Tomas Solomek, Jakob Wirz, Petr Klan, "Searching for Improved Photoreleasing Abilities of Organic Molecules", Acc. Chem. Res., 2015, 48, 3064-3072.
Conspectus: Photoremovable protecting groups (PPGs) are chemical auxiliaries that provide spatial and temporal control over the release of various molecules: bioagents (neurotransmitters and cell-signaling molecules, Ca2+ ions), acids, bases, oxidants, insecticides, pheromones, fragrances, etc. A major challenge for the improvement of PPGs lies in the development of organic chromophores that release the desired bioagents upon continuous irradiation at wavelengths above 650 nm, that is, in the tissue-transparent window. Understanding of the photorelease reaction mechanisms, investigated by laser flash photolysis and rationalized with the aid of quantum chemical calculations, allows for achieving this goal. In particular, simple Hückel calculations provide useful guidelines for designing new PPGs, because both the lowest excited singlet and triplet states of conjugated systems can be reasonably well described by a single electronic configuration formed by promotion of a single electron from the highest occupied molecular orbital (HOMO) to the lowest unoccupied MO (LUMO) of the ground state configuration. Here we show that Hückel calculations permit rapid identification of common features in the nodal properties of the frontier orbitals of various chromophores that can be classified into distinct chromophore families. If the electronic excitation involves a substantial electron density transfer to an sp2 carbon atom at which HOMO and LUMO are nearly disjoint, for example, by virtue of symmetry, favorable photoheterolysis can be expected when the corresponding atom carries a leaving group at the alpha-position. We show examples of photoheterolytic reactions that indicate that the efficiency of photoheterolysis diminishes for chromophores absorbing in the NIR region. We provide a rationale for more efficient photoheterolytic reactions occurring via the triplet state, and we demonstrate the advantages of this mechanistic pathway. Analogies in the structure-reactivity relationships of PPGs can therefore lead to new strategies for the development of more efficient NIR-absorbing photoremovable protecting groups.