Fermi liquid features of the one-dimensional Luttinger liquid
离子液体
收稿:2002年9月,收修改稿:2003年3月 3通讯联系人 e 2m ail :yuankou @pku .edu .cn不断壮大的离子液体家族杨雅立 王晓化 寇 元3 闵恩泽(北京大学化学与分子工程学院 北京100871)摘 要 本文对近10年来出现的新型离子液体进行了分类综述,并对其发展前景提出了一些见解。
关键词 离子液体 任务专一性中图分类号:O 64514;O 646117 文献标识码:A 文章编号:10052281X (2003)0620471206The Expand i ng Fam ily of Ion ic L iqu idsY ang Y a li W ang X iaohua K ou Y uan 3 M in E nz e(Co llege of Chem istry and M o lecu lar Engineering ,Pek ing U n iversity ,B eijing 100871,Ch ina )Abstract N ew i on ic liqu ids w h ich em erged du ring the recen t 10years are review ed .T he au tho rs’ow n op in i on s concern ing the fu tu re developm en t of th is field are p ropo sed .Key words i on ic liqu ids ;task sp ecific 性质上符合目前称之为离子液体的物质,早在1914年就有所报道。
但“离子液体”作为低温熔融盐(熔点低于100℃)普遍接受的统称并得到化学家们的广泛关注,却是近十年来的事。
短短的时间,从传统的三氯化铝体系,到水稳定阴离子的引入,到今天涌现出的大量功能化的离子液体,离子液体家族正快速地发展与壮大。
肠道黏膜的水合状态
肠道黏膜的水合状态英文回答:The intestinal mucosa is a complex and dynamic tissue that forms a barrier between the intestinal lumen and the underlying immune system. It is composed of a single layer of epithelial cells that are covered by a layer of mucus. The mucus layer helps to protect the epithelial cells from damage and provides a barrier to the entry of pathogens.The intestinal mucosa is constantly exposed to avariety of challenges, including mechanical stress, chemical irritation, and microbial invasion. In order to maintain its integrity, the intestinal mucosa must be able to maintain a state of hydration.Water is essential for the proper function of the intestinal mucosa. It helps to maintain the structural integrity of the epithelial cells and the mucus layer. It also helps to transport nutrients and waste products acrossthe intestinal mucosa.There are a number of factors that can affect the hydration status of the intestinal mucosa. These include:Dietary intake: A diet that is high in fiber and water can help to maintain the hydration status of the intestinal mucosa. Fiber helps to retain water in the stool, while water helps to lubricate the intestinal mucosa and prevent it from becoming dry.Intestinal motility: The movement of the intestines helps to mix and distribute water throughout the intestinal mucosa. This helps to ensure that all areas of theintestinal mucosa are well-hydrated.Blood flow: The blood supply to the intestinal mucosa helps to provide it with nutrients and oxygen. It also helps to remove waste products from the intestinal mucosa.A reduced blood supply to the intestinal mucosa can lead to dehydration.Inflammatory processes: Inflammation of the intestinal mucosa can lead to a loss of fluid and electrolytes. This can result in dehydration of the intestinal mucosa.Maintaining the hydration status of the intestinal mucosa is essential for its proper function. A number of factors can affect the hydration status of the intestinal mucosa, including dietary intake, intestinal motility, blood flow, and inflammatory processes.中文回答:肠黏膜是一个复杂而动态的组织,形成肠腔和底层免疫系统之间的屏障。
Coulomb interactions in mesoscopic systems介观系统中库仑相互作用
• Clean case: Exactly solvable • Disorder strongly relevant, localization • Multichannel generalization possible
2020/5/13
Luttinger liquid phenomena
• No Landau quasiparticles, but Laughlintype quasiparticles (solitons of field theory)
– Replica Field Theory (sigma models)
• Local density of states in disordered multichannel wires
2020/5/13
Disorder in noninteracting systems
• Quantum coherent systems • Some manifestations of phase coherence
– Field describes charge or spin density
– Free Gaussian field theory, interactions are nonperturbatively included in g and velocity u
S L[L ]2 1 gdx u 1 d ( )2 u ( x )2
2020/5/13
Time and energy scales
• Ballistic particle motion up to mean free timte
• Diffusion for E > Thouless energyEc D/L2 t tD L 2/D ,D u 2/d
非水介质酶促反应中水的作用
知识讲座非水介质酶促反应中水的作用许志国 夏咏梅 方 云(江南大学化学工程与材料学院 无锡 214036)The Role of Water in Enzymatic Reactions in Non -aqueous MediaXu Zhiguo Xia Yongmei F ang Yun(School of Chemical and Material E ngineering ,Southern Yangtze U niversity ,Wuxi 214036)AbstractThe role of water in enzymatic reactions in non -aqueous media was summarized.Distribution of water and rates of dis 2tributing equilibration ,kinetic effect of water as well as methods for measuring and controlling water activity in enzymatic reac 2tions in non -aqueous media were discussed respectively.K ey w ords enzymatic reaction non -aqueous media water activity摘要对非水介质酶促反应体系中水的作用以及相关因素进行了初步总结,着重讨论了水在体系中的分配及影响因素、水的分配平衡速度、水活度的测定及控制方法和水作为反应物的动力学影响。
关键词 酶促反应 非水介质 水活度 与在水溶液中进行的酶催化反应相比,酶在非水相中进行催化反应有如下优越性:(1)有利于疏水性底物的反应;(2)可使用简单的吸附或包埋法固定化酶或直接使用不溶性酶粉,有利于酶的回收和重复利用;(3)可以使水解反应平均向有利于合成的方向移动(如酯合成),防止依赖于水的副反应发生;(4)能提高酶的稳定性,可扩大反应的p H 值适应范围;(5)可控制底物的专一性等。
高分子专业英语课文翻译
A 高分子化学和高分子物理UNIT 1 What are Polymer?第一单元什么是高聚物?What are polymers? For one thing, they are complex and giant molecules and are different from low molecular weight compounds like, say, common salt. To contrast the difference, the molecular weight of common salt is only 58.5, while that of a polymer can be as high as several hundred thousand, even more than thousand thousands. These big molecules or ‘macro-molecules’ are made up of much smaller molecules, can be of one or more chemical compounds. To illustrate, imagine that a set of rings has the same size and is made of the same material. When these things are interlinked, the chain formed can be considered as representing a polymer from molecules of the same compound. Alternatively, individual rings could be of different sizes and materials, and interlinked to represent a polymer from molecules of different compounds.什么是高聚物?首先,他们是合成物和大分子,而且不同于低分子化合物,譬如说普通的盐。
fermi liquid
费米液体理论(朗道-费米液体理论)费米液体理论是朗道在1956年提出的相互作用费米子理论模型,通常可用于绝大多数金属低温下的正常态。
该理论解释了为什么相互作用费米子系统的有些性质与费米气体的性质如此相似,而另一些性质却明显不同。
费米液体理论中的基本观点:1)准粒子,包括准电子和准空穴。
尽管费米子之间的相互作用可能很强,但是准粒子之间的相互作用很弱。
2)准粒子跟电子或空穴量子数相同。
如动量k,自旋1/2,以及电荷±1。
3)费米液态的状态可以用准粒子的集体来描述。
4)准粒子之间存在弱相互作用(加俐略平移不变性要求)费米液体可以用费米液体理论(弱相互作用准粒子)描述的费米子体系,我们通称为费米液体。
比如,低温下大多数金属中的电子以及未进入超流态的He-3液体。
费米液体与费米气体比较:费米液体的低能激发及动力学行为,可以用弱相互作用的准粒子来描述,而弱相互作用准粒子与费米气体有着十分类似的性质,比如费米气体和费米液体的比热在温度T<<Tf 都呈线性,而且低能激发形式()*Fp F Fpp pmεε-=-(p Fεε-分别是激发能与费米能级,*m为有效质量)相同,不同的是准粒子的质量此时用有效质量来描述,值得一提的是,有效质量正是对准粒子之间存在相互作用的一种反应。
以He-3费米子为例,虽然He-3原子之间存在强相互作用,但其行为可以很好的用准粒子来描述,低能激发形式与费米气体相同,动量空间的粒子数分布仍然可能看成阶跃函数。
关键字:费米液体,费米气体(无相互作用),低能激发。
Damping of IVGDR - Fermi-liquid or Fermi-gas
Focused on nuclear physics:
NUCOLEX99 20.03.-24.03.1999
1
Damping of IVGDR - Fermi-liquid or Fermi-gas ?
Klaus Morawetz,∗1 Uwe Fuhrmann,∗1
where n is the equilibrium distribution. Clearly two contributions have to be distinguished, the one from the quasiparticle energy and the one from occupation factors1) . First we concentrate on the Fermi gas model where we have only the contribution of the occupation factors and will later add the contribution of the quasiparticle energies for Fermi liquid model. We obtain after Fourier transform of the time − iΩδf1 = ¯ h [δ+ (∆ǫ + Ω) + δ− (∆ǫ − Ω)] 2 (4)
2
energy h ¯ /ǫf :
∞
2g ∂t f1 (t) = 2 h ¯ t−τ × cos
t
dτ
0
¯ ¯ ¯ ¯ ∆ǫ(τ )dτ /¯ hδ (∆p) f 1 f2 f3 f4 − f1 f2 f3 f4
英语文献翻译---溶液除湿
溶液除湿/再生器叉流热质交换模型刘晓华,江亿,曲凯阳摘要建立了叉流溶液除湿/再生器中模拟热质传递的理论模型。
模型以NTU为输入参数,且NTU可以使用实验数据关联。
在已知进口参数的情况下,模型能够预测除湿/再生器中的空气和溶液参数,同样可以预测空气与溶液的出口参数。
对模型计算的结果与实验结果进行了比较。
对于284组除湿实验数据,焓效率与湿效率的平均误差分别为7.9%与8.5%;对于82组再生实验数据,焓效率与湿效率的平均误差分别为5.8%与6.9%。
测量了除湿与再生过程溶液出口温度的分布,模型预测的溶液出口温度与实验结果很好的一致。
关键词:溶液除湿,叉流,热质传递,模型,实验1 引言近年来,由于处理建筑潜热负荷的优势,研究者对溶液除湿系统进行了大量的研究。
溶液除湿可以减小能量消耗,将能量消耗从电能转移到可再生能源和更便宜的燃料[1–4]。
另外,溶液除湿的另一个好处是可以从气流中去除污染物[4,5]。
除湿器和再生器是溶液除湿系统两个关键的部件。
除了方向相反发生在除湿器和再生器中的热质传递过程相同。
因为实际的除湿/再生器复杂,单纯的理论分析很难预测真实设备的性能。
许多研究者实验测试了除湿器/再生器的热质传递性能。
在实验过程中,进口和出口参数容易测量然而除湿器/再生器中的温度和浓度分布难以直接测量。
在研究热质交换设备的温度场和浓度场时,数值模拟有许多优势。
逆流和叉流的热质交换模型总结在表1中。
除了运行工况不同,除湿器和再生器模型相同。
如表1所示,模型可以分为简单模型和复杂模型。
在简单模型中,空气与溶液接触的表面滞留这一假设通常被接受。
这种模型已经被许多研究接受[4,6-12],例如Jain[13]等的绝热逆流除湿器,Khan[14]等内冷逆流和叉流再生器。
然而还没有叉流绝热除湿器使用简单模型。
在复杂模型中[15-20],首先通过求解连续性和动量方程得到除湿器中的速度场,然后通过求解能量守恒和质量守恒方程获得浓度场和温度场。
翻译
甲基咪唑对纤维素/离子液体溶液以及由此而来的可再生材料的影响摘要纤维素,尤其是人造纤维素,对制造日常材料越来越重要,例如,通过溶解和后续沉淀产生的人造可再生的纺织纤维等材料。
本文对助溶剂在离子液体促进纤维素溶解的影响进行了探讨。
对微晶纤维素和溶解有年轮硬木成纸浆都进行了研究。
三种不同助溶剂结合离子液体后,利用浊度测量和粘度对其进行了评估。
离子液体的前体N-甲基咪唑被证明是一种有前景的候选助溶剂,从而被选择用于进一步研究离子液体1-乙基-3-甲基咪唑醋酸。
结果表明,助溶剂的增加可使得溶解速率增加,粘度明显减小。
在室温下,通过空隙纺纱和传统湿纺,稳定的溶液剂随着时间的推移可以转变为具有良好的力学性能的再生纺织纤维。
引言由于其结构影响,纤维素不能溶解或只能部分溶于最常见的溶剂。
由于葡萄糖单元结构两亲性出现、氢键和疏水性相互作用都产生了,而且为了完全溶解聚合物[1,2],选择的溶剂要能够消弱这两种作用。
离子液体是熔点低于100摄氏度,而且有时甚至低于室温的有机盐。
成对的阴离子和阳离子有可能形成几乎无尽的离子液体库,他们被用在许多领域,如分离技术、电化学、催化,溶剂(3、4)。
在过去的十年中,离子液体作为普通的生物质溶剂,特别是纤维素溶剂已被广泛用于研究[5 -7],自2002年斯瓦特罗斯基发表了关于作纤维素在1丁基-3-甲基咪唑氯化物中的溶解的开创性著作。
这个相对较新的溶剂类在纤维素技术领域展示了重大而广泛的用途,包括以再生为目的的溶解,同类衍生以及包括木材组件分离的生物质处理。
这种能够溶解纤维素离子液体包含几类阳离子和大量的阴离子。
一些最常见的阳离子有咪唑鎓盐,吡啶,铵和磷衍生物[16]。
尽管以咪唑鎓盐为基本成分的离子液体在某些情况下已知能与纤维素形成共价键,他们仍在离子液体和纤维素学术研究中最常用而且对于生物质处理方面仍然高度令人关注。
有人建议,通过测量电荷参数可以找到适当的助溶剂,如已被报道的N-甲基咪唑(MIM)。
室温离子液体在电分析化学中的应用研究
1.1.3 固定在琼脂糖膜中蛋白质在亲水性 IL[bmim][BF4] 中的电化学行为
Fig. 1.1.9. CVs in [bmim][BF4] containing 6.10%, 6.10%, 5.21%, 5.88 % (v/v) of H2O for (a) agarose, (b) Mb–agarose, (c) Hb– agarose, and (d) Cat–agarose.
