Il'ichev Yuri V, Schwörer Markus A, Wirz Jakob
Departement Chemie der Universität Basel, Klingelbergstr. 80, CH-4056 Basel, Switzerland.
J Am Chem Soc. 2004 Apr 14;126(14):4581-95. doi: 10.1021/ja039071z.
The mechanism of methanol photorelease from 2-nitrobenzyl methyl ether (1) and 1-(2-nitrophenyl)ethyl methyl ether (2), and of ATP release from adenosine-5'-triphosphate-[P(3)-(1-(2-nitrophenyl)ethyl)] ester ('caged ATP', 3) was studied in various solvents by laser flash photolysis with UV-vis and IR detection. In addition to the well-known primary aci-nitro transients (A, lambda(max) approximately 400 nm), two further intermediates preceding the release of methanol, namely the corresponding 1,3-dihydrobenz[c]isoxazol-1-ol derivatives (B) and 2-nitrosobenzyl hemiacetals (C), were identified. The dependencies of the reaction rates of A-C on pH and buffer concentrations in aqueous solution were studied in detail. Substantial revision of previously proposed reaction mechanisms for substrate release from 2-nitrobenzyl protecting groups is required: (a) A novel reaction pathway of the aci-tautomers A prevailing in buffered aqueous solutions, e.g., phosphate buffer with pH 7, was found. (b) The cyclic intermediates B were identified for the first time as the products formed by the decay of the aci-tautomers A in solution. A recently proposed reaction pathway bypassing intermediates B (Corrie et al. J. Am. Chem. Soc., 2003, 125, 8546-8554) is shown not to be operative. (c) Hemiacetals C limit the release rate of both 1 (pH < 8) and 2 (pH < 10). This observation is in contrast to a recent claim for related 2-nitrobenzyl methyl ethers (Corrie et al.). Our findings are important for potential applications of the 2-nitrobenzyl protecting group in the determination of physiological response times to bioagents ('caged compounds').
通过紫外可见和红外检测的激光闪光光解技术，在各种溶剂中研究了2-硝基苄基甲基醚（1）和1-（2-硝基苯基）乙基甲基醚（2）中甲醇的光释放机制，以及腺苷-5'-三磷酸-[P(3)-(1-(2-硝基苯基)乙基)]酯（“笼状ATP”，3）中ATP的释放机制。除了众所周知的初级酸式硝基瞬态（A，λmax约400nm）外，还鉴定出了在甲醇释放之前的另外两种中间体，即相应的1,3-二氢苯[c]异恶唑-1-醇衍生物（B）和2-亚硝基苄基半缩醛（C）。详细研究了A-C的反应速率在水溶液中对pH值和缓冲液浓度的依赖性。需要对先前提出的从2-硝基苄基保护基团释放底物的反应机制进行重大修订：（a）发现了在缓冲水溶液（例如pH值为7的磷酸盐缓冲液）中占主导地位的酸式互变异构体A的新反应途径。（b）首次将环状中间体B鉴定为溶液中酸式互变异构体A衰变形成的产物。最近提出的绕过中间体B的反应途径（Corrie等人，《美国化学会志》，2003年，125，8546 - 8554）被证明是无效的。（c）半缩醛C限制了1（pH < 8）和2（pH < 10）的释放速率。这一观察结果与最近对相关2-硝基苄基甲基醚的说法（Corrie等人）相反。我们的发现对于2-硝基苄基保护基团在确定对生物制剂的生理反应时间（“笼状化合物”）的潜在应用中具有重要意义。
