Unexpected Substituent Effects in Offset π−π Stacked Interactions in Water

Abstract

We have measured the rotational barriers of meta- and para-substituted N-benzyl-2-(2-fluorophenyl)pyridinium bromides in aqueous solution by dynamic NMR as a model system for offset-stacking interactions in proteins. Because the benzyl ring can stack with the 2-fluorophenyl ring in the offset conformation in the ground state, but not the transition state, the rotational barrier reflects the magnitude of the stacking interaction. Only a small (0.1 kcal/mol) change in rotational barrier was found for para substituents relative to hydrogen. A much larger energy difference was found for electronegative meta substituents (up to 0.66 kcal/mol for CF3). Evidence suggests that this is due at least in part to an electrostatic interaction between electron-poor hydrogens on one ring with the electronegative substituents on the other ring.

Theoretical Study on Interactions between N-Butylpyridinium Nitrate and Thiophenic Compounds

“…37 The interactions of S···C2 (3.576 Å), − (−0.88946). Nowadays it seems quite well accepted that hydrogen bonding influences the structures of ionic liquids.…”

Fluorinated DNA Bases as Probes of Electrostatic Effects in DNA Base Stacking

“…Studies in nonpolar solvents using aromatic compounds containing various electron-donating and -withdrawing substituents have demonstrated significant electrostatic effects in stacking energetics and geometries. [15][16][17] Although in aqueous systems the electrostatic dipole effects are greatly diminished, localized electrostatic effects are still believed to play a role in governing neighboring base-pair geometries in DNA. [6,12] Studies with smallmolecule model systems in water have suggested that electrostatic effects are relatively weak, and that dispersive effects are a major factor governing stacking stability.…”

Specific Nonpeptide Inhibitors of Puromycin-Sensitive Aminopeptidase with a 2,4(1H,3H)-Quinazolinedione Skeleton

“…2). The electrostatic potential surfaces of these molecules [39][40][41][42][43] generated by means of computer calculations 43) are shown in the lower part of Fig. 2.…”