Abstract 4767: Reaction of singlet oxygen with hydrazone prodrugs for the photochemical release of N-nitrosoamine drugs

Abstract

Abstract Very few visible-light activated photocleavable groups are available for drug delivery applications. Our research was interested in assessing the visible-light photolability of hydrazone C=N bonds via a Type II (singlet oxygen) dye-sensitized oxygenation reaction. We have explored the photooxidized cleavage of N-nitrosoamine by-products from N-methylbenzophenone phenylhydrazone and methylenehydrazine model compounds. The former was studied by gas chromatography mass spectrometry and the latter by density functional theory calculations (DFT). We quantified benzophenone that arose from the phenylhydrazone photooxidation. The DFT calculations predicted a low energy route to C=N bond fragmentation via a [2+2] pathway and an 1,2,3-dioxazetidine reactive intermediate. The reaction was predicted to occur in stepwise process via zwitterionic intermediates prior to forming the dioxazetidine, and cleavage to the nitrosamine product. Further studies are underway regarding the photolytic and hydrolytic stability of the hydrazone C=N bond to give better insight including structure-activity relationships, of singlet oxygen triggered photo-release of nitrosoamines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4767. doi:1538-7445.AM2012-4767