BACKGROUND & AIMS: :The influence of solvent interactions on absorption properties, fluorescence properties (emission spectra and quantum yields) and relative photochemical degradation rates of primaquine has been investigated, in order to evaluate photochemical reaction mechanisms and chemical properties of the compound. The first absorption band (n - pi*) of primaquine is only slightly dependent on properties of the solvent, which can be ascribed to a strong, intramolecular hydrogen bond between the quinoline N and amine group in the ground state (S0). Amphiprotic solvents with predominant acidic properties (water and methanol) will to some extent stabilize the molecule and initiate hypsochromic shifts of the absorption band by protic interactions, while the other solvents (amphiprotic, basic and neutral) influence the absorption spectrum by general solvent effects only. The excited singlet (S1*) state of primaquine interacts more efficiently with the surrounding solvents than the S0 state, as evaluated by the Stokes shifts. The pKa value of the quinoline N is likely to increase in the S1* state, which is important for the observed protic interactions with amphiprotic solvents of predominant acidity. Specific solvent effects are highly important for the efficiency of the fluorescence (fluorescence quantum yields; phi f). The fluorescence is quenched by amphiprotic solvents, likely due to a rupture of the intramolecular bond and protonation of the quinolone N, and enhanced by polar, non-protic (basic) solvents, probably by stabilization of the delta intramolecular hydrogen bond. The observed photochemical degradation rates of primaquine in amphiprotic media are positively correlated with phi f, indicating that the photochemical degradation of primaquine is dependent on intramolecular hydrogen bonding and non protonated lone-pair electrons at the quinoline N. The intramolecular ring-formation with a subsequent increased lipophilic character and (lack of) interactions with the surroundings, are important factors for biological behavior as well as pharmaceutical properties of primaquine. Knowledge about solvent interactions with primaquine in the S0 and S1* states is essential for the proceeding evaluation of photostability and phototoxicity of the drug.

背景与目标： 研究了溶剂相互作用对primaquine的吸收性能、荧光性能 (发射光谱和量子产率) 和相对光化学降解速率的影响，以评价该化合物的光化学反应机理和化学性质。primaquine的第一吸收带 (n - pi *) 仅略微取决于溶剂的性质，这可以归因于喹啉N和基态 (S0) 的胺基之间的强分子内氢键。具有主要酸性 (水和甲醇) 的双质子溶剂将在一定程度上稳定分子并通过质子相互作用引发吸收带的低变色移动，而其他溶剂 (双质子，碱性和中性) 仅通过一般溶剂影响吸收光谱。根据斯托克斯位移评估，primaquine的激发单线态 (S1 *) 与周围溶剂的相互作用比S0态更有效。喹啉N的pKa值可能在S1 * 状态下增加，这对于观察到的质子与主要酸度的双质子溶剂的相互作用很重要。特定的溶剂效应对于荧光效率 (荧光量子产率; phi f) 非常重要。荧光被双质子溶剂猝灭，这可能是由于分子内键的破裂和喹诺酮N的质子化，并被极性非质子 (碱性) 溶剂增强，可能是通过稳定 δ 分子内氢键。观察到的两质子介质中primaquine的光化学降解速率与phi f呈正相关，表明primaquine的光化学降解取决于分子内氢键和非质子化的孤对电子在喹啉N上。分子内环的形成以及随后的亲脂性增强和 (缺乏) 与周围环境的相互作用，是生物行为以及primaquine的药物特性的重要因素。了解S0和S1 * 状态下与primaquine的溶剂相互作用对于继续评估药物的光稳定性和光毒性至关重要。

BACKGROUND & AIMS: :The complexes of NO with CuB of cytochrome c oxidase in which cytochrome a3 may or may not be ligated to cyanide or fluoride are photodissociable. NO does not appear to react with CuB in complexes of cytochrome c oxidase in which sulphide or mercaptans are ligated to the haem iron of cytochrome a3. A comparison is made between the photoreactivity of the complexes of NO with cytochrome c oxidase and those with ceruloplasmin, ascorbate oxidase, and haemocyanin. It is shown that the photoreactivity of CuB 2+.NO in cytochrome c oxidase is not unique for this enzyme, but may also be observed in the complexes of NO with type-1 copper-containing enzymes. This would suggest that the ligation of CuB in cytochrome c oxidase shows some similarity to type-1 copper in blue oxidases.

