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

6. Rehybridization of the Acceptor (RICT) 3908 7. Planarization of the Molecule (PICT) 3909 III. Fluorescence Spectroscopy 3909 A. Solvent Effects and the Model Compounds 3909 1. Solvent Effects on the Spectra 3909 2. Steric Effects and Model Compounds 3911 3. Bandwidths 3913 4. Isoemissive Points 3914 B. Dipole Moments 3915 C. Radiative Rates and Transition Moments 3916 1. Quantum Yields and Radiationless Deactivation Processes 3916

Structural Changes Accompanying Intramolecular Electron Transfer: Focus on Twisted Intramolecular Charge-Transfer States and Structures

Functional π-Gelators and Their Applications

Halogen bonding is the noncovalent interaction where halogen atoms function as electrophilic species. The energetic and geometrical features of the interaction are described along with the atomic characteristics that confer molecules with the specific ability to interact through this interaction. Halogen bonding has an impact on all research fields where the control of intermolecular recognition and self-assembly processes plays a key role. Some principles are presented for crystal engineering based on halogen-bonding interactions. The potential of the interaction is also shown by applications in liquid crystals, magnetic and conducting materials, and biological systems.

Halogen Bonding in Supramolecular Chemistry

Molecular recognition in biological systems relies on the existence of specific attractive interactions between two partner molecules. Structure-based drug design seeks to identify and optimize such interactions between ligands and their host molecules, typically proteins, given their three-dimensional structures. This optimization process requires knowledge about interaction geometries and approximate affinity contributions of attractive interactions that can be gleaned from crystal structure and associated affinity data.

Here we compile and review the literature on molecular interactions as it pertains to medicinal chemistry through a combination of careful statistical analysis of the large body of publicly available X-ray structure data and experimental and theoretical studies of specific model systems. We attempt to extract key messages of practical value and complement references with our own searches of the CSDa,(1) and PDB databases.(2) The focus is on direct contacts between ligand and protein functional groups, and we restrict ourselves to those interactions that are most frequent in medicinal chemistry applications. Examples from supramolecular chemistry and quantum mechanical or molecular mechanics calculations are cited where they illustrate a specific point. The application of automated design processes is not covered nor is design of physicochemical properties of molecules such as permeability or solubility.

Throughout this article, we wish to raise the readers’ awareness that formulating rules for molecular interactions is only possible within certain boundaries. The combination of 3D structure analysis with binding free energies does not yield a complete understanding of the energetic contributions of individual interactions. The reasons for this are widely known but not always fully appreciated. While it would be desirable to associate observed interactions with energy terms, we have to accept that molecular interactions behave in a highly nonadditive fashion.3,4 The same interaction may be worth different amounts of free energy in different contexts, and it is very hard to find an objective frame of reference for an interaction, since any change of a molecular structure will have multiple effects. One can easily fall victim to confirmation bias, focusing on what one has observed before and building causal relationships on too few observations. In reality, the multiplicity of interactions present in a single protein−ligand complex is a compromise of attractive and repulsive interactions that is almost impossible to deconvolute. By focusing on observed interactions, one neglects a large part of the thermodynamic cycle represented by a binding free energy: solvation processes, long-range interactions, conformational changes. Also, crystal structure coordinates give misleadingly static views of interactions. In reality a macromolecular complex is not characterized by a single structure but by an ensemble of structures. Changes in the degrees of freedom of both partners during the binding event have a large impact on binding free energy.

The text is organized in the following way. The first section treats general aspects of molecular design: enthalpic and entropic components of binding free energy, flexibility, solvation, and the treatment of individual water molecules, as well as repulsive interactions. The second half of the article is devoted to specific types of interactions, beginning with hydrogen bonds, moving on to weaker polar interactions, and ending with lipophilic interactions between aliphatic and aromatic systems. We show many examples of structure−activity relationships; these are meant as helpful illustrations but individually can never confirm a rule.

http://pubs.acs.org/doi/pdf/10.1021/jm100112j

A Medicinal Chemist’s Guide to Molecular Interactions

An attempt to predict the gelation ability of hydrogen-bond-based gelators utilizing a glycoside library

Further evidence for the gelation ability-structure correlation in sugar-based gelators.

Non-covalent interactions of organic halogen compounds with aromatic systems: Analyses of crystal structure data

The solvent effect on organogel formation in nitrobenzene and chlorobenzene using 1,2-O-(1-ethylpropylidene)-α-d-glucofuranose (1) as the gelator is presented. Fourier transform infrared (FTIR) spectroscopy revealed that hydrogen bonding between the molecules of gelator 1 is the main driving force for gelator self-aggregation. The gels are characterized by different hydrogen-bonding patterns, which are reflected in a different microstructure of the networks. The morphology of fibers of nitrobenzene organogel consists of straight, rod-like, and thinner fibers, in comparison to the elongated but generally not straight and thicker fibers in chlorobenzene organogel. The thermal stability of gels also differs, and the ΔH is equal to 50.1 and 65.0 kJ/mol for nitrobenzene and chlorobenzene gels, respectively. The properties of the gels reported here were compared to benzene and toluene gels of 1 presented in previous work and correlated with different solvent parameters: e, δ, and ET(30). We have shown that the ...

Solvent Effect on 1,2-O-(1-Ethylpropylidene)-α-d-glucofuranose Organogel Properties

It was found that methyl-4,6-O-p-nitrobenzylidene-α-D-galactopyranoside (1) and methyl-4,6-O-benzylidene-α-D-mannopyranoside (2), which are scarcely soluble in apolar solvents, act as “supergelators” when they are enforcedly dissolved above their bp’s in a sealed tube. The minimum gelator concentrations (Cmin) were 0.03–0.07% [g mL−1] which are one of the lowest concentrations achieved so far. The coupled study of TEM observation with partial solvent exchange established that the organogel stability is related to the superstructure in the fibril network constructed in specific solvents.

Roman Luboradzki

Papers

An attempt to predict the gelation ability of hydrogen-bond-based gelators utilizing a glycoside library

Further evidence for the gelation ability-structure correlation in sugar-based gelators.

Non-covalent interactions of organic halogen compounds with aromatic systems: Analyses of crystal structure data

Solvent Effect on 1,2-O-(1-Ethylpropylidene)-α-d-glucofuranose Organogel Properties

Sugar-integrated "Supergelators" which can form organogels with 0.03-0.05% [g mL-1]