Physical Chemistry

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

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.

Version notes

First submitted full version

Content

Thumbnail image of PhotoSNAr_200909.pdf

Supplementary material

Thumbnail image of SI_PhotoSNAr_200909.pdf
SI PhotoSNAr 200909
Thumbnail image of PhotoSNAr_200909.docx
PhotoSNAr 200909
Thumbnail image of SI_PhotoSNAr_200909.docx
SI PhotoSNAr 200909
Thumbnail image of cartesian_coordinates.zip
cartesian coordinates 200909