背景与目标： : NO与细胞色素c氧化酶CuB的复合物是可光解的，其中细胞色素a3可能与氰化物或氟化物连接或不连接。NO似乎不会与细胞色素c氧化酶配合物中的CuB反应，其中硫化物或硫醇与细胞色素a3的血红素铁连接。比较了NO与细胞色素c氧化酶的配合物与铜蓝蛋白，抗坏血酸氧化酶和血色素的配合物的光反应活性。结果表明，细胞色素c氧化酶中CuB 2.NO的光反应不是该酶唯一的，但也可以在NO与1型含铜酶的复合物中观察到。这表明CuB在细胞色素c氧化酶中的连接与蓝色氧化酶中的1型铜有些相似。

BACKGROUND & AIMS: :Coherent multidimensional electronic spectroscopy is commonly used to investigate photophysical phenomena such as light harvesting in photosynthesis in which the system returns back to its ground state after energy transfer. By contrast, we introduce multidimensional spectroscopy to study ultrafast photochemical processes in which the investigated molecule changes permanently. Exemplarily, the emergence in 2D and 3D spectra of a cross-peak between reactant and product reveals the cis-trans photoisomerization of merocyanine isomers. These compounds have applications in organic photovoltaics and optical data storage. Cross-peak oscillations originate from a vibrational wave packet in the electronically excited state of the photoproduct. This concept isolates the isomerization dynamics along different vibrational coordinates assigned by quantum-chemical calculations, and is applicable to determine chemical dynamics in complex photoreactive networks.

背景与目标： : 相干多维电子光谱学通常用于研究光物理现象，例如光合作用中的光收集，其中系统在能量转移后返回其基态。相比之下，我们引入多维光谱学来研究超快光化学过程，其中所研究的分子会永久变化。示例性地，反应物和产物之间的交叉峰在2D和3D光谱中出现，揭示了花色苷异构体的顺反光异构化。这些化合物在有机光伏和光学数据存储中具有应用。交叉峰振荡源自光积的电子激发态中的振动波包。此概念隔离了沿量子化学计算分配的不同振动坐标的异构化动力学，适用于确定复杂的光反应性网络中的化学动力学。

BACKGROUND & AIMS: :A2E (2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E, 3E,5E,7E-octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6(2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]pyridinium) is a blue-absorbing molecular constituent of human ocular lipofuscin and contributes to the golden-yellow emission of this pigment. Lipofuscin photoproduces toxic reactive oxygen intermediates (ROI), but the specific molecular components responsible for this phototoxicity remain unidentified. In this article the aerobic photoreactivity of A2E is quantified by comparison with its biosynthetic precursor, all-trans-retinal, and with other appropriate standards. Under blue-light exposure the efficacies for formation of cholesterol (Ch) hydroperoxides and the superoxide radical anion (O2*-) were determined using high-pressure liquid chromatography with electrochemical detection and electron spin resonance oximetry and spin trapping, respectively. Photogeneration of singlet oxygen after blue-light excitation of A2E was demonstrated unambiguously by the Ch peroxidation assay. After blue-light irradiation of A2E, O2*- were detected, but the concentration was insufficient to account for the measured production of O2*- by the solvent extract of lipofuscin granules. The collective data support the conclusion that A2E does not produce sufficient concentrations of ROI to be the primary phototoxic constituent of lipofuscin.

背景与目标： : A2E (2-[2,6-二甲基-8-(2,6，6-三甲基-1-环己烯-1-基)-1E，3E，5E，7e-八四烯基]-1-(2-羟乙基)-4-[4-甲基-6(2,6，6-三甲基-1-环己烯-1-基)-1E，3E，5e-己三烯基] 吡啶鎓) 是人眼脂褐素的一种吸收蓝色的分子成分，有助于这种色素的金黄色发射。脂褐素光产生有毒的活性氧中间体 (ROI)，但是导致这种光毒性的特定分子成分仍然未知。在本文中，A2E的需氧光反应通过与其生物合成前体全反式视网膜进行比较来量化。和其他适当的标准。在蓝光照射下，使用高压液相色谱电化学检测，电子自旋共振血氧饱和度和自旋捕获法测定了胆固醇 (Ch) 氢过氧化物和超氧化物自由基阴离子 (O2 *-) 的形成效率。分别。通过Ch过氧化试验明确证明了A2E在蓝光激发后单线态氧的光生。在A2E的蓝光照射后，检测到O2 *-，但是浓度不足以说明脂褐素颗粒的溶剂提取物测得的O2 *-的产生。集体数据支持以下结论: A2E不能产生足够浓度的ROI作为脂褐素的主要光毒性成分。

BACKGROUND & AIMS: Wetlands are recognized for the importance of their hydrological function and biodiversity, and there is now a consensus to protect and restore them as well as to complete the knowledge on their functioning. Here, we studied the dissolved organic matter (DOM) of a wetland composed of the Auzon cut-off meander, the Allier River, the alluvial fluvial flow, and watershed aquifer. Water was sampled at different locations, in spring, summer, and autumn. For each sample, DOM was characterized for its chemical and optical properties and its photooxidant capacity through its ability to generate DOM triplet excited states (3DOM*) and singlet oxygen upon simulated solar light exposure. UV-visible and fluorescence indices revealed that DOM was mainly microbial-derived whatever the sampling sites with spatial and temporal variations in terms of aromaticity (5.5-22%), specific UV absorbance at 254 nm (0.28-2.82 L m-1mgC-1), ratio of the absorbance at 254 and 365 nm (4.6-10.8), fluorescence index (1.35-166), and biological index (0.812-2.25). All the samples generated 3DOM* and singlet oxygen, rates of formation of which showed parallel variations. Using principal component analysis (PCA), we found positive correlations between the sensitizing properties of DOM samples and parameters associated to the abundance of low molecular weight and low absorbing chromophores. Moreover, the parameter variation across the wetland reinforced the hydrological movements observed in a previous study, suggesting that these parameters could be used as water connection tracers.

