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.     

8-hydroxyquinoline monomer, water adducts, and dimer. Environmental influences on structure, spectroscopic properties, and relative stability of cis and trans conformers

The low fluorescence quantum yield of 8-hydroxyquinoline cannot be correctly interpreted without knowing the form that such a compound assumes in different environments. The commonly accepted emission-quenching excited-state proton transfer can follow different reaction paths if 8-hydroxyquinoline is dimeric or monomeric or if it exists in the form of cis and trans conformers; in this light, the knowledge of the compound form in a particular environment is basic. We have performed a spectroscopic and computational investigation aimed at the determination of the form of 8-hydroxyquinoline in different solvents. UV-vis, fluorescence, and IR spectral features have been assigned by ab initio computations based on the density functional theory and time-dependent density functional theory; the density functional theory and MP2 computations have been applied to the determination of the relative stability of the dimeric and monomeric cis and trans forms of 8-hydroxyquinoline in different solvents. Molecular dynamics computations have been used to determine the compound behavior in water solutions. According to our results, 8-hydroxyquinoline shows a clear preference for the cis conformation (as dimer or monomer), but, in water solutions, a small fraction of the trans conformation is also present.     

Chloromethylation of 8-hydroxyquinoline

The reaction of formaldehyde on a hydrochloric acid solution of 8-hydroxyquinoline, in the presence of hydrochloric acid gas, gave a chloromethyl derivative which is probably 7-chloromethyl-8-hydroxyquinoline hydrochloride. This compound is readily converted into the 7-hydroxymethyl derivative in alkaline solution. The 7-chloromethyl compound has been investigated as an analytical reagent for metal ions in acid solutions.     

Excited-state tautomerization dynamics of 7-hydroxyquinoline in beta-cyclodextrin

The excited-state tautomerization dynamics of 7-hydroxyquinoline encapsulated in beta-cyclodextrin is compared with that in pure water by measuring isotope-dependent fluorescence kinetics as well as absorption and emission spectra. The normal species tautomerizes stepwise via forming anionic intermediate species in both systems. However, the enol-deprotonation time (40 ps in water) becomes as large as 170 ps whereas the imine-protonation time of the anionic intermediate (160 ps in water) becomes as short as 85 ps in beta-cyclodextrin. The slow formation and the fast decay of the anionic species are attributed to the unstability of the charged species in hydrophobic cages. Encapsulation can be utilized to enhance fluorescence enormously and to accelerate selective reactions by retarding other processes.     

Biphasic tautomerization dynamics of excited 7-hydroxyquinoline in reverse micelles

The excited-state tautomerization dynamics of 7-hydroxyquinoline in the water pools of reverse micelles has been investigated by monitoring time-resolved fluorescence spectra and kinetics as well as static absorption and emission spectra with a variation of water content and isotopic fractionation. The normal and the tautomeric species are found to reside preferentially in the bound- and the free-water regions of the micelles, respectively. The excited-state tautomerization of the normal species in the bound-water layers is suggested to occur via two different channels, depending on rotamers at the moment of excitation. The cis tautomerizes via proton relay from the enol group to the imino group along a hydrogen-bonded water bridge, unusual in water but common in alcohols, whereas the trans tautomerizes via the stepwise individual acid-base reactions of two prototropic groups as found in bulk water. Proton relay can take place because water in the pools has substantially reduced polarity and disrupted hydrogen-bond networks compared with bulk water.     

