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

26 June 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

photochemistry
Amiloride
Nucleophilic Aromatic Substitutions
Photoionization
DFT

Supplementary materials

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SI PhotoSNAr 200624
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PhotoSNAr 200624
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cartesian coordinates
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