We seek to understand the effects that govern non-covalent interactions with aromatic systems through the application of computational quantum chemistry and to quantify the role of these non-covalent interactions in organic chemistry, materials science, and molecular biology. To this end, we employ computational chemistry spanning the full gamut of techniques, ranging from high-accuracy ab initio methods [MP2, CCSD(T), etc] and density functional theory to classical molecular dynamics simulations. A hallmark of our work is the emphasis on building simple, physically-motivated conceptual models that are of great utility for chemists. Close ties and collaborations with experimental chemists are highly valued, since they enable us to maximize the impact of our work on the greater community of chemistry researchers.
Substituent Effects in Non-Covalent Interactions with Aromatic Rings
From a broader perspective, one of our main aims is to understand how substituents can be used to tune the strength of non-covalent interactions.
To this end, we have developed simple, qualitative models of substituent effects in general π-stacking interactions and prototypical cation/π and anion/π complexes. These models deviate significantly from prevailing ideas in the literature, but are beginning to gain traction among experimental and computational chemists. The prevailing model of substituent effects in p-stacking interactions hinges on the polarization of the aromatic π-system by the substituents. This has been used for decades to explain why electron-withdrawing substituents enhance π-stacking interactions while electron-donors hinder π-stacking.
We have developed an alternative model in which substituent effects arise solely from direct interactions between the substituents and the nearest vertex of the unsubstituted ring. Although this local, direct interaction model provides similar predictions to popular p-polarization models for simple monosubstituted benzene dimers, for more complex systems, including heteroaromatic dimers and polysubstituted systems, our model provides clear predictions that are in much better agreement with robust computational results.
Stacking Interactions in Organic Electronic Materials
Conjugated organic oligomers are central to the development of efficient organic electronic devices and organic photovoltaics. There has been significant progress in our understanding of the effect of monomer composition on the electronic properties of the resulting oligomers. However, only recently has the often substantial effects of non-covalent interchain interactions come into focus.
We are carrying out detailed and systematic computational studies of non-covalent stacking and edge-to-face interactions between conjugated heterocyclic oligomers. Targeted systems range from simple heterocyclic dimers such as those of thiophene pictured, to large, realistic heterocyclic oligomers utilized in organic electronic devices.
We are also studying non-covalent interactions between large polycyclic aromatic hydrocarbons as well as carbon nanotubes and graphene sheets. These carbon-based materials are key potential materials for advanced electronic materials, but little is known about how stacking interactions operate in these extended systems, and how these interactions compare to those between smaller aromatic molecules.
Stereoselectivity of Organocatalyzed Reactions
Organocatalysis is a rapidly developing area of synthetic organic chemistry. Driven by a desire to develop catalysts that do not rely on transition metals, many highly stereoselective catalytic reactions have been developed over the last decade that utilize small organic molecules. Although a great deal of progress has been made in this field, there is still only limited information available regarding how these catalysts achieve such a high degree of reactivity and stereoselectivity.
We are using computational chemistry to unravel the mechanisms of organocatalyzed reactions and to provide structural information regarding the stereocontrolling transition states in these reactions. This information can then be used to devise new catalysts with improved reactivity and selectivity.
One particular target is N-oxide and N,N'-dioxide catalyzed allylation and propargylation reactions, such as the N-oxide catalyzed propargylation depicted above. Allylations and propargylations are key synthetic transformations leading to enantiopure allylic and propargylic alcohols. These, in turn, are key building blocks for a wide range of chiral products. We have developed alternative models of the origin of stereoselectivity in allylation and propargylation reactions catalyzed by the bipyridine N-oxides, and are currently designing novel N-oxide catalysts for asymmetric propargylation reactions. We are also pursuing computational studies of many other organocatalyzed reactions.
"Local Nature of Substituent Effects in Stacking Interactions", S. E. Wheeler, J. Am. Chem. Soc., 133, 10262-10274 (2011).
"Taking the Aromaticity out of Aromatic Interactions", J. W. G. Bloom and S. E. Wheeler, Angew. Chem. Int. Ed., 50, 7847-7849 (2011).
"Substituent Effects on Non-Covalent Interactions with Aromatic Rings: Insights from Computational Chemistry", R. K. Raju, J. W. G. Bloom, Y. An, and S. E. Wheeler ChemPhysChem 12, 3116-3130 (2011).
"Origin of Enantioselectivity in the Propargylation of Aromatic Aldehydes Catalyzed by Helical N-Oxides", T. Lu, R. Zhu, Y. An, and S. E. Wheeler J. Am. Chem. Soc. 134, 3095-3102 (2012).
"Measurement and Theory of Hydrogen Bonding Contribution to Isosteric DNA Base Pairs", O. Khakshoor, S. E. Wheeler, K. N. Houk, and E. T. Kool J. Am. Chem. Soc. 134, 3154-3163 (2012).
"Impact of Neighboring Chains on Torsional Defects in Oligothiophenes", E. C. Vujanovich, J. W. G. Bloom, and S. E. Wheeler, J. Phys. Chem. A 116, 2997-3003 (2012).
"Accurate Thermochemistry of Hydrocarbon Radicals via an Extended Generalized Bond Separation Reaction Scheme", M. D. Wodrich, C. Corminboeuf, and S. E. Wheeler, J. Phys. Chem. A 116, 34363447 (2012).
"Controlling the Local Arrangements of π-Stacked Polycyclic Aromatic Hydrocarbons through Substituent Effects", S. E. Wheeler, CrystEngComm 14, 6140-6145 (2012).
"Vibrational Spectroscopy and Theory of the Protonated Benzene Dimer and Trimer", B. Bandyopadhyay, T. C. Cheng, S. E. Wheeler, and M. A. Duncan, J. Phys. Chem. A 116, 7065-7073 (2012).
"Physical Nature of Substituent Effects in XH/π Interactions", J. W. G. Bloom, R. K. Raju, and S. E. Wheeler, J. Chem. Theory Comput. 8, 3167-3174 (2012).
"Explaining the Disparate Stereoselectivities of N-Oxide Catalyzed Allylations and Propargylations of Aromatic Aldehydes", T. Lu, M. A. Porterfield, and S. E. Wheeler, Org. Lett. 14, 5310-5313 (2012).