Simulations and Potentiometric Titrations Enable Reliable Determination of Effective pK_a Values of Various Polyzwitterions

Abstract

We synthesized three different polyzwitterions� poly(N,N-diallyl glutamate) (PDAGA), poly(dehydroalanine) (PDha), and poly(2-(imidazol-1-yl)acrylic acid) (PImAA)�and investigated how their ionization states respond to changes in solution pH. We used molecular simulations to determine how the net charge per monomer and the ionization states of individual acidic and basic groups differ from the ideal (Henderson− Hasselbalch) behavior. To complement the