Table 2.

Primary kinetic isotope effects (KIEs) on 2′ nucleophile (¹⁸k_Nu) and 5′ leaving (¹⁸k_Lg) oxygens, and secondary KIEs on O1P (¹⁸k_O1P) and O2P (¹⁸k_O2P) oxygens in aqueous solution for the TS₁ and TS₂ transition states, along with the most relevant available experimental results for comparison.[^[a]]

Reaction	TS1		TS2		Expt
	18kNu	18/34kLg	18kNu	18/34kLg	18kNu	18/34kLg
Native	1.017	1.006	0.968	1.059	0.981(3)[[b]]	1.034(4)[[b]]
S3′	1.043[[c]]	1.008[[c]]	0.992[[c]]	1.049[[c]]	1.119(6)[[d]]	1.0118(3)[[d]]
S5′	1.042[[c]]	1.002[[c]]	n.a.[[e]]	n.a.[[e]]	1.025(5)[[d]]	1.0009(1)[[d]]

Reaction	TS1		TS2		Expt
	18kO1P	18kO2P	18kO1P	18kO2P	18kO1P	18kO2P
Native	1.004	1.004	1.005	1.003	0.999(1)[[f]]	0.999(1)[[f]]
S3′	1.004[[c]]	1.004[[c]]	1.002[[c]]	1.003[[c]]	n.d.[[g]]	n.d.[[g]]
S5′	1.004[[c]]	1.004[[c]]	n.a.[[e]]	n.a.[[e]]	n.d.[[g]]	n.d.[[g]]

^[a]Temperatures used in calculations are identical to those used in the experiments that are being compared: 37°C for native reactions, and 80°C for thio-substituted reactions. All primary KIE values are computed using the second order Kleinert’s variational perturbation theory with decoupled instantaneous normal coordinate approximation, while the secondary KIE values are computed using the Bigeleisen equation in the decoupled rigid-rotor harmonic-oscillator approximation.^{[27, 28]} Boldface type represents the rate controlling KIE value as determined by comparison with experimental KIE measurements. Experimental errors in the last decimal place are given in parenthesis.

^[b]Extracted from Ref. ^[12] in which the observed ¹⁸k_Nu has been corrected for deprotonation.

^[c]To be consistent with the experiments in Ref. ^[13], the KIE values are calculated with the nucleophile O2′ protonated in the reactant state.

^[d]Extracted from Ref. ^[13], in which the nucleophile O2′ is protonated in the reactant state.

^[e]Not applicable as TS₂ cannot be found.

^[f]New experimental data given in this work; values represent an average observed for O1P and O2P positions.

^[g]Not determined yet by experiments.