IR spectra and structures of 3-hydroxyquinoline, 4-hydroxyisoquinoline,and their derivatives

From an examination of the frequencies, integral intensities, and half-widths of the absorption bands of the stretching vibrations of the hydroxyl groups in the IR spectra, it was concluded that 3-hydroxyquinoline, 4-hydroxyisoquinoline, and their derivatives exist in the phenol form in dilute CCl₄ solutions. Strong intermolecular hydrogen bonds, which are destroyed on dilution, exist in 3-hydroxyquinoline, 4-methyl-3-hydroxyquinoline, 4-hydroxyisoquinoline, and 1-chloro-3-methyl-4-hydroxyquinoline at concentrations above 10² M in CCl₄. From an examination of the values of halo derivatives of 3-hydroxyquinoline and 4-hydroxyisoquinoline, it was concluded that an intramolecular hydrogen bond of the OH...Hal type is present in these compounds. The shift in the OH band increases in the order Cl< Br< I. Weak bands of a free OH group that pertain to the s-trans form are observed in the spectrum. Strong intramolecular hydrogen bonds exist in 3-nitro-4-hydroxyisoquinoline and 3-piperidinomethyl-4-hydroxyisoquinoline.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1535–1539, November, 1971     

Raman spectra of flavins: avoidance of interference from fluorescence

Raman spectra of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) in neutral aqueous solutions have been observed with excitations at 600.0, 363.8, 351.1, 337.1, and 257.3 nm. It has been suggested that, in general, an excitation in the absorption band of the second or the third longest waveleng (instead of the first) is an effective means for observing a resonance Raman spectrum of a chromophore without fluorescence disturbance.     

Spectral behavior and pH dependence of N-hexadecyl-5-iminomethyl-8-hydroxyquinoline

A new kind of amphiphile derived from 8-hydroxyquinoline, N-hexadecyl-5-iminomethyl-8-hydroxyquinoline (HIHQ) was synthesized and characterized by different physical methods. The influence of pH value on UV-vis absorption, fluorescence spectra were investigated and the surface pressure area isotherms were recorded under different pH subphase. The linear response range between the emission intensity and the concentration of HIHQ was 1-4 x 10(-6) mol L(-1). The strongest emission of HIHQ about 460 nm was obtained at pH 8.2 and the acid-base equilibrium of HIHQ in monolayer and solution was also discussed.     

Tautomerism in 7-hydroxyquinoline: a combined experimental and theoretical study in water

Tautomerism in the ground and excited states of 7-hydroxyquinoline (7HQ) was studied in different solvents using steady-state and lifetime spectroscopic measurements, density functional theory (DFT) calculations, and molecular dynamics (MD) simulations. Equilibrium between the enol and the keto/zwitterion tautomers exists in 7HQ, which is solvent-dependent. Of the solvents used in this study, only in water does the absorbance spectrum of 7HQ show absorption from both the enol and zwitterion tautomers. In addition, in aqueous media, fluorescence is observed from the zwitterion tautomer only, which is attributed to self-quenching of the enol fluorescence by energy transfer to the ground-state zwitterion tautomer and energetically favorable excited-state proton transfer. Solvation of the hydrogen bonding sites of 7HQ was studied in binary mixtures of 1,4-dioxane and water, and three water molecules were estimated to connect the polar sites and induce intermolecular proton transfer. The results are confirmed by DFT calculations showing that three water molecules are the minimum number required to form a stable solvent wire. Mapping the water density around the polar sites using MD simulations shows well-defined hydrogen bonds around the amino and hydroxyl groups of the enol tautomer and slightly less well-defined hydrogen bonds for the zwitterion tautomer. The presence of three-member water wires connecting the polar centers in 7HQ is evident in the MD simulations. The results point to the unique spectral signatures of 7HQ in water, which make this molecule a potential probe to detect the presence of water in nanocavities of macromolecules.     

The absorption spectrum and dissociation constants of 4-hydroxybenzthiazole

The absorption spectra of 4-hydroxybenzthiazole and the parent compound, benzthiazole, have been determined in acidic, basic and neutral solutions, and compared with the corresponding absorption spectra of 8-hydroxyquinoline and quinoline. The dissociation constants of 4-hydroxybenzthiazole obtained by a spectrophotometric method as well as a potentiometric method, show that it is a stronger acid and a weaker base than 8-hydroxyquinoline.     

