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Degradation of Pharmaceuticals Through Sequential Photon Absorption and Photoionization – the Case of Amiloride Derivatives

preprint
revised on 09.09.2020 and posted on 09.09.2020 by Kjell Jorner, Wangchuk Rabten, Tomas Slanina, Nathalie Proos Vedin, Sara Sillén, Jufang Wu Ludvigsson, Henrik Ottosson, Per-Ola Norrby
Photodegradation of pharmaceutical and agrochemical compounds is an important concern for health and the environment. Amiloride derivatives undergo clean photosubstitution in protic solvents. We have studied this apparent photo-SNAr reaction with a range of experimental and computational techniques. Available evidence points to a mechanism starting with photoexcitation followed by absorption of a second photon to eject an electron to give a radical cation intermediate. Subsequent substitution reaction with the protic solvent is assisted by a general base, possibly strengthened by the proximal solvated electron. Final recombination with the solvated electron generates the observed product. Quantum chemical computations reveal that excited state antiaromaticity is relieved when an electron is ejected from the photoexcited molecule by the second photon, leading to a weakly aromatic radical cation. The mechanism indicated here could have wide applicability to photoinduced degradation of similar heteroaromatic compounds in the environment as well as in protic solvents. There are also strong similarities to a class of increasingly popular synthetic photoredox methods.

Funding

Olle Engkvist Byggmästare Foundation 184-390

Olle Engkvist Byggmästare Foundation 194-677

The Czech Grant Agency 19-20467Y

The Swedish Research Council 2015-04538

The Swedish Research Council 2019-05618

Vinnova 2016-04572

History

Email Address of Submitting Author

per-ola.norrby@astrazeneca.com

Institution

AstraZeneca

Country

Sweden

ORCID For Submitting Author

0000-0002-2419-0705

Declaration of Conflict of Interest

No conflict of interest

Version Notes

First submitted full version

Exports