Predicting pK_a Values of Quinols and Related Aromatic Compounds with Multiple OH Groups

Abstract

Quinonoid compounds play central roles as redox-active agents in photosynthesis and respiration and are also promising replacements for inorganic materials currently used in batteries. To design new quinonoid compounds and predict their state of protonation and redox behavior under various conditions, their pK a values must be known. Methods that can predict the pK a values of simple phenols cannot reliably handle complex analogues in which multiple OH groups are present and may form intramolecular hydrogen bonds. We have therefore developed a straightforward method based on a linear relationship between experimental pK a values and calculated differences in energy between quinols and their deprotonated forms. Simple adjustments allow reliable predictions of pK a values when intramolecular hydrogen bonds are present. Our approach has been validated by showing that predicted and experimental values for over 100 quinols and related compounds differ by an average of only 0.3 units. This accuracy makes it possible to select proper pK a values when experimental data vary, predict the acidity of quinols and related compounds before they are made, and determine the sites and orders of deprotonation in complex structures with multiple OH groups.

Diphenoquinhydrones and Related Hydrogen-Bonded Charge-Transfer Complexes

“…This conclusion is consistent with the fact that the redox potential of 4,4′-diphenoquinone 3a ( E red1 ° = −0.608 V vs Fc + /Fc) is much higher than that of benzoquinone ( E ° = −0.882 V) . In addition, 4,4′-dihydroxybiphenyl (p K a1 9.7) is slightly more acidic than hydroquinone (p K a1 9.9), and 3,3′,5,5′-tetrachloro-4,4′-dihydroxybiphenyl ( 4d ) is still more acidic (p K a1 6.8) . Partial proton transfer in the hydrogen-bonded chains should enhance the capacity of dihydroxybiphenyls to serve as π-donors and the ability of diphenoquinones to act as π-acceptors.…”

“…36 In addition, 4,4′-dihydroxybiphenyl (pK a1 9.7) is slightly more acidic than hydroquinone (pK a1 9.9), and 3,3′,5,5′-tetrachloro-4,4′-dihydroxybiphenyl (4d) is still more acidic (pK a1 6.8). 37 Partial proton transfer in the hydrogenbonded chains should enhance the capacity of dihydroxybiphenyls to serve as π-donors and the ability of diphenoquinones to act as π-acceptors. The mutually reinforcing effects of hydrogen bonding and charge transfer thereby exert strong control over molecular organization in diphenoquinhydrones.…”

An Accurate Approach for Computational pKa Determination of Phenolic Compounds

“…Therefore, a wide range of experimental values (between −252.6 and −271.7 kcal⋅mol −1 ) [ 11 ] is usually adopted, although this method is highly questioned [ 12 ]. Alternatively, correction factors and linear regressions are commonly used to obtain reliable results, leading to relatively accurate data [ 15 , 16 , 17 , 18 ].…”

Computational Estimation of the Acidities of Pyrimidines and Related Compounds

“…The results for pK a2 were also very good: pK a2 (exp.) = 0.95 (±0.05) • pK a1 (ACD) + 0.92 (±0.52) (4) where n = 13, R 2 = 0.966, s = 0.612, and F = 316.…”

“…As a result, there has been a long-standing interest in estimating the pK a s of chemical compounds using theoretical approaches [1,2]. This interest continues, as demonstrated by the broad range of methods employed in recent pK a studies [3][4][5][6][7][8][9][10]. In an earlier study by our group [11], we presented computational estimates of the pK a s of the biologically related purines and indoles.…”