Cation-n-interactions

The pseudoisocyanine J-aggregate formation in the lipid bilayer was suggested to occur as follows. First the dye molecules bind to the bilayer because of electrostatic attraction and because of cation—n interaction (i.e., interaction between the dye 7i-electron cloud and the lipid head cation) then reorientation of the lipids bound to the dyes occurs so that the dye J-aggregate structures are formed. This is supposed to be due to the energy gain upon dyes stacking, while the reorientation of lipid molecules does not require energy [29],... 

When the guest used is p-nitrophenylcholine carbonate (PNPCC) the Lewis acid zinc(n) activates the well-positioned carbonyl group in the P PCC Zn-cavitand towards reactions with external nucleophiles. The energy minimized structure of the PNPCC Zn-cavitand complex shows that cation-n interactions and C —O -Zn coordination bond occurs simultaneously. 

Figure 16.6 Modulation of cation-n interactions using fluorinated amino acids, (a) Structures of acetylcholine (ACh) and 5-hydroxytryptamine (5-HT). (b) Receptor activation (log[ECS0/ ECso(wt)]) vs. calculated gas phase cation-n binding ability. Data from references [76] and 1771.

Many kinds of interactions are possible for aromatic amino acids. Aromatic aromatic (n - - n) interactions and cation n interactions [33] are well known. Weak hydrogen-bonding interactions such as CH n, NH n, OH n, and CH O play important roles in biological systems [31]. In effect aromatic amino acids can recognize a variety of structures. Moreover, as mentioned above, the high hydrophobicity of aromatic amino acids enhances binding interactions. 

Fig.1 Inversion of the electronic character of Lewis-basic centers a the lone pair of an amine is a good binding site for a cation while the protonated ammonium group is complementary to anions b the ii-system of an electronically rich aromatic compound establishes attractive interactions with cations (cation-n interaction) the introduction of electro-withdrawing substituents produces the depletion of electronic density of the K-system giving rise to attractive interaction with anions...

The last paragraph of a chapter like this one asks the writer to predict if the non-covalent interaction of anions with jt-system will be as important and useful as the nowadays well-established cation-n interaction. We are cautious in answering this question affirmatively, but we have to confess that we are currently working in the construction of synthetic receptors for anions that do incorporate electron deficient ir-aromatic systems. We hope that our designs will be valuable for the experimental evaluation of the anion-JT interaction in solution and we will report shortly our findings. Once the strength of the anion-jt interaction in solution is determined, it will be easier to evaluate its possible use in the construction of selective receptors for anions making use of the directionality properties that we have discussed in the chapter. 

Calixarenes Synthesis and Historical Perspectives, p. 1.53 Cation-n Interactions, p. 214 Crown Ethers, p. 326... 

Cation-n Interactions, p. 214 Crown Ethers, p. 326 Fluorescent Sensors, p. 572 lonophores, p. 760 Organic Zeolites, p. 996 Platonic and Archimedean Solids, p. 1100 Protein Supramolecular Chemistry, p. 1161 Simultaneous Binding of Cations and Neutral Molecules, p. 1295... 

Fig. 1 The cation-n interaction. Shown is the interaction of a generic cation with the face of a benzene ring. (View this art in color at www.dekker.com.)...

What is the origin of this electrostatic effect Simply, all the major observations concerning the cation-n interaction can be understood by recognizing that sp carbon is more electronegative than hydrogen. This introduces bond dipoles into the system. In... 

While the gas-phase studies provide insights into the fundamental nature of the cation-n interaction, a key question is the viability of the interaction in solution. A recent computational studyindicated that, unlike an ion pair (salt bridge) interaction, the cation-n interaction is not dramatically attenuated when it moves from the gas phase to an aqueous medium. In fact, in water, a simple cation-rt interaction is predicted to be stronger than a comparable salt bridge. The many examples of biological... 

Systems that combine a crown ether-like structure with an appropriately positioned k system have proven to form effective binding sites for alkali metal cations. Cation-n interactions were also used to incorporate n facial selectivity into catalysts for asymmetric synthesis. ... 

It has been known for some time that Phe, Tpr, and Tip are overrepresented at protein-binding sites, and part of the reason for this is, no doubt, the potential to use cation-n interactions in binding. Antibody binding sites. 

A considerable array of small molecules of biological importance make use of cation-n interactions when binding to their protein targets. A well-documented example is the neurotransmitter acetylcholine (ACh). At two different binding sites — acetylcholine esterase (AChE), the enzyme that terminates synaptic transmission by hydrolyzing ACh and the nicotinic acetylcholine receptor (nAChR), a prototype membrane-spanning neuroreceptor involved in synaptic transmission—the quaternary ammonium ion of ACh makes close contact with a Trp side chain. Note that this was anticipated by earlier cyclophane studies. 

All possible combinations of amino acids and interacting geometries were documented to occur in protein structures. The key feature of course, is that the cation must be oriented toward the face of the Phe/Tyr/Trp side chain, not the edge. An especially iinpressive cation-n interaction was first noted by Wilson in the erythropoietin receptor extracellular domain.An interdigitated stack of side chains follows the sequence Lys-Tyr-Arg-Phe-Arg -Trp-Lys, a remarkable string of cation-Ti interactions. Similar motifs are seen in growth hormone receptors and related structures. 

Another prominent role for cation-n interactions is in stabilizing the secondary structures of proteins. The cationic amino acids Arg and Lys can interact with Phe, Tyr, and Trp in favorable ways. His, if protonated, can serve as the cation of a cation-n interaction, and several studies showed that the pK., of a His side chain can be modulated by a cation-Tc interaction. Neutral His is not a favorable n system for a cation-jr interaction. A pioneering analysis by Burley and Petsko considered the amino-aromatic interaction." in which NH groups from Arg. Lys, Asn. or Gin contact Phe. Tyr. or Trp. It is now appreciated that Arg and Lys are invoh ed in cation-n interactions, while interactions involving Asn or Gin must be polar-n interactions, which are inherently much weaker than cation-n interactions. While this coupling of two different interactions clouded the statistics. " the importance of pointing out the potential for such interactions was substantial. 

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