背景与目标： 湿地因其水文功能和生物多样性的重要性而得到认可，现在已经达成共识，以保护和恢复湿地并完成有关其功能的知识。在这里，我们研究了由Auzon截流曲折，Allier河，冲积河流流和分水岭含水层组成的湿地的溶解有机物 (DOM)。在春季，夏季和秋季的不同位置对水进行了采样。对于每个样品，DOM的化学和光学性质以及通过在模拟太阳光照射下产生DOM三重激发态 (3DOM *) 和单线态氧的能力来表征其光氧化剂容量。紫外可见和荧光指数表明，DOM主要是微生物来源的，无论采样点在芳香性 (5.5-22%)，254 nm (0.28-2.82 L m-1mgC-1) 的特定紫外吸收，在254和365 nm处的吸光度比 (4.6-10.8)，荧光指数 (1.35-166) 和生物指数 (0.812-2.25)。所有样品均产生3DOM * 和单线态氧，其形成速率显示出平行变化。使用主成分分析 (PCA)，我们发现DOM样品的敏化特性与与低分子量和低吸收发色团的丰度相关的参数之间存在正相关。此外，整个湿地的参数变化加强了先前研究中观察到的水文运动，表明这些参数可以用作水连接示踪剂。

BACKGROUND & AIMS: :The photoreactivity of chlorothalonil was studied by means of steady-state irradiation and laser-flash photolysis. Experiments were conducted in water containing acetonitrile as a co-solvent. This fungicide undergoes very slow phototransformation in the first stages of the reaction, but the consumption profile is auto-accelerated. To understand the reaction mechanism, we undertook a detailed study of the rates, products and transient species. The rates and photoproduct distribution vary greatly with the oxygen concentration. Concerning the transient species, we measured the absorption of the triplet, its yield of formation, and its reactivity with oxygen in various water-acetonitrile mixtures and with isopropanol. The reduced radical, CTH˙, could be produced and its transient spectrum was recorded. Combining all the experimental data, it is hypothesized that in the first step of the reaction CT is excited to the triplet state. The triplet has several possible fates including reduction by organic constituents to form the radical which gives photoproducts. Another characteristic of the CT triplet is its capacity to generate singlet oxygen. The production of this species was measured by phosphorescence and compared to the percentage of the triplet trapped by oxygen in air-saturated solutions. The yield varies from 0.88 in pure acetonitrile to 0.48 in water-acetonitrile (95 : 5, v/v). Therefore, in surface waters, chlorothalonil is expected to sensitize the photooxidation of micropollutants, and to be competitively phototransformed through reaction with any H donor or electron donor water constituents.

背景与目标： : 通过稳态辐射和激光闪光光解研究了百菌清的光反应。实验是在含有乙腈作为共溶剂的水中进行的。这种杀菌剂在反应的第一阶段经历非常缓慢的光转化，但是消耗曲线是自动加速的。为了了解反应机理，我们对反应速率，产物和瞬态物种进行了详细研究。速率和光产物分布随氧气浓度的变化而变化很大。关于瞬态物质，我们测量了三重态的吸收，其形成率以及在各种水-乙腈混合物和异丙醇中与氧的反应性。可以产生还原的自由基cth ˙，并记录其瞬态光谱。结合所有实验数据，假设在反应的第一步，CT被激发为三重态。三重态有几种可能的命运，包括通过有机成分的还原形成产生光产物的自由基。CT三重态的另一个特征是它产生单线态氧的能力。通过磷光测量该物种的产量，并将其与空气饱和溶液中氧气捕获的三重态的百分比进行比较。产率从纯乙腈中的0.88到水-乙腈中的0.48 (95 :  5，v/v) 变化。因此，在地表水中，百菌清有望使微污染物的光氧化敏感，并通过与任何H供体或电子供体水成分的反应竞争性光转化。