8-羟基喹啉及其铝配合物的合成、表征及发光性能——推荐一个综合化学实验

首先采用Skraup法制备8-羟基喹啉(HQ),涉及到有机实验中的回流加热、水蒸气蒸馏、结晶与重结晶等基本操作;然后利用合成的8-羟基喹啉来制备AlQ_3,通过返滴定法测定其中的铝含量;最后测量8-羟基喹啉与AlQ_3的红外光谱、核磁共振氢谱、紫外-可见光谱和荧光发射光谱。本实验涵盖合成、表征到性能测试,让学生认识和完成了一个基本的科研过程。     

Extraction of tungsten with 8-hydroxyquinoline and some of its derivatives

The extraction of tungsten by chloroform solutions of 8-hydroxyquinoline(I), 2-methyl-8-hydroxyquinoline(II), 5,7-dibromo-8-hydroxyquinoline(III) and 8-mercaptoquinoline(IV), as a function of the concentration of tungsten and reagent and the acidity of the aqueous phase, has been studied. Evidence was obtained for the quantitative extraction of tungsten over a wide range of acidity. The degree of extraction of tungsten at 10(-5)M concentration with I,III and IV gives two maxima when plotted against acidity. The extraction maximum for the more acidic solutions lies in the region where the reagents exist in the protonated form and its position depends on the reagent used. It is suggested that different tungsten complexes are extracted, depending on the acidity of the aqueous phase.     

5,7''''-(亚甲胺基)-二-8-羟基喹啉的合成及其理论研究

以4-甲基苯磺酸作催化剂、用三乙胺调节pH值约为9的条件下,由5-甲酰基-8-羟基喹啉和5-氨基-8-羟基喹啉合成了新的5,7'-(亚甲胺基)-二-8-羟基喹啉,利用IR,UV,1HNMR,MS确认了分子结构,比较研究了其光致发光特性,运用Gaussian98量子化学程序包,采用B3LYP密度泛函(DFT)的方法,在6-31G(d,p)水平上对分子的几何构型进行结构优化;并对目标化合物的稳定结构通过计算预测其振动光谱,计算结果与实验值基本相符.     

UV-vis, IR and (1)H NMR spectroscopic studies of some Schiff bases derivatives of 4-aminoantipyrine

Five Schiff bases derived from 4-aminoantipyrine and benzaldehyde derivatives (I) are prepared and their UV-vis, IR, (1)H NMR and fluorescence spectra are investigated and discussed. The electronic absorption spectra of the hydroxy 4-aminoantipyrine Schiff bases Ib and Ie as well as the fluorescence spectra of Ie are studied in the organic solvents of different polarity. The UV-vis absorption spectra of 4-aminoantipyrine Schiff bases Ib, Id and Ie are investigated in aqueous buffer solutions of varying pH and utilized for the determination of pK(a) and DeltaG of the ionization process. The reactions of the hydroxy compounds Ib and Ie with Ni(II) and Cu(II) ions are also studied. The results of spectral studies are supported by some molecular orbital calculations using an atom superposition and electron delocalization molecular orbital theory for a compound Ib.     

Spectrophotometric determination of halogenated 8-hydroxyquinoline derivatives

A spectrophotometric method is proposed for the determination of 8-hydroxyquinoline and three of its iodinated derivatives: 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol), 5,7-di-iodo-8-hydroxy-quinoline (iodoquinol) and 8-hydroxy-7-iodo-quinolone-5-sulphonic acid (chinoform). The suggested method depends on the reaction with 4-aminoantipyrine in the presence of an alkaline oxidizing agent. A red antipyrine dye with an absorption peak at 500 nm is produced in all cases. The reacting ratio has been determined and a reaction mechanism is presented. The proposed method can be applied to the analysis of pharmaceutical preparations containing the compounds studied, and the results obtained compare favourably with those obtained with the standard methods.     

