利用具極性響應性之基態互變異構現象驅動激發態分子內質子轉移放光：新穎3-羥基黃酮–吡唑潛在雷射染料

Abstract

3-羥基黃酮 (3HF) 及其眾多衍生物自發現以來，因其在激發態分子內質子轉移 (excited-state intramolecular proton transfer, ESIPT) 過程中的表現而受到廣泛研究，並開啟了其在生物影像與光電材料領域中的多元應用。然而，3HF 的光穩定性問題仍是一項限制其實際應用的重要挑戰，使其在雷射方面發展受阻。本研究旨在開發一種具備雙氫鍵結構的新型3HF 類似物，透過氫鍵調控加強羥基酸度，增加ESIPT效果，使其螢光量子產率提升，減少非輻射途徑釋放激發態能量的發生，以改善其光穩定性問題，最後策略性地引入吡唑環並成功合成了化合物PRA-3HC，並且利用其極性響應性設計出分子內雙氫鍵-單氫鍵之可控開關，同時也在螢光強-弱之間變換。在溶液中，PRA-3HC 存在兩種吡唑互變異構體3-hydroxy-2-(1H-pyrazol-5-yl)-4H-chromen-4-one (N1-H) 與3-hydroxy-2-(1H-pyrazol-3-yl)-4H-chromen-4-one (N2-H) 之間的平衡態，其中 N1-H 結構具備雙分子內氫鍵，在非極性溶劑中為主要存在形式；隨著溶劑極性的提高，平衡則轉向僅具有單一氫鍵、極性較大的 N2-H 結構。為了進一步探討此平衡，我們合成了對應的甲基化參考化合物 N1-Me 與 N2-Me，並結合其 ¹H NMR 光譜分析，在二氯甲烷 (DCM) 中測得 N1-H 向 N2-H 的平衡常數為 0.81，乙腈 (ACN) 中為2.66，此結果與理論計算 (DFT) 結果相符。此外，透過PRA-3HC在不同酸鹼值水溶液中的吸收光譜，測定出3號位羥基pKa為8.36，與3HF pKa=10.16 相比較酸度提升了1.8個單位，證實PRA-3HC 引入吡唑的雙氫鍵設計能提升3號位羥基酸度。在光物理行為上，N1-H 能進行快速的 ESIPT 過程，其激發態互變異構體的發光波長為520 nm；而經由穩態吸收、激發光譜和理論計算分析，N2-H 由於其最低激發態為nπ* 組態，在室溫下幾乎無發光現象。在非極性溶劑中，PRA-3HC的ESIPT螢光量子產率約66%，且表現出明顯的放大自發放射 (ASE)，但其穩定性受制於溶解度。相對地，N1-Me 與N2-Me 在非極性溶劑中溶解度提高，均可進行 ESIPT，並能夠展現出穩定的ASE 行為。綜上所述，PRA-3HC 展現了氫鍵在調控基態異構化、ESIPT 動力學方面的多重角色，為設計具光學功能的小分子材料提供了新的策略與視角，此種吡唑衍生物之高螢光量子產率也適合進一步修飾功能基團，極具應用潛能。

3-Hydroxyflavone (3HF) and its numerous derivatives have been extensively studied since their discovery due to their performance in the excited-state intramolecular proton transfer (ESIPT) process, which has diverse applications in bioimaging and optoelectronic materials. However, low photostability of 3HF limits its practical applications, particularly in laser applications. This research aims to develop a novel 3HF derivative with a dual intramolecular hydrogen bond structure, with the goal of enhancing the acidity of the hydroxyl group through hydrogen bonding, thereby strengthening the EISPT process. Increasing the fluorescence quantum yield reduces non-radiative deactivation pathways to improve its photostability. The compound PRA-3HC was strategically designed and synthesized, which exhibits a solvent polarity-responsive equilibrium between dual and single intramolecular hydrogen bonding, functioning as a switchable fluorophore that can toggle between “on” and “off” fluorescence states. In solution, PRA-3HC exists in a tautomeric equilibrium between two pyrazole tautomers 3-hydroxy-2-(1H-pyrazol-5-yl)-4H-chromen-4-one (N1-H) and 3-hydroxy-2-(1H-pyrazol-3-yl)-4H-chromen-4-one (N2-H), where the N1-H structure features dual hydrogen bonds and is the predominant form in nonpolar solvents. As the solvent polarity increases, the equilibrium shifts towards the N2-H structure, which has only a single hydrogen bond and larger dipole moment, which is more polar. To further investigate this equilibrium, the corresponding methylated compounds N1-Me and N2-Me were synthesized. Combined with their ¹H NMR spectral analysis, the N1-H to N2-H equilibrium constant was determined to be 0.81 in DCM and 2.66 in ACN, which is consistent with the results of theoretical calculations. In addition, the absorption spectra of PRA-3HC in aqueous solutions with varying pH values revealed that the pKa of the hydroxyl group at the 3-position is 8.36. Compared to 3HF, which has a pKa of 10.16, the acidity is increased by 1.8 units, confirming that the introduction of the pyrazole moiety and the dual hydrogen-bonding design in PRA-3HC effectively enhances the acidity of the 3-position hydroxyl group. In terms of photophysical behavior, N1-H can undergo a fast ESIPT process with 520 nm emission wavelength of its excited-state tautomer. In contrast, through steady-state absorption, excitation spectra, and theoretical calculations, N2-H exhibits almost no fluorescence due to its lowest excited state being an nπ* configuration. In nonpolar solvents, the fluorescence quantum yield of PRA-3HC was determined to be about 66%, and it exhibits obvious amplified spontaneous emission (ASE), but limited by its solubility. However, both N1-Me and N2-Me demonstrate increased solubility in nonpolar solvent and can undergo ESIPT, exhibit stable ASE behavior. In summary, PRA-3HC demonstrates the multiple roles of hydrogen bonds in regulating ground-state isomerization, ESIPT kinetics, providing new strategies and perspectives for the design of small molecule materials with optical functions. The high fluorescence quantum yield of the pyrazole installed chromone scaffold also makes it a promising candidate for further modification of functional groups, indicating significant application potential.