BACKGROUND & AIMS: :Combined use of photochemical and pharmacokinetic (PK) data for phototoxic risk assessment was previously proposed, and the system provided reliable phototoxic risk predictions of chemicals in same chemical series. This study aimed to verify the feasibility of the screening system for phototoxic risk assessment on dermally-applied chemicals with wide structural diversity, as a first attempt. Photochemical properties of test chemicals, 2-acetonaphthalene, 4'-methylbenzylidene camphor, 6-methylcoumarin, methyl N-methylanthranilate, and sulisobenzone, were evaluated in terms of UV absorption and reactive oxygen species (ROS) generation, and PK profiles of the test chemicals in rat skin were characterized after dermal co-application. All test chemicals showed strong UVA/B absorption with molar extinction coefficients of over 3000 M-1⋅cm-1, and irradiated 2-acetonaphthalene, 6-methylcoumarin, and methyl N-methylanthranilate exhibited significant ROS generation. Dermally-applied 2-acetonaphthalene and 4'-methylbenzylidene camphor indicated high and long-lasting skin deposition compared with the other test chemicals. Based on the photochemical and PK data, 2-acetonaphthalene was predicted to have potent phototoxic risk. The predicted phototoxic risk of the test chemicals by integration of obtained data was mostly consistent with their in vivo phototoxicity observed in rat skin. The screening strategy employing photochemical and PK data would have high prediction capacity and wide applicability for photosafety evaluation of chemicals.

背景与目标： : 先前提出了将光化学和药代动力学 (PK) 数据联合用于光毒性风险评估的建议，该系统提供了相同化学系列化学品的可靠光毒性风险预测。这项研究旨在验证筛选系统对具有广泛结构多样性的皮肤应用化学物质进行光毒性风险评估的可行性，这是首次尝试。根据紫外线吸收和活性氧 (ROS) 产生以及PK来评估测试化学品，2-乙萘，4 '-甲基亚苄基樟脑，6-甲基香豆素，N-甲基邻氨基苯甲酸甲酯和磺基苯甲酸酯的光化学性质。真皮共同应用后，对大鼠皮肤中的测试化学品进行了表征。所有测试化学品均显示出很强的UVA/B吸收，摩尔消光系数超过3000 M-1·cm-1，辐照的2-乙萘，6-甲基香豆素和N-甲基邻氨基苯甲酸甲酯表现出明显的ROS生成。与其他测试化学品相比，皮肤上施用的2-乙萘和4 '-甲基苄基樟脑表明皮肤沉积高且持久。根据光化学和PK数据，预测2-乙萘具有强烈的光毒性风险。通过整合获得的数据，预测的测试化学品的光毒性风险与在大鼠皮肤中观察到的体内光毒性基本一致。采用光化学和PK数据的筛选策略将具有很高的预测能力，并且在化学物质的光安全性评估中具有广泛的适用性。

BACKGROUND & AIMS: :The drugs commonly used in the treatment of malaria are photochemically unstable. Several of these compounds accumulate in melanin-rich tissues and cause toxic reactions which may be light induced. As part of the screening of the photochemical properties and phototoxic capabilities of antimalarials, the in vitro interaction of eight antimalarials with melanin was studied. The dissociation constant for the drug-melanin complex and the relative number of binding sites on melanin were estimated for six of the drugs using a curve-fitting program. The reaction rate for the formation of the melanin-drug complex was determined, and the complexes were further characterized by zeta potential measurements.

背景与目标： : 治疗疟疾常用的药物光化学不稳定。这些化合物中的几种积聚在富含黑色素的组织中，并引起可能由光诱导的毒性反应。作为筛选抗疟药的光化学特性和光毒性能力的一部分，研究了八种抗疟药与黑色素的体外相互作用。使用曲线拟合程序估算了六种药物的药物-黑色素复合物的解离常数和黑色素上结合位点的相对数量。确定了黑色素-药物复合物形成的反应速率，并通过zeta电位测量进一步表征了复合物。

BACKGROUND & AIMS: :The bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) is formed as a byproduct of visual cycle in retinal pigment epithelium (RPE). It contributes to golden-yellow fluorescence of the age pigment lipofuscin, which accumulates in RPE. Lipofuscin can generate a variety of reactive oxygen species (ROS) upon blue-light excitation. Although in model systems photoreactivity of A2E has been determined to be low, this bis-retinoid exhibited significant phototoxicity in RPE cells in vitro. Although the mechanism of A2E-mediated phototoxicity remains mostly unknown, we hypothesize that formation of A2E-adducts with different biomolecules may play an important role. In this study, we investigated the photochemical reactivity of A2E and its complex with bovine serum albumin (BSA) using UV-Vis absorption and emission spectroscopy, EPR-spin trapping, EPR-oximetry, time-resolved singlet oxygen phosphorescence, and the fluorogenic CBA probe. Our data show that A2E after complexation with this model protein photogenerated an increased level of ROS, particularly singlet oxygen. We also demonstrated the ability of A2E to oxidize BSA upon excitation with blue light in aqueous model systems. The data suggest that pyridinium bis-retinoid could oxidatively modify cellular proteins under physiological conditions.

