New Singlet Oxygen Donors Based on Naphthalenes: Synthesis, Physical Chemical Data, and Improved Stability

Abstract

Singlet oxygen donors are of current interest for medical applications, but suffer from a short half-life leading to low singlet oxygen yields and problems with storage. We have synthesized more than 25 new singlet oxygen donors based on differently substituted naphthalenes in only a few steps. The influence of functional groups on the reaction rate of the photooxygenations, thermolysis, half-life, and singlet oxygen yield has been thoroughly studied. We determined various thermodynamic data and compared them with density functional calculations. Interestingly, remarkable stabilities of functional groups during the photooxygenations and stabilizing effects for some endoperoxides during the thermolysis have been found. Furthermore, we give evidence for a partly concerted and partly stepwise thermolysis mechanism leading to singlet and triplet oxygen, respectively. Our results might be interesting for "dark oxygenations" and future applications in medicine.

Photooxygenation of oxygen‐substituted naphthalenes

“…Furthermore, it has been photooxygenated previously, but no endoperoxides 2e were detected and only rearrangement products isolated . We generated 1 O 2 by irradiation of the sensitizer TPP with a sodium lamp (400 W) in the presence of molecular oxygen in deuterochloroform at −20°C (Experimental), a procedure, which was very convenient in our previous studies . However, 1,4‐dimethoxynaphthalene (X = Me, 1e ) gave no conversion after 60 minutes and only 30% conversion after 240 minutes (Table , entries 1 and 2).…”

“…Therefore, such labile EPOs can be used as 1 O 2 sources under very mild conditions. Although we developed other singlet oxygen donors very recently, it was hitherto not possible to release this reactive species at such low temperatures from organic compounds.…”

“…Additional methyl groups in other positions of the naphthalene further increase their stability. Very recently, we described the influence of esters and amides in the 2‐position of naphthalenes on the kinetics of the reversible reaction with 1 O 2 and applied such compounds for an intramolecular transfer of singlet oxygen for the first time …”

Molecular devices based on reversible singlet oxygen binding in optical and photomedical applications

“…Moreover, the endoperoxides have to be isolated and purified under cooling, an inconvenient method especially when column chromatography is required. 26 An alternative approach uses self-sensitized singlet oxygen addition. The formation of such self-sensitized endoperoxides was first noticed by Rodgers and co-workers with 1,6,10,15,19,24,28,33-octabutoxynaphthalocyanine 5.…”

Chemisch induzierte Freisetzung von Singulettsauerstoff aus aromatischen Endoperoxiden

“…[8,16] Es ist bedeutend, dass die Methylierung das EPO 1 p-O 2 zu einem wasserlçslichen Sauerstoffdonor macht, was Perspektiven füri nteressante biologische Anwendungen erçffnet. Tatsächlich verkürzte sich die Halbwertszeit t 1/2 von 1 pMe-O 2 bei 90 8 8Ca uf 1.4 h. Die Berechnung der Aktivierungsenthalpie mittels Eyring-Plot bei drei verschiedenen Temperaturen (Abbildung S8) ergab einen Wert von DH # = 84 kJ mol À1 (siehe die Hintergrundinformationen fürDetails), vergleichbar mit den reaktiveren EPOs von Naphthalinen.…”