Maximizing the Reactivity of Phenolic and Aminic Radical-Trapping Antioxidants: Just Add Nitrogen!
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Hydrocarbon autoxidation, the archetype free radical chain reaction, challenges the longevity of both living organisms and petroleum-derived products. The most important strategy in slowing this process is via the intervention of radical-trapping antioxidants (RTAs), which are abundant in nature and included as additives to almost every petroleum-derived product as well as several other commercial products. Accordingly, a longstanding objective of many academic and industrial scientists has been the design and development of novel RTAs that can outperform natural and industrial standards, such as α-tocopherol, the most biologically active form of vitamin E, and dialkylated diphenylamines, respectively. Some time ago we recognized that attempts to maximize the reactivity of phenolic RTAs had largely failed because substitution of the phenolic ring with electron-donating groups to weaken the O-H bond and accelerate the rate of H atom transfer to radicals leads to compounds that are unstable in air. We surmised that incorporating nitrogen into the phenolic ring would render them more stable to one-electron oxidation, enabling their substitution with strong electron-donating groups. Guided by computational chemistry, we demonstrated that replacing the phenyl ring in very electron-rich phenols with either 3-pyridyl or 5-pyrimidyl rings leads to phenolic-like RTAs with good air stability and great reactivity. In fact, rate constants determined for the reactions of some compounds with peroxyl radicals were almost 2 orders of magnitude greater than those for α-tocopherol and implied that the reactions proceeded without an enthalpic barrier. Following extensive thermochemical and kinetic characterization, we took our studies of these compounds to more physiologically relevant media, such as lipid bilayers and human low density lipoproteins, where the heterocyclic analogues of vitamin E shone, displaying unparalleled abilities to inhibit lipid peroxidation and prompting their current investigation in animal models of degenerative disease. Moreover, we carried out studies of these compounds in several industrially relevant contexts and in particular demonstrated that they could be used synergistically with less reactive, less expensive, phenolic RTAs. More recently, our attention has turned to the application of these ideas to maximizing the reactivity of diarylamine RTAs that are common in additives to petroleum-derived products, such as lubricating oils, transmission and hydraulic fluids, and rubber. In doing so, we have developed the most reactive diarylamines ever reported. The 3-pyridyl- and 5-pyrimidyl-containing diarylamines are easily accessed using Pd- and/or Cu-catalyzed cross-coupling reactions, and display an ideal compromise between reactivity and stability. The most reactive compounds are characterized by rate constants for reactions with peroxyl radicals that are independent of temperature, implying that-as for the most reactive heterocyclic phenols-these reactions proceed without an enthalpic barrier. Unprecedented reactivity was also observed when hydrocarbon autoxidations were carried out at elevated temperatures, real-world conditions where diarylamines are uniquely effective because of a catalytic RTA activity that makes use of the hydrocarbon substrate as a sacrificial reductant. Our studies to date suggest that heterocyclic diarylamines have real potential to increase the longevity of petroleum-derived products in a variety of applications where diphenylamines are currently used.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it