5,7′-(亚甲胺基)-二-8-羟基喹啉的合成及其理论研究

以4-甲基苯磺酸作催化剂、用三乙胺调节pH值约为9的条件下, 由5-甲酰基-8-羟基喹啉和5-氨基-8-羟基喹啉合成了新的5,7′-(亚甲胺基)-二-8-羟基喹啉, 利用IR, UV, ¹H NMR, MS确认了分子结构, 比较研究了其光致发光特性, 运用Gaussian 98量子化学程序包, 采用B3LYP密度泛函(DFT)的方法, 在6-31G(d,p)水平上对分子的几何构型进行结构优化; 并对目标化合物的稳定结构通过计算预测其振动光谱, 计算结果与实验值基本相符.     

Excited-state proton-transfer dynamics of 7-hydroxyquinoline in room temperature ionic liquids

Excited-state proton transfer (ESPT) reaction of 7-hydroxyquinoline (7-HQ) mediated by methanol molecules has been studied in two room temperature ionic liquids (RTILs) using steady-state and time-resolved fluorescence measurements. While no ESPT is observable in neat RTILs, characteristic tautomer fluorescence of 7-HQ could be observed in the presence of small quantity of methanol (0.5-4.1 M). The observation of a rise time (350 ps-1.4 ns) associated with the tautomer fluorescence suggests that proton transfer in 7-HQ is indeed an excited-state phenomenon that requires considerable solvent reorganization prior to the relay of proton from the hydroxyl group to the distant ring nitrogen atom through suitably organized dimeric chain of methanol molecules. The rise time of the tautomer fluorescence, which has been found to decrease with increasing methanol concentration, is attributed to the change of viscosity of the medium upon methanol addition. While the influence of viscosity on the ESPT kinetics is evident from the data, lack of any definite correlation between the bulk viscosity and the rise time has been interpreted in terms of the microheterogeneous nature of the media that does not allow assessment of the microviscosity around 7-HQ from the bulk viscosity.     

Initial excited-state structural dynamics of 2'-deoxyguanosine determined via UV resonance Raman spectroscopy

The resonance Raman spectra of 2'-deoxyguanosine, a DNA nucleoside, were measured in aqueous solution at wavelengths throughout its 260 nm absorption band. Self-consistent analysis of the resulting resonance Raman excitation profiles and absorption spectrum using a time-dependent wave packet formalism with two electronic states yielded the initial excited-state structural dynamics in both states. The vibrational modes containing the N(7)═C(8) stretching and C(8)-H bending internal coordinates were found to exhibit significant initial structural dynamics upon photoexcitation to either state and are coincident with the photochemical reaction coordinate involving the formation of the 2'-deoxyguanosine cation radical.     

Host-guest interaction of Hoechst 34580 and Cucurbit[7]uril

To track nuclear dynamic processes by fluorescence imaging, nuclear stains should be highly fluorescent, resistant to photobleaching, and inert to nuclear processes. The nuclear stains of the Hoechst family, such as Hoechst 34580, show bright fluorescence only on groove binding to DNA, and therefore may interfere with visualization of nuclear dynamic processes induced by other stimuli. We study host-guest interactions between Hoechst 34580 and Cucurbit[7]uril (CB7) in aqueous solutions. The formation of CB7-Hoechst 34580 inclusion complexes with stoichiometry of 2:1 in water and 1:1 in phosphate-buffered saline (PBS) solution (pH 7.0) is confirmed by (1)H NMR, absorption spectra, fluorescence spectra, MALDI-TOF MS, and molecular modeling. Compared to Hoechst 34580, the inclusion complex exhibits redshifted absorption, intensified fluorescence, improved photostability, weakened DNA binding affinity, comparable ability to penetrate cell nuclei, and better nuclear-staining capability, and thus a new avenue for the application of cucurbituril in fluorescence imaging is opened.