Department of Chemistry and RECETOX, Masaryk University , Kamenice 5, 625 00 Brno, Czech Republic.
Department of Chemistry, University of Basel , Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
Acc Chem Res. 2015 Dec 15;48(12):3064-72. doi: 10.1021/acs.accounts.5b00400. Epub 2015 Nov 16.
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, Ca(2+) 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 sp(2) 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 α-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.
光致保护基团 (PPG) 是一种化学助剂，可提供对各种分子释放的空间和时间控制：生物试剂（神经递质和细胞信号分子、Ca(2+) 离子）、酸、碱、氧化剂、杀虫剂、信息素、香料等。提高 PPG 的主要挑战在于开发有机生色团，使其在波长大于 650nm 的连续照射下释放所需的生物试剂，即在组织透明窗口中。通过激光闪光光解研究光释放反应机制，并借助量子化学计算进行合理化，可实现这一目标。特别是，简单的休克尔计算为设计新的 PPG 提供了有用的指导原则，因为共轭体系的最低激发单线态和三线态都可以通过从最高占据分子轨道 (HOMO) 到基态构型的最低未占据 MO (LUMO) 中促进单个电子来合理地描述。在这里，我们表明休克尔计算允许快速识别各种生色团前线轨道节点性质的共同特征，这些特征可以分为不同的生色团家族。如果电子激发涉及到一个实质性的电子密度转移到一个 sp(2) 碳原子上，其中 HOMO 和 LUMO 几乎不相交，例如，由于对称性，当相应的原子在α位带有离去基团时，可以预期有利的光杂裂。我们展示了一些光杂裂反应的例子，表明在近红外区域吸收的生色团的光杂裂效率会降低。我们提供了通过三重态发生更有效的光杂裂反应的原理，并展示了这种机制途径的优势。因此，PPG 的结构-反应性关系的类比可以为开发更有效的近红外吸收光致保护基团提供新策略。
