抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.

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Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

Thiol-ene “click” reactions and recent applications in polymer and materials synthesis

The photopolymerization of mixtures of multifunctional thiols and enes is an efficient method for the rapid production of films and thermoset plastics with unprecedented physical and mechanical properties. One of the major obstacles in traditional free-radical photopolymerization is essentially eliminated in thiol–ene polymerizations because the polymerization occurs in air almost as rapidly as in an inert atmosphere. Virtually any type of ene will participate in a free-radical polymerization process with a multifunctional thiol. Hence, it is possible to tailor materials with virtually any combination of properties required for a particular application. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5301–5338, 2004

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/pola.20366

Thiol–enes: Chemistry of the past with promise for the future

Water is the lingua franca of life on our planet and is the solvent of choice for Nature to carry out her syntheses.1 In contrast, our methods of making complex organic molecules have taken us far away from the watery milieu of biosynthesis. Indeed, it is fair to say that most organic reactions commonly used both in academic laboratories and in industry fail in the presence of water or oxygen. As a direct consequence of our attempts to mimick Nature's way of making new chemical bonds, we learned to rely on highly reactive nucleophilic and electrophilic reagents to gain control of the chemical reactivity and to channel chemical reactions down a desired pathway. The requirement for the protection of all protic functional groups, such as alcohols and amines, is another corollary of our reliance on these energetic species. Nevertheless, chemical transformations in aqueous solvents are not new to organic chemists. On the contrary, they have attracted attention of scientists for many years: the first use of water for an organic reaction could be dated back to Wohler's synthesis of urea from ammonium cyanate.2 From a true organic synthesis perspective, the earliest example could be the synthesis of indigo by Baeyer and Drewsen in 1882 (Scheme 1).3 In their synthesis, a suspension of o-nitrobenzaldehyde 1 in aqueous acetone was treated with a solution of sodium hydroxide. The immediate formation of the characteristic blue color of indigo 2 ensued, and the product subsequently precipitated.



Scheme 1



Water possesses many unique physical and chemical properties: large temperature window in which it remains in the liquid state, extensive hydrogen bonding, high heat capacity, large dielectric constant, and optimum oxygen solubility to maintain aquatic life forms. These distinctive properties are the consequence of the unique structure of water.4,5 The structure and properties of water have been studied by scientists representing almost all fields of knowledge, and new theoretical models continue to emerge.6,7 Water is also known to enhance the rates and to affect the selectivity of a wide variety of organic reactions.8,9

In spite of these potential advantages, water is still not commonly used as a sole solvent for organic synthesis, at least in part because most organic compounds do not dissolve in water to a significant extent, and solubility is generally considered a prerequisite for reactivity: “corpora non agunt nisi soluta” (substances do not react unless dissolved). Consequently, in the many examples of “aqueous reactions” organic co-solvents are employed in order to increase the solubility of organic reactants in water.9,10 Alternatively, hydrophilicity of the reactants is increased by the introduction of polar functional groups, again to make the resulting compound at least partially water soluble.11 However, these manipulations tend to diminish and even negate the advantages of low cost, simplicity of reaction conditions, ease of workup, and product isolation that water has over traditional solvents. Therefore, the currently burgeoning field of organic synthesis in aqueous media encompasses a large family of reactions. The solubility of reacting species and products can range from complete to partial to practically none, so that reaction mixtures can be both homogeneous and heterogeneous. The amount of water can also range widely, from substoichiometric quantities to a large volume in which the reactants are suspended or dissolved. Several terms have been used in the literature to describe reactions in aqueous millieu. In water, in the presence of water, and on water are commonly found in the recent publications and are often used interchangeably to describe reactions that proceed under very different conditions.12,13 There is also a growing number of examples micellar catalysis in the presence of non-ionic surfactants, such as Triton X-100 and PTS (a tocopherol-based amphiphile).14-18

In this review, we attempt to survey organic transformations that benefit from being performed on water under the conditions defined by Sharpless and co-workers: when insoluble reactant(s) are stirred in aqueous emulsions or suspensions without the addition of any organic co-solvents. In many cases, it is impossible to ascertain whether the reaction is occuring in or on water, but as long as the reaction mixture remains heterogeneous and the overall process appears to benefit from it (either in terms of increased reaction rate or enhanced selectivity), it qualifies.

