TY - JOUR
T1 - Computational and experimental studies of (2,2)-Bis(indol-1-yl- methyl)acetate suggest the importance of the hydrophobic effect in aromatic stacking interactions
AU - Pang, Yuan Ping
AU - Miller, Jennifer L.
AU - Kollman, Peter A.
PY - 1999/3/3
Y1 - 1999/3/3
N2 - To understand the driving forces of aromatic stacking interactions in water, we have performed conformational searches, molecular dynamics simulations, potential of mean force (PMF) and free energy perturbation (FEP) calculations, syntheses, and NMR studies on sodium (2,2)-bis(indol-1-yl- methyl)acetate (1), sodium 3-indol-1-yl-2-methyl-propionate (2), and sodium 3-indol-1-yl-propionate (3). The conformational searches on 1 revealed that the isobutyric acid linker of 1 allows the molecule to adopt the tilted T- shaped stacked, off-center stacked, face-to-face stacked, and nonstacked conformations in a vacuum. The PMF and FEP calculations suggested that the most thermodynamically stable conformers in water are the tilted T-shaped stacked and nonstacked conformers. Independent NMR spectroscopic studies of 1-3 revealed that both the tilted T-shaped stacked and nonstacked conformers are populated in D2O and in d6-DMSO, and they are in a rapid equilibrium. Furthermore, the NMR studies found (i) a larger population of the tilted T, shaped stacked conformation of 1 at 22 °C in D2O than in d6-DMSO and (ii) more different populated stacked conformations of 1 at 60 °C in D2O than in d6-DMSO. One would expect larger populations of the stacked conformations in d6-DMSO, whose dielectric constant is smaller than that of water, if the electrostatic interaction were the only driving force of the aromatic stacking interactions. The results, therefore, suggest that the hydrophobic effect plays an important role in the stacking interaction of 1 in water.
AB - To understand the driving forces of aromatic stacking interactions in water, we have performed conformational searches, molecular dynamics simulations, potential of mean force (PMF) and free energy perturbation (FEP) calculations, syntheses, and NMR studies on sodium (2,2)-bis(indol-1-yl- methyl)acetate (1), sodium 3-indol-1-yl-2-methyl-propionate (2), and sodium 3-indol-1-yl-propionate (3). The conformational searches on 1 revealed that the isobutyric acid linker of 1 allows the molecule to adopt the tilted T- shaped stacked, off-center stacked, face-to-face stacked, and nonstacked conformations in a vacuum. The PMF and FEP calculations suggested that the most thermodynamically stable conformers in water are the tilted T-shaped stacked and nonstacked conformers. Independent NMR spectroscopic studies of 1-3 revealed that both the tilted T-shaped stacked and nonstacked conformers are populated in D2O and in d6-DMSO, and they are in a rapid equilibrium. Furthermore, the NMR studies found (i) a larger population of the tilted T, shaped stacked conformation of 1 at 22 °C in D2O than in d6-DMSO and (ii) more different populated stacked conformations of 1 at 60 °C in D2O than in d6-DMSO. One would expect larger populations of the stacked conformations in d6-DMSO, whose dielectric constant is smaller than that of water, if the electrostatic interaction were the only driving force of the aromatic stacking interactions. The results, therefore, suggest that the hydrophobic effect plays an important role in the stacking interaction of 1 in water.
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U2 - 10.1021/ja9828410
DO - 10.1021/ja9828410
M3 - Article
AN - SCOPUS:0033518870
SN - 0002-7863
VL - 121
SP - 1717
EP - 1725
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 8
ER -