Recently the Coote group has reported significant stabilizing interactions between non-conjugated remote anions and radicals in SOMO-HOMO converted distonic radical anions.1,2 Distonic radicals are a family of radical ions, in which spin and charge are spatially separated, in contrast to conventional radical ions, where the spin and charge reside on the same atom or conjugated fragment.3 Although electronically unusual, distonic ions are not uncommon and a number of studies have been devoted to the reactivity characteristics of these stable gas-phase species, often revealing very pronounced differences in stability and reactivity between distonic radicals and their conventional, neutral radical or charged closed-shell counterparts.4-8 Several studies have demonstrated that radical ions in which spin and charge are in close proximity (i.e. separated by one or two chemical bonds) can be stabilized or destabilized by polar effects, which implies that these effects could potentially have significant influence on bond dissociation energies and therefore reaction kinetics.9-12 For example, theoretical studies have shown that deprotonation at the heteroatom in •CH2XH radicals (X=NH2, OH, PH2, and SH) results in
electron-donation present with the radical anion.11 Furthermore, formic and acetic acid radicals RCOO˙ were predicted to have abnormally low pKa values for the loss of C-H
protons.12 Similar effects at larger separations, up to 10 Å, are also known, provided that the radical and charge are directly π-conjugated.13-15 In the absence of π-conjugation,
through-space or through-bond polar effects are possible but insignificant at separations larger than 5 Å.16 For instance, calculations showed that remote C-H bonds could be
activated via intramolecular hydrogen-atom transfer involving an amine radical cation intermediate.17 Another computational study demonstrated that polar and inductive field effects could deactivate backbone and side-chain positions towards hydrogen abstraction by chlorine atoms in peptides, contributing to their resistance against radical damage.18 More recently, destabilizing effects of protonation of the nitroxide part in alkoxyamines were used to control pH-sensitive C-ON bond homolysis both computationally and experimentally.19
In the light of the abovementioned studies, stabilization of distonic radicals computationally discovered by Gryn’ova and Coote, stands out as an unprecedented example of a truly remote interaction between a negative charge and a radical without any type of orbital conjugation and at separations greater than 5 Å.1,2 The authors reported that deprotonation of an acidic group such as carboxylate, alkoxide or sulfate results in significant stabilization of a remote radical by lowering the bond dissociation energy (BDE) of its bonds to carbon-centered radicals by approximately 20 kJ mol-1 compared to the protonated form (Figure 2.1). In other words, species such as alkoxyamines bearing suitable acidic groups should be releasing carbon-centered radicals, generated by cleavage of the C-ON bond more readily when deprotonated.
Figure 2.1 Deprotonation of the remote carboxylic acid group makes the oxygen-carbon bond weaker by ca. 20 kJ mol -1.Bond dissociation free energies of C-ON bond in gas
phase at 25 °C, kJ mol-1. Calculated by Ganna Gryn’ova (Coote group).
These theoretical results were verified experimentally by gas phase thermochemistry measurements obtained via mass spectrometry and so called BDE switches derived experimentally were in excellent agreement with the calculated values.1 It was also shown that the stabilization decays with increasing distance between the charge and the radical and interestingly no bonding between the two entities is required in order to maintain the effect. The physical origin of the effect was initially linked to orbital conversion observed in all switched species, but it was unclear whether the unusual orbital configuration was the primary cause or just an effect associated with radical switching.1
The electronic configuration in atoms and molecules generally follows the Aufbau principle, according to which the orbitals are filled by a maximum of two electrons each in the order of increasing energy.20,21 There are however examples of fully organic molecules that violate this principle,21 including radical species,22-24 where the singly occupied molecular orbital (SOMO) is not necessarily the highest occupied molecular orbital (HOMO). This is referred to as SOMO-HOMO energy level conversion and according to Coote et al it occurs in virtually any distonic radical anion that contains a sufficiently stabilized radical, non-π-conjugated with a negative charge.1 Moreover, calculations revealed that upon protonation of the anion, the regular orbital order is restored, suggesting that the orbital configuration could by switched by changing the pH.1 Following their
initial report of this discovery, the authors provided a more detailed explanation of the physical origin of the effect.2 Irregular electronic configuration seems to be closely related
to additional radical stabilization, which was described as a “new type of polar effect- electronic stabilization of a delocalized radical via deprotonation of a remote acidic group forming an anion”.2
In general, the stabilization in distonic species is significant if the corresponding, relatively stable, neutral radical (aminoxyl, aminyl and peroxyl radicals were initially reported as most promising) is paired with a relatively destabilized conjugate base of a weak acid such as carboxylate, phosphate or sulfate.1 Furthermore, the effect is not only
limited to synthetic molecules, and switches as large as 40 kJ mol-1 were calculated for
guanine containing nucleotide building blocks of DNA and RNA (Figure 2.2).1
Figure 2.2 Selected examples of compatible radicals and anions and gas-phase BDE- switch in guanine nucleotide.
4.2 Effect of external conditions on radical stabilization and its consequences