蛋白质在离子液体中的稳定性
Fig. 1.1.11. Thermal stability and prolonged immersion time Stability of HRP in [bmim][BF4] with 4.53% (v/v) water.
血红素蛋白质对H2O2的催化
Fig. 1.1.12. A. CVs of an HRP-AG/GC in [bmim][BF4] with 4.53% (v/v) water and different H2O2; B. Plots of ipc vs. concentration of H2O2.
相关参数的计算
Table 1.4 Electrocatalytic parameters and relationship between ip and H2O2 concentrations
Electrochemistry Communications 9 (2007) 1648–1654
1.1.5固定在碳包镍-壳聚糖膜中蛋白质在 IL[bmim][BF4]中的电化学
Fig 1.1.5. CVs of Hb-agarose film at 0.1 V s-1 in (a) [bmim][PF6], (b) [emim][BF4], and (c) [bmim][BF4]
益生菌对阿尔茨海默病作用的研究进展
益生菌对阿尔茨海默病作用的研究进展发布时间:2021-12-14T06:08:15.523Z 来源:《中国结合医学杂志》2021年12期作者:宋鑫萍1,2,李盛钰2,金清1[导读] 阿尔茨海默病已成为威胁全球老年人生命健康的主要疾病之一,患者数量逐年攀升,其护理的经济成本高,给全球经济造成重大挑战。
近年来研究显示,益生菌在适量使用时作为有益于宿主健康的微生物,在防治阿尔茨海默病方面具有积极影响,其作用机制可能通过调节肠道菌群,影响神经免疫系统,调控神经活性物质以及代谢产物,通过肠-脑轴影响该病发生和发展。
宋鑫萍1,2,李盛钰2,金清11.延边大学农学院,吉林延吉 1330022.吉林省农业科学院农产品加工研究所,吉林长春 130033摘要:阿尔茨海默病已成为威胁全球老年人生命健康的主要疾病之一,患者数量逐年攀升,其护理的经济成本高,给全球经济造成重大挑战。
近年来研究显示,益生菌在适量使用时作为有益于宿主健康的微生物,在防治阿尔茨海默病方面具有积极影响,其作用机制可能通过调节肠道菌群,影响神经免疫系统,调控神经活性物质以及代谢产物,通过肠-脑轴影响该病发生和发展。
本文综述了近几年来国内外益生菌对阿尔茨海默病的作用进展,以及其预防和治疗阿尔茨海默病的潜在作用机制。
关键词:益生菌;阿尔茨海默病;肠道菌群;机制Recent Progress in Research on Probiotics Effect on Alzheimer’s DiseaseSONG Xinping1,2,LI Shengyu2,JI Qing1*(1.College of Agricultural, Yanbian University, Yanji 133002,China)(2.Institute of Agro-food Technology, Jilin Academy of Agricultural Sciences, Chanchun 130033, China)Abstract:Alzheimer’s disease has become one of the major diseases threatening the life and health of the global elderly. The number of patients is increasing year by year, and the economic cost of nursing is high, which poses a major challenge to the global economy. In recent years, studies have shown that probiotics, as microorganisms beneficial to the health of the host, have a positive impact on the prevention and treatment of Alzheimer’s disease. Its mechanism may be through regulating intestinal flora, affecting the nervous immune system, regulating the neuroactive substances and metabolites, and affecting the occurrence and development of the disease through thegut- brain axis. This paper reviews the progress of probiotics on Alzheimer’s disease at home and abroad in recent years, as well as its potential mechanism of prevention and treatment.Key words:probiotics; Alzheimer’s disease; gut microbiota; mechanism阿尔茨海默病(Alzheimer’s disease, AD),系中枢神经系统退行性疾病,属于老年期痴呆常见类型,临床特征主要包括:记忆力减退、认知功能障碍、行为改变、焦虑和抑郁等。
室温离子液体AmimCl中纤维素的降解与均相衍生化
室温离子液体Am imCl中纤维素的降解与均相衍生化刘传富 李维英 孙润仓 叶 君(华南理工大学制浆造纸工程国家重点实验室,广州,510640)摘 要:探讨了纤维素在离子液体中的溶解,发现在室温离子液体Am i m Cl中纤维素发生一定程度的降解,纤维素聚合度由1276.6降低至933.8。
通过纤维素均相衍生化反应发现,无需添加任何催化剂,纤维素在室温离子液体Am i m Cl中即可与P A发生均相衍生化反应,纤维素的取代度随反应时间、酸酐用量、反应温度的提高而提高。
FT-I R和固体CP/MAS13C-NMR分析表明,反应后的纤维素衍生物中富含羧基。
研究还发现,纤维素在C6、C2和C3位置的游离羟基均参与了化学反应。
关键词:离子液体;纤维素;绿色溶剂;均相衍生化中图分类号:TS743 文献标识码:A 文章编号:1671-4571(2007)0620037204 纤维素是自然界中最丰富的可再生资源,在植物界中纤维素的总量约达2.6×1012t。
据估计,全世界每年通过光合作用新生成的纤维素约有1.000×1011t[1]。
目前,纤维素材料已经在纤维、造纸、薄膜、聚合物、涂料等工业领域[10]得到广泛应用。
然而,其应用潜力还没有完全被开发出来,每年仅有2.0×106t纤维素用于再生纤维素纤维的生产,占纤维素年生成量的0.002%[3,4]。
这主要是由于以下四个方面的原因造成的:一、二十世纪40年代以来人们的注意力都集中在石油产品上;二、缺少环境友好的纤维素分离方法;三、纤维素的定向转化存在困难;四、缺乏有效的纤维素溶剂[5]。
近年来,随着石油、煤炭等不可再生的化石资源总量的日趋减少,纤维素资源的重要性日益显著。
特别是80年代以来,各国对环境污染问题日益关注和重视,迫使人们把注意力重新集中到纤维素这一具有生物可降解性、环境协调性的可再生资源上来。
许多国家特别是发达国家已将纤维素等可再生资源的转化利用列为经济和社会发展的重大战略。
黄色短杆菌中L-异亮氨酸同位素丰度及分布的分析方法研究
第43 卷第 3 期2024 年3 月Vol.43 No.3496~500分析测试学报FENXI CESHI XUEBAO(Journal of Instrumental Analysis)黄色短杆菌中L-异亮氨酸同位素丰度及分布的分析方法研究赵雅梦1,2,范若宁1,2,雷雯1,2*(1.上海化工研究院有限公司,上海 200062;2.上海市稳定同位素检测及应用研发专业技术服务平台,上海 200062)摘要:随着代谢组学、蛋白质组学等生命科学领域的迅猛发展,稳定同位素标记试剂,尤其是标记氨基酸,因无放射性、与非标记化合物理化性质一致等优势得到广泛应用。
该文建立了一种稳健、快速的氨基酸同位素丰度分析方法。
方法采用Hypersil Gold Vanquish(100 mm × 2.1 mm,1.9 μm)色谱柱,以水和含0.1%甲酸的甲醇为流动相,正离子模式下进行液相色谱-高分辨质谱联用(LC-HRMS)分析;测得细菌发酵液中L-异亮氨酸-15N的同位素丰度为98.58%,相对标准偏差为0.03%,可应用于不同稳定同位素(15N或13C)示踪的黄色短杆菌中L-异亮氨酸同位素丰度及分布的准确测定。
该方法具有简便、灵敏、稳健等优点,有望在合成生物学、同位素示踪代谢流等研究中发挥重要作用。
关键词:同位素标记氨基酸;液相色谱-高分辨质谱(LC-HRMS);黄色短杆菌;同位素分布及丰度中图分类号:O657.72;O629.7文献标识码:A 文章编号:1004-4957(2024)03-0496-05Analysis of Isotope Abundance and Distribution for L-Isoleucinein Brebvibacterium flavumZHAO Ya-meng1,2,FAN Ruo-ning1,2,LEI Wen1,2*(1.Shanghai Research Institution of Chemical Industry Co. Ltd.,Shanghai 200062,China;2.Shanghai Professional Technology Service Platform on Detection and Application Development for Stable Isotope,Shanghai 200062,China)Abstract:In the rapidly advancing life science fields such as metabolomics and proteomics,stable isotope labeling reagents that are non-radioactive and have similar physiochemical properties with un⁃labeled compounds have been widely utilized. Biological fermentation is one of the major synthesis ap⁃proaches for labeled amino acids. In this study,we have established an accurate,robust,and rapid method to determine the isotope abundance of the amino acids in the fermentation broth to aid in early assessment of batch quality and optimization of fermentation conditions and amino acid yield. A Hy⁃persil Gold Vanquish column(100 mm × 2.1 mm,1.9 μm)with water and methanol containing 0.1%formic acid as mobile phase and a liquid chromatography-high resolution mass spectrometry(LC-HRMS) system in positive ion mode were used for the study. The isotopic abundance of L-iso⁃leucine-15N samples was determined to be 98.58%,closely matching the indicated value(>98%),with a relative standard deviation of 0.03%,demonstrating excellent accuracy and precision for the method. Then the method was successfully applied to determine the isotopic abundance and distribu⁃tion of L-isoleucine in Brevibacterium flavum labeled with 15N or 13C. The proposed method is simple to perform,convenient,highly sensitive,and robust,holding wide application potentials in syn⁃thetic biology and research in stable isotope traced metabolic pathways.Key words:stable isotope labeled amino acid;liquid chromatography-high resolution mass spec⁃trometry(LC-HRMS);Brebvibacterium flavum;isotope distribution and abundance利用同位素标记技术将化合物中普通原子替换为同位素核素所合成的稳定同位素标记化合物,结合质谱技术,已在蛋白质组学、代谢组学、生物靶标发现、临床诊断等生命科学研究中发挥重要作用[1-4]。
原子核集体激发的费米液体模型研究
The isovector giant dipole resonance of the nucleus is a shift of the center of mass, which corresponds to the creation of the L=1 collective excitation of protons or neutrons.
i u Hu l , m, q , t t
with the Hamiltonian
H l ,l q W T KW q alm l 1,l al 1,m l 1,l
2 2 * * kF kF v f l , l v f l , l F F 3 F 3 F (2 ) (2 ) 1 2 1 2
Giant resonances of finite nuclei
The proton and neutron densities can be written approximately
Giant monopole resonances of finite nuclei
L=0 M*/M E0(p) E0(n) E0(p) ES +E0(n) 23.33 14.17 +-0.28 24.26 15.39 +-0.28 24.26 16.07 +-0.12 30.7 31.16 17.89 +-0.20 EV
with
and
Potential between nucleons in the linear Walecka model
Fermi liquid function
Fermi liquid functionFra bibliotekwith
大环多胺
New1H-Pyrazole-Containing Polyamine Receptors Able ToComplex L-Glutamate in Water at Physiological pH ValuesCarlos Miranda,†Francisco Escartı´,‡Laurent Lamarque,†Marı´a J.R.Yunta,§Pilar Navarro,*,†Enrique Garcı´a-Espan˜a,*,‡and M.Luisa Jimeno†Contribution from the Instituto de Quı´mica Me´dica,Centro de Quı´mica Orga´nica Manuel Lora Tamayo,CSIC,C/Juan de la Cier V a3,28006Madrid,Spain,Departamento de Quı´mica Inorga´nica,Facultad de Quı´mica,Uni V ersidad de Valencia,c/Doctor Moliner50, 46100Burjassot(Valencia),Spain,and Departamento de Quı´mica Orga´nica,Facultad deQuı´mica,Uni V ersidad Complutense de Madrid,A V plutense s/n,28040Madrid,SpainReceived April16,2003;E-mail:enrique.garcia-es@uv.esAbstract:The interaction of the pyrazole-containing macrocyclic receptors3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene1[L1],13,26-dibenzyl-3,6,9,12,13,16,-19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene2[L2],3,9,12,13,16,22,-25,26-octaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene3[L3],6,19-dibenzyl-3,6,9,12,13,-16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene4[L4],6,19-diphenethyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene5[L5],and 6,19-dioctyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetra-ene6[L6]with L-glutamate in aqueous solution has been studied by potentiometric techniques.The synthesis of receptors3-6[L3-L6]is described for the first time.The potentiometric results show that4[L4]containing benzyl groups in the central nitrogens of the polyamine side chains is the receptor displaying the larger interaction at pH7.4(K eff)2.04×104).The presence of phenethyl5[L5]or octyl groups6[L6]instead of benzyl groups4[L4]in the central nitrogens of the chains produces a drastic decrease in the stability[K eff )3.51×102(5),K eff)3.64×102(6)].The studies show the relevance of the central polyaminic nitrogen in the interaction with glutamate.1[L1]and2[L2]with secondary nitrogens in this position present significantly larger interactions than3[L3],which lacks an amino group in the center of the chains.The NMR and modeling studies suggest the important contribution of hydrogen bonding andπ-cation interaction to adduct formation.IntroductionThe search for the L-glutamate receptor field has been andcontinues to be in a state of almost explosive development.1 L-Glutamate(Glu)is thought to be the predominant excitatory transmitter in the central nervous system(CNS)acting at a rangeof excitatory amino acid receptors.It is well-known that it playsa vital role mediating a great part of the synaptic transmission.2However,there is an increasing amount of experimentalevidence that metabolic defects and glutamatergic abnormalitiescan exacerbate or induce glutamate-mediated excitotoxic damageand consequently neurological disorders.3,4Overactivation ofionotropic(NMDA,AMPA,and Kainate)receptors(iGluRs)by Glu yields an excessive Ca2+influx that produces irreversible loss of neurons of specific areas of the brain.5There is much evidence that these processes induce,at least in part,neuro-degenerative illnesses such as Parkinson,Alzheimer,Huntington, AIDS,dementia,and amyotrophic lateral sclerosis(ALS).6In particular,ALS is one of the neurodegenerative disorders for which there is more evidence that excitotoxicity due to an increase in Glu concentration may contribute to the pathology of the disease.7Memantine,a drug able to antagonize the pathological effects of sustained,but relatively small,increases in extracellular glutamate concentration,has been recently received for the treatment of Alzheimer disease.8However,there is not an effective treatment for ALS.Therefore,the preparation of adequately functionalized synthetic receptors for L-glutamate seems to be an important target in finding new routes for controlling abnormal excitatory processes.However,effective recognition in water of aminocarboxylic acids is not an easy task due to its zwitterionic character at physiological pH values and to the strong competition that it finds in its own solvent.9†Centro de Quı´mica Orga´nica Manuel Lora Tamayo.