Table 1.

Calculated Relative Stabilities^a (in kcal/mol) for the Tautomers of Warfarin in Gas and Aqueous Phase (PCM Solvation Model) at Different Computational Levels of Theory, with Population Percentages and Frontier Orbital Energy Differences Given

		Gas phase	Aqueous phase
Tautomer	Form	DFTb	DFTb	DFT-Dc	Boltzmann ratiod,e	HOMOe	LUMOe	AE
T0S	chain	7.17	6.07	7.2	0.003	−6.67	−1.81	4.86
T1S_R	chain	7.33	7.83	5.46	0	−7.09	−2.59	4.5
T1S_S	chain	7.03	7.48	5.29	0	−7.1	−2.6	4.5
T2S_E	chain	22.52	20.59	22.46	0	−6.55	−1.83	4.73
T2S_Z	chain	16.72	19.41	21.14	0	−6.64	−1.86	4.78
T3S	chain	24.87	23.29	23.93	0	−6.59	−1.85	4.74
T4S	chain	0	2.6	2.86	1.022	−6.7	−2.05	4.65
T5S_RE	chain	20.38	18.11	18.08	0	−6.52	−2.55	3.97
T5S_RZ	chain	20.15	16.54	17.21	0	−6.4	−2.49	3.9
T5S_SE	chain	19.96	18.27	18.12	0	−6.54	−2.52	4.02
T5S_SZ	chain	19.58	16.6	17.22	0	−6.37	−2.49	3.88
T6S_R	chain	21.7	19.29	18.73	0	−6.65	−2.54	4.11
T6S_S	chain	22.12	20.73	19.89	0	−6.63	−2.55	4.09
T7S_E	chain	15.03	12.96	14.7	0	−6.52	−1.96	4.56
T7S_Z	chain	10.14	11.87	13.46	0	−6.61	−2.01	4.6
T8S	chain	17.38	15.56	16.07	0	−6.61	−2.02	4.59
T9S_R	ring	9.42	8.07	8.35	0	−6.8	−1.85	4.95
T9S_S	ring	10	9.01	10.19	0	−6.73	−1.85	4.87
T10S_R	ring	1.59	0	0	82.817	−6.74	−1.97	4.76
T10S_S	ring	2.1	0.97	1.89	16.158	−6.71	−1.99	4.71

^aThe Gibbs free energy of the most stable tautomer is taken as the reference (0.0 kcal/mol); this is tautomer T4S for the gas phase and T10S_R for the aqueous phase.

^bDFT calculations performed using B3LYP/6-311++G(d,p).

^cDFT-D calculations performed using empirical dispersion method D3 added to the DFT computation as in [b].

^dCalculated according to the Boltzmann equation at T = 298.15 K.

^eCalculated based on DFT calculations in the aqueous phase.