S. Miao, C. Beddie, C. E. Webster, M. B. Hall, N. Dalal, N. Kaur, D. Zipse. J. Organometallic Chem. 2008, in press.
• L. M. Pérez, C. E. Webster, A. A. Low, M. B. Hall. "Theoretical study of the biologically important dioxo diiron diamond core structures." Theor Chem Acc 2008, 120, 467-478.
• T. T. To, C. B. Duke, C. S. Junker, C. M. O'Brien, C. R. Ross, C. E. Barnes, C. E. Webster, T. J. Burkey, "Linkage Isomerization as a Mechanism for Photochromic Materials: Cyclopentadienylmanganese Tricarbonyl Derivatives with Chelatable Functional Groups" Organometallics 2008, 27, 289-296.
• A. J. Blake, M. W. George, M. B. Hall, J. McMaster, P. Portius, X. Z. Sun, M. Towrie, C. E. Webster, C. Wilson, S. D. Zaric, "Probing the Mechanism of Carbon-Hydrogen Bond Activation by Photochemically Generated Hydridotris(pyrazolyl)borato Carbonyl Rhodium Complexes: New Experimental and Theoretical Investigations" Organometallics 2008, 27, 189-201.
• C. E. Webster, "Computational Insights into Degenerate Ethylene Exchange with a Grubbs-Type Catalyst" J. Am. Chem. Soc. 2007, 129, 7490-7491.
• C. E. Webster, C. L. Gross, D. M. Young, G. S. Girolami, A. J. Schultz, M. B. Hall, J. Eckert, "Electronic and Steric Effects on Molecular Dihydrogen Activation in [Cp*OsH₄(L)]⁺, L = PPh₃, AsPh₃, and PCy₃" J. Am. Chem. Soc. 2005, 127, 15091-15101.
• J. F. Hartwig, K. S. Cook, M. Hapke, C. D. Incarvito, Y. Fan, C. E. Webster, M. B. Hall, "Rhodium-Boryl Complexes in the Catalytic, Terminal Functionalization of Alkanes" J. Am. Chem. Soc. 2005, 127, 2538-2552.
• R. D. Adams, B. Captain, M. B. Hall, J. L. Smith, Jr., C. E. Webster, "High Nuclearity Iridium-Platinum Clusters: Synthesis, Structures, Bonding, and Reactivity" J. Am. Chem. Soc. 2005, 127, 1007-1014.
• R. D. Adams, B. Captain, J. L. Smith, Jr., M. B. Hall, C. L. Beddie, C. E. Webster "Superloading of Tin Ligands into Rhodium and Iridium Carbonyl Cluster Complexes" Inorg. Chem. 2004, 43, 7576-7578.
• K. S. Cook, C. D. Incarvito, C. E. Webster, Y. Fan, M. B. Hall, J. F. Hartwig, "Rhodium silyl boryl hydride complexes. Comparison of bonding and the rates of elimination of borane, silane, and dihydrogen" Angew. Chem. Int. Ed. 2004, 43, 5474-5477.
• C. E. Webster, "High-energy intermediate or stable transition state analogue: theoretical perspective of the active site and mechanism of β-phosphoglucomutase" J. Am. Chem. Soc. 2004, 126, 6840-6841.
• C. E. Webster, M. Y. Darensbourg, P. A. Lindahl, M. B. Hall, "Structures and energetics of models for the active site of acetyl-coenzyme A synthase: role of distal and proximal metals in catalysis" J. Am. Chem. Soc. 2004, 126, 3410-3411.
• C. E. Webster, Y. Fan, M. B. Hall, D. Kunz, J. F. Hartwig, "Experimental and computational evidence for a boron-assisted, σ-bond metathesis pathway for alkane borylation" J. Am. Chem. Soc. 2003, 125, 858-859.