Cation-pi interactions

SDS solutionsThese cation-pi interactions have been observed in many different fields in... 

Ikeda, A., Tsuzuki, H., Shinkai, S. 1994. X-ray crystallographic studies of a 1,3-al-temate-calix[4]arene Na+ complex - Is the cation-pi interaction operative between the benzene rings and Na+ Tetrahedron Lett. 35 8417-8420. 

Gokel, G. W., Barbour, L. J., Ferdani, R., Hu, J. X., Lariat ether receptor systems show experimental evidence for alkali metal cation-pi interactions. Acc. Chem. Res. 2002, 35, 878-886. 

Meadows, E. S. DeWall, S. L. Barbour, L. J., Gokel, G. W., (2001) Alkali metal cation-pi interactions observed by using a lariat ether model system J. Am. Chem. Soc. 123, 3092-3107. 

Beene DL, Brandt GS, Zhong W, Zacharias NM, Lester HA, Dougherty DA. Cation-pi interactions in ligand recognition by serotonergic (5-HT(3A)) and nicotinic acetylcholine receptors the anomalous binding properties of nicotine. Biochemistry 2002 41(32) 10,262-10,269. 

Crown Ethers as Tools to Explore Cation-Pi Interactions 809... 

Heteromacrocycles Used to Study Double and Triple Bond Cation-Pi Interactions 813... 

The two center structures show the complex that forms between iV,iV -bis(2-phenylethyl)-4,13-diaza-18-crown-6 and KI <2000PNAS6271>. The K+ ion is bound in the center of the macroring, as expected for any 18-crown-6 macrocycle. The twin sidearms of the bibracchial lariat ether turn inward in this complex and the arenes serve as apical donors. The top center structure shows the symmetrically bound cation and illustrates that the iodide anion is excluded from the cation s solvation sphere. The bottom center structure shows the superimposition of the two benzene rings upon each other and upon the K+ ion. Note in the bottom center structure that the iodide anion is not illustrated. The ideal sandwich of arene-cation-arene confirms the cation-pi interaction between benzene and K+. 

In tryptophan, the indole residue is attached to the amino acid s side chain at indole s position 3. When the point of attachment was moved to indole position 5, however, macrocycle 13 complexed NaBPli4 in the pi-fashion but benzene rather than pyrrole was clearly the donor group <2002JA10940>. One may conclude that 12 is a less reasonable model than is 13. In fact, both unequivocally confirm the cation-pi interaction. Further, the fact that cation-pi interactions are prominent in both cases means that in the natural environment, the rarest of the 20 common amino acids is a truly versatile pi donor. 

Another control experiment was run to further confirm the significance of the cation-pi interaction in these bibracchial lariat ether model complexes. In this case, a diaza-18-crown-6 derivative was prepared in which a 2-phenylethyl pi-donor sidearm was attached to one nitrogen and a 2-methoxyethyl sigma donor was attached to the other <2002CC1808>. The structure is illustrated as 14, above. The solid-state structure of the 14 KI complex showed the typical apical solvation of the ring bound cation. In this case, however, one apex was solvated in the pi-fashion (benzene) and the other by the oxygen sigma donor. 

Ting AY, Shin 1, Lucero C, Schultz PG. Energetic analysis of an engineered cation-pi interaction in staphylococcal nuclease. J. Am. Chem. Soc. 1998 120 7135-7136. 

Figure 4 Moiecuiar modeis of binding subsites in the Drosophila or vertebrate nicotinic acetyichoiine-reguiated receptors. (Reprinted with permission from Tomizawa etal. (2003) The neonicotinoid eiectronegative pharmacophore piays the cruciai roie in the high affinity and seiectivity for the Drosophila nicotinic receptor An anomaiy for the nicotinoid cation-pi interaction modei. Biochemistry 42 7819-7827 American Chemicai Society.)...

Padgett, C. L., Hanek, A. P., Lester, H. A., et al. (2007) Unnatural amino acid mutagenesis of the GABA(A) receptor binding site residues reveals a novel cation-pi interaction between GABA and beta(2)Tyr97. Journal of Neuroscience, 27(4), 886-892. 

Pi-complexes, also called donor-acceptor complexes, are often a weak association of an electron-rich molecule with an electron-poor species. The donor is commonly the electron cloud of a pi bond or aromatic ring the acceptor can be a metal ion, a halogen, or another organic compound. In the absence of solvent, as can occur in an enzyme cavity, the cation-pi interaction can be stronger than hydrogen bonding. The cation snuggles into the face of the aromatic pi cloud (see aromaticity. Sections 1.9.3 and 12.3). 

The gas phase attraction between benzene and various cations decreases with increasing cation size (Li" " at 38 kcal/mol, Na" " at 27 kcal/mol, and K" " at 18 kcal/mol). Figure 1.16 shows the cation-pi interaction between an alkene and silver ion. 

Scharer, K., Morgenthaler, M., Paulini, R., Obst-Sander, U., Banner, D. W., Schlatter, D., Benz, J., Stihle, M., Diederich, F. Quantification of cation-pi interactions in protein-ligand complexes crystal-structure analysis of factor Xa bound to a quaternary anunonium ion ligand. Angew. Chem. Int. Ed. Engl. 2005, 44, 4400-4404. 

Crowley, P.B., and Golovin, A. (2005) Cation-pi interactions in protein-protein interfaces. Proteins 59, 231-9. 

Cation-pi interactions typically contribute between 2 and 6 kcal/mol. 

Prajapati RS et al (2006) Contribution of cation-pi interactions to protein stability. Biochemistry 45(50) 15000-15010... 

Mecozzi S, West A P, Dougherty D A (1996). Cation-pi interactions in aromatics of biological and medicinal interest Electrostatic potential surfaces as a useful qualitative guide. Proc. Natl. Acad. Sci. USA. 93 10566-10571. 

See, for instance C. Biot, R. Wintjens, and M. Rooman, Stair motifs at protein-DNA interfaces Nonadditivity of H-bond, stacking and cation-pi interactions, J. Am. Chem. Soc., 126 (2004) 6220-6221. 

Mo, G. G. H. and Yip, C. M. 2009. Supported lipid bilayer templated J-aggregate growth Role of stabilizing cation-pi interactions and headgroup packing, Langmuir 25,10719-10729. 

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