Cycloreversion performance of coumarin and hetero-coumarin dimers under aerobic conditions: unexpected behavior triggered by UV-A light.

Photochemical [2+2]-cycloadditions of coumarin-like monomers are the textbook paradigms of photo-formation and photo-cleavage reactions. The electronic conjugation length of monomers and dimers is quite different which results in almost fully separated UV/Vis absorption bands in the UV-A and UV-C. This feature enables the selective light-controlled conversion between monomeric and dimeric forms by the choice of the appropriate wavelengths. Several applications are based on this kind of reversible photo linker without absorption in the visible range. But which is the best molecule from the coumarin family for such an application? Within this study, we compared the photochemical cleavage behavior of twelve coumarin-type cyclobutane dimers. In particular, the influence of isomer structure and substitution pattern was studied. Two dimers with an unexpected high quantum yield for cyclobutane cleavage were identified. This behavior is explained through the differing ring strain of the cyclobutane moiety. Electron donating substitutions of the framework, e.g. with a methoxy function (+M-effect), leads to a decreased oxidation potential, making the dimers sensitive towards oxidative dimer splitting. This result disqualifies coumarins, e.g. attached to a polymer backbone via an ether bond, often in the 7-position, because of their instabilities and side reactions in an aerobic environment. The methylated dimers (+I-effect) show excellent stability towards this undesired side reaction as well as a high cleavage efficiency upon irradiation with 265 nm. All twelve investigated dimers are ranked for their quantum efficiency and rate constant for cleavage at 265 nm, as well as their oxygen tolerance. As the most promising derivative within our scope for applications the methylated coumarin dimer was identified.

Oxidative formation of bis-N-methylquinolinone from anti-head-to-head N-methylquinolinone cyclodimer.

The light-driven formation and cleavage of cyclobutane structural motifs resulting from [2 + 2]-pericyclic reactions, as found in thymine and coumarin-type systems, is an important and intensively studied photochemical reaction. Various applications are reported utilizing these systems, among others, in cross-linked polymers, light-triggered drug release, or other technical applications. Herein coumarin is most frequently used as the photoactive group. Quite often, a poor quantum yield for dimerization and cyclobutane-cleavage and a lack of reversibility are described. In this work, we present the identification of a heterogeneous pathway of dimer cleavage found in a rarely studied coumarin analog molecule, the N-methyl-quinolinone (NMQ). The monomer was irradiated in a tube flow-reactor and the reaction process was monitored using online HPLC measurements. We found the formation of a pseudo-equilibrium between monomeric and dimeric NMQ and a continuous rise of a side product via oxidative dimer splitting and proton elimination which was identified as 3,3'-bis-NMQ. Oxidative conversion by singlet oxygen was identified to be the cause of this non-conventional cyclobutane cleavage. The addition of antioxidants suppressing singlet oxygen enables achieving a 100% photochemical conversion from NMQ to the anti-head-to-head-NMQ-dimer. Using dissolved oxygen upon light activation to singlet oxygen limits the reversibility of the photochemical [2 + 2]-cycloaddition and cycloreversion of NMQ and most likely comparable systems. Based on these findings, the development of highly efficient cycloaddition-cycloreversion systems should be enabled.

Substituting Coumarins for Quinolinones: Altering the Cycloreversion Potential Energy Landscape.

The light-activated cleavage of cyclobutane-based systems via [2 + 2] cycloreversions, such as thymine and coumarin dimers, is an important but still poorly understood ultrafast photochemical reaction. Systems displaying reversible cycloreversion have found various uses in cross-linked polymers, enhancing gas adsorption affinities in inorganics, and light-activated medical therapies. We report the identification of a heterogeneous mode of cycloreversion for a rarely examined coumarin analogue system. Quinolinone monomers and dimers were probed using ultraviolet pumped, transient absorption spectroscopy and demonstrated radically different photophysical properties than coumarins. Monomers displayed enhanced intersystem crossing at almost 1:1 versus the combined nonradiative and radiative singlet decay, while the dimers underwent cycloreversion to a one excited-one ground state monomer photoproduct pair. The change in both systems was directly linked to the lactame group in the quinolinone motif. This discovery highlights the dramatic effects that small chemical changes can have on photoreaction pathways and opens up a new means to produce and develop more efficient cycloaddition-cycloreversion systems.

Photocleavage of coumarin dimers studied by femtosecond UV transient absorption spectroscopy.

Coumarins are a class of UV absorbing compounds which exhibit fast, photoinduced cyclobutane ring formation and cleavage reactions. The photophysics behind such processes hold significant relevance for biomedical and photoresponsive materials research. In order to further understand the underlying dynamics of the cleavage reaction, and develop strategies for increasing the reaction efficiency, UV transient absorption spectroscopy was applied to three unsubstituted, isomeric coumarin dimers: anti-head-to-head (anti-hh), syn-head-to-head (syn-hh) and syn-head-to-tail (syn-ht). The experiments performed under 280 nm excitation and broadband (300-620 nm) probing revealed that the cleavage reaction of coumarin dimers occurs through non-radiative, short-lived (<200 fs) singlet states. From the data, two branched kinetic models were developed to describe the monomer formation and dimer relaxation dynamics, identify possible intermediate states, and determine the quantum yields of the dimer cleavage. The anti-hh dimer shows the highest cleavage efficiency with a value of about 20%. The differences in the cleavage efficiency for the three isomers are interpreted in terms of differing steric hindrances of the benzene groups attached to the cyclobutane ring and charge delocalisation of the intermediate state.