Department of Chemistry , Oregon State University , 153 Gilbert Hall , Corvallis , Oregon 97331 , United States.
Institute of Bioorganic Chemistry , Russian Academy of Sciences , Miklukho-Maklaya 16/10 , Moscow 117997 , Russia.
J Phys Chem B. 2019 May 2;123(17):3804-3821. doi: 10.1021/acs.jpcb.9b03201. Epub 2019 Apr 18.
Proton transfer remains one of the most fundamental processes in chemistry and biology. Superphotoacids provide an excellent platform to delineate the excited-state proton transfer (ESPT) mechanism on ultrafast time scales and enable one to precisely control photoacidity and other pertinent functionalities such as fluorescence. We modified the GFP core ( p-HBDI chromophore) into two series of highly fluorescent photoacids by fluorinating the phenolic ring and conformationally locking the backbone (i.e., biomimetics). The trifluorinated derivatives, M3F and P3F, represent two of the strongest superphotoacids with p K* values of -5.0 and -5.5, respectively, and they can efficiently transfer a proton to organic solvents like methanol. Tunable femtosecond stimulated Raman spectroscopy (FSRS) and femtosecond transient absorption (fs-TA) were employed to dissect the ESPT of M3F and P3F in methanol, particularly with structural dynamics information. By virtue of resonantly enhanced FSRS signal and global analysis of fs-TA spectra, we revealed an inhomogeneous ESPT mechanism consisting of three parallel routes following the initial small-scale proton motion and contact ion-pair formation within ∼300 fs: The first route consists of ultrafast protolytic dissociation facilitated by the pre-existing, largely optimized H-bonding chain; the second route is limited by solvent reorientation that establishes a suitable H-bonding wire for proton separation; the third route is controlled by rotational diffusion that requires rotation of the anisotropically reactive photoacid in a bulky solvent with a complex H-bonding structure over larger distances. Furthermore, we provided new design principles of enhancing photoacidity in a synergistic manner: incorporating electron-withdrawing groups into proximal (often as "donor") and distal (often as "acceptor") ring moieties of the dissociative hydroxyl group to lower the ground-state p K and increase the Δp K, respectively.
质子转移仍然是化学和生物学中最基本的过程之一。超酸为描绘超快时间尺度上的激发态质子转移（ESPT）机制提供了极好的平台，并能够精确控制光酸度和其他相关功能，如荧光。我们通过氟化酚环并构象锁定骨架（即仿生），将 GFP 核心（p-HBDI 生色团）修饰成两个系列的高荧光超酸。三氟代衍生物 M3F 和 P3F 分别代表两种最强的超酸，其 pK* 值分别为-5.0 和-5.5，它们可以有效地将质子转移到甲醇等有机溶剂中。可调谐飞秒受激拉曼光谱（FSRS）和飞秒瞬态吸收（fs-TA）被用于剖析 M3F 和 P3F 在甲醇中的 ESPT，特别是具有结构动力学信息。凭借共振增强的 FSRS 信号和 fs-TA 光谱的全局分析，我们揭示了一种不均匀的 ESPT 机制，该机制由三个平行途径组成，最初是在大约 300 fs 内进行小尺度质子运动和接触离子对形成：第一个途径由预存在的、很大程度上优化的氢键链促进的超快质子离解组成；第二个途径受溶剂取向的限制，该限制建立了适合质子分离的氢键键；第三个途径受旋转扩散的控制，这需要在具有复杂氢键结构的大体积溶剂中旋转各向异性反应性光酸以实现更大距离的旋转。此外，我们提供了以协同方式增强光酸度的新设计原则：在离解羟基的近端（通常为“供体”）和远端（通常为“受体”）环部分引入吸电子基团，以分别降低基态 pK 和增加ΔpK。
