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85083138514
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note
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50). A549: 3 , 35 nM; 4, 0.49 nM; paclitaxel, 3.6 nM. A121: 3, 76 nM; 4, 1.3 nM; paclitaxel, 6.3 nM.
-
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43
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85083125403
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note
-
2O (3:1) could be performed at -20 °C (see ref 24), but we did not have any luck in keeping the solution from freezing below 0 °C although we were able to obtain clean NMR spectra in the glassy state at -20 °C.
-
-
-
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44
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85083128804
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-
note
-
2O clearly shows a +127° dihedral angle that is, in fact, consistent with our RMD results in water just mentioned above. Consequently, we did not include these two conformers for detailed discussion in this paper.
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85083122431
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note
-
The energies for each conformer in an aqueous environment (9 Å layer of discrete water molecules) were calculated on the basis of average minimized energy of 25 frames collected at 1 ps intervals during the restrained molecular dynamics sequence (Discover 95.0, CVFF force field, Biosym Technologies/Molecular Simulations Inc.). The average total energies, incorporating a solvation term, calculated for each conformer were the following: conformer A (184.8 ± 3.6 kcal/mol), conformer B (179.8 ± 3.6 kcal/mol), and conformer C (183.9 ± 2.4 kcal/mol). The average solvation energies (calculated as the summation of intermolecular van der Waals and Coulombic interactions) for each conformer were the following: conformer A (-82.6 ± 6.1 kcal/mol), conformer B (-82.6 ± 4.4 kcal/ mol), and conformer C (-93.1 ± 4.1 kcal/mol). It should be noted that the numerical values of the total energies depend on the force field used and, as such, are meaningful only for the comparison of relative energies of conformers. It is assumed that the above calculation provides an average energy for the different conformers possible at ambient temperature for each constrained dihedral. However, different factors such as the orientation of water molecules in any particular frame may influence the energy terms without actually being associated with the actual conformational and solvation energies. This study must therefore be considered an approximation only. See the Experimental Section for further details.
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50
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