Calculated conformer energies for organic molecules with multiple polar functionalities are method dependent: Taxol (case study)

Table 5 MM2* energetics of Taxol conformations denuded of polar groups; Relative energies; kcal/mol.a

	Taxol ^b			Taxol-HCl^c			Taxol-HC2^d			Taxol-HC3^e
Conf	Gas	CHCl₃	H₂O	Gas	CHCl₃	H₂O	Gas	CHCl₃	H₂O	Gas	CHCl₃	H₂O
1	4.8	3.1	0.0	0.1	2.1	0.0	0.5	0.2	0.0	1.4	0.0	1.3
2	6.6	2.4	5.4	0.0	1.2	1.6	1.3	2.6	3.4	2.6	3.3	2.4
3	8.8	6.0	4.7	7.4	6.1	6.7	1.8	2.4	2.5	1.7	0.1	2.0
4	0.0	0.0	5.8	1.8	2.0	0.5	0.0	0.0	0.4	0.0	0.0	0.0
5	3.5	0.6	3.9	0.6	0.0	0.3	1.3	1.0	1.7	0.6	0.0	1.0
6^f	4.8	1.9	6.2	3.6	3.2	3.4	6.2	5.4	7.2	9.1	8.2	9.5
7^f	11.3	5.0	11.9	7.5	4.2	6.5	9.1	6.7	11.8	8.6	7.2	9.9
ΔE^g	8.8	6.0	5.8	7.4	6.1	6.7	1.8	2.6	3.4	2.6	3.3	2.4

^a The number of low quality MM2* parameters for the hydrocarbon (HC) analogs are very few (HC1 1.0, HC2 1.0, HC3 0.0%). Thus, the energetic changes are primarily electrostatic in origin. ^b MM2* relative energies as presented in Table 1. ^c Cl, C7 and C2' OHs in 1 were replaced with CH₃; C5 ether with CH, and C9=O with C=CH₂. ^d C2, C4, C10 and C13 esters and C3' amide were replaced with trans- CH=CH. ^e All ten polar groups replaced with hydrocarbon as in b and c. ^f Taxol conformations determined in the solid state¹³; optimized using AMBER* with all non-terpenoid core dihedral angles frozen; 6 polar; 7 extended. ^g The energy spread (kcal/mol) between the highest and lowest unconstrained energy conformations; i.e. 1-5.