. Author manuscript; available in PMC: 2015 Aug 14.

Published in final edited form as: Phys Chem Chem Phys. 2014 Aug 14;16(30):15846–15855. doi: 10.1039/c4cp01050g

Table 1.

Free energies (kcal/mol) of transition states (ΔG^≠), intermediates (ΔG_i) and products (ΔG) relative to reactants in RNA transesterification model reactions (Scheme 1) with different leaving groups as well as their experimental pK_as in water at 25°C.

	UFF				UAKS				Expt. pK_a
Leaving Group	$Δ G_{1}^{\neq}$	Δ G_i	$Δ G_{2}^{\neq}$	Δ G	$Δ G_{1}^{\neq}$	Δ G_i	$Δ G_{2}^{\neq}$	Δ G	Expt. pK_a
(CH₃)₂CHO^–	20.26	20.25	25.96	−1.56	20.03	17.66	23.82	−10.95	17.1
CH₃CH₂CH₂O^–	18.94	19.11	24.26	−1.40	18.61	15.61	22.73	−9.40	16.1
CH₃CH₂O^–	20.25	20.19	25.84	−0.04	19.73	16.80	23.17	−7.55	16
CH₃O^–	18.96	19.07	24.43	−0.59	19.00	15.94	22.36	−6.51	15.54

HOCH₂CH₂O^–	18.25	16.61	19.64	−6.44	19.10	17.01	22.99	−12.68	15.07
ClCH₂CH₂O^–	17.23	16.03	18.55	−6.94	18.13	15.44	20.08	−19.23	14.31
FCH₂CH₂O^–	17.72	16.52	20.11	−5.52	19.88	5.67	21.08	−17.44	14.2
CHCCH2O^–	16.85	15.27	17.75	−7.40	17.27	13.85	17.66	−16.66	13.55
CF₃CH₂O^–	15.87	12.49	13.59	−11.28	16.62	11.91	15.11	−21.17	12.37

CH₃CH₂S^–	14.42	· · ·	· · ·	−33.36	16.17	· · ·	· · ·	−30.04	10.61
CH₃S^–	14.94	· · ·	· · ·	−32.68	15.67	· · ·	· · ·	−29.45	10.33

PhO^–	14.76	· · ·	· · ·	−23.07	15.70	· · ·	· · ·	−23.59	9.95
3-CNPhO^–	13.87	· · ·	· · ·	−26.92	14.05	· · ·	· · ·	−28.18	8.61
4-CNPhO^–	12.62	· · ·	· · ·	−30.50	13.96	· · ·	· · ·	−29.78	7.95
p-NO₂PhO^–	11.99	· · ·	· · ·	−32.69	13.80	· · ·	· · ·	−30.65	7.14
2,3,5,6-F₄PhO^–	10.96	· · ·	· · ·	−36.10	10.97	· · ·	· · ·	−37.23	5.53

CH₃COO^–	11.91	· · ·	· · ·	−32.87	11.22	· · ·	· · ·	−34.95	4.46

$Δ G_{1}^{\neq}$ and $Δ G_{2}^{\neq}$ are free energy barriers of early and late transition states (TS1 and TS2), respectively. All the experimental pK_as are taken from IUPAC chemical data series (No. 23),⁷¹ except those of ethylene glycol and 2,3,5,6-tetrafluorophenol, which are taken from the CRC Handbook⁷² and Bourne et al.,⁷³ respectively. The pK_a values of ethylene glycol and acetic acid have been corrected for statistical factors by adding log(p/q), where p and q are the number of reactive positions available in the acid and in the base, respectively.^58,74