背景与目标： : 双视黄醇N-视黄醇-N-亚视黄醇乙醇胺 (A2E) 是视网膜色素上皮 (RPE) 视觉循环的副产品。它有助于年龄色素脂褐素的金黄色荧光，该色素在RPE中积累。脂褐素在蓝光激发时可以产生多种活性氧 (ROS)。尽管在模型系统中，A2E的光反应活性已被确定为低，但这种双类维生素a在体外RPE细胞中表现出明显的光毒性。尽管A2E-mediated光毒性的机制仍然未知，但我们假设具有不同生物分子的A2E-adducts的形成可能起着重要作用。在这项研究中，我们使用UV-Vis吸收和发射光谱，EPR-自旋捕获，EPR-血氧饱和度，时间分辨单线态氧磷光和荧光CBA探针研究了A2E及其与牛血清白蛋白 (BSA) 的配合物的光化学反应性。我们的数据表明，与该模型蛋白复合后的A2E光产生的ROS水平增加，尤其是单线态氧。我们还证明了A2E在水性模型系统中用蓝光激发时氧化BSA的能力。数据表明，吡啶鎓双类维生素a可以在生理条件下氧化修饰细胞蛋白。

BACKGROUND & AIMS: :Chemically and biologically modified nanoparticles are increasingly considered as viable and multifunctional tools to be used in cancer theranostics. Herein, we demonstrate that coordination of alizarin blue black B (ABBB) to the TiO(2) nanoparticle surface enhances the resulting nanoparticles by (1) creating distinct fluorescence emission spectra that differentiate smaller TiO(2) nanoparticles from larger TiO(2) nanoparticle aggregates (both in vitro and intracellular) and (2) enhancing visible light activation of TiO(2) nanoparticles above previously described methods to induce in vitro and intracellular damage to DNA and other targets. ABBB-TiO(2) nanoparticles are characterized through sedimentation, spectral absorbance, and gel electrophoresis. The possible coordination modes of ABBB to the TiO(2) nanoparticle surface are modeled by computational methods. Fluorescence emission spectroscopy studies indicate that ABBB coordination on TiO(2) nanoparticles enables discernment between nanoparticles and nanoparticle aggregates both in vitro and intracellular through fluorescence confocal microscopy. Visible light activated ABBB-TiO(2) nanoparticles are capable of inflicting increased DNA cleavage through localized production of reactive oxygen species as visualized by plasmid DNA damage detected through gel electrophoresis and atomic force microscopy. Finally, visible light excited ABBB-TiO(2) nanoparticles are capable of inflicting damage upon HeLa (cervical cancer) cells by inducing alterations in DNA structure and membrane associated proteins. The multifunctional abilities of these ABBB-TiO(2) nanoparticles to visualize and monitor aggregation in real time, as well as inflict visible light triggered damage upon cancer targets will enhance the use of TiO(2) nanoparticles in cancer theranostics.

背景与目标： : 化学和生物修饰的纳米颗粒越来越被认为是用于癌症治疗的可行和多功能工具。在此，我们证明了茜素蓝黑B (ABBB) 与TiO(2) 纳米颗粒表面的配位通过 (1) 创建独特的荧光发射光谱，将较小的TiO(2) 纳米颗粒与较大的TiO(2) 纳米颗粒聚集体区分开来 (在体外和细胞内) 和 (2) 增强TiO(2) 纳米颗粒的可见光活化上述方法诱导体外和细胞内损伤DNA和其他靶标。ABBB-TiO(2) 纳米颗粒通过沉降，光谱吸光度和凝胶电泳进行表征。通过计算方法对ABBB与TiO(2) 纳米颗粒表面的可能协调模式进行了建模。荧光发射光谱研究表明，在TiO(2) 纳米颗粒上的ABBB配位能够通过荧光共聚焦显微镜在体外和细胞内识别纳米颗粒和纳米颗粒聚集体。可见光激活的ABBB-TiO(2) 纳米颗粒能够通过通过凝胶电泳和原子力显微镜检测到的质粒DNA损伤来观察，从而通过局部产生活性氧而导致DNA裂解增加。最后，可见光激发的ABBB-TiO(2) 纳米颗粒能够通过诱导DNA结构和膜相关蛋白的改变而对HeLa (宫颈癌) 细胞造成损害。这些ABBB-TiO(2) 纳米颗粒实时可视化和监测聚集以及对癌症靶标造成可见光触发损害的多功能能力将增强TiO(2) 纳米颗粒在癌症治疗中的应用。

