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

Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.

Molecular self-assembly and nanochemistry: A chemical strategy for the synthesis of nanostructures

The halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. In this fairly extensive review, after a brief history of the interaction, we will provide the reader with a snapshot of where the research on the halogen bond is now, and, perhaps, where it is going. The specific advantages brought up by a design based on the use of the halogen bond will be demonstrated in quite different fields spanning from material sciences to biomolecular recognition and drug design.

The Halogen Bond

THE JOURNAL OF BIOLOGICAL CHEMISTRY: The Biochemical Behavior of LeadL I. Influence of Calcium, Phosphorus, and Vitamin D on Lead in Blood and Bone

This review describes a multidimensional treatment of molecular recognition phenomena involving aromatic rings in chemical and biological systems. It summarizes new results reported since the appearance of an earlier review in 2003 in host-guest chemistry, biological affinity assays and biostructural analysis, data base mining in the Cambridge Structural Database (CSD) and the Protein Data Bank (PDB), and advanced computational studies. Topics addressed are arene-arene, perfluoroarene-arene, S⋅⋅⋅aromatic, cation-π, and anion-π interactions, as well as hydrogen bonding to π systems. The generated knowledge benefits, in particular, structure-based hit-to-lead development and lead optimization both in the pharmaceutical and in the crop protection industry. It equally facilitates the development of new advanced materials and supramolecular systems, and should inspire further utilization of interactions with aromatic rings to control the stereochemical outcome of synthetic transformations.

Aromatic rings in chemical and biological recognition: energetics and structures.

Supramolecular chemistry is a field of scientific exploration that probes the relationship between molecular structure and function. It is the chemistry of the noncovalent bond, which forms the basis of highly specific recognition, transport, and regulation events that actuate biological processes. The classic design principles of supramolecular chemistry include strong, directional interactions like hydrogen bonding, halogen bonding, and cation-π complexation, as well as less directional forces like ion pairing, π-π, solvophobic, and van der Waals potentials. In recent years, the anion-π interaction (an attractive force between an electron-deficient aromatic π system and an anion) has been recognized as a hitherto unexplored noncovalent bond, the nature of which has been interpreted through both experimental and theoretical investigations. The design of selective anion receptors and channels based on this interaction represent important advances in the field of supramolecular chemistry. The objectives of this Review are 1) to discuss current thinking on the nature of this interaction, 2) to survey key experimental work in which anion-π bonding is demonstrated, and 3) to provide insights into the directional nature of anion-π contact in X-ray crystal structures.

Putting anion-π interactions into perspective.

The w(hole) picture: A tetrel bond is a directional noncovalent interaction between a covalently bonded atom of Group IV and a negative site, for example, the lone pair of a Lewis base or an anion. It involves a region of positive electrostatic potential (σ hole), and energetically, they are comparable to hydrogen bonds and other σ-hole-based interactions.

Tetrel‐Bonding Interaction: Rediscovered Supramolecular Force?

Non-covalent interactions play a crucial role in (supramolecular) chemistry and much of biology. Supramolecular forces can indeed determine the structure and function of a host–guest system. Many sensors, for example, rely on reversible bonding with the analyte. Natural machineries also often have a significant non-covalent component (e.g. protein folding, recognition) and rational interference in such ‘living’ devices can have pharmacological implications. For the rational design/tweaking of supramolecular systems it is helpful to know what supramolecular synthons are available and to understand the forces that make these synthons stick to one another. In this review we focus on σ-hole and π-hole interactions. A σ- or π-hole can be seen as positive electrostatic potential on unpopulated σ* or π(*) orbitals, which are thus capable of interacting with some electron dense region. A σ-hole is typically located along the vector of a covalent bond such as XH or XHlg (X=any atom, Hlg=halogen), which are respectively known as hydrogen and halogen bond donors. Only recently it has become clear that σ-holes can also be found along a covalent bond with chalcogen (XCh), pnictogen (XPn) and tetrel (XTr) atoms. Interactions with these synthons are named chalcogen, pnigtogen and tetrel interactions. A π-hole is typically located perpendicular to the molecular framework of diatomic π-systems such as carbonyls, or conjugated π-systems such as hexafluorobenzene. Anion–π and lone-pair–π interactions are examples of named π-hole interactions between conjugated π-systems and anions or lone-pair electrons respectively. While the above nomenclature indicates the distinct chemical identity of the supramolecular synthon acting as Lewis acid, it is worth stressing that the underlying physics is very similar. This implies that interactions that are now not so well-established might turn out to be equally useful as conventional hydrogen and halogen bonds. In summary, we describe the physical nature of σ- and π-hole interactions, present a selection of inquiries that utilise σ- and π-holes, and give an overview of analyses of structural databases (CSD/PDB) that demonstrate how prevalent these interactions already are in solid-state structures.

The Bright Future of Unconventional σ/π-Hole Interactions

Anions are essential species in biological systems and, particularly, in enzyme–substrate recognition. Therefore, the design and preparation of anion receptors is a topical field of supramolecular chemistry. Most host–guest systems successfully developed are based on noncovalent (ionic and hydrogen-bonded) interactions between anions and ammonium-type functionalities or Lewis acid groups. However, since the past 5 years, an alternative route toward the synthesis of efficient anion hosts has emerged, namely, the use of “anion–π” interactions involving nitrogen-containing electron-deficient aromatic rings, as the result of several favorable theoretical investigations. In this Account, the state of the (new) art in this growing area of anion-binding research is presented and several selected examples from our work and that of other groups will be discussed.

Anion Binding Involving π-Acidic Heteroaromatic Rings

Anion–π interactions have been receiving a great deal of attention from the scientific community for the past five years. This type of non-covalent bond is being recognized as a supramolecular interaction by chemists. Remarkably, the status for the lone pair(lp)-π interaction, namely the bonding association between a neutral electron-rich molecule and an electron-poor π ring, is hardly studied. The importance of lp–π interactions was clearly evidenced in a number of biological systems more than ten years ago; amazingly, only a few examples of lp–π interactions involving small synthetic molecules have been reported so far in the literature. Are these examples unique? Actually, a detailed analysis of the Cambridge Structure Database shows that such interactions are not unusual in organic compounds, but apparently have been overlooked in the past.

Tiddo J. Mooibroek

Papers

Putting anion-π interactions into perspective.

Tetrel‐Bonding Interaction: Rediscovered Supramolecular Force?

The Bright Future of Unconventional σ/π-Hole Interactions

Anion Binding Involving π-Acidic Heteroaromatic Rings

Lone pair–π interactions: a new supramolecular bond?