Dispersion stabilized molecules are molecules where the London dispersion force (LDF), a non-covalent attractive force between atoms and molecules, plays a significant role in promoting the molecule's stability. Distinct from steric hindrance, dispersion stabilization has only recently been considered in depth by organic and inorganic chemists after earlier gaining prominence in protein science and supramolecular chemistry.[1] Although usually weaker than covalent bonding and other forms of non-covalent interactions like hydrogen bonding, dispersion forces are known to be a significant if not dominating stabilizing force in certain organic, inorganic, and main group molecules, stabilizing otherwise reactive moieties and exotic bonding.
Dispersion interactions are a stabilizing force arising from quantum mechanical electron correlation.[2] Although quantum mechanical in nature, the energy of dispersion interactions can be approximated classically, showing a R−6 dependence on the distance between two atoms. This distance dependence helps make dispersion interactions weak for individual atoms and has led to dispersion effects being historically neglected in molecular chemistry. However, in larger molecules dispersion effects can become significant. Dispersion forces in molecular chemistry are most apparent in molecules with large, bulky functional groups. Dispersion stabilization is often signified by atomic contacts below their van der Waals radii in a molecule's crystal structure. Especially for H•••H contacts between bulky, rigid, polarizable groups, short contacts may indicate that a dispersion force is overcoming the Pauli repulsion present between the two H atoms.
Dispersion forces stabilizing a reactive moiety within a molecule is distinct from using steric bulk to protect that reactive moiety. Adding "steric hindrance" to a molecule's reactive site through bulky groups is a common strategy in molecular chemistry to stabilize reactive moieties within a molecule.[3] In this case bulky ligands like terphenyls, bulky alkoxides, aryl-substituted NHCs, etc. serve as a protective wrapper on the molecule. Under the steric hindrance model, the filled orbitals of a bulky group repel other molecules and/or functional groups through Pauli repulsion. These bulky groups inhibit the approach to a molecule's reactive site, kinetically stabilizing the molecule. By contrast dispersion stabilization occurs when these bulky ligands form energetically favorable non-covalent interactions. In molecules where dispersion forces are a dominant factor, the attractive interactions between bulky groups is greater than repulsive interactions between the groups, providing overall thermodynamic stability to the molecule. Although dispersion stabilization and steric hindrance are distinct, dispersion stabilized molecules frequently benefit from steric protection of the molecule's reactive moiety.
Advances in quantum computational chemistry methods have allowed for faster theoretical examination of dispersion effects in molecular chemistry. Standard density functional theory (DFT) does not account well for dispersion effects, but corrections like the popular -D3 correction can be used with DFT to provide efficient dispersion energy corrections.[4] The -D3 correction is a force field type correction that does not take into account electronic structure, but nonetheless the popular correction works with many functionals and produces values that often fall within 5-10% of more sophisticated calculations. The "gold standard" computational method are coupled-cluster methods like CCSD(T) that account for the electron correlation origin of dispersion interactions.
Richard Bader's theory of Atoms in Molecules (AIM) has also been invoked to computationally identify dispersion interactions. Bader proposed that a bond critical point, or a critical point in the electron density, between two electronically similar, closed-shell hydrogen atoms is evidence for a stabilizing dispersion interaction between those two atoms.[5] Although there is controversy about accepting bond critical points as evidence for net attractive interactions, AIM analysis has been invoked by different research groups to show dispersion effects in a variety of molecules.[6]
Alternative computational analysis methods include Yang's electron density based non-covalent interaction (NCI) analysis, and the local energy decomposition (LED) analysis to produce a dispersion interaction density (DID) plot.[7] [8]
Dispersion stabilization explains the reactivity patterns of bulky hydrocarbon radicals. •CPh3 radicals have been known since 1900. In the mid-1960s, the dimer form of the radical was observed, and instead of forming the expected Ph3CCPh3 product, the radical instead undergoes head to tail addition. By contrast, adding two tBu groups to the meta positions on the phenyl rings causes the radical to readily dimerize to (3,5-tBu2H3C6)3C–C(C6H3-3,5-tBu2)3. Initially this discovery puzzled researchers because •CPh3 head-to-tail addition seemed to suggest steric repulsion disfavored direct addition; however, the more sterically crowded molecule underwent head-to-head addition. More recently, computational analysis has shown the formation of the tBu substituted dimer to be stabilized through dispersion interactions.[9] The study suggests that dispersion interactions between tBu groups provide ~60kcal/mol of stabilization to the molecule, enough to overcome the unfavorable steric interactions from the additional tBu groups. Further, the dimer contains a 1.67Å C-C single bond, much longer than the canonical 1.54Å C-C single bond.[10] Despite the long C-C bond, the molecule remains stable at room temperature through dispersion based stability.