Table 1.
Comparison of KIE values for phosphate/phosphorothioate ester hydrolysis reactions. Most experimental results are from Ref. 26 while the 18knonbridge value for EtOpNPP– (0.9974) comes from Ref. 13. Structures and abbreviations of all reactants are shown in Scheme 1. Different classes of mechanisms are illustrated in Scheme 2. 18knonbridge values for the hydrolysis of (MeO)2pNPPT are not applicable because there is no non-bridging oxygen in this reactant. Numbers in parentheses are the signed differences multiplied by 104. R is Pearson's correlation coefficient, MSD and MAD stand for mean signed difference and mean absolute difference, respectively.
| Reactant (Mechanism) | Substitution | B3LYP |
M06-2X UAKS | Expt. | |
|---|---|---|---|---|---|
| UFF | UAKS | ||||
| pNPP2–(95°C) (A1) | 15 k | 1.0033 (+5) | 1.0050 (+22) | 1.0049 (+21) | 1.0028 |
| 18 k bridge | 1.0229 (+40) | 1.0122 (−67) | 1.0142 (−47) | 1.0189 | |
| 18 k nonbridge | 0.9986 (−8) | 0.9994 (0) | 0.9906 (−88) | 0.9994 | |
| pNPPT2–(50°C) (A2) | 15k | 1.0047 (+20) | 1.0045 (+18) | 1.0099 (+72) | 1.0027 |
| 18 k bridge | 1.0273 (+36) | 1.0246 (+9) | 1.0352 (+115) | 1.0237 | |
| 18 k nonbridge | 1.0005 (−130) | 1.0048 (−87) | 0.9922 (−213) | 1.0135 | |
| pNPP–(95°C) (B) | 15 k | 0.9998 (−6) | 0.9997 (−7) | 0.9996 (−8) | 1.0004 |
| 18 k bridge | 1.0008 (−79) | 1.0004 (−83) | 1.0016 (−71) | 1.0087 | |
| 18 k nonbridge | 1.0117 (−67) | 1.0138 (−46) | 1.0176 (−8) | 1.0184 | |
| pNPPT– (30°C) (B) | 15 k | 1.0001 (−4) | 1.0002 (−3) | 0.9994 (−11) | 1.0005 |
| 18 k bridge | 1.0034 (−57) | 1.0041 (−50) | 1.0019 (−72) | 1.0091 | |
| 18 k nonbridge | 1.0077 (−144) | 1.0100 (−121) | 1.0153 (−68) | 1.0221 | |
| EtOpNPP–(95°C) (C) | 15 k | 1.0016 (+6) | 1.0025 (+15) | 1.0018 (+8) | 1.0010 |
| 18 k bridge | 1.0058 (+16) | 1.0062 (+20) | 1.0052 (+10) | 1.0042 | |
| 18 k nonbridge | 1.0007 (+33) | 1.0010 (+36) | 1.0018 (+44) | 0.9974 | |
| EtOpNPPT–(95°C) (C) | 15 k | 1.0014 (+4) | 1.0019 (+9) | 1.0015 (+5) | 1.0010 |
| 18 k bridge | 1.0033 (+13) | 1.0031 (+11) | 1.0037 (+17) | 1.0020 | |
| 18 k nonbridge | 1.0013 (−6) | 1.0000 (−19) | 1.0005 (−14) | 1.0019 | |
| (EtO)2pNPP(25°C) (D) | 15 k | 1.0010 (+3) | 1.0014 (+7) | 1.0012 (+5) | 1.0007 |
| 18 k bridge | 1.0037 (−23) | 1.0035 (−25) | 1.0033 (−27) | 1.0060 | |
| 18 k nonbridge | 1.0029 (−34) | 1.0020 (−43) | 0.9996 (−67) | 1.0063 | |
| (MeO)2pNPPT(30°C) (D) | 15 k | 1.0008 (+4) | 1.0010 (+6) | 1.0008 (+4) | 1.0004 |
| 18 k bridge | 1.0018 (−27) | 1.0018 (−27) | 1.0020 (−25) | 1.0045 | |
| R | 0.79 | 0.85 | 0.73 | ||
| MSD | −0.0018 | −0.0018 | −0.0018 | ||
| MAD | 0.0033 | 0.0032 | 0.0044 | ||