Pi-stacking interactions

Pi-pi stacking interactions (183-185) An interaction between two aromatic groups arising from numerous forces, primary of which are attractive van der Waals forces. There are also contributions from electrostatics, induction, and exchange-repulsion. 

This interaction orients the rest of the diketopiperazine core toward the mobile H-loop where it forms a pi-stacking interaction above and below the plane of the ring with Phe786 and Phe820, respectively. The interaction with Gln817 orients the benzodioxol substituent into the same hydrophobic pocket utilized by the ethoxyphenyl of sildenafil and vardenafil. A recent review of the SAR of a large number of PDE5 inhibitors from... 

Fustero,S. Navarro,A. Pina,B. Soler,J.G. Bartolome,A. Asensio,A. Simon,A. Bravo, R Fronza, G. Volonterio, A. Zanda, M. Enantioselective s3mthesis of fluorinated alpha-amino acids and derivatives in combination with ring-closing metathesis intramolecular pi-stacking interactions as a source of stereocontrol. Org. Lett. 2001, 3(17), 2621-2624. 

McGaughey GB, Gagne M, Rappe AK. pi-Stacking interactions. Alive and weU in proteins. Biol Chem. 1998 273(25) 15458-15463. 

A final example of complex assembly of small molecules via H bonds is shown in Figure 3.20c (Yagai et al, 2008). The formation of a toroidal aggregate is described via a combination of (a) hydrogen bonds of the barbituric acid/2,4,6-triamino-1,3,5-triazine system (Whitesides and Grzybowski, 2002) (b) pi-pi stacking interactions and (c) steric constraints of... 

Huang F, Zhou L, Jones JW, Gibson HW, Ashraf-Khorassani M (2004) Formation of dimers of inclusion cryptand/paraquat complexes driven by dipole-dipole and face-to-face [small pi]-stacking interactions. Chem Commun 2670-2671... 

The Lewis acid Hg3( i-C6F4)3 also forms a pi-acid/pi-base interaction with TR(carb). In addition to the crystal structure demonstrating the ABBABB pattern observed in other stacked materials which retain the aurophilic Au-Au interactions between four of the six basic Au(I) atoms of the BB moieties, studies have shown that the oligomeric acid/base interection is retained in solution. Pulsed gradient diffusion NMR studies [70] suggesting the oligomeric sizes and coupling... 

Stereo view of the peptidomimetic inhibitor Ro 31-8959 (saquinavir) bound to the active site of HIV PR. The distribution of the specificity subsites S and S is identical to that shown in Figure 2. Note the stacking interaction between the quinoline moiety and the PI side chain of phenylalanine. 

Because of the absence of any further contacts with the HIV PR active site residues, the contribution of the quinoline moiety to the free energy of binding remains unclear. Perhaps in solution, a stacking interaction of the PI phenyl ring and the aromatic quinoline restricts the conformational freedom of Ro-31-8959, in effect diminishing the free-energy loss due to the entropic and desolvation effects. 

Pi-stacking and electron donor-acceptor interactions have also been extensively used for designing host-guest complexes in a predictable manner [8]. 

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