Basil II of PhizantiumA and Günther SchlonkB*
Abstract: The following article is rated GP for “Gratuitous Puerility”. This is possibly the stupidest thing we’ve ever written. Specific: Did you know that one in ten molecules suffers from electrile dysfunction? Electrile dysfunction (ED) is a mechanistic condition in which the electron density within a molecule becomes constricted, preventing it from reaching a functional group. The result is a loss of steric rigidity which quite frequently causes impaired reactivity. Conversely, rigor moietis (RI) can occur as a result of orbital scrambling. This work describes a treatment for ED and RI using energy transfer catalysis.
For chemistry to happen, elections need to be in the right place at the right time. When the electrons go astray, problems arise. These problems broadly fall within two categories. The first is a scenario in which the electrons aren’t where they need to be. Such an insufficiency occurs predominantly in Csp hybridised environments, and results in a deviation from optimal 180˚ bond angles. This molecular declination is termed electrile dysfunction, or ED for short. The converse condition is an excess of electron density, most likely to occur at Csp2 carbons. In this case, a decrease in bond angles from 120˚ to ~90˚ is observed, which is termed rigor moietis.1 These conditions are relatively widespread, though chemists are not always open in confronting them. Even the editors of scientific journals sometimes prefer to pretend that they don’t exist.2 Almost any molecule can be afflicted with electrile dysfunction, but certain moieties are more susceptible (Figure 1).
Electrile Dysfunction In the case of electrile dysfunction, nitriles and alkynes are by far the most susceptible, while allenes, ketenes and carbonyls constitute the minority of cases. Rigor moietis is less selective: esters, acids and ketones are all prone to this affliction, and alkenes are not immune.
The electronic underpinnings of ED and RI are complex and nuanced, which is a jargonistic way of saying we can’t be fucked explaining them in depth. To put the case of electrile dysfunction simply, it arises (or not, as the case may be) from a hermeneutic intransigence of leptonic obstinance, intrinsically but not axiomatically incommensurate with the subatomic demands of an alkynic linkages. In such instances, perturbance and electronic turbulence of the molecular orbitals causes topological reverberations to resonate within the harmonic atomic network. Discord resultant from these entangled frequencies erodes the intramolecular electronic concordat and induces substantial localised atomic declination.
Translated into simple English, this means that when the flow of electrons to a functional group is constricted, things go floppy. Figure 2 shows an electrostatic potential map of a wildtype benzonitrile molecule (PhCN), as well as an electromer afflicted with ED (PhCÑ).
This diagram clearly demonstrates the root cause of the different reactivities of PhCN and PhCÑ. As a ligand, PhCÑ is incapable of effective metal binding, as the distorted C-C bond sterically constrains the nitrile lone pair. Furthermore, the nitrile HOMO is contracted, and the Not Quite Highest Occupied Molecular Orbital (NQHOMO) is swollen. This has the effect of reversing the polarity (umpolung) of the nitrile and totally munting its traditional reactivity.
Rigor Moietis: The mechanism by which rigor moietis occurs is still poorly understood,3 but it is suspected that orbital scrambling is at least partially responsible. Orbital scrambling is a phenomenon most likely to occur during the formation of molecular orbitals, though it appears that rapid changes in pressure and temperature may also induce it. Figure 3 shows a hypothesised breakdown of the oxygen-centred MO’s present in a molecule of water afflicted with rigor moietis.
The interpretation of this diagram is trivial and thus left as an exercise for the reader. Suffice to say that when orbital scrambling has occurred, traditional modes of reactivity are impaired by the unusual distribution of electrons.
Several treatments for electrile disfunction have been published to date. The first was a study by Alfred Wood, who sparged solutions of dysfunctional molecules with nitric oxide.4 This method has some merit, though the chemoselectivity is poor and NO can be explosive. Other methods entail ultrasonic stimulation of a reaction mixture, or just waiting a while.5 No effective treatments for rigor moietis have been reported.6 Our research group has a longstanding infatuation with energy transfer catalysis, so naturally we have tried to apply it to the treatment of ED and RM. In this case, it is more than just blatant opportunism that has motivated us. Energy transfer catalysis uses visible light and a photocatalyst to excite an organic molecule. Essentially, it shuffles the electrons within the target around, without net transfer to or from the substrate. We hypothesised that by doing this, it might shake loose any recalcitrant elections inhabiting orbitals in which they don’t belong, thereby alleviating any associated problems. This is the chemical equivalent of whacking a faulty appliance to restore its function, a sort of molecular percussive maintenance.
We began by conducting an initial screen of standard energy transfer catalysts in the conversion of PhCÑ to PhCN (scheme 1).
Metal complexes such as [Ru(bpy)3]Cl2 and [Cu(fap)2]PF6 gave only traces of product, while significant decomposition was noted. Organic sensitisers delivered higher yields but were still beset by side reactions, such as [2+2] dimerization to form 2,4-diphenyl-1,3-diazacyclobutadiene. We interpreted this to mean that our conditions were too harsh, and that less energetic photosensitiser was required. To this end, we have synthesised a novel photocatalyst with a maximum absorbance at 708 nm, resulting in a low-energy triplet excited state of 15 kcal/mol (Figure 4). At this decreased energy, side-reactions are supressed, while molecules afflicted with ED and RM may still enter excited states. The catalyst may be readily prepared from a widely available precursor.6
We trialled the new photosensitiser under the previous screening conditions and found it to be extremely effective, even at catalyst loadings as low as 0.000001%. In fact, sildenofluor is efficacious in quantities too small to conveniently measure. We addressed this issue by adsorbing the catalyst onto silica at a 0.1% w/wt loading. Thus, a 100 mg portion of this material can be easily weighed out, or even pressed into pill-sized aliquots (figure 5).
We optimised the reaction conditions using our new solid-supported catalyst and explored the substrate scope of this transformation (Scheme 2). We found it was effective in the treatment of both electrile dysfunction and rigor moietis.
Naturally, we have examined several hundred molecules in this reaction, but unlike some crass individuals (not to mention any names7) we don’t feel the need to show them all.
We have proposed a novel treatment for electrile dysfunction and rigor moietis in organic molecules. By using energy transfer catalysts to induce an excited state transition in afflicted substrates, electron density can be restored to normal. A novel low-energy organophotosensitiser was developed to facilitate this reaction.
Experimental conditions, substrate syntheses and spectra may be obtained from the electronic unsupported information, available from https://onlyfans.com/schlonkitup.
G.S. acknowledges Pfizantium Pty Ltd for the provision of financial support to help get this project up.
Notes and references
1 From the latin: rigor (stiffness or rigidity) and moitis (moiety or functional group)
2 See the cover of Green Chemistry issue 11, 2018.
3 “The mechanism of rigor moietis is poorly understood” R. Rocket, 2021, Chem. Sox. Rev. 4, 12–16.
3 “Oh NO, my nitrile’s gone soft” A. Wood, D. Todger, 2005, PNAS 12, 420–456.
4 “Shake it up: battle those bulging bonds with base ” A. Richard, X. L. Wang, 2005, Anal. Chem. 2, 784–788.
5 “There are no treatments for rigor moitis” R. Rocket, 2022, Chem. Sox. Rev. 5, 888–888.05.
7 Bill Pharan