‡Universidad de Valencia.§Universidad Complutense de Madrid.(1)Jane,D.E.In Medicinal Chemistry into the Millenium;Campbell,M.M.,Blagbrough,I.S.,Eds.;Royal Society of Chemistry:Cambridge,2001;pp67-84.(2)(a)Standaert,D.G.;Young,A.B.In The Pharmacological Basis ofTherapeutics;Hardman,J.G.,Goodman Gilman,A.,Limbird,L.E.,Eds.;McGraw-Hill:New York,1996;Chapter22,p503.(b)Fletcher,E.J.;Loge,D.In An Introduction to Neurotransmission in Health and Disease;Riederer,P.,Kopp,N.,Pearson,J.,Eds.;Oxford University Press:New York,1990;Chapter7,p79.(3)Michaelis,E.K.Prog.Neurobiol.1998,54,369-415.(4)Olney,J.W.Science1969,164,719-721.(5)Green,J.G.;Greenamyre,J.T.Prog.Neurobiol.1996,48,613-63.(6)Bra¨un-Osborne,H.;Egebjerg,J.;Nielsen,E.O.;Madsen,U.;Krogsgaard-Larsen,P.J.Med.Chem.2000,43,2609-2645and references therein.(7)(a)Shaw,P.J.;Ince,P.G.J.Neurol.1997,244(Suppl2),S3-S14.(b)Plaitakis,A.;Fesdjian,C.O.;Shashidharan,S Drugs1996,5,437-456.(8)Frantz,A.;Smith,A.Nat.Re V.Drug Dico V ery2003,2,9.Published on Web12/30/200310.1021/ja035671m CCC:$27.50©2004American Chemical Society J.AM.CHEM.SOC.2004,126,823-8339823There are many types of receptors able to interact with carboxylic acids and amino acids in organic solvents,10-13yielding selective complexation in some instances.However,the number of reported receptors of glutamate in aqueous solution is very scarce.In this sense,one of the few reports concerns an optical sensor based on a Zn(II)complex of a 2,2′:6′,2′′-terpyridine derivative in which L -aspartate and L -glutamate were efficiently bound as axial ligands (K s )104-105M -1)in 50/50water/methanol mixtures.14Among the receptors employed for carboxylic acid recogni-tion,the polyamine macrocycles I -IV in Chart 1are of particular relevance to this work.In a seminal paper,Lehn et al.15showed that saturated polyamines I and II could exert chain-length discrimination between different R ,ω-dicarboxylic acids as a function of the number of methylene groups between the two triamine units of the receptor.Such compounds were also able to interact with a glutamic acid derivative which has the ammonium group protected with an acyl moiety.15,16Compounds III and IV reported by Gotor and Lehn interact in their protonated forms in aqueous solution with protected N -acetyl-L -glutamate and N -acetyl-D -glutamate,showing a higher stability for the interaction with the D -isomer.17In both reports,the interaction with protected N -acetyl-L -glutamate at physiological pH yields constants of ca.3logarithmic units.Recently,we have shown that 1H -pyrazole-containing mac-rocycles present desirable properties for the binding of dopam-ine.18These polyaza macrocycles,apart from having a highpositive charge at neutral pH values,can form hydrogen bonds not only through the ammonium or amine groups but also through the pyrazole nitrogens that can behave as hydrogen bond donors or acceptors.In fact,Elguero et al.19have recently shown the ability of the pyrazole rings to form hydrogen bonds with carboxylic and carboxylate functions.These features can be used to recognize the functionalities of glutamic acid,the carboxylic and/or carboxylate functions and the ammonium group.Apart from this,the introduction of aromatic donor groups appropriately arranged within the macrocyclic framework or appended to it through arms of adequate length may contribute to the recognition event through π-cation interactions with the ammonium group of L -glutamate.π-Cation interactions are a key feature in many enzymatic centers,a classical example being acetylcholine esterase.20The role of such an interaction in abiotic systems was very well illustrated several years ago in a seminal work carried out by Dougherty and Stauffer.21Since then,many other examples have been reported both in biotic and in abiotic systems.22Taking into account all of these considerations,here we report on the ability of receptors 1[L 1]-6[L 6](Chart 2)to interact with L -glutamic acid.These receptors display structures which differ from one another in only one feature,which helps to obtain clear-cut relations between structure and interaction(9)Rebek,J.,Jr.;Askew,B.;Nemeth,D.;Parris,K.J.Am.Chem.Soc.1987,109,2432-2434.(10)Seel,C.;de Mendoza,J.In Comprehensi V e Supramolecular Chemistry ;Vogtle,F.,Ed.;Elsevier Science:New York,1996;Vol.2,p 519.(11)(a)Sessler,J.L.;Sanson,P.I.;Andrievesky,A.;Kral,V.In SupramolecularChemistry of Anions ;Bianchi,A.,Bowman-James,K.,Garcı´a-Espan ˜a,E.,Eds.;John Wiley &Sons:New York,1997;Chapter 10,pp 369-375.(b)Sessler,J.L.;Andrievsky,A.;Kra ´l,V.;Lynch,V.J.Am.Chem.Soc.1997,119,9385-9392.(12)Fitzmaurice,R.J.;Kyne,G.M.;Douheret,D.;Kilburn,J.D.J.Chem.Soc.,Perkin Trans.12002,7,841-864and references therein.(13)Rossi,S.;Kyne,G.M.;Turner,D.L.;Wells,N.J.;Kilburn,J.D.Angew.Chem.,Int.Ed.2002,41,4233-4236.(14)Aı¨t-Haddou,H.;Wiskur,S.L.;Lynch,V.M.;Anslyn,E.V.J.Am.Chem.Soc.2001,123,11296-11297.(15)Hosseini,M.W.;Lehn,J.-M.J.Am.Chem.Soc.1982,104,3525-3527.(16)(a)Hosseini,M.W.;Lehn,J.-M.Hel V .Chim.Acta 1986,69,587-603.(b)Heyer,D.;Lehn,J.-M.Tetrahedron Lett.1986,27,5869-5872.(17)(a)Alfonso,I.;Dietrich,B.;Rebolledo,F.;Gotor,V.;Lehn,J.-M.Hel V .Chim.Acta 2001,84,280-295.(b)Alfonso,I.;Rebolledo,F.;Gotor,V.Chem.-Eur.J.2000,6,3331-3338.(18)Lamarque,L.;Navarro,P.;Miranda,C.;Ara ´n,V.J.;Ochoa,C.;Escartı´,F.;Garcı´a-Espan ˜a,E.;Latorre,J.;Luis,S.V.;Miravet,J.F.J.Am.Chem.Soc .2001,123,10560-10570.(19)Foces-Foces,C.;Echevarria,A.;Jagerovic,N.;Alkorta,I.;Elguero,J.;Langer,U.;Klein,O.;Minguet-Bonvehı´,H.-H.J.Am.Chem.Soc.2001,123,7898-7906.(20)Sussman,J.L.;Harel,M.;Frolow,F.;Oefner,C.;Goldman,A.;Toker,L.;Silman,I.Science 1991,253,872-879.(21)Dougherty,D.A.;Stauffer,D.A.Science 1990,250,1558-1560.(22)(a)Sutcliffe,M.J.;Smeeton,A.H.;Wo,Z.G.;Oswald,R.E.FaradayDiscuss.1998,111,259-272.(b)Kearney,P.C.;Mizoue,L.S.;Kumpf,R.A.;Forman,J.E.;McCurdy,A.;Dougherty,D.A.J.Am.Chem.Soc.1993,115,9907-9919.(c)Bra ¨uner-Osborne,H.;Egebjerg,J.;Nielsen,E.;Madsen,U.;Krogsgaard-Larsen,P.J.Med.Chem.2000,43,2609-2645.(d)Zacharias,N.;Dougherty,D.A.Trends Pharmacol.Sci.2002,23,281-287.(e)Hu,J.;Barbour,L.J.;Gokel,G.W.J.Am.Chem.Soc.2002,124,10940-10941.Chart 1.Some Receptors Employed for Dicarboxylic Acid and N -AcetylglutamateRecognitionChart 2.New 1H -Pyrazole-Containing Polyamine Receptors Able To Complex L -Glutamate inWaterA R T I C L E SMiranda et al.824J.AM.CHEM.SOC.9VOL.126,NO.3,2004strengths.1[L1]and2[L2]differ in the N-benzylation of the pyrazole moiety,and1[L1]and3[L3]differ in the presence in the center of the polyamine side chains of an amino group or of a methylene group.The receptors4[L4]and5[L5]present the central nitrogens of the chain N-functionalized with benzyl or phenethyl groups,and6[L6]has large hydrophobic octyl groups.Results and DiscussionSynthesis of3-6.Macrocycles3-6have been obtained following the procedure previously reported for the preparation of1and2.23The method includes a first dipodal(2+2) condensation of the1H-pyrazol-3,5-dicarbaldehyde7with the corresponding R,ω-diamine,followed by hydrogenation of the resulting Schiff base imine bonds.In the case of receptor3,the Schiff base formed by condensation with1,5-pentanediamine is a stable solid(8,mp208-210°C)which precipitated in68% yield from the reaction mixture.Further reduction with NaBH4 in absolute ethanol gave the expected tetraazamacrocycle3, which after crystallization from toluene was isolated as a pure compound(mp184-186°C).In the cases of receptors4-6, the precursor R,ω-diamines(11a-11c)(Scheme1B)were obtained,by using a procedure previously described for11a.24 This procedure is based on the previous protection of the primary amino groups of1,5-diamino-3-azapentane by treatment with phthalic anhydride,followed by alkylation of the secondary amino group of1,5-diphthalimido-3-azapentane9with benzyl, phenethyl,or octyl bromide.Finally,the phthalimido groups of the N-alkyl substituted intermediates10a-10c were removed by treatment with hydrazine to afford the desired amines11a-11c,which were obtained in moderate yield(54-63%).In contrast with the behavior previously observed in the synthesis of3,in the(2+2)dipodal condensations of7with 3-benzyl-,3-phenethyl-,and3-octyl-substituted3-aza-1,5-pentanediamine11a,11b,and11c,respectively,there was not precipitation of the expected Schiff bases(Scheme1A). Consequently,the reaction mixtures were directly reduced in situ with NaBH4to obtain the desired hexaamines4-6,which after being carefully purified by chromatography afforded purecolorless oils in51%,63%,and31%yield,respectively.The structures of all of these new cyclic polyamines have been established from the analytical and spectroscopic data(MS(ES+), 1H and13C NMR)of both the free ligands3-6and their corresponding hydrochloride salts[3‚4HCl,4‚6HCl,5‚6HCl, and6‚6HCl],which were obtained as stable solids following the same procedure previously reported18for1‚6HCl and2‚6HCl.As usually occurs for3,5-disubstituted1H-pyrazole deriva-tives,either the free ligands3-6or their hydrochlorides show very simple1H and13C NMR spectra,in which signals indicate that,because of the prototropic equilibrium of the pyrazole ring, all of these compounds present average4-fold symmetry on the NMR scale.The quaternary C3and C5carbons appear together,and the pairs of methylene carbons C6,C7,and C8are magnetically equivalent(see Experimental Section).In the13C NMR spectra registered in CDCl3solution, significant differences can be observed between ligand3,without an amino group in the center of the side chain,and the N-substituted ligands4-6.In3,the C3,5signal appears as a broad singlet.However,in4-6,it almost disappears within the baseline of the spectra,and the methylene carbon atoms C6and C8experience a significant broadening.Additionally,a remark-able line-broadening is also observed in the C1′carbon signals belonging to the phenethyl and octyl groups of L5and L6, respectively.All of these data suggest that as the N-substituents located in the middle of the side chains of4-6are larger,the dynamic exchange rate of the pyrazole prototropic equilibrium is gradually lower,probably due to a relation between proto-tropic and conformational equilibria.Acid-Base Behavior.To follow the complexation of L-glutamate(hereafter abbreviated as Glu2-)and its protonated forms(HGlu-,H2Glu,and H3Glu+)by the receptors L1-L6, the acid-base behavior of L-glutamate has to be revisited under the experimental conditions of this work,298K and0.15mol dm-3.The protonation constants obtained,included in the first column of Table1,agree with the literature25and show that the zwitterionic HGlu-species is the only species present in aqueous solution at physiological pH values(Scheme2and Figure S1of Supporting Information).Therefore,receptors for(23)Ara´n,V.J.;Kumar,M.;Molina,J.;Lamarque,L.;Navarro,P.;Garcı´a-Espan˜a,E.;Ramı´rez,J.A.;Luis,S.V.;Escuder,.Chem.1999, 64,6137-6146.