Mechanistic insights into the novel glucose-sensitive behavior of P(NIPAM-co-2-AAPBA)

Abstract

Aglucose-sensitive polymer, poly(N-isopropylacrylamide-co-2acrylamidophenylboronic acid) (P(NIPAM-co-2-AAPBA)), was synthesized by RAFT copolymerization. Addition of glucose results in reduced solubility and hence increased turbidity, rather than the normal increase in solubility (decreased turbidity) observed for other PBA-based glucose-sensitive polymers. The novel glucose-sensitive behavior is explained by a new mechanism, in which glucose acts as an additive and depresses the lower critical solution temperature (LCST) of the polymer, instead of increasing solubility by increasing the degree of ionization of the PBA groups. Experimental and theoretic analysis for the influence of glucose on the thermal behavior of P(NIPAM-co-2-AAPBA) reveals that glucose depresses the LCST of P(NIPAM-co-2-AAPBA) copolymers in a two-stage manner, a fast decrease at low glucose concentrations followed by a slow decrease at high glucose concentrations. For low glucose concentrations, the binding of glucose with PBA groups on the polymer chain increases the number of glucose molecules proximal to the polymer which influences the thermal behavior of the polymer, causing a rapid decrease in LCST. Importantly, the transition occurs at a glucose concentration equal to the reciprocal of the binding constant between PBA and glucose, thus providing a novel method to determine the binding constant. Other saccharides, including mannose, galactose and fructose, also depresses the LCST of P(NIPAM-co-2-AAPBA) copolymer in the same way.

Novel glucose-responsive nanoparticles based on p-hydroxyphenethyl anisate and 3-acrylamidophenylboronic acid reduce blood glucose and ameliorate diabetic nephropathy

“…2 d. It was observed that with an increase in the AAPBA ratio, the zeta potential of nano-gels became increasingly negative, which may be due to the higher hydrophobic AAPBA content, protecting them from any damage in the aqueous solution and providing relative stability. This is consistent with relevant studies [ 32 ], suggesting that p(AAPBA-b-HPA) nanoparticles are stable in aqueous solutions.…”

Investigation of interaction between boronic acids and sugar: effect of structural change of sugars on binding affinity using steady state and time resolved fluorescence spectroscopy and molecular docking

“…Equilibrium composition in aqueous medium at 25 °C in sucrose is 6% β-furanose and 10% α-furanose, in D-galactose it is 8.4% α-furanose and 15.5% β-furanose. The only significant forms in sucrose are α and β pyranose forms whereas α and β furanose forms in water are only about 0.08% at 31 °C 30 , 44 , 45 , 46 , 47 ]. Our study also shows the effect of these changes in structure on the binding process.…”

“…Boronic acids are continuing to gain interest in scaffold designing of sensors for carbohydrate cognition because of their high sugar intrinsic affinity and reversible rapid equilibrium. Even in simple cells, carbohydrates are found to be endogenous and vital in many of the biochemical processes [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Also, they are often linked to proteins that affect activity and cell surfaces.…”

“…Due to their ability of binding tightly with diols which are found in sugar molecules, boronic acids are used for designing chemo sensors. It has a covalent reaction with 1,2 or 1,3-diols and forms cyclic esters of five or six members in aqueous solution which is a reversible complexation, and that makes it an ideal interaction in designing of sensors [ 44 , 45 , 46 , 47 ]. For determining compounds that contain diol, efforts based on interaction of boronic acid and diol are being made to focus on developing fluorometric and colorimetric sensors [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

“…Two esters are produced as a result of diol binding in tetrahedral or trigonal form. Various factors like concentration and nature of buffer, pH of medium, temperature, dihedral angle of diol, the and pKa value of formed ester, influences the process of binding [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. To have a quantitative study of process of binding, calculation of binding constant, here association constant (Ka) is important.…”