The ‘on water’ moniker reflects the defining attribute of these reactions: the lack of solubility of the reactant(s) in water. A considerable rate acceleration is often observed in reactions carried out under these conditions over those in organic solvents.19 Furthermore, in many cases a significant rate increase of on water reactions over reactions carried out neat indicates that rate acceleration is not merely a consequence of increased concentration of the reacting species. Naturally, the degree of on water acceleration varies between different reaction classes, and even when it is modest, there are other advantages to carrying out reactions in this manner. Firstly, water is an excellent heat sink due to its large heat capacity, making exothermic processes safer and more selective, especially when they are carried out on large scale. Secondly, reactions of water-insoluble substrates usually lead to the formation of water-insoluble products. In such cases, product isolation simply involves filtration of solid products (or phase separation in case of liquids). Finally, the growing list of examples wherein reactions performed on water are not only faster but also more selective (whether chemo-, regio-, or enantio-) underscores the significant potential for process intensification for reactions performed on water.

Although claims of the ecological advantages and “greenness” of water are almost invariably found in the opening paragraphs of reports describing aqueous reactions, they should be taken with a grain of salt. The low cost, relative abundance, and inherent safety of water notwithstanding, the environmental impact of a process is determined by many factors, such as the efficiency of the reaction in terms of atom economy,20 the nature of solvents used in the reaction workup, the residual concentration of regulated organic compounds and metal catalysts remaining in the aqueous waste, and the costs of its clean up or disposal.21,22 The mere finding that a process performs as well in water as it does in an organic solvent tells us little about its potential environmental impact.

The field of aqueous organic synthesis has been regularly and comprehensively reviewed.9,10,23-27 In addition, recent reviews focusing on microwave assisted organic synthesis in water,28 reactions in near-critical water,29 and biocatalysis in water30 have been published. Accordingly, these topics are not covered in the present review.

Organic Synthesis “On Water”

This review is an update on tris(trimethylsilyl)silane, TTMSS, in organic chemistry, focusing on the advancements of the past decade. The overview includes a wide range of chemical processes and synthetic strategies under different experimental conditions, including functional group insertion and transformations, as well as preparation of complex molecules, natural products, polymers, surfaces, and new materials. These results reveal how TTMSS has matured over the past 30 years, and they further establish its value as a free radical reagent with widespread academic and industrial applications.

Thirty Years of (TMS)3SiH: A Milestone in Radical-Based Synthetic Chemistry.

Lipid geometrical isomerism: from chemistry to biology and diagnostics.

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na+/K+-ATPase activity (−66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-ω3 with a consequent increase in ω6/ω3 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD.

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Oxidative stress and erythrocyte membrane alterations in children with autism: correlation with clinical features

5′,8-Cyclo-2′-deoxyadenosine and 5′,8-cyclo-2′-deoxyguanosine in their 5′R and 5′S diastereomeric forms are tandem-type lesions observed among the DNA modifications and identified in mammalian cellular DNAin vivo. These lesions result from the chemistry of the C5′ radicals generated by the attack of HO˙ radicals to 2-deoxyribose units. Quantitative determination of these lesions in biological samples as biomarkers of free radical damage is a challenge. Results reported for irradiated samples of calf thymus DNA have been critically reviewed, underlining the need of further research for the potential involvement of these lesions in human health (76 references).

Purine 5′,8-cyclonucleoside lesions: chemistry and biology

Free radical-catalyzed cis-trans isomerization of unsaturated lipids and its outcome in biomimetic conditions are reviewed. They provided indications for an endogenous origin of trans unsaturated fatty acids in humans by the attack of thiyl radicals. A multidisciplinary approach highlights the relevance of this topic. The role of cis lipid geometry and its maintenance in the biological environment is an emerging question, with future developments in the fields of lipidomics, biology, and medicine.

Carla Ferreri

Papers

Thirty Years of (TMS)3SiH: A Milestone in Radical-Based Synthetic Chemistry.

Lipid geometrical isomerism: from chemistry to biology and diagnostics.

Oxidative stress and erythrocyte membrane alterations in children with autism: correlation with clinical features

Purine 5′,8-cyclonucleoside lesions: chemistry and biology

Trans lipids: the free radical path.