(24)(a)Yuen Ng,C.;Motekaitis,R.J.;Martell,A.E.Inorg.Chem.1979,18,2982-2986.(b)Anelli,P.L.;Lunazzi,L.;Montanari,F.;Quici,.Chem.1984,49,4197-4203.Scheme1.Synthesis of the Pyrazole-Containing MacrocyclicReceptorsNew1H-Pyrazole-Containing Polyamine Receptors A R T I C L E SJ.AM.CHEM.SOC.9VOL.126,NO.3,2004825glutamate recognition able to address both the negative charges of the carboxylate groups and the positive charge of ammonium are highly relevant.The protonation constants of L 3-L 6are included in Table 1,together with those we have previously reported for receptors L 1and L 2.23A comparison of the constants of L 4-L 6with those of the nonfunctionalized receptor L 1shows a reduced basicity of the receptors L 4-L 6with tertiary nitrogens at the middle of the polyamine bridges.Such a reduction in basicity prevented the potentiometric detection of the last protonation for these ligands in aqueous solution.A similar reduction in basicity was previously reported for the macrocycle with the N -benzylated pyrazole spacers (L 2).23These diminished basicities are related to the lower probability of the tertiary nitrogens for stabilizing the positive charges through hydrogen bond formation either with adjacent nonprotonated amino groups of the molecule or with water molecules.Also,the increase in the hydrophobicity of these molecules will contribute to their lower basicity.The stepwise basicity constants are relatively high for the first four protonation steps,which is attributable to the fact that these protons can bind to the nitrogen atoms adjacent to the pyrazole groups leaving the central nitrogen free,the electrostatic repulsions between them being therefore of little significance.The remaining protonation steps will occur in the central nitrogen atom,which will produce an important increase in the electrostatic repulsion in the molecule and therefore a reduction in basicity.As stated above,the tertiary nitrogen atoms present in L 4-L 6will also contribute to this diminished basicity.To analyze the interaction with glutamic acid,it is important to know the protonation degree of the ligands at physiological pH values.In Table 2,we have calculated the percentages ofthe different protonated species existing in solution at pH 7.4for receptors L 1-L 6.As can be seen,except for the receptor with the pentamethylenic chains L 3in which the tetraprotonated species prevails,all of the other systems show that the di-and triprotonated species prevail,although to different extents.Interaction with Glutamate.The stepwise constants for the interaction of the receptors L 1-L 6with glutamate are shown in Table 3,and selected distribution diagrams are plotted in Figure 1A -C.All of the studied receptors interact with glutamate forming adduct species with protonation degrees (j )which vary between 8and 0depending on the system (see Table 3).The stepwise constants have been derived from the overall association constants (L +Glu 2-+j H +)H j LGlu (j -2)+,log j )provided by the fitting of the pH-metric titration curves.This takes into account the basicities of the receptors and glutamate (vide supra)and the pH range in which a given species prevails in solution.In this respect,except below pH ca.4and above pH 9,HGlu -can be chosen as the protonated form of glutamate involved in the formation of the different adducts.Below pH 4,the participation of H 2Glu in the equilibria has also to be considered (entries 9and 10in Table 3).For instance,the formation of the H 6LGlu 4+species can proceed through the equilibria HGlu -+H 5L 5+)H 6LGlu 4+(entry 8,Table 3),and H 2Glu +H 4L 4+)H 6LGlu 4(entry 9Table 3),with percentages of participation that depend on pH.One of the effects of the interaction is to render somewhat more basic the receptor,and somewhat more acidic glutamic acid,facilitating the attraction between op-positely charged partners.A first inspection of Table 3and of the diagrams A,B,and C in Figure 1shows that the interaction strengths differ markedly from one system to another depending on the structural features of the receptors involved.L 4is the receptor that presents the highest capacity for interacting with glutamate throughout all of the pH range explored.It must also be remarked that there are not clear-cut trends in the values of the stepwise constants as a function of the protonation degree of the receptors.This suggests that charge -charge attractions do not play the most(25)(a)Martell,E.;Smith,R.M.Critical Stability Constants ;Plenum:NewYork,1975.(b)Motekaitis,R.J.NIST Critically Selected Stability Constants of Metal Complexes Database ;NIST Standard Reference Database,version 4,1997.Table 1.Protonation Constants of Glutamic Acid and Receptors L 1-L 6Determined in NaCl 0.15mol dm -3at 298.1KreactionGluL 1aL 2aL 3bL 4L 5L 6L +H )L H c 9.574(2)d 9.74(2)8.90(3)9.56(1)9.25(3)9.49(4)9.34(5)L H +H )L H 2 4.165(3)8.86(2)8.27(2)8.939(7)8.38(3)8.11(5)8.13(5)L H 2+H )L H 3 2.18(2)7.96(2) 6.62(3)8.02(1) 6.89(5)7.17(6)7.46(7)L H 3+H )L H 4 6.83(2) 5.85(4)7.63(1) 6.32(5) 6.35(6) 5.97(8)L H 4+H )L H 5 4.57(3) 3.37(4) 2.72(8) 2.84(9) 3.23(9)L H 5+H )L H 6 3.18(3) 2.27(6)∑log K H n L41.135.334.233.634.034.1aTaken from ref 23.b These data were previously cited in a short communication (ref 26).c Charges omitted for clarity.d Values in parentheses are the standard deviations in the last significant figure.Scheme 2.L -Glutamate Acid -BaseBehaviorTable 2.Percentages of the Different Protonated Species at pH 7.4H 1L aH 2LH 3LH 4LL 11186417L 21077130L 3083458L 4083458L 51154323L 6842482aCharges omitted for clarity.A R T I C L E SMiranda et al.826J.AM.CHEM.SOC.9VOL.126,NO.3,2004outstanding role and that other forces contribute very importantly to these processes.26However,in systems such as these,which present overlapping equilibria,it is convenient to use conditional constants because they provide a clearer picture of the selectivity trends.27These constants are defined as the quotient between the overall amounts of complexed species and those of free receptor and substrate at a given pH[eq1].In Figure2are presented the logarithms of the effective constants versus pH for all of the studied systems.Receptors L1and L2with a nonfunctionalized secondary amino group in the side chains display opposite trend from all other receptors. While the stability of the L1and L2adducts tends to increase with pH,the other ligands show a decreasing interaction. Additionally,L1and L2present a close interaction over the entire pH range under study.The tetraaminic macrocycle L3is a better(26)Escartı´,F.;Miranda,C.;Lamarque,L.;Latorre,J.;Garcı´a-Espan˜a,E.;Kumar,M.;Ara´n,V.J.;Navarro,mun.2002,9,936-937.(27)(a)Bianchi,A.;Garcı´a-Espan˜a,c.1999,12,1725-1732.(b)Aguilar,J.A.;Celda,B.;Garcı´a-Espan˜a,E.;Luis,S.V.;Martı´nez,M.;Ramı´rez,J.A.;Soriano,C.;Tejero,B.J.Chem.Soc.,Perkin Trans.22000, 7,1323-1328.Table3.Stability Constants for the Interaction of L1-L6with the Different Protonated Forms of Glutamate(Glu) entry reaction a L1L2L3L4L5L6 1Glu+L)Glu L 3.30(2)b 4.11(1)2HGlu+L)HGlu L 3.65(2) 4.11(1) 3.68(2) 3.38(4) 3Glu+H L)HGlu L 3.89(2) 4.48(1) 3.96(2) 3.57(4) 4HGlu+H L)H2Glu L 3.49(2) 3.89(1) 2.37(4) 3.71(2)5HGlu+H2L)H3Glu L 3.44(2) 3.73(1) 2.34(3) 4.14(2) 2.46(4) 2.61(7) 6HGlu+H3L)H4Glu L 3.33(2) 3.56(2) 2.66(3) 4.65(2) 2.74(3) 2.55(7) 7HGlu+H4L)H5Glu L 3.02(2) 3.26(2) 2.58(3) 4.77(2) 2.87(3) 2.91(5) 8HGlu+H5L)H6Glu L 3.11(3) 3.54(2) 6.76(3) 4.96(3) 4.47(3) 9H2Glu+H4L)H6Glu L 2.54(3) 3.05(2) 3.88(2) 5.35(3) 3.66(4) 3.56(3) 10H2Glu+H5L)H7Glu L 2.61(6) 2.73(4) 5.51(3) 3.57(4) 3.22(8) 11H3Glu+H4L)H7Glu L 4.82(2) 4.12(9)a Charges omitted for clarity.b Values in parentheses are standard deviations in the last significantfigure.Figure1.Distribution diagrams for the systems(A)L1-glutamic acid, (B)L4-glutamic acid,and(C)L5-glutamicacid.Figure2.Representation of the variation of K cond(M-1)for the interaction of glutamic acid with(A)L1and L3,(B)L2,L4,L5,and L6.Initial concentrations of glutamate and receptors are10-3mol dm-3.Kcond)∑[(H i L)‚(H j Glu)]/{∑[H i L]∑[H j Glu]}(1)New1H-Pyrazole-Containing Polyamine Receptors A R T I C L E SJ.AM.CHEM.SOC.9VOL.126,NO.3,2004827receptor at acidic pH,but its interaction markedly decreases on raising the pH.These results strongly suggest the implication of the central nitrogens of the lateral polyamine chains in the stabilization of the adducts.Among the N-functionalized receptors,L4presents the largest interaction with glutamate.Interestingly enough,L5,which differs from L4only in having a phenethyl group instead of a benzyl one,presents much lower stability of its adducts.Since the basicity and thereby the protonation states that L4and L5 present with pH are very close,the reason for the larger stability of the L4adducts could reside on a better spatial disposition for formingπ-cation interactions with the ammonium group of the amino acid.In addition,as already pointed out,L4presents the highest affinity for glutamic acid in a wide pH range,being overcome only by L1and L2at pH values over9.This observation again supports the contribution ofπ-cation inter-actions in the system L4-glutamic because at these pH values the ammonium functionality will start to deprotonate(see Scheme2and Figure1B).Table4gathers the percentages of the species existing in equilibria at pH7.4together with the values of the conditional constant at this pH.In correspondence with Figure1A,1C and Figure S2(Supporting Information),it can be seen that for L1, L2,L5,and L6the prevailing species are[H2L‚HGlu]+and[H3L‚HGlu]2+(protonation degrees3and4,respectively),while for L3the main species are[H3L‚HGlu]+and[H4L‚HGlu]2+ (protonation degrees4and5,respectively).The most effective receptor at this pH would be L4which joins hydrogen bonding, charge-charge,andπ-cation contributions for the stabilization of the adducts.To check the selectivity of this receptor,we have also studied its interaction with L-aspartate,which is a competitor of L-glutamate in the biologic receptors.The conditional constant at pH7.4has a value of3.1logarithmic units for the system Asp-L4.Therefore,the selectivity of L4 for glutamate over aspartate(K cond(L4-glu)/K cond(L4-asp))will be of ca.15.It is interesting to remark that the affinity of L4 for zwiterionic L-glutamate at pH7.4is even larger than that displayed by receptors III and IV(Chart1)with the protected dianion N-acetyl-L-glutamate lacking the zwitterionic charac-teristics.Applying eq1and the stability constants reported in ref17,conditional constants at pH7.4of 3.24and 2.96 logarithmic units can be derived for the systems III-L-Glu and IV-L-Glu,respectively.Molecular Modeling Studies.Molecular mechanics-based methods involving docking studies have been used to study