On the kinetics and reaction mechanisms of boronic acid in interaction with diols for non-enzymatic glucose monitoring applications: a hybrid DFT study

Abstract

Boronic acids are well-known for their ability to complex with saccharides and to form cyclic boronic esters or cyclic boronate ions. Increasing the reactivity of boronic acids would lead towards the design of a highly responsive sensor for non-enzymatic glucose monitoring applications. Many studies have been carried out to investigate the reactivity of boronic acids towards diols in different environmental effects. The symmetry around boron in their reactive species, however, is still an open question. In this study, we used computational quantum chemistry calculations to propose a model in which boronic acid is highly reactive towards diols. B3LYP/6-31+G(d,p) model chemistry was used in water to calculate the transition states of several proposed reaction mechanisms and the rates of the reactions were calculated using the transition state theory. The reaction takes place in two steps with the first step known as the rate determining step. The model we proposed in this study includes two different electronegative R-groups attached to boronic acid (i.e. CF 3 and CH 3) which highly influence the interaction of boron with diols. The kinetic results in our study show that boronate ion with a low electronegative R-group is a better sensor in alkaline medium and boronic acid with a high electronegative R-group is a better sensor in acidic medium. Using the latter in alkaline medium results in a very poor sensor since it is highly reactive and promptly forms a tetrahedral boronate ion. The high electronegative R-group on boronate ion decreases its basic characteristics and results in a low reactive sensor. The same scenario goes for the former i.e. boronate ion attached to a low electronegative R-group in acidic medium. As a result, we can conclude that boronic acid's reactivity is not mainly due to the symmetry around boron, it is due to the characteristics of boron itself which can be affected by both the R-group and the medium.

Ideal reversible polymer networks

“…The kinetic parameters of the reversible crosslink measured by our proposed method were in the same range as published activation energy values (note that the reported numbers are for different boronic acid and diol species). 73,74 In Fig. 8, we repeated the process with identical 4-arm PEG reversible networks at a higher pH of 7.7.…”

Fast and Tight Boronate Formation for Click Bioorthogonal Conjugation

“…[10] Thedesign of atight boronate conjugation system is hampered by mechanistic ambiguities [11] and ad earth of comprehensive kinetic data (k ON , k OFF , K eq )o n boronate formation in water. [12] This information would enable as ystematic optimization of both diol and boronic acid partners.A sacondensation reaction, boronic ester formation is intrinsically unfavored in water owing to Le Châteliers principle.T hermodynamically,t he process is driven solely by the enthalpy of ring formation because the balance of bond enthalpy is neutral (two O À Hand two B À O bonds are broken to form four similar bonds). It is also wellestablished that hindered, pre-organized vicinal diols mitigate the loss of entropy in the diol substrate,a nd are thus preferred.…”

“…On the other hand, whereas an electron-donating group (OMe) impeded the reactivity (lower k ON ), it improved K eq specifically when placed in the para position (compare entry 4 vs.9 ,10; 5v s. 12,13). Even though ortho-fluoro derivatives 2h-2j enabled high reactivity,their lower hydrolytic stability caused concerns towards their use under the conditions of bioorthogonal conjugation at micromolar concentrations.…”

DOSY NMR as a tool for predicting optimal conditions for hydrogel formation: The case of a hyperbranched polyglycidol cross-linked with boronic acids

“… Schematic representation of the complexation between HbPGL macromolecules and boronic cross‐linkers under basic conditions. In aqueous solution, boronic acid preferentially reacts with diols at a pH above the pKa of boronic acid when boronic acid is in the form of a tetrahedral anion …”