Characterization of Acid-Neutralizing Basic Monomers in Co-Solvent Systems by NMR

Abstract

Metabolic activity of the oral microbiota leads to acidification of the microenvironment and promotes demineralization of tooth structure at the margin of composite restorations. The pathogenic impact of the biofilm at the margin of the composite restoration could be reduced by engineering novel dentin adhesives that neutralize the acidic micro-environment. Integrating basic moieties into methacrylate derivatives has the potential to buffer against acid-induced degradation, and we are investigating basic monomers for this purpose. These monomers must be compatible with existing formulations, which are hydrophobic and marginally miscible with water. As such, cosolvent systems may be required to enable analysis of monomer function and chemical properties. Here we present an approach for examining the neutralizing capacity of basic methacrylate monomers in a water/ethanol co-solvent system using NMR spectroscopy. NMR is an excellent tool for monitoring the impact of co-solvent effects on pKa and buffering capacity of basic monomers because chemical shift is extremely sensitive to small changes that most other methods cannot detect. Because lactic acid (LA) is produced by oral bacteria and is prevalent in this microenvironment, LA was used to analyze the effectiveness of basic monomers to neutralize acid. The 13C chemical shift of the carbonyl in lactic acid was monitored as a function of ethanol and monomer concentration and each was correlated with pH to determine the functional buffering range. This study shows that the buffering capacity of even very poorly water-soluble monomers can be analyzed using NMR.

Compositional design and optimization of dentin adhesive with neutralization capability

“…Armes et al have reported that the MEMA homopolymer’s p K a value was 4.9 by titration methodology [40]. In our group, the titration method was used to measure the p K a value of MEMA monomer (6.2) [26]. The relatively low p K a of MEMA homopolymer is due to the polymer chains resisting the local build-up of cationic charge density so that it becomes progressively harder to protonate the remaining neutral amine groups.…”

“…Monomers that have basic functional groups have the potential to mitigate acidic excursions in pH. 2-(dimethylamino) ethyl methacrylate (DMAEMA) is a basic monomer (p K a 8.2) [26] and its polymer (poly(2-(dimethylamino)ethyl methacrylate, PDMAEMA) is a weak polybase, which is water-soluble both at neutral pH and in acidic media due to protonation of the tertiary amine groups. PDMAEMA is a polybase that has a critical pH point around 7, which is close to the physiological pH [27].…”

“…However, DMAEMA has been shown to be unstable in basic solution by nuclear magnetic resonance (NMR) and can be completely hydrolyzed into methacrylic acid and dimethylaminoethanol, as shown in our previous work [28]. 2- N -morpholinoethyl methacrylate (MEMA) is another basic monomer with a p K a 6.2 and is able to neutralize LA more effectively than DMAEMA [26]. Because the p K a of MEMA is lower than DMAEMA, it begins buffering and raising the pH of the solution under more acidic conditions.…”

“…As reported, the neutralization and physicochemical properties were measured based on tertiary amine monomers, linear polymers or low crosslinking density polymers (hydrogel) [26–28,30,31]. The neutralization behavior of amine-containing dentin adhesive copolymer has not been investigated systematically and the composition-structure-properties relationship of this kind of functionalized adhesive has not been studied before.…”

Grafting MAP peptide to dental polymer inhibits MMP‐8 activity

“…The effect may emanate from variation in the formulation’s overall hydrophobicity, which may perturb the pKa and/or reactivity of the amine differently in the context of resin mixtures having differing properties. 29 Relative proportions of individual components may also affect surface accessibility of the amine groups and crosslinking density by modulating viscosity and/or miscibility. Our results here demonstrate increasing the proportion of amine-containing monomer in the formulation disproportionately elevates the solvent accessible amine content, facilitating grafting to these moieties.…”