the binding orientations and affinities for the complexation of glutamate by L1-L6receptors.The quality of a computer simulation depends on two factors:accuracy of the force field that describes intra-and intermolecular interactions,and an adequate sampling of the conformational and configuration space of the system.28The additive AMBER force field is appropriate for describing the complexation processes of our compounds,as it is one of the best methods29in reproducing H-bonding and stacking stabiliza-tion energies.The experimental data show that at pH7.4,L1-L6exist in different protonation states.So,a theoretical study of the protonation of these ligands was done,including all of the species shown in5%or more abundance in the potentiometric measurements(Table4).In each case,the more favored positions of protons were calculated for mono-,di-,tri-,and tetraprotonated species.Molecular dynamics studies were performed to find the minimum energy conformations with simulated solvent effects.Molecular modeling studies were carried out using the AMBER30method implemented in the Hyperchem6.0pack-age,31modified by the inclusion of appropriate parameters. Where available,the parameters came from analogous ones used in the literature.32All others were developed following Koll-man33and Hopfinger34procedures.The equilibrium bond length and angle values came from experimental values of reasonable reference compounds.All of the compounds were constructed using standard geometry and standard bond lengths.To develop suitable parameters for NH‚‚‚N hydrogen bonding,ab initio calculations at the STO-3G level35were used to calculate atomic charges compatible with the AMBER force field charges,as they gave excellent results,and,at the same time,this method allows the study of aryl-amine interactions.In all cases,full geometry optimizations with the Polak-Ribiere algorithm were carried out,with no restraints.Ions are separated far away and well solvated in water due to the fact that water has a high dielectric constant and hydrogen bond network.Consequently,there is no need to use counteri-ons36in the modelization studies.In the absence of explicit solvent molecules,a distance-dependent dielectric factor quali-tatively simulates the presence of water,as it takes into account the fact that the intermolecular electrostatic interactions should vanish more rapidly with distance than in the gas phase.The same results can be obtained using a constant dielectric factor greater than1.We have chosen to use a distance-dependent dielectric constant( )4R ij)as this was the method used by Weiner et al.37to develop the AMBER force field.Table8 shows the theoretical differences in protonation energy(∆E p) of mono-,bi-,and triprotonated hexaamine ligands,for the (28)Urban,J.J.;Cronin,C.W.;Roberts,R.R.;Famini,G.R.J.Am.Chem.Soc.1997,119,12292-12299.(29)Hobza,P.;Kabelac,M.;Sponer,J.;Mejzlik,P.;Vondrasek,put.Chem.1997,18,1136-1150.(30)Cornell,W.D.;Cieplak,P.;Bayly,C.I.;Gould,I.R.;Merz,K.M.,Jr.;Ferguson,D.M.;Spelmeyer,D.C.;Fox,T.;Caldwell,J.W.;Kollman,P.A.J.Am.Chem.Soc.1995,117,5179-5197.(31)Hyperchem6.0(Hypercube Inc.).(32)(a)Fox,T.;Scanlan,T.S.;Kollman,P.A.J.Am.Chem.Soc.1997,119,11571-11577.(b)Grootenhuis,P.D.;Kollman,P.A.J.Am.Chem.Soc.1989,111,2152-2158.(c)Moyna,G.;Hernandez,G.;Williams,H.J.;Nachman,R.J.;Scott,put.Sci.1997,37,951-956.(d)Boden,C.D.J.;Patenden,put.-Aided Mol.Des.1999, 13,153-166.(33)/amber.(34)Hopfinger,A.J.;Pearlstein,put.Chem.1984,5,486-499.(35)Glennon,T.M.;Zheng,Y.-J.;Le Grand,S.M.;Shutzberg,B.A.;Merz,K.M.,put.Chem.1994,15,1019-1040.(36)Wang,J.;Kollman,P.A.J.Am.Chem.Soc.1998,120,11106-11114.Table4.Percentages of the Different Protonated Adducts[HGlu‚H j L](j-1)+,Overall Percentages of Complexation,andConditional Constants(K Cond)at pH7.4for the Interaction ofGlutamate(HGlu-)with Receptors L1-L6at Physiological pH[H n L‚HGlu]an)1n)2n)3n)4∑{[H n L‚HGlu]}K cond(M-1)L13272353 2.44×103L2947763 4.12×103L31101324 3.99×102L423737581 2.04×104L51010222 3.51×102L6121224 3.64×102a Charges omitted for clarity.A R T I C L E S Miranda et al. 828J.AM.CHEM.SOC.9VOL.126,NO.3,2004。
Anomalous Charge Dynamics in the Superconducting State of Underdoped Cuprates
a r X i v :c o n d -m a t /9709222v 1 [c o n d -m a t .s t r -e l ] 19 S e p 1997Anomalous Charge Dynamics in the Superconducting State ofUnderdoped Cuprateslis Department of Physics and Astronomy,The Johns Hopkins University,3400North Charles Street,Baltimore,MD 21218S.M.Girvin Department of Physics,Indiana University,Swain Hall W 117,Bloomington,IN 47405L.B.Ioffe Department of Physics,Rutgers University,Piscataway,NJ rkin Department of Physics,University of Minnesota,Minneapolis,MN 55455Abstract We present fermi liquid expressions for the low temperature behavior of the superfluid stiffness,explain why they differ from those suggested recently by Lee and Wen,and discuss their applicability to data on high-T c super-conductors.We find that a consistent description requires a strong,doping dependent anisotropy,which affects states near the zone corners much morestrongly than those near the zone diagonals.The work reported here was motivated by a recent paper of Lee and Wen on”Unusual Superconducting State of Underdoped Cuprates”1.Their point of view,which we share,is that because the superconducting state of the high-T c materials is apparently conventional and in particular supports well-defined quasiparticle excitations,it is appropriately described in terms of fermi liquid theory.Their main conclusion,that the temperature dependence of the superfluid stiffness is anomalous and implies unusual properties,is important and interesting.Their specific results must be interpreted with caution because their formulation of fermi liquid theory in the superconducting state(Eqs1-4of their paper)disagrees in an important way with the standard formulation2.In this note we present the usual fermi liquid theory of the charge response of the superconducting state,explain why it differs from Eqs 1-4of Lee and Wen,and apply it to penetration-depth data and discuss the underlying physics.We begin,however,with data.We write the penetration depthλ,in terms of a superfluid stiffness per CuO2planeρs viaρs=¯h2c2b/16πe2λ2.Here b is the mean interplane spacing. This definition yields the coefficient of the12)(v F/a)/d∆/dθwhere d∆/dθis the angular derivative of the gap function at thegap node and a=3.8˚A is the lattice constant.Photoemission results13on BSCCO showthat if the gap is defined as the displacement of the midpoint of the leading edge of the photoemission spectrum from the fermi level,then d∆/dθ≈40meV≈450K;using the band theory v F≈4eV−˚A yields dρs/dT=0.5meV/K.We now interpret these data in terms of fermi liquid theory.Fermi liquid theory is specified by the quasiparticle velocity v F(θ)and the Landau interaction function f(θ,θ′); these are functions defined on the fermi surface which for the electronically two-dimensional high-T c materials is a simple closed curve p F(θ)withθthe usual polar angle(we neglect the chain bands and any bonding-antibonding splitting arising from the bilayer structure).A basic assumption of the fermi liquid analysis is that the low-T dependence is due to thermally excited quasiparticles.Several authors have claimed6,7that phasefluctuations of the superconducting order parameter can also lead to such a T-dependence.However, these models require a large density of normal electrons at T=0to screen the Coulomb interaction.In high-T c materials there are no such electrons at T=0;the phasefluctuations will therefore be gapped,giving an exponentially small contribution.Even if screening is included,we believe the models of refs6,7yield a T2temperature dependence.Claims to thecontrary seem to have arisen from Eq7of ref8in which a term involving the Matsubara sum n=∞n=−∞was written as2∗ ∞n=0so that the n=0term was counted twice.Evaluation of n=∞n=−∞yields a T2temperature dependenceThe fermi velocity may be determined from the dispersion of quasiparticle peaks ob-served in photoemission.The interpretation of photoemission data on high-T c materials is still controversial,but there is general agreement that for momenta near the zone diagonal, well-defined peaks exist from which a dispersion can be extracted.The most detailed studies have focused on the BSCCO family of materials;the data for YBCO seem quite similar9. Fig.3of ref10shows the dispersion along the zone diagonal for overdoped,optimally doped, and underdoped BSCCO samples.The data imply a doping-independent quasiparticle ve-locity v=1.3eV−˚A;this is reduced from the band-structure value(v F≈4eV)by about afactor of3,presumably because of electron-electron interaction effects.It is conventionally assumed(and has been demonstrated in some models11,12)that the many-body renormal-izations which change the zone-diagonal velocity by a factor of three are relatively isotropic around the fermi surface,so we might expect that the velocity everywhere to be changed by about the same factor.This,combined with the observation that the charge response should be dominated by the zone diagonals where the velocity is largest,suggests that if the Landau parameter contribution were negligibleρs would be renormalized by about a doping-independent factor of three from the band theory prediction.The smaller value and especially the doping dependenceρs therefore suggests that the Landau interaction function plays an important role as predicted theoretically11,12.We now show that while the Landau function may be important,the conventional picture makes predictions for dρs/dT which are inconsistent with the data.The fermi liquid theory of the superconducting state was developed in2.The result may be written:¯h2bρsab=Eq.4differs from that written in ref1by the two factors of(1−f)−1.The authors of1ob-tained their result by analogy to Leggett’s theory of the spin susceptibility of3He;the results of2show the analogy is not appropriate.The physics is this:Landau parameters enter ex-pressions for physical quantities because a perturbingfield H excites quasiparticle-quasihole pairs at all points on the fermi line;i.e.it modifies the underlying fermi distribution and because of the electron-electron interaction this changes the quasiparticle energy dispersion to order H,and thus affecting the number of excitations.This effect must be treated self-consistently.Now in3He the condensate does not respond at linear order to a magneticfield (at least in the low-T”BW”phase),and because of the superconducting gap the number of quasiparticles at low T is very small;thus at low T changes to the quasiparticle dispersion may be neglected and Landau parameters drop out.By contrast a superconducting con-densate does respond to a magneticfield(by producing a supercurrent);this supercurrent does correspond