BACKGROUND & AIMS: :Currently available test models for the differentiation of photoallergic and photoirritant reactions are extremely time consuming and the protocols are very heterogeneous. In vitro tests are of proven value in predicting irritant or toxic effects, but these tests fail to predict chemical-induced allergic side effects. We developed test systems for this endpoint which is not easily detected by existing assays. In a previous publication we were able to discriminate between a contact sensitizer and a skin irritant with a combination of primary ear swelling analysis and cell counting of the ear-draining lymph nodes [Toxicol. Appl. Pharm. 153 (1998) 83; Arch. Toxicol. 73 (2000) 501]. This combination of tests was called the Integrated Model for the Differentiation of chemical-induced allergic and irritant Skin reactions (IMDS). In addition, it had been shown before that inclusion of UV irradiation in the local lymph node assay enables discrimination of photoallergic from photoirritant reactions after dermal application [Photodermatol. Photoimmunol. Photomed. 10 (1994) 57]. Because of the fact that fluoroquinolones are known to induce photoreactions after oral but not dermal treatment, the aim of the present study was to apply the IMDS for the fast and reliable differentiation of photoreactions due to fluoroquinolones after oral treatment. Enoxacin, lomefloxacin, ofloxacin, sparfloxacin and BAY y 3118 were tested in this system. We found a good correlation between the results of UV light-irradiated IMDS and a guinea pig model with the quinolones as far as photoirritancy was concerned. This holds true also for the photoallergic standard olaquindox and the photoirritant standard 8-methoxypsoralen. However, in contrast to the guinea pig assays the IMDS is fast and extremely predictive for the risk of both photosensitization and photoirritancy depending on the route of exposure. Thus, the UV light-irradiated IMDS turned out to be a good tool for the preclinical risk assessment procedure in terms of discriminating photoreactions. In addition, flow cytometric analyses were used to underline the fact that antigen-independent activation occurred after the induction of photoirritant reactions.

背景与目标： : 目前可用的用于区分光过敏和光刺激反应的测试模型非常耗时，并且协议非常不同。体外测试在预测刺激性或毒性作用方面具有已证明的价值，但是这些测试无法预测化学引起的过敏副作用。我们为此终点开发了测试系统，而现有的检测方法不容易检测到。在以前的出版物中，我们能够通过初级耳肿胀分析和耳引流淋巴结细胞计数的组合来区分接触敏化剂和皮肤刺激物 [毒理学。应用。Pharm。153 (1998) 83; Arch。毒理学。73 (2000) 501]。这种测试的组合被称为用于区分化学引起的过敏性和刺激性皮肤反应 (imd) 的综合模型。此外，之前已经表明，在局部淋巴结测定中包含紫外线照射能够区分皮肤应用后的光过敏与光刺激反应 [Photodermatol. Photoimmunol.Photomode.10 (1994) 57]。由于已知氟喹诺酮类药物在口服而不是皮肤治疗后会诱导光反应，因此本研究的目的是应用IMDS来快速可靠地区分口服治疗后由于氟喹诺酮类药物引起的光反应。在该系统中测试依诺沙星、洛美沙星、氧氟沙星、司帕沙星和BAY y 3118。就光刺激性而言，我们发现紫外线照射的IMDS结果与喹诺酮类豚鼠模型之间存在良好的相关性。光过敏标准喹乙醇和光刺激剂标准8-甲氧基补骨脂素也适用。然而，与豚鼠测定相反，IMDS是快速且非常可预测光敏性和光刺激的风险，具体取决于暴露途径。因此，就区分光反应而言，紫外线照射的imd被证明是临床前风险评估程序的好工具。此外，流式细胞仪分析用于强调以下事实: 在诱导光刺激反应后发生了与抗原无关的激活。

BACKGROUND & AIMS: :The formation and reactivity of the triplet state and free radicals of mefloquine hydrochloride (MQ) have been investigated by pulse radiolysis and flash photolysis. The excited triplet, cation radical and anion radical have been produced and their absorption characteristics determined. The triplet-triplet absorption spectrum of MQ showed a maximum at 430 nm, with a molar absorption coefficient of 3600 M(-1) cm(-1) and the quantum yield for intersystem crossing was determined to be close to unity. Deactivation of the triplet, in the absence of oxygen, led to the formation of MQ cation and/or anion radicals. The molar absorption coefficient of the cation radical at 330 nm was determined to be 2300 M(-1) cm(-1), whilst that for the anion radical was 2400 M(-1) cm(-1) at 620 nm and 3600 M(-1) cm(-1) at 350 nm. The molar absorption coefficients of the proposed neutral radical at 320 nm and 520 nm were 4000 M(-1) cm(-1) and 1300 M(-1) cm(-1) respectively. The quantum yield for the formation of singlet oxygen, sensitized by MQ triplet, was determined to be close to unity. Aqueous solutions of MQ were found to photoionize to yield hydrated electron and cation radical of MQ in a biphotonic process. The influences of pH, buffer concentration, oxygen concentration and addition of sodium azide on the formation and reactivity of the transients were evaluated. The reactions between MQ and solvated electrons and superoxide anion were also studied.

