Impact of Long-Range van der Waals Forces on Chiral Recognition in a Cinchona Alkaloid Chiral Selector System

Singly-charged complexes of (8S,9R)-tert-butylcarbamoylquinine (tBuCQN), N-3,5-dinitrobenzoyl-(S,R)-leucine (DNB-S/R-leucine), and alkali metal counter ions (Li(+), Na(+), K(+)) were investigated by density-functional theory. It is shown that the cations prefer formation of an ionic pair with the carboxylate group of DNB-Leu over the formation of a cation-π interaction. The [tBuCQN·DNB-S/R-Leu·Na](+) complex is bound by a coulombic attraction, a hydrogen bond, a π-π interaction and van der Waals forces. The tBuCQN chiral selector preferentially complexes with the DNB-S-Leu enantiomer, because the favourable stereochemistry allows the stabilization of the complex by at least one binding mode more compared to the complex containing the DNB-R-Leu molecule. Weakening of the binding modes is observed using the lithium counter ion compared to the sodium one. The weakening is more pronounced in [tBuCQN·DNB-R-Leu·Li](+) than in [tBuCQN·DNB-S-Leu·Li](+). The exact opposite effect is observed using the potassium counter ion. Hence, the lithium counter ion enhances the enantioselectivity of tBuCQN while the potassium counter ion reduces the enantioselectivity of tBuCQN.


The NCI Plots and the Optimized Structures
Fig. S6 The optimized structures of the 1 S Li + complex (B97D/6-311++G**/DFBS).Hydrogen atoms were removed except of important ones to improve the clarity of the pictures.Colour codes: light blue, white, red, blue, and brown correspond to carbon, hydrogen, oxygen, nitrogen, and lithium, respectively.Colour codes of the isosurfaces: the weak-, the strong attractive-, and the strong repulsive interactios are in green, blue, and red, respectively.The black arrows indicate the isosurfaces discussed in the text.
Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics This journal is © The Owner Societies 2013 Fig. S7 The optimized structures of the 1 R Li + complex (B97D/6-311++G**/DFBS).Hydrogen atoms were removed except of important ones to improve the clarity of the pictures.Colour codes: light blue, white, red, blue, and brown correspond to carbon, hydrogen, oxygen, nitrogen, and lithium, respectively.Colour codes of the isosurfaces: the weak-, the strong attractive-, and the strong repulsive interactios are in green, blue, and red, respectively.The black arrows indicate the isosurfaces discussed in the text.

Fig. S8
The optimized structures of the 1 S K + complex (B97D/6-311++G**/DFBS).Hydrogen atoms were removed except of the important ones to improve the clarity of the pictures.Colour codes: light blue, white, red, blue, and cyan correspond to carbon, hydrogen, oxygen, nitrogen, and potassium, respectively.Colour codes of the isosurfaces: the weak-, the strong attractive-, and the strong repulsive interactios are in green, blue, and red, respectively.The black arrows indicate the isosurfaces discussed in the text.
Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics This journal is © The Owner Societies 2013 Fig. S9 The optimized structures of the 1 R K + complex (B97D/6-311++G**/DFBS).Hydrogen atoms were removed except of the important ones to improve the clarity of the pictures.Colour codes: light blue, white, red, blue, and cyan correspond to carbon, hydrogen, oxygen, nitrogen, and potassium, respectively.Colour codes of the isosurfaces: the weak-, the strong attractive-, and the strong repulsive interactios are in green, blue, and red, respectively.The black arrows indicate the isosurfaces discussed in the text.Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics This journal is © The Owner Societies 2013

The NBO Analysis of the 1 S Na + Isomer
The NBO analysis of 1 S Na + isomer was done at the PBE0/6-311G**//B97D/6-311++G**/DFBS level of theory using the NBO program version 3.1 as is implemented in Gaussian 09.S1,S2 Wiberg bond indexes (WBI) of about 1.4 of both C-O bonds in the carboxylate group demonstrate the π-electron delocalization over the COO -group.In the main text, it is shown using the NCI plot that the O -(3)−H + (4) ionic pair has a non-negligible covalent character.This agrees with a low value of WBI of the O -(3)−H + (4) pair.The strong interaction of between O -(3) and H + (4) affects the H + (4)−N( 5) bond resulting in a low WBI of the H + (4)−N( 5) bond.One lone pair orbital of O -(3) is involved in the charge transfer to the σ* orbital of the H + (4)−N( 5) bond, while the second one is involved in the delocalization of the electrons over the COO -moiety.In summary, the Lewis structure can be draw as the COO -moiety with delocalized π-electrons that interacts with the σ* orbital of the H + (4)−N( 5) bond.This interaction has mostly Coulombic character however it has a slight covalent character in agreement with the NCI plot.

The Relaxed Potential Energy Surface Scans
Fig. S14 The relaxed PES scan the proton migration from N( 5) to O-(3) in 1 S Na + at the B97D/6-311++G**/DFBS level of theory.

Fig. S1
Fig. S1 Dependence of the reduced density gradient on the electron density multiplied by the sign of the second Hessian eigenvalue, so called NCIplot for 2 S Na + .

Fig. S2
Fig. S2 Dependence of the reduced density gradient on the electron density multiplied by the sign of the second Hessian eigenvalue, so called NCIplot for 3 S Na + .

Fig. S5
Fig. S5 Dependence of the reduced density gradient on the electron density multiplied by the sign of the second Hessian eigenvalue, so called NCIplot for 3 R Na + .

Fig. S10
Fig. S10 Dependence of the reduced density gradient on the electron density multiplied by the sign of the second Hessian eigenvalue -so calledNCI plot for 1 S Li + .

Fig. S13
Fig. S13 Dependence of the reduced density gradient on the electron density multiplied by the sign of the second Hessian eigenvalue -so called NCIplot for 1 R K + .