to a displacement of the underlying fermi distribution which does affect the superconducting quasiparticles,causing Landau parameter effects in the temperature dependence.In fermi liquid theory one defines the Landau parameters A1s,F1s via<v a(1−f)−1v a>=<v2a>/(1−A1s/2)=<v2a>(1+F1s/2).If the renormalization of the velocity is isotropic over the fermi surface we may evaluate<v2a>by dividing the band theoryρs by three(recall the density of states factor in the definition of<>)to obtain<v2a>=23meV. By comparing this to the data we conclude that(1+F1s/2)≈1/2(O7)and(1+F1s/2)≈1/4 (O6.6).Now in a Galilean-invariant fermi liquid v F=p F/m∗and<v2a>≈n/m∗.In a two dimensional Galilean-invariant system the Landau parameter obeys1+F1s/2=m∗/m so the Landau parameter cancels the mass renormalization.In non-Galilean-invariant systems such as the high-T c superconductors there is no a-priori relation between F1s and m∗/m.As we see,in the actual materials the observedρs is smaller than one would expect from the observed v;thus F1s acts in the same direction as m∗,instead of compensating it.In many fermi liquids the angular dependence of the interaction is not too strong,so one expands the operator f in appropriate harmonics and retains only the one most closelycorresponding to v v;this amounts to replacing the operator(1−f)−1by the scalar1+F1s/2 in both eqs.3and4.We refer to this as the“conventional fermi liquid”approximation.A particular realization of such a fermi liquid is found in the slave boson calculations of11,12.To compute dρs/dT in this conventional fermi liquid approach we take the”band theory”value of0.5meV/K obtained earlier,divide by a factor of three for the velocity renormalization and a further factor of4for Y Ba2Cu3O7and16for Y Ba2Cu3O6.63,yielding dρs/dT= 0.04meV/K for O7and0.01meV/K for O6.6.Although the estimate of dρs/dT for O7is within a factor of two of the measured value of0.06meV/K,the estimate for O6.6is badly off.Similarly,ref11foundρs(T)=<vL(T)v>/(1+c<vL(T)v>with c≈−A1s∼1/x, so dρs/dT∼ρs(T=0)<vdL/dT v>/c∼1/x2.Thus both the conventional fermi liquid approach and explicit calculations predict a strong doping dependence where none exists experimentally.In ref1the disagreement of the result of ref11with the observed dρs/dT was argued to indicate the inadequacy of the U(1)gauge theory formalism used in11.The present analysis makes it clear that the difficulty is more general.The doubtful point of the discussion given above is the assumption of weak angular dependence around the fermi surface.This enters the argument in two places:first,that the factor-of-three velocity renormalization observed for quasiparticles along the zone diagonal applies all over the fermi surface,and second that the Landau interaction operator(1−f)−1 could be replaced by the Landau parameter1+F1s/2.These two issues are clearly related: an interaction giving a relatively larger velocity renormalization at the zone corners than at the zone diagonals will lead to a Landau function with a stronger angular dependence.If the velocity renormalization increases rapidly as one moves away from the zone diagonal then the estimate of the renormalization ofρs relative to band theory increases and the value of the Landau parameter decreases.There is evidence of anomalousflatness of bands and shortness of lifetimes in the vicinity of the zone corners14.In order to explain the data the size of the”non-flat”regions must be small and x-dependent.Evidence on this point is not conclusive.Consider now the possibility of strong anisotropy in the Landau function.We see fromEq.4that because the quasiparticle excitations are concentrated in the nodes,at low T the temperature-dependent quantity dL/dT is non-zero only near the zone diagonal.If the Landau function f(θ1,θ2)were anomalously small for eitherθ1orθ2near this point then the effect of the Landau function on dρs/dT would be greatly reduced in agreement with data. The range of angles over which this occurs must be small and f must be x-dependent.To summarize:the temperature dependence of the superfluid stiffness strongly suggests that some process acting in the high-T c superconductors strongly suppresses the contribution of the particles away from the zone diagonal to the current.Acknowledgements We thank E.Abrahams,I.Aleiner and B.G.Kotliar for helpful conversations.L.B.I.,A.I.L.and A.J.M.thank NEC research for hospitality.S.M.G. and A.J.M.thank the Aspen Center for Physics.S.M.G.was supported by D.O.E.grant DE-FG02-90ER45427and A.J.M.by NSF DMR-9707701.REFERENCES1P.A.Lee and X.G.Wen,Phys.Rev.Lett.784111(1997).rkin,J.Exptl.Theoret.Phys.(U.S.S.R.)462188(1964)Sov.Phys.J.E.T.P.46 1478(1965)and A.J.Leggett,Phys.Rev.140A1869(1965);see also F.Gross et.al.,Z. Phys.B64p.175(1986)and D.Xu,S.K.Yip and J.A.Sauls,Phys.Rev.B5116233 (1995).3D.A.Bonn et.al.,J.Phys.Chem.Sol.561941(1995).4J.Orenstein et.al.,Phys.Rev.426342(1990).This reference discusses band structure calculations and their comparison to optical and penetration depth data.5It should be noted however that although theρsaa values we have quoted seem quite small, the phase stiffness controlling a possible Kosterlitz-Thouless temperature is much larger. First,one must use(ρsaaρsbb)1/2(the b direction is parallel to the chains);second the YBCO materials have a bilayer structure in which pairs of planes are strongly coupled,implying a further factor of two bining these factors wefind that the Kosterlitz-Thouless transition temperature implied by the T=0ρs is T KT≡πρs(T=0)/2=600K(O7)and 300K O6.6,much greater than the observed T c of these materials.6V.J.Emery and S.Kivelson,Nature,374,p.434-7(1995).7E.Roddick and D.Stroud,Phys.Rev.Lett.,74,p.1430-3(1995).8S.Chakravarty et.al.,Phys.Rev.Lett.562303(1986).9J.Campuzano et.al.,Phys.Rev.Lett.642308(1990).10D.S.Marshall,D.S.Dessau,A.G.Loeser,C-H Park,A.Y.Matsuura,J.N.Eckstein, I.Bozovic,P.Fournier,A.Kapitulnik,W.E.Spicer and Z-X Shen,Phys.Rev.Lett.76 4841(1996).11L.B.Ioffe and rkin,Phys.Rev.B398988(1989).12M.Grilli and B.G.Kotliar,Phys.Rev.Lett.641170(1990)and B.G.Kotliar,p.197in Les Houches Session LVI1991,Elsevier(1995).13J.M.Harris,Z.-X.Shen,P.J.White,D.S.Marshall,M.C.Schabel,J.N.Eckstein and I.Bozovic,Phys.Rev.B5415665(1996).14D.S.Dessau et.al,Phys.Rev.Lett.712781(1993).。
次级胆汁酸与短链脂肪酸对结直肠癌发生发展的影响
心[10]等研究表明肺泡灌洗术联合免疫球蛋白治疗能有效改善SMPP 患儿血清炎症因子水平,可能也是联合治疗较单独应用免疫球蛋白有效改善影像学表现的原因之一㊂综上所述,支气管肺泡灌洗术联合免疫球蛋白能有效提高重症支原体肺炎患儿治疗有效率,并促进患儿肺部影像学病灶吸收,值得临床推广㊂ʌ参考文献ɔ[1]㊀喻文清,陈欣,王浩入,等.重症肺炎支原体肺炎的影像学研究进展[J ].中国中西医结合影像学杂志,2022,20(5):494-496,500.[2]㊀庞卫花,刘永涛,曹智丽,等.支原体肺炎患儿肺泡灌洗液MP -DNA 载量㊁免疫炎性指标与治疗效果的关系研究[J ].河北医药,2020,42(6):857-860.[3]㊀Li S ,Zhang QL ,Guo RJ ,Lv XZ ,et al.Quantitative evaluationand significance of ultrasound in bronchoalveolar lavage forlung consolidation in children with severe mycoplasma pneu-monia [J ].Transl Pediatr ,2021,10(9):2325-2334.[4]㊀‘诸福棠实用儿科学“[M ].第8版.临床儿科杂志,2015.308.[5]㊀中华医学会儿科学分会呼吸组,中华儿科杂志编辑委员会.儿童慢性咳嗽与诊断指南[J ].中华儿科杂志,2008,46(2):104-107.[6]㊀涂志蓉,刘焱钗,林菁,等.C 反应蛋白㊁D -二聚体联合CT表现预测小儿重症支原体肺炎的价值[J ].中国国境卫生检疫杂志,2022,45(1):71-74.[7]㊀Wang H ,Lu Z ,Bao Y ,et al.Clinical diagnostic application ofmetagenomic next -generation sequencing in children with se-vere nonresponding pneumonia [J ].PLoS One.2020;15(6):232610.[8]㊀黄翔.免疫球蛋白联合甲基泼尼松龙对重症支原体肺炎患儿炎性因子与免疫功能的影响[J ].中国医刊,2017,52(2):98-100.[9]㊀Wang K ,Gao M ,Yang M ,et al.Transcriptome analysis ofbronchoalveolar lavage fluid from children with severe myco-plasma pneumoniae pneumonia reveals novel gene expression and immunodeficiency [J ].Hum Genomics ,2017,11(1):4.[10]㊀张称心,李琳琳,张艳波.肺泡灌洗术联合免疫球蛋白及甲强龙对重症支原体肺炎患儿的治疗评价[J ].中国现代应用药学,2020,37(4):475-477.文献综述ʌ文章编号ɔ1006-6233(2023)07-1226-05次级胆汁酸与短链脂肪酸对结直肠癌发生发展的影响肖㊀昕1,㊀孙建飞2,㊀肖㊀刚2,㊀郭㊀辉2,㊀曹丽娟1,㊀任玉静1(1.陕西中医药大学,㊀陕西㊀咸阳㊀7120462.陕西中医药大学附属医院,㊀陕西㊀咸阳㊀712000)ʌ关键词ɔ㊀结直肠癌;㊀肠道微生物群;㊀次级胆汁酸;㊀短链脂肪酸ʌ文献标识码ɔ㊀A㊀㊀㊀㊀㊀ʌdoi ɔ10.3969/j.issn.1006-6233.2023.07.033㊀㊀结直肠癌(Colorectal cancer ,CRC )发病率和死亡率呈逐年递增的趋势,是恶性肿瘤死亡的主要原因之一㊂据2008年中国癌症统计公报表明:我国结直肠癌的发病率㊁死亡率在世界恶性肿瘤中居于第三位及第五位,新发病例37.6万,死亡病例19.1万[1]㊂饮食对CRC 发病影响至关重要,高脂饮食习惯和低膳食纤维含量的 西方 饮食会增加体内次级胆汁酸含量从而导致结肠炎症和肿瘤形成㊂而短链脂肪酸(short -chain fatty acids ,SCFAs )作为肠道微生物群分解膳食纤维的一种代谢物,随着膳食纤维的摄入增加可有效预防结直肠癌变㊂目前国内外就次级胆汁酸和短链脂肪酸对CRC 的影响及其关联性研究还不够深入,因此探讨次级胆汁酸和短链脂肪酸对CRC 的影响因素及其后续防治意义至关重大㊂㊃6221㊃ʌ基金项目ɔ陕西省中医药管理局科技产业与发展处,(编号:2021-ZZ -LC012);陕西中医药大学科学研究项目,(编号:2020XK03);陕西中医药大学科研项目院内课题,(编号:2020QN005)ʌ通讯作者ɔ孙建飞1㊀次级胆汁酸与SCFAs1.1㊀次级胆汁酸产生㊁运输及代谢:次级胆汁酸由初级胆汁酸分泌,在肠道菌群代谢作用下进行7α-脱羟基作用分解所产生㊂初级胆汁酸是以肝细胞中胆固醇为主要原料直接合成的一种甾醇化合物㊂合成后的胆汁酸由甘氨酸或牛磺酸结合后排出并储存在胆囊中,再经回肠顶端钠依赖性胆汁酸转运蛋白(apical sodi-um-dependent bile salt transporter,ASBT)主动吸收及结肠的被动吸收进行重吸收,重吸收的胆汁酸在肠黏膜细胞内与回肠胆汁酸结合蛋白(ileal bile acid bind-ing protein,IBABP)结合,并通过OSTα-OSTβ转运系统转运至基底膜外侧并通过门脉血入肝脏完成 肠-肝循环 ㊂只有5%的胆汁酸真正进入到结肠,并通过肠道菌群代谢,其中的初级胆汁酸如胆酸(cholic acid, CA)和鹅脱氧胆酸(chenodeoxycholic acid,CDCA)则转化为次级胆汁酸:脱氧胆酸(deoxycholic acid,DCA)和石胆酸(lithocholic acid,LCA)㊂当两者水平升高,又会破坏肠道微生物平衡,损害肠黏膜,引发氧化应激反应,进而促使结直肠炎症和癌变的发生㊂1.2㊀SCFAs的组成及作用:SCFAs是一个具有1~6个碳键原子的羧酸,并由复杂的碳水化合物被肠道微生物区代谢成低聚糖并发酵形成㊂作为大肠内游离阴离子(SCFA-)的主要组成部分,SCFAs基本被肠黏膜直接吸收,且种类繁多,以丁酸盐㊁丙酸盐㊁乙酸盐为主,在人体肠道中占全部短链脂肪酸的比重超95%且达到50~200mmoL/L的总浓度㊂它们通过肠黏膜被有效吸收,并作为能量来源㊁基因表达调节剂和被特异性受体识别的信号分子对宿主生理学影响重大㊂丁酸盐作为结肠上皮细胞的主要能量源,低浓度会导致哺乳动物细胞和结肠癌细胞的分化㊂而短链脂肪酸作为健康和疾病中氧化还原信号的调节剂,尤其是丁酸盐,表现出与其氧化还原信号传导活性相关的抗炎和抗增殖特性㊂2㊀次级胆汁酸、SCFAs影响CRC的相关因素2.1㊀肠道微生物群2.1.1㊀次级胆汁酸与肠道微生物群的稳态失调致使结直肠癌变:高脂肪饮食习惯不仅会引起肠道微生物群的紊乱㊁破坏肠屏障功能并诱导炎症,还会异常代谢出诸如次级胆汁酸等致癌产物,进而促使CRC形成㊂长期的高脂肪低纤维饮食人群,在其粪便中可明显检测到高水平的DCA㊁LCA,这些都使得CRC发病率显著提高㊂次级胆汁酸作为结直肠中一种肿瘤促进剂,当肠道微生物菌群长期暴露于其中,其细胞膜结构的相对完整性也会遭到一定程度的损害甚至导致肠道菌群死亡㊂一则临床研究发现[2],在通过对比正常人与CRC患者体内胆汁酸水平得出,CRC患者次级胆汁酸表达水平显著升高于正常人群(P<0.05),且癌变处的肠道微生物群受到显著改变(P<0.05),说明次级胆汁酸影响肠道微生物进而促进肿瘤的发生发展㊂另一方面,肠道微生物群能显著改变胆汁酸的理化性质,产生宿主核受体(法尼醇X受体㊁维生素D受体(VDR)㊁孕烷X受体)和G偶联蛋白受体5(TGR-5)的高亲和力配体,并激活一系列如JNK㊁ERK㊁Akt等信号通路㊂肠道微生物群失衡同样使得胆汁酸硫酸化降低,进而抑制其对FXR的激活㊂在一项动物实验中得出[3],在无菌(GF)和常规饲养(CONV-R)小鼠整个肠-肝系统的胆汁酸组成中CONV-R小鼠的鼠胆酸(啮齿动物体内的一种次级胆汁酸)水平显著降低㊂这些研究表明,肠道微生物群在调节次级胆汁酸代谢时,通过上调FXR来抑制肝脏中胆汁酸合成起到了重要作用㊂有研究证明7α-脱羟基梭菌的浓度在所调查的CRC患者粪便中均有所升高[4]㊂7α-脱羟基梭菌加剧了次级胆汁酸的异常分泌,增加了CRC发病率㊂由此看出, CRC的发生发展离不开次级胆汁酸与肠道微生物菌群两者的相互影响㊂因此,改变饮食习惯㊁减少高脂肪摄入㊁调节次级胆汁酸与肠道微生物之间的稳态平衡,可以有效预防结直肠炎症及癌变的发生㊂2.1.2㊀SCFAs与肠道微生物群对结直肠癌的影响:素食及其他高纤维饮食可以有效的预防CRC,SCFAs作为结肠微生物群酵解膳食纤维的产物,同样在预防CRC中起到了重要作用㊂在SCFAs中,属丁酸盐的含量最高㊂进入人体的膳食纤维经肠道微生物群利用,使得丁酸盐含量升高,减少亚硝酸盐的毒性从而降低癌变率㊂肠道微生物群失衡的显著特征便是丁酸盐及其代谢菌群的减少㊂有研究发现通过周期性的摄入酸奶可以有效增加肠道中的益生菌,显著升高SCFAs水平,进而加速结直肠癌细胞的凋亡[5]㊂研究指出,在丁酸衣原体的作用下,结直肠肿瘤细胞的增殖明显减少,同时还加速其凋亡㊂此外,丁酸芽孢杆菌抑制了Wnt/β-连环蛋白信号通路并调节了肠道微生物群组成㊂以及通过高脂肪饮食(HFD)诱导的APCmin/+小鼠,在丁酸梭状芽孢杆菌(丁酸盐的产物之一)的作用下显著抑制了其肠道肿瘤的发展㊂因此,丁酸梭菌在降低了粪便次级胆汁酸含量同时增加了盲肠SCFA含量,并激活了G蛋白偶联受体(GPR),说明丁酸衣原体可以通过调节Wnt信号传导和肠道微生物群来抑制肠道肿瘤的发展,从而证明了产生丁酸盐的菌群对CRC有着潜在抑制功能㊂㊃7221㊃2.2㊀对结直肠细胞增殖的影响2.2.1㊀次级胆汁酸促进结直肠癌细胞增殖:次级胆汁酸对结直肠癌细胞增殖的影响程度可以反映在其浓度变化上㊂低浓度DCA(5-50μmoL/L)通过反式激活表皮生长因子受体(EGFR)诱导COX-2表达,增强结肠癌细胞增殖和侵袭性;而在高脂肪饮食下,次级胆汁酸浓度可高达1mmoL/L,并通过激活蛋白1(AP1)和c-髓细胞瘤(c-Myc)靶向通路激活β-连环蛋白细胞信号㊁细胞外信号调节蛋白1和2(ERK1/2)信号通路,刺激结肠癌细胞增殖和侵袭性㊂另一方面,生理浓度(0.05~0.3mmoL/L)的次级胆汁酸(如DCA)会根据不同类型细胞不同程度的抑制结直肠细胞的增殖㊂具体来说,DCA和LCA主要通过产生细胞内活性氧(ROS)㊁基因组DNA断裂㊁激活ERK1/2㊁caspase-3和聚(ADP-核糖)聚合酶(PARP)来促进细胞周期停滞和凋亡,但降低了细胞周期蛋白E(CyclinE)的表达,从而抑制结肠细胞增殖[6]㊂此外,DCA激活细胞信号通路,导致对凋亡㊁血管生成㊁增殖和氧化应激的选择性抵抗㊂因此,次级胆汁酸暴露造成的反复DNA损伤,使得结直肠(和其他胃肠道)上皮细胞中的大量细胞代谢并诱导结直肠细胞癌变㊂2.2.2㊀SCFAs抑制结直肠癌细胞增殖:丁酸盐被认为是结直肠上皮细胞中对生长和分化最有效的SCFA㊂组蛋白去乙酰化酶(HDAC)活性通过浓缩染色质包装抑制转录活性,导致肿瘤抑制基因(如p21)的表观遗传学介导沉默㊂而丁酸盐作为一种HDAC抑制剂(HDACI)强烈激活细胞周期蛋白依赖性激酶抑制剂p21的表达,并促进结肠癌细胞的细胞周期停滞㊁分化和凋亡,是一种潜在的抗肿瘤药物㊂丁酸盐被结肠上皮组织通过单羧酸转运体1和其他转运体选择性吸收,并满足能量平衡为结肠细胞提供约70%的能量;细胞内丁酸盐在低浓度(<0.5mmoL/L)时符合细胞的能量需求,并促进正常结肠细胞的增殖;当浓度超过其能量所需浓度(取决于细胞类型,范围:0.5~5mmoL/ L)时,丁酸盐则充当组蛋白脱乙酰酶抑制剂(HDA-Ci);此外,丁酸盐在生理浓度(0.5~5mmoL/L)时,以p53依赖和非依赖的方式诱导细胞周期停滞和凋亡㊂在0.5mmoL/L或更高的浓度下,丁酸盐通过增加抗转移基因(如金属蛋白酶)的表达和抑制促转移基因(如基质金属蛋白酶)的激活来抑制癌细胞的迁移和侵袭能力㊂尽管测试的每种SCFAs都显着降低了原发性细胞侵袭,但丁酸盐是最有效的㊂Wang[7]等将癌性HCT116结肠细胞暴露于生理相关剂量的丁酸钠(丁酸盐的一种),发现丁酸钠抑制NRF2/NRF2信号轴靶基因并阻断NRF2-ARE信号传导,证明丁酸盐通过调节KEAP1/NRF2信号传导并起到预防和治疗CRC的作用㊂另一项研究表明与短链脂肪酸联合放疗时,丁酸盐作为一种候选放射增敏剂可以在保护正常黏膜的同时增强放射治疗的疗效[8]㊂且丁酸盐不会增加辐射诱导的细胞死亡,也不会提高正常类器官辐射后的再生能力㊂由此可见,SCFAs对结直肠癌的治疗将成为未来新的研究方向㊂2.3㊀相关信号通路2.3.1㊀次级胆汁酸影响结直肠癌的相关通路及分子机制:CRC的发生过程循序渐进,包括从腺瘤到癌的一系列细胞突变,其中一些突变导致Wnt和凋亡信号通路的失控㊂在结肠肿瘤发生发展中,细胞对次级胆汁酸的反应包括激活Wnt和NF-κB信号通路,DNA 氧化损伤和核分裂活性受损,从而导致结肠细胞过度增殖和侵袭㊂次级胆汁酸作用于癌细胞表面的TGR5或癌细胞细胞核内的VDR后,可激活各种信号通路,抑制癌细胞凋亡,诱导癌细胞周期的进展,增强癌细胞转移和侵袭的能力,并促进细胞向肿瘤干细胞(CSCs)的转化㊂此外,次级胆汁酸可以降低肝窦内皮细胞中趋化因子CXCL16的水平,从而抑制NKT细胞上CX-CR6蛋白的积累㊂作为对胆汁酸毒性浓度的响应,由FXR㊁VDR㊁PXR和CAR组成复杂的核受体网络协调胆汁酸摄取和解毒㊂一项对肠道肿瘤和其附近正常黏膜的研究指出,在从正常上皮向肿瘤转化上皮的转变过程中,FXR 的表达显著减少[9]㊂FXR表达下调是引起结直肠炎症及肿瘤形成的重要因素㊂而应用FXR激动剂可维持干细胞的正常增殖及染色体的稳定性[10],上调促凋亡基因的表达,抑制CRC的进展㊂在Renga等的实验中,与WT小鼠相比,FXR-/-小鼠(FXR缺陷)表现出结肠炎和癌症风险的增加㊂证实结直肠癌细胞中FXR的激活抑制了结肠上皮细胞的增殖,并诱导了促凋亡基因p21,同时抑制了抗凋亡基因Bcl2㊂2.3.2㊀SCFA影响结直肠癌的相关通路及分子机制:丁酸盐在结肠上皮组织中发挥抗增殖和促凋亡作用的相关信号通路是最近研究的焦点㊂有研究指出,TGF-β/Smad3通路激活对结肠细胞促凋亡有着显著作用,而其通路的下调会导致癌症进展[11]㊂且丁酸盐的机制作用与TGF-β上调介导的Wnt通路有关,这也涉及到多种组蛋白乙酰转移酶中的任何一种,即cAMP 反应元件结合蛋白(CREB)㊁CREB结合蛋白(CBP)或p300:CBP介导的Wnt信号与结肠细胞增殖有关,而p300介导的Wnt信号与分化更密切相关;因此,CBP-㊃8221㊃Wnt活性可能在癌症中占主导地位㊂随后,丁酸盐(或其他HDACis)对该通路的过度激活导致与结肠癌细胞凋亡有关的Wnt信号相关蛋白的转录增强㊂丁酸盐作为正常结肠上皮细胞的主要能量来源,并通过维持低水平的Wnt信号来支持细胞增殖[12]㊂因此,丁酸盐诱导的肿瘤细胞中Wnt信号的过度激活有望增加Wnt的活性水平,从而导致细胞凋亡;而胆汁酸对正常结肠细胞的刺激可能导致中等水平的Wnt活性,从而促进肿瘤细胞生长㊂除了具有Wnt信号通路的激活突变外,癌细胞往往会异常代谢,增加对有氧糖酵解的依赖㊂这将使结肠肿瘤细胞会优先利用葡萄糖而非丁酸作为主要供能,并允许更多的丁酸盐作为HDACi发挥作用,刺激Wnt信号转导和诱导细胞凋亡㊂因此,经过丁酸盐处理的结直肠癌细胞中Wnt信号的过度激活是促使这些细胞高水平凋亡所必需的条件㊂然而,适度的Wnt 活性也与癌细胞增殖相关,癌细胞可能逐渐对丁酸盐的作用产生抗药性㊂这种抗药性可以表现为从依赖β-连环蛋白的Wnt途径转变为不依赖于β-连环蛋白下游效应的修饰途径㊂总体而言,丁酸盐过度激活由于突变而表现出Wnt信号失控的结肠癌细胞系中的Wnt信号,这种突变是大多数结直肠癌类型的共同特征㊂因此,Wnt通路的过度激活与丁酸诱导的结肠肿瘤细胞的凋亡有关,这一作用可以解释丁酸盐对结肠癌的预防作用㊂3㊀肠道微生物组将成为免疫治疗结直肠癌的新目标多项研究证明,微生物群有望成为免疫治疗的新靶点㊂微生物群可以直接或间接激活和调节宿主的免疫系统,并且癌症免疫疗法对抗肿瘤的新思路,与微生物群的关系密切㊂近期一项研究表明,肠道微生物群可以与其宿主的免疫检查点抑制剂(ICI)协同作用,尤其是在增强程序性死亡1(PD-1)蛋白及其配体程序性死亡配体1(PD-L1)阻断治疗癌症的方面[13]㊂Montalban-Arques等[14]发现四种产丁酸梭菌:罗氏菌属㊁哈利氏真细菌㊁普氏杆菌和卡卡厌氧杆菌(CC4)可以预防CRC发展:补充CC4可增加肿瘤浸润IFN-γ+ CD8+T细胞的频率和活性㊂另有研究发现,鸡乳杆菌可通过分泌一种保护性代谢产物吲哚-3-乳酸,促进CRC细胞的凋亡,从而阻止CRC的发生㊂总之,微生物的改造和应用对肿瘤免疫治疗有很大的贡献,不仅能提高疗效,还能降低副作用㊂同时,微生物群作为治疗靶点,在肿瘤治疗和预防中也发挥着重要作用㊂这些微生物组促进癌症和癌症免疫治疗的机制,还需要更多的理论支持和数据研究,但无疑是现代医学新的治疗方向㊂4㊀讨㊀论通过肠道微生物群㊁结肠细胞增殖㊁相关信号通路及分子机制等方面概述了次级胆汁酸与SCFAs对CRC的影响㊂总体而言,次级胆汁酸和SCFAs这两种肠道主要代谢物在结直肠细胞增殖中起到的作用既有相似点也有不同点㊂在低浓度下这些微生物代谢物可促进结肠细胞增殖,在高浓度时,次级胆汁酸和SCFAs 通过共同或不同的分子途径抑制结肠细胞的增殖;以及这两者在长期的高生理水平上对结肠炎症及CRC 产生相反的作用㊂通过文献总结,次级胆汁酸和SC-FAs之间的关联可能通过改变结肠微生物群组成而发生㊂然而,哪些特定的生化途径可能导致胆汁酸和SCFAs信号之间的潜在关联仍需要进一步研究,因为它们的影响不仅基于浓度和持续时间,还取决于细胞类型㊂由于肠道微生物群失调会改变次级胆汁酸和SCFAs的产生,并促使结直肠炎最终形成恶性肿瘤,因此平衡营养摄入量与高纤维低饱和脂肪摄入量对于维持健康的肠道微生物群至关重要㊂另一方面,在近期的不断研究下,微生物群和癌症免疫治疗已经逐渐临床上得到尝试,在临床研究中一些关于肠道微生物群在癌症免疫治疗中的初步报告表明,这将是对抗癌症的一种新的方法㊂因此,更多地了解这些微生物及其代谢产物的相互作用很可能在结直肠癌的预防和治疗方向有新的突破㊂ʌ参考文献ɔ[1]㊀中华人民共和国国家卫生健康委员会.中国结直肠癌诊疗规范(2020年版)[J].中国实用外科杂志,2020,40(6):601-625.[2]㊀郭磊,朱海杭,周步良.结肠直肠癌与胆汁酸代谢㊁肠道菌群分布水平的相关性研究[J].实用临床医药杂志,2019,23(2):95-96.[3]㊀Sayin S I,Wahlstrom A,Felin J,et al.Gut microbiota regu-lates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid,a naturally occurring FXR antagonist[J].Cell Metab,2013,17(2):225-235.[4]㊀Nguyen T T,Ung T T,Kim N H,et al.Role of bile acids incolon carcinogenesis[J].World Clin Cases,2018,6(13):577-588.[5]㊀徐仁应,卞玉海,万燕萍,等.短链脂肪酸与结直肠肿瘤细胞凋亡关系的研究[J].肠外与肠内营养,2013,20(5):259-262.[6]㊀Ha Y H,Park D G.Effects of DCA on cell cycle proteins incolonocytes[J].Korean Soc Coloproctol,2010,26(4):254-259.[7]㊀Wang L,Shannar A,Wu R,et al.Butyrate drives metabolic㊃9221㊃rewiring and epigenetic reprogramming in human colon canc-er cells [J ].Mol Nutr Food Res ,2022,66(12):2200028.[8]㊀Park M ,Kwon J ,Shin H J ,et al.Butyrate enhances the effi-cacy of radiotherapy via FOXO3A in colorectal cancer pa-tientderived organoids [J ].Int Oncol ,2020,57(6):1307-1318.[9]㊀Bailey A M ,Zhan L ,Maru D ,et al.FXR silencing in humancolon cancer by DNA methylation and KRAS signaling [J ].Am Physiol Gastrointest Liver Physiol ,2014,306(1):G48-G58.[10]㊀Fu T ,Coulter S ,Yoshihara E ,et al.FXR regulates intestinalcancer stem cell proliferation [J ].Cell ,2019,176(5):1098-1112.[11]㊀Haque S ,Morris J C.Transforming growth factor -beta :atherapeutic target for cancer [J ].Hum Vaccin Immunoth-er ,2017,13(8):1741-1750.[12]㊀Sears C L ,Garrett W S.Microbes ,microbiota ,and coloncancer [J ].Cell Host Microbe ,2014,15(3):317-328.[13]㊀Rezasoltani S ,Yadegar A ,Asadzadeh A H ,et al.Modulatoryeffects of gut microbiome in cancer immunotherapy :a novel paradigm for blockade of immune checkpoint inhibitors [J ].Cancer Med ,2021,10(3):1141-1154.[14]㊀Montalban -arques A ,Katkeviciute E ,Busenhart P ,et al.Commensal clostridiales strains mediate effective anti -cancer immune response against solid tumors [J ].Cell HostMicrobe ,2021,29(10):1573-1588.病例报告ʌ文章编号ɔ1006-6233(2023)07-1230-03输尿管畸形伴下段结石合并肾盂尿路上皮癌伴鳞状化生1例报告附文献复习张㊀鹏1,2,㊀刘㊀霞2,㊀韩从辉1,2,㊀刘大闯1,2(1.蚌埠医学院研究生院,㊀安徽㊀蚌埠㊀2330302.江苏省徐州市中心医院,㊀江苏㊀徐州㊀221009)ʌ关键词ɔ㊀输尿管畸形;㊀下段结石;㊀肾盂尿路上皮癌;㊀鳞状化生ʌ文献标识码ɔ㊀A㊀㊀㊀㊀㊀ʌdoi ɔ10.3969/j.issn.1006-6233.2023.07.0341㊀病例报告患者女,45岁,于2022年2月无明显诱因下出现右腰腹部疼痛,当地医院影像学检查(泌尿系彩超㊁腹部CT )示:右输尿管下段结石,大小约25mm ,伴肾周积脓(见图1),抗感染治疗后行经尿道输尿管镜碎石取石术,术后放置DJ 管,复查腹部CT 未见明显结石影,肾周感染稍减轻㊂术后1月拔除DJ 管,2周后开始出现低热,于当地医院抗感染对症治疗,情况反复发作持续到2022年5月底㊂于2022年6月出现高热,体温达39.5ħ,加强抗感染退热对症治疗,多次尿培养均示阴性,后尿培养提示真菌(+),予口服氟康唑治疗出院㊂情况未见好转,当地医院予行右输尿管DJ 管置入术,术后予以亚胺培南西司他丁治疗,体温仍未下降,于2022年7月1日入住我科㊂入院时间为2022年7月1日,血常规:红细胞3.28ˑ1012L -1,血红蛋白81g /L ,血小板439.0ˑ109L -1,白细胞18.24ˑ109L -1,中性粒细胞绝对值16.71ˑ109L -1,淋巴细胞绝对值0.64ˑ109L -1,超敏C 反应蛋白(HS -CRP )248.19mg /L ㊂2022年7月2日尿常规:尿胆原阳性(+),蛋白质阳性(+),尿白蛋白0.08g /L ,白蛋白肌酐比值阳性(+)g /L ,尿潜血阳性(++)g /L ,尿白细胞阳性(+++)g /L ,红细胞(尿沉)10.01HPF ,白细胞(尿沉)232.25HPF ,鳞状上皮细胞5.1p /ul ㊂胸部+输尿管CT 平扫:右肺实性小结节㊁少许炎症,右肾形态不整㊁体积增大,多发低密度灶,双肾盂,右侧输尿管置管后改变,右侧输尿管扩张㊁壁增厚,周围多发渗出,所见肝右叶低密度灶,膀胱壁厚,腹主动脉旁类软组织密度影㊂2022年7月4日全腹部CT 增强扫描:右肾不规则肿块㊁双肾盂,肝右叶多发类囊性占位,腹主动脉旁多发肿大淋巴结,腰椎局部椎体破坏,考虑肾脏恶性㊃0321㊃ʌ基金项目ɔ江苏省徐州市引进临床医学专家团队项目,(编号:2018TD004);江苏省徐州医科大学附属医院发展基金项目,(编号:XYFM2020001)ʌ通讯作者ɔ刘大闯。
手性离子液体的合成
收稿:2007年6月,收修改稿:2007年8月 3通讯联系人 e 2mail :gaoge @手性离子液体的合成孙洪海1,2 高 宇3 翟永爱1 张 青1 刘凤岐1 高 歌13(11吉林大学化学学院 长春130023;21大庆师范学院化学系 大庆163712;31北京大学医学部 北京100083)摘 要 近年来,研究者对室温离子液体极为关注,因为这些离子液体可以作为潜在的替代试剂用于有机合成、提取与分离、电化学和材料科学等方面。
在离子液体中,手性离子液体由于可用在手性识别、不对称合成、消旋体的拆分、立体选择聚合、气相色谱、NMR 位移试剂和液晶等方面而受到特别注意。
尽管手性离子液体由于合成困难和费用昂贵而限制了其广泛应用,但其在不对称合成中可作为手性诱导物的应用前景促使研究者不断地去开发新型的手性离子液体。
手性离子液体的制备既可以使用手性源(如氨基酸、胺、氨基醇以及生物碱类),也可以利用不对称合成的手段,其所具有的手性可位于分子的中心、轴或者平面上。
本文综述了手性离子液体合成的最新进展,并按照阴离子或阳离子的种类将其分为咪唑类、吡啶类、铵类和噻唑啉盐类,同时简要介绍了一些新的合成技术。
关键词 手性 离子液体 合成中图分类号:O62113,O64514 文献标识码:A 文章编号:10052281X (2008)0520698215Synthesis of Chiral Ionic LiquidsSun Honghai1,2 Gao Yu 3 Zhai Yongai 1 Zhang Qing 1 Liu Fengqi 1 Gao G e13(1.C ollege of Chemistry ,Jilin University ,Changchun 130023,China ;2.Department of Chemistry ,Daqing NormalUniversity ,Daqing 163712,China ;3.Health Science Center ,Peking University ,Beijing 100083,China )Abstract The interest in using room tem perature ionic liquids (RTI Ls )as potential replacement s olvents for organic synthesis ,extraction ,electrochemistry ,and materials science has increased tremendously in the recent years.Am ong them ,chiral ionic liquids are particularly attractive due to their potential for chiral discrimination ,asymmetric synthesis ,optical res olution of racemates ,stereoselective polymerization ,gas chromatography ,NMR shift reagents and liquid crystals.Even though the difficult syntheses of chiral ionic liquids and their high cost often precluded their use ,the possibility to use chiral ionic liquids as inducers for asymmetric reactions has greatly prom pted researchers to continuely synthesize new chiral s olvents.The chiral ionic liquids are designed either from the chiral pool (aminoacids ,amines ,aminoalcohols ,and alkaloids )or by asymmetric synthesis ;they can bear central ,axial or planar chirality.This review deals mainly with recent advances in synthesis of chiral ionic liquids.Based on the species of cation or anion ,they are classified into imidazolium 2based ,pyridinium 2based ,amm onium 2based ,and thiazolinium 2based etc.In addtion ,s ome new synthesis techniques are als o introduced.K ey w ords chirality ;ionic liquids ;synthesis 以离子液体(I Ls )为溶剂进行有机合成反应是近年来的新兴研究领域之一。
- 1、下载文档前请自行甄别文档内容的完整性,平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益,请联系客服反馈,我们会尽快为您处理(人工客服工作时间:9:00-18:30)。
a r X i v :c o n d -m a t /9712300v 2 [c o n d -m a t .s t r -e l ] 28 A p r 1999Fermi-liquid features of the one-dimensional Luttinger liquidYupeng Wang 1,21Laboratory of Ultra-Low Temperature Physics,Chinese Academy of Sciences,P.O.Box 2711,Beijing 100080,China2Institut f¨u r Physik,Universit¨a t Augsburg,86135Augusburg,GermanyWe show that the one-dimensional (1D)electron systemscan also be described by Landau’s phenomenological Fermi-liquid theory.Most of the known results derived from the Luttinger-liquid theory can be retrieved from the 1D Fermi-liquid theory.Exact correspondence between the Landau pa-rameters and Haldane parameters is established.The expo-nents of the dynamical correlation functions and the impu-rity problem are also discussed based on the finite size cor-rections of elementary excitations with the predictions of the conformal field theory,which provides a bridge between the 1D Fermi-liquid and the Luttinger liquid.71.10.Pm,71.10.Ay,72.15.NjLandau’s Fermi-liquid theory (FLT)[1]is a fundamen-tal paradigm in condensed matter physics.However,as suggested by many authors,the situation in reduced di-mensions may be different.Especially in 1D,it is gen-erally believed that the systems are marginal [2–4]and the low temperature properties of the 1D gapless quan-tum systems can be described by the Luttinger-liquid theory (LLT)[5,6].Even in 2D,Anderson showed that a strongly correlated electron system may exhibit the main characters of a Luttinger liquid [7].A Luttinger liquid generally has the following characteristics:(i).Its low en-ergy excitations can be completely described by the col-lective density waves,i.e.,the sound waves (charge den-sity fluctuation)and the spin density waves characterized by two velocities v ρand v σrespectively;(ii).Various op-erators exhibit anomalous dimensions determined by two stiffness constants K ρand K σ,which lead to the nonuni-versal power-law decay of correlation functions;(iii).The momentum distribution of the