背景与目标： : 已通过脉冲辐射分解和快速光解研究了盐酸甲氟喹 (MQ) 的三重态和自由基的形成和反应性。产生了激发的三重态，阳离子自由基和阴离子自由基，并确定了它们的吸收特性。MQ的三重态-三重态吸收光谱在430 nm处显示最大值，摩尔吸收系数为3600 M(-1) cm(-1)，并且确定了系统间交叉的量子产率接近于1。在没有氧气的情况下，三重态的失活导致MQ阳离子和/或阴离子自由基的形成。测定阳离子自由基在330 nm处的摩尔吸收系数为2300 M(-1) cm(-1)，而阴离子自由基在620为2400 M(-1) cm(-1)，在350为3600 M(-1) cm(-1)。所提出的中性自由基在320 nm和520 nm处的摩尔吸收系数分别为4000 M(-1) cm(-1) 和1300 M(-1) cm(-1)。被MQ三重态敏化的单线态氧形成的量子产率被确定为接近于1。在双光子过程中，发现MQ的水溶液会发生光电离，从而产生MQ的水合电子和阳离子自由基。评估了pH，缓冲液浓度，氧气浓度和叠氮化钠的添加对瞬态形成和反应性的影响。还研究了MQ与溶剂化电子和超氧阴离子之间的反应。

BACKGROUND & AIMS: BACKGROUND:The brain of migraineurs is hyperexcitable, particularly the occipital cortex, which is probably hypersensitive to light. Photophobia or hypersensitivity to light may be accounted for by an increased excitability of trigeminal, the visual pathways, and the occipital cortex. OBJECTIVE:To study light sensitivity and photophobia by assessing the response to light stimuli with functional magnetic resonance imaging-blood oxygenation level dependent (fMRI-BOLD) of the occipital cortex in migraineurs and in controls. Also, to try to decipher the contribution of the occipital cortex to photophobia and whether the cortical reactivity of migraineurs may be part of a constitutional (defensive) mechanism or represents an acquired (sensitization) phenomenon. METHODS:Nineteen patients with migraine (7 with aura and 12 without aura) and 19 controls were studied with fMRI-BOLD during 4 increasing light intensities. Eight axial image sections of 0.5 cm that covered the occipital cortex were acquired for each intensity. We measured the extension and the intensity of activation for every light stimuli. Photophobia was estimated according to a 0 to 3 semiquantitative scale of light discomfort. RESULTS:Migraineurs had a significantly higher number of fMRI-activated voxels at low (320.4 for migraineurs [SD = 253.9] and 164.3 for controls [SD = 102.7], P = .027) and medium-low luminance levels (501.2 for migraineurs [SD = 279.5] and 331.1 for controls [SD = 194.3], P = .034) but not at medium-high (579.5 for migraineurs [SD = 201.4] and 510.2 for controls [SD = 239.5], P = .410) and high light stimuli (496.2 for migraineurs [SD = 216.2] and 394.7 for controls [SD = 240], P = .210). No differences were found with respect to the voxel activation intensity (amplitude of the BOLD wave) between migraineurs and controls (8.98 [SD = 2.58] vs 7.99 [SD = 2.57], P = .25; 10.82 [SD = 3.27] vs 9.81 [SD = 3.19], P = .31; 11.90 [SD = 3.18] vs 11.06 [SD = 2.56], P = .62; 11.45 [SD = 2.65] vs 10.25 [SD = 2.22], P = .16). Light discomfort was higher in the group of migraineurs at all the intensities tested, but there was no correlation with the number of activated voxels in the occipital cortex and photophobia. Repetitive light stimuli failed to demonstrate a lack of habituation in migraineurs. CONCLUSIONS:Migraineurs during interictal periods showed hyperxcitability of the visual cortex with a wider photoresponsive area, the underlying mechanism probably being dual: constitutional-defensive and acquired-sensitizating.

背景与目标：

BACKGROUND & AIMS: :The synthesis and photobiological activity of four new 4'-methyl derivatives of 5-MOP (5-methoxypsoralen) and 5-MOA (5-methoxyangelicin), i.e., 4,4'-dimethyl-5-methoxypsoralen, 3,4'-dimethyl-5-methoxypsoralen, 4,4'-dimethyl-5-methoxyangelicin, and 3,4'-dimethyl-5-methoxyangelicin, are described. All these compounds photobind efficiently to DNA. The DNA-photobinding process was investigated using various nucleic acid structures such as double-helix DNA, bacterial DNA, and synthetic polydeoxyribonucleotides. Photoreaction experiments showed that, unlike 8-MOP (8-methoxypsoralen) and 5-MOP, both angular derivatives bind thymine and cytosine with the same efficiency. The principal nucleoside-psoralen monoadducts were isolated and characterized after enzymatic digestion or acid hydrolysis. Biological activity studies revealed a good correlation with the extent of covalent photoaddition. Moreover, the two angular derivatives and the 4,4'-dimethyl-5-methoxypsoralen were unable to induce skin erythema, in striking contrast with the reference drugs, 8-MOP and 5-MOP; only the 3,4'-dimethyl-5-methoxypsoralen caused erythema, although to a substantially lower extent than that induced by the two parent compounds.

