Journal of the American Chemical Society
Article
CH3 can be estimated from half of the measured stacking
energy of m,m-(CH3)2.
REFERENCES
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EXPERIMENTAL SECTION
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Measurement of the Folded/Unfolded Ratios. The folding
ratios for balances 1a−u and control balances 2a−u were measured
from the relative peak areas of the succinimide methine protons in the
1H NMR spectra (CDCl3, 25 °C, 30 mM) as previously described.31,32
Briefly, the peak areas of the succinimide methine singlets in the 4.2 to
4.7 ppm region for the folded and unfolded conformers were measured
using the line fitting method as implemented in the Mnova NMR
software. In cases where these peaks overlapped with other protons,
the folded/unfolded ratios for the succinimide methine protons were
verified by comparison with the folded/unfolded ratios measured from
the most downfield aromatic protons (8.0−8.7 ppm). The folded and
unfolded peaks were assigned based on comparison of their peak areas
to the upfield shifted doublet for the ortho-proton of the N-aryl ring
(4.6−4.7 ppm for balance 1, 5.7−5.8 ppm for balance 2), which was
assigned to the unfolded conformer. This peak was assigned to the
unfolded conformer because this proton is directly over the aromatic
shelf in the unfolded conformer. The corresponding folding energies
(ΔG at 298 K) were calculated from the equation: ΔG = −RT
ln[folded]/[unfolded].
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Error Analyses. The error in measuring the folded/unfolded ratio
from the peak areas in the 1H NMR spectra was conservatively
estimated at 1% for balances 1a−u. This estimate is based on the
literature studies that have found that concentrations can be accurately
measured by 1H NMR with an accuracy of <1%.46−48 In particular, the
use of line shape analysis software can improve the accuracy to <0.3%
even for overlapped peaks.49 To ensure this level of accuracy, the
NMR spectra were collected at a high concentration (30 mM). At this
concentration, the minor conformer concentration (folded or unfolded)
remained ≥10 mM for the entire series of balances 1a−u.
Despite the measurement of the folded/unfolded ratios under similar
conditions, a larger measurement error of 5% was estimated for
control balances 2a−u. Control balances 2a−u had folding ratios
ranging from 1:8 to 1:15. Thus, at 30 mM, the concentration of the
minor isomer could be as low as 2 mM. At this lower concentration,
we conservatively estimated the peak area measurement error at 5%
based on literature precedent.46
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Propagation of these measurement errors in the folded/unfolded
ratios through the Gibbs free energy equation gave errors of 0.008
and 0.03 kcal/mol for the measured folding energies for 1 and 2
(ΔG1 and ΔG2), respectively. Propagation of these errors in ΔG1 and
ΔG2 through the SE definition equation (eq 1) yielded an error of
0.03 kcal/mol in SEmeasd values.
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ASSOCIATED CONTENT
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S
* Supporting Information
(26) Cozzi, F.; Annunziata, R.; Benaglia, M.; Baldridge, K. K.;
Aguirre, G.; Estrada, J.; Sritana-Anant, Y.; Siegel, J. S. Phys. Chem.
Chem. Phys. 2008, 10, 2686−2694.
Experimental details, synthetic procedures, H and 13C NMR
1
spectra, X-ray data. This material is available free of charge via
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10854−10855.
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106.
AUTHOR INFORMATION
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Corresponding Author
(29) Cozzi, F.; Ponzini, F.; Annunziata, R.; Cinquini, M.; Siegel, J. S.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1019−1020.
(30) Liu, T. J.; Schneider, H. J. Angew. Chem. Int. Ed. 2002, 41,
1368−1370.
Present Address
†Tennessee Tech University, Chemistry, Foster Hall (FOST)
107/Box 5055, Cookeville, TN 38505
(31) Carroll, W. R.; Pellechia, P.; Shimizu, K. D. Org. Lett. 2008, 10,
3547−3550.
(32) Li, P.; Zhao, C.; Smith, M. D.; Shimizu, K. D. J. Org. Chem.
2013, 78, 5303−5313.
Notes
The authors declare no competing financial interest.
(33) Paliwal, S.; Geib, S.; Wilcox, C. S. J. Am. Chem. Soc. 1994, 116,
4497−4498.
ACKNOWLEDGMENTS
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(34) Mati, I. K.; Cockroft, S. L. Chem. Soc. Rev. 2010, 39, 4195−4205.
(35) Arnstein, S. A.; Sherrill, C. D. Phys. Chem. Chem. Phys. 2008, 10,
2646−2655.
This work was supported by the National Science Foundation
(CHE 1310139, CHE 1048629, and CHE 0911616).
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dx.doi.org/10.1021/ja504378p | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX