Design of Biosolvents Through Hydroxyl Functionalization of Compounds with High Dielectric Constant

Abstract

We proposed basic principles for biosolvent design on the viewpoint of ionization. Two classes of biosolvents, based on cyclic carbonate moiety and amide moiety, were designed through hydroxyl functionalization of highly dielectric compound. The newly designed compounds, glycerol carbonate (GC) and N-hydroxymethyl formamide (HOF), were synthesized for the development of soluble enzymatic systems and characterized by (13)C NMR and (1)H NMR. All the characterization data were consistent with the expected structures. Using conductance measurements, the pK (a) values of trichloroacetic acid in GC and HOF were determined as 0.80 and 0.85 at 25.0 °C, which was very close to that in water (pK (a) = 0.70), suggesting that the ionizing and dissociating abilities of GC and HOF are similar to those of water. The effects of various reaction parameters on activity and stability of Candida antarctica lipase B and lipase from Pseudomonas cepacia were investigated using the transesterification of ethyl butyrate with n-butanol as a model reaction. The activities of lipases in GC and HOF were comparable to those in water, indicating that the newly designed compounds were biocompactible. Biosolvent design is a promising and versatile method for developing new biosolvents.

Ionization basis for activation of enzymes soluble in ionic liquids

“…Walker and Bruce [11,12] were the first to describe the design of an IL in which the cation contained a hydroxyalkyl group to stabilize the dissolved enzyme. The incorporation of a hydroxyl-functionality in the solvents for dissolving enzymes with modest to good catalytic activity was also demonstrated by several groups [13][14][15] including our own [16][17][18]. ILs based on other functional groups such as NO 3 − , lactate, EtSO 4 − , and CH 3 COO − may also dissolve enzymes, however, most of them cause severe enzyme deactivation [3,[19][20][21].…”

“…According to the above analysis, solvents need to have water-like ionizing-dissociating abilities in order to dissolve active enzymes (In this paper we will refer to such solvents as "biocompatible".). Recently, we have proposed basic principles for biocompatible organic solvent design [18], which involve the introduction of hydroxyl groups into high dielectric constant compounds. The main objective of the solvent design is to improve ionizing-dissociating abilities of the studied solvent.…”

“…The main objective of the solvent design is to improve ionizing-dissociating abilities of the studied solvent. The great success in designing biocompatible organic solvents in our previous studies [17,18] inspired us to design and synthesize biocompatible ILs. The basic principles for biocompatible IL design are:…”

“…Hydroxyl group possesses high DN and AN values, therefore, hydroxyl-functionalization of the lead with high dielectric constant value may be advantageous for ionizing and dissociating enzyme functional groups. The incorporation of a hydroxyl-functionality in the high dielectric organic solvents for ionizing and dissociating enzymes with high catalytic activity was demonstrated by our group [17,18].…”

“…The reason for the high initial reaction rate in the newly designed ILs is that the cation and anion of the IL possess a hydroxyl group with high DN and AN value and both cationic and anionic units have high dielectric constant lead structures. The incorporation of a hydroxyl-functionality in the high dielectric organic solvents for ionizing and dissociating enzymes with high catalytic activity was demonstrated by our group [17,18]. In addition, the newly designed ILs are salts of a strong acid and a strong base, thereby they are neutral media.…”