背景与目标： 描述了5-MOP (5-甲氧基补骨脂素) 和5-MOA (5-甲氧基当归素) 的四种新的4 '-甲基衍生物，即4,4'-dimethyl-5-methoxypsoralen、3,4 '-dimethyl-5-methoxypsoralen、4,4'-dimethyl-5-methoxyangelicin和3,4 '-dimethyl-5-methoxyangelicin的合成和光生物活性。所有这些化合物与DNA有效结合。使用各种核酸结构 (例如双螺旋DNA，细菌DNA和合成的聚脱氧核糖核苷酸) 研究了DNA光结合过程。光反应实验表明，与8-MOP (8-甲氧基补骨脂素) 和5-MOP不同，两种角衍生物均以相同的效率结合胸腺嘧啶和胞嘧啶。在酶消化或酸水解后，分离并鉴定了主要的核苷-补骨脂素单加合物。生物活性研究表明，与共价光添加的程度具有良好的相关性。此外，与参考药物8-MOP和5-MOP形成鲜明对比的是，两种角衍生物和4,4 '-dimethyl-5-methoxypsoralen不能诱发皮肤红斑; 只有3,4'-dimethyl-5-methoxypsoralen引起红斑，尽管其程度远低于两种母体化合物诱发的程度。

BACKGROUND & AIMS: :Ruthenium polypyridyl complexes may act as light-activatable anticancer prodrugs provided that they are protected by well-coordinated ligands that i) prevent coordination of other biomolecules to the metal center in the dark and ii) can be removed by visible light irradiation. In this paper, the use of monodentate thiol ligands RSH as light-cleavable protecting groups for the ruthenium complex [Ru(tpy)(bpy)(OH2)](PF6)2 ([1](PF6)2; tpy=2,2';6',2″-terpyridine, bpy=2,2'-bypyridine), is investigated. The reaction of [1](2+) with RSH=H2Cys (L-cysteine), H2Acys (N-acetyl-L-cysteine), and HAcysMe (N-acetyl-L-cysteine methyl ester), is studied by UV-visible spectroscopy, NMR spectroscopy, and mass spectrometry. Coordination of the monodentate thiol ligands to the ruthenium complex takes place upon heating to 353 K, but full conversion to the protected complex [Ru(tpy)(bpy)(SR)]PF6 is only possible when a large excess of ligand is used. Isolation and characterization of the two new thiolato complexes [Ru(tpy)(bpy)(κS-HCys)]PF6 ([2]PF6) and [Ru(tpy)(bpy)(κS-HAcys)]PF6 ([3]PF6) is reported. [3]PF6 shows a metal-to-ligand charge-transfer absorption band that is red shifted (λmax=492 nm in water) compared to its methionine analogue [Ru(tpy)(bpy)(κS-HAmet)](Cl)2 ([5](Cl)2, λmax=452 nm; HAmet=N-acetyl-methionine). In the dark the thiolate ligand coordinated to ruthenium is oxidized even by traces of oxygen, which first leads to the sulfenato, sulfinato, and disulfide ruthenium complexes, and finally to the formation of the aqua complex [1](2+). [3]PF6 showed slow photosubstitution of the thiolate ligand by water under blue light irradiation, together with faster photooxidation of the thiolate ligand compared to dark conditions. The use of thiol vs. thioether monodentate ligands is discussed for the protection of anticancer ruthenium-based prodrugs.

背景与目标： : 钌多吡啶复合物可以充当可光活化的抗癌前药，前提是它们受到配位良好的配体的保护，即i) 阻止其他生物分子在黑暗中与金属中心的配位，ii) 可以通过可见光去除照射。在本文中，使用单齿硫醇配体RSH作为钌配合物 [Ru(tpy)(bpy)(OH2)](PF6)2 ([1](PF6)2; tpy = 2,2 ';6'，2 ”-特吡啶，研究了bpy = 2,2 '-bypyridine)。研究了 [1](2) 与RSH = H2Cys (L-半胱氨酸)，H2Acys (N-乙酰基-L-半胱氨酸) 和HAcysMe (N-乙酰基-L-半胱氨酸甲酯) 的反应。紫外可见光谱，NMR光谱和质谱。在加热至353 K时，发生单齿硫醇配体与钌络合物的配位，但是只有当使用大量过量的配体时，才可能完全转化为受保护的络合物 [Ru(tpy)(bpy)(SR)]PF6。报道了两种新的硫代络合物 [Ru(tpy)(bpy)(κ s-HCys)]PF6 ([2]PF6) 和 [Ru(tpy)(bpy)(κ s-HAcys)]PF6 ([3]PF6) 的分离和表征。[3] 与甲硫氨酸类似物 [Ru(tpy)(bpy)(κ s-HAmet)](Cl)2 ([5](Cl)2相比，PF6显示出红移的金属-配体电荷转移吸收带 (在水中 λ max = 492 nm)，Λ max = 452 nm; HAmet = N-乙酰基-甲硫氨酸)。在黑暗中，与钌配位的硫醇盐配体甚至被痕量的氧氧化，这首先导致磺胺酸酯，磺胺酸酯和二硫化物钌配合物，最后形成水配合物 [1](2)。[3]PF6显示，在蓝光照射下，硫醇盐配体被水的光取代缓慢，并且与黑暗条件相比，硫醇盐配体的光氧化更快。讨论了使用硫醇与硫醚单齿配体保护基于钌的抗癌前药。