physical particles is con-tinuous at the Fermi surface.In fact,the low temperature properties of a 1D gap-less electron system are uniquely determined by four con-stants v ρ,v σ,K ρand K σand the Haldane relations hold:v N γv J γ=v γ2,v J γ=K γv γ,γ=ρ,σ,(1)where v N γand v J γ(γ=ρ,σ)are the velocities of excita-tions induced by additional charges and currents,respec-tively [5,6].Some important thermodynamic quantities such as the specific heat C ,the susceptibility χand the compressibility κare given by C =ππv N σ,κ=2that if we use the Green’s function of the quasiparticlesrather than that of the real particles,the imaginary part of the self energy may be very small compared to thereal part,as long as the creation and annihilation oper-ators of the quasiparticles are well-defined.This can beseen in the following discussion for the integrable mod-els.For the second case,we note that the relaxation time is nothing but the response time of a quasiparticleto an external perturbation.Without external perturba-tion,the system must be in equilibrium and the collision integral is exactly zero[9].Therefore,the quasiparti-cle relaxation time makes no sense to the equilibrium properties.To clarify this,we consider the pure states(eigenstates)of a1D system.For afinite non-interacting1D system,the quantum states are described by a se-quence of integers I j.Each I j corresponds to a singleparticle state with the momentum2πI j/L.If we turn onthe interaction continuously,the distribution{I j}must not be changed since I j are discrete while the interac-tion is continuous.Therefore,an eigenstate of the in-teracting system corresponds exactly to one of the non-interacting system with the same quantum number{I j}and each allowed I j may describe a quasiparticle state. Without external perturbation,the distribution{I j}istime independent.Therefore,in a pure quantum statewe can say a quasiparticle has an infinite life-time and is thus well defined.In the ground state,only N(parti-cle number)states of I j with the smallest absolute val-ues are occupied.These occupied I j states form a per-fect Fermi sphere.In such a sense,the Luttinger theo-rem is satisfied.In addition,the particle-hole excitations can be constructed by moving some particles from theFermi sphere(thus leaving some I j holes)up to higher I jstates.This can be exactly shown in the integrable mod-els[10].In these models,the excitation energy is exactlygiven by∆E= pǫ(I p)− hǫ(I h),whereǫ(I p)(ǫ(I h)) is the dressed energy of the quasiparticles(holes)[10]. Also,the exact creation(annihilation)operator of thequasiparticles R†(p)(R(p))for the integrable models can be constructed in the framework of the algebraic Betheansatz[11].Though these operators satisfy an nonlocalcommutation relation R†(p)R†(q)=S(p,q)R†(q)R†(p), the Pauli exclusion principle holds for these quasiparti-cles since the scattering matrix S(p,q)takes the value-1when p=q.In fact,R†(p)is the exact creation opera-tor of the eigenstates and has the perfect time evolution form R†(p,t)=exp(iǫ(p))R†(p,0).Based on the above discussions,we can see that at leastfor the equilibrium state,Landau’s Fermi liquid theoryis applicable in1D.Caution should be taken only for the transport properties and other non-equilibrium proper-ties.We note a different approach,the so-called Landau-Luttinger-liquid theory[12]based on the exact solution of the Hubbard model was established by Carmelo et al..The quasi-particles are defined in the charge-and spin-sectors respectively rather than in the conventional way.This is the poineering work approaching to the 1D quantum systems along the line of the generalized Fermi-liquid theory and obtained the related quantities in a microscopic way[13,14].The main conclusion of the present letter is that almost all the known results derived from the LLT can be retrieved from Landau’s phenomenological FLT.The one-to-one correspondence between the Landau parameters and the Haldane param-eters can be established.The present results strongly suggests that the Luttinger-liquid,the Landau-Luttinger liquid and Landau’s conventional Fermi liquid are essen-tially paralell in1D.A microscopic state of the Fermi liquid is described by the quasiparticle distribution{n ps}.In an equilibrium state,n ps takes the well known Fermi-Dirac form n ps= {exp[(ǫp−µ)/T]+1}−1,whereµis the chemical potential. Notice that the quasiparticle energyǫp is no longer a c-number but a functional of{n p′s′},ǫp=ǫ0p+12 r=± s′f p F s,rp F s′,f s1=1v F=1+F s1.(5)In another hand,the density of states per unit length of the quasiparticles at the Fermi surface isN(0)=1πv F,(6)where v F is the Fermi velocity.Notice that we have taken the particle mass m as our unit.To derive some im-portant quantities such as the compressibilityκand the Drude weight D,we considerδn ps induced by the exter-nal pressure andfluxΦδn ps=∂n ps|p|δΦ).(7)At low temperatures,with eq.(3)wefind the following relations hold∂n1+F s0,1∂Φ=2N(0)πn2C Nρ=21+F s0,D≡2πv F1∂H =2N(0)L∂Jσ1+F a1,(10)and the magnetic susceptibilityχand the spin Drude weight Dσare given byχ≡1πv F1πC Jσ=11+F a1,(11)where M and Jσare the magnetization and the spin current induced by the magneticfield H and the spin fluxΦσrespectively.Notice above four new parametersC Nρ,C Jρ,C Nσ,C Jσare defined.They are nothing butthe zero sounds in a1D Fermi liquid.As the tempera-ture is lowered,the mean quasiparticle scattering timeτincreases and,forfixed frequency,ωτincreases.Asωτnears one,the quasiparticles no longer have time to relax in one period of the sound;the liquid then no longer re-mains in local thermodynamic equilibrium,and the char-acter of the sound propagation begins to change.If thereis no quasiparticle collision,f ps,p′s′,then in the collision regimeωτ>>1,the excess quasiparticles in afluid ele-ment with increased density simply diffuse away,withoutdriving the neighboring elements.However,as Landau observed,if there are quasiparticle interactions,then a local increase in the density of afluid element can drive neighboring elements via the modification of the effec-tivefield p′s′f ps,p′s′δn p′s′(x,t).Such restoring forces between neighboring elements can give rise to a sound-like collective modes of oscillation of thefluid,called zero sound.For the liquid in nonequilibrium and inhomogeneous situations that differ slightly from the equilibrium state of the homogeneous liquid,the state of the liquid can be specified by the quasiparticle distribution n ps(x,t)as a function of position and time,which satisfies the Landau kinetic equation[1,9]∂n ps(x,t)∂pǫp(x,t)∂∂xǫp(x,t)∂∂t+v p∂∂ǫp)v p∂L p′s′f ps,p′s′δn p′s′(x,t).(14) Assuming the externalfield U(x,t)=U exp i(qx−ωt), we haveδn ps(x,t)=δn ps(q,ω)exp i(qx−ωt),and ∂n0psL p′s′f psp′s′δn ps(q,ω))+(ω−qv p)δn ps(q,ω)=0.(15) If we writeδn ps in the formδn ps=−∂n0ps/∂ǫpνps,then theνps obeyνps−qv pω−qv pU.(16)Notice above p=±p F and v±pF=±v F.By solving the four coupled linear equations,we easily obtain the velocities of the four branch zero soundsC0ρ=v F(1+F s0),C0Jρ=v F(1+F s1),C0σ=v F(1+F a0),C0Jσ=v F(1+F a1).(17) These quantities are exactly the same given in(9)and (11).The former two correspond to the zero sounds of charges and the latter two correspond to those of the spins,respectively.In fact,the zero sounds describe the motions of the whole Fermi sphere’s deformation in the extreme collisionless limitωτ>>1.For each sector(spin and charge),there are only two such modes in1D.One is the breath mode of the Fermi sphere and the other is the oscillation of the whole Fermi sphere around the equilibrium position.The situation is very different from that of the Fermi liquid in3D,where there are an infinite number of zero sounds.At frequenciesωsufficiently small thatωτ<<1,sound in Fermi liquids takes the form of ordinary hydrody-namic;orfirst sound.The sound velocity Cρcan be given byC ρ=(1+F s 0)(1+F s 1).(18)In fact,in the hydrodynamic limit,the density fluctua-tion δn (x,t )satisfy the following equation∂2δn∂x 2δP =0,(19)where δP is the variation of the pressure and can beapproximated by n (∂µ/∂n )T =0δn =C ρ2δn .If we put δn (x,t )as a quantum field rather than a semiclassical quantity,with the canonical quantization[δn (x,t ),∂t δn (x ′,t )]=iδ(x −x ′),(20)the density fluctuations in 1D Fermi liquid can be simply “bosonized”asH b =[(∂δn∂x )2]dx.(21)Such an effective Hamiltonian is exactly the same derived in the Luttinger liquid theory.The spin density fluctu-ations can be quantized in a similar way with the spin wave sound velocityC σ=v F3(1C σ)T.(23)By comparing the measurable quantities derived from FLT and those from LLT,we can easily deduce that an exactly one-to-one correspondence exists between the pa-rameters of the 1D Fermi liquid and those of the Lut-tinger liquid:C N γ=v N γ,C J γ=v J γ,C γ=v γ,γ=σ,ρ.(24)In addition,the Haldane relations are also satisfied in the Fermi liquid descriptionC N γC J γ=C 2γ,C J γ=K γC γ,(25)where the stiffness constants in the Luttinger liquid the-ory can be expressed by the Fermi liquid parameters as K ρ,σ=1+F s,a 0.(26)An interesting fact is that all the quantities of the forward scattering g-ology model (spin-1/2Luttinger model)ob-tainedfromthebosonization method [5,6]are exactly thesame to those derived from FLT with the notation cor-respondence:g 4ss ′=f p F s,p F s ′,g 2ss ′=f p F s,−p F s ′.Such a correspondence has also been pointed out in a recent review [15].The correlation functions can not be derived from FLT in a microscopic way since the theory itself is phenomeno-logical.However,we know that 1D quantum systems are conformally invariant at zero temperature [16]and the exponents of a variety of correlation functions are directly related to the finite size corrections of the corresponding elementary excitations [17]which can be easily derived from the present theory.In a 1D Fermi liquid,there are only three types of elementary excitations in each sector,i.e.,the small momentum particle-holes,the 2k F particle-holes or the currents and the additional charges.The finite size correction for the excitation energy of a 1D Fermi liquid can be derived from (8),(10)and (21)as ∆F =γ=ρ,σ2πC γ8K γ+14K γ],(28)where I γare non-negative integers characterizing the particle-hole excitations.Suppose the impurity is sited at the origin.The tunneling current through it can be written asJ (x,y )∼−i [C †σ(x )C σ(y )−h.c ],x ∼0+,y ∼0−.(29)¿From(28)we obtain the asymptotic time correlation function<[J(x,y|τ),J(x,y|0)]>∼τ−K−1ρ−K−1σ.(30) Therefore,the tunneling resistivity for the spin-rotational invariant systems(Kσ=1)has the asymptotic formρi(T)∼T1−K−1ρ,(31) which also coincides with the result derived from LLT [18,21,22].The author acknowledges thefinancial supports of China National Foundation of Natural Science and Alexander von Humboldt-Stiftung.。