Fast reactivity of a cyclic nitrone-calix[4]pyrrole conjugate with superoxide radical anion: theoretical and experimental studies.
Fast reactivity of a cyclic nitrone-calix[4]pyrrole conjugate with superoxide radical anion: theoretical and experimental studies.
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DOI：
10.1021/ja105198c
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发表时间：
2010-12-08
影响因子：
15
通讯作者：
Villamena, Frederick A.
中科院分区：
文献类型：
--
作者：
Kim, Shang-U;Liu, Yangping;Nash, Kevin M.;Zweier, Jay L.;Rockenbauer, Antal;Villamena, Frederick A.
硝酮自旋阱已被用作探针，用于使用电子顺磁共振（EPR）光谱法鉴定化学和生物系统中的瞬态自由基物种，并已发现对氧化应激介导的疾病的药理活性。由于超氧阴离子自由基（O2·−）是大多数活性氧的主要前体，而杯[4]吡咯对阴离子表现出很高的亲和力，因此设计、合成了杯[4]吡咯的环状硝酮共轭物（CalixMPO），并对其进行了表征。在PCM/B3 LYP/6-31+G（d，p）//B3 LYP/6- 31 G（d）上的计算研究表明杯[4]吡咯和硝酮之间的悬挂型连接是自旋捕获O2·−的最有效设计，给出的放能反应焓（Δ H298 K，aq）和自由能（Δ G298 K，aq）分别为-16.9和-2.1 kcal/mol。1H NMR研究揭示了CalixMPO中溶剂依赖性的构象变化，导致硝酰基基团在与吡咯基团H-键合后的电子性质变化，这也通过计算证实。CalixMPO自旋捕获的O2·−表现出独特的EPR谱。使用UV-vis停流和EPR方法对极性非质子溶剂中O2·−加合物的形成和衰减进行动力学分析，与常用的硝酮相比，CalixMPO的捕获速率常数更大，其O2·−加合物的半衰期更长。CalixMPO对O2·−的异常高的反应性被合理化是由于杯[4]吡咯部分分别对O2·−和硝酮的α-和静电效应之间的协同作用。这项工作首次证明了阴离子受体用于检测生物和化学系统中最重要的自由基中间体之一（即，O2·−）。
Nitrone spin traps have been employed as probes for the identification of transient radical species in chemical and biological systems using electron paramagnetic resonance (EPR) spectroscopy, and have found pharmacological activity against oxidative stress-mediated diseases. Since superoxide radical anion (O2•−) is a major precursor to most reactive oxygen species and that calix[4]pyrroles have shown to exhibit high affinity to anions, cyclic nitrone conjugate of calix[4]pyrrole (CalixMPO) was designed, synthesized, and characterized. Computational studies at the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) suggest a pendant-type linkage between the calix[4]pyrrole and the nitrone to be the most efficient design for spin trapping of O2•−, giving exoergic reaction enthalpies (ΔH298K,aq) and free energies (ΔG298K,aq) of -16.9 and -2.1 kcal/mol, respectively. 1H NMR study revealed solvent-dependent conformational changes in CalixMPO leading to changes in electronic properties of the nitronyl group upon H-bonding with the pyrrole groups as also confirmed by calculations. CalixMPO spin trapping of O2•− exhibited distinctive EPR spectra. Kinetic analysis of O2•− adduct formation and decay in polar aprotic solvents using UV-vis stopped-flow and EPR method gave larger trapping rate constant for CalixMPO and longer half-life for its O2•− adduct compared to the commonly used nitrones. The unusually high reactivity of CalixMPO to O2•− was rationalized to be due to the synergy between α- and electrostatic effects by the calix[4]pyrrole moiety on the O2•− and nitrone, respectively. This work demonstrates for the first time the application of an anion receptor for the detection of one the most important radical intermediates in biological and chemical systems (i.e., O2•−).
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