Unraveling the mechanism of the photodeprotection reaction of 8-bromo- and 8-chloro-7-hydroxyquinoline caged acetates.

Photoremovable protecting groups (PPGs) when conjugated to biological effectors forming "caged compounds" are a powerful means to regulate the action of physiologically active messengers in vivo through 1-photon excitation (1PE) and 2-photon excitation (2PE). Understanding the photodeprotection mechanism is important for their physiological use. We compared the quantum efficiencies and product outcomes in different solvent and pH conditions for the photolysis reactions of (8-chloro-7-hydroxyquinolin-2-yl)methyl acetate (CHQ-OAc) and (8-bromo-7-hydroxyquinolin-2-yl)methyl acetate (BHQ-OAc), representatives of the quinoline class of phototriggers for biological use, and conducted nanosecond time-resolved spectroscopic studies using transient emission (ns-EM), transient absorption (ns-TA), transient resonance Raman (ns-TR(2)), and time-resolved resonance Raman (ns-TR(3)) spectroscopies. The results indicate differences in the photochemical mechanisms and product outcomes, and reveal that the triplet excited state is most likely on the pathway to the product and that dehalogenation competes with release of acetate from BHQ-OAc, but not CHQ-OAc. A high fluorescence quantum yield and a more efficient excited-state proton transfer (ESPT) in CHQ-OAc compared to BHQ-OAc explain the lower quantum efficiency of CHQ-OAc relative to BHQ-OAc.

Comparison of the absorption, emission, and resonance Raman spectra of 7-hydroxyquinoline and 8-bromo-7-hydroxyquinoline caged acetate.

To better understand the deprotection reaction of the new promising phototrigger compound BHQ-OAc (8-bromo-7-hydroxyquinoline acetate), we present a detailed comparison of the UV-vis absorption, resonance Raman, and fluorescence spectra of BHQ-OAc with its parent compound 7-hydroxyquinoline in different solvents. The steady-state absorption and resonance Raman spectra provide fundamental information about the structure, properties, and population distribution of the different prototropic forms present under the different solvent conditions examined. The species present in the excited states that emit strongly were detected by fluorescence spectra. It is shown that the ground-state tautomerization process of BHQ-OAc is disfavored compared with that of 7-HQ in aqueous solutions. The observation of the tautomeric form of BHQ-OAc in neutral aqueous solutions demonstrates the occurrence of the excited-state proton-transfer process, which would be a competing process for the deprotection reaction of BHQ-OAc in aqueous solutions.

Resonance Raman characterization of different forms of ground-state 8-bromo-7-hydroxyquinoline caged acetate in aqueous solutions.

The 8-bromo-7-hydroxyquinolinyl group (BHQ) is a derivative of 7-hydroxyquinoline (7-HQ) and BHQ molecules coexisting as different forms in aqueous solution. Absorption and resonance Raman spectroscopic methods were used to examine 8-bromo-7-hydroxyquinoline protected acetate (BHQ-OAc) in acetonitrile (MeCN), H(2)O/MeCN (60:40, v/v, pH 6 approximately 7), and NaOH-H(2)O/MeCN (60:40, v/v, pH 11 approximately 12) to obtain a better characterization of the forms of the ground-state species of BHQ-OAc in aqueous solutions and to examine their properties. The absorption spectra of BHQ-OAc in water show no absorption bands of the tautomeric species unlike the strong band at about 400 nm observed for the tautomeric form in 7-HQ aqueous solution. The resonance Raman spectra in conjunction with Raman spectra predicted from density functional theory (DFT) calculations reveal the observation of a double Raman band system characteristic of the neutral form (the nominal C=C ring stretching, C-N stretching, and O-H bending modes at 1564 and 1607 cm(-1)) and a single Raman band diagnostic of the enol-deprotonated anionic form (the nominal C=C ring, C-N, and C-O(-) stretching modes in the 1593 cm(-1) region). These results suggest that the neutral form of BHQ-OAc is the major species in neutral aqueous solution. There is a modest increase in the amount of the anionic form and a big decrease in the amount of the tautomeric form of the molecules for BHQ-OAc compared to 7-HQ in neutral aqueous solution. The presence of the 8-bromo group and/or competitive hydrogen bonding that hinder the formation and transfer process of a BHQ-OAc-water cyclic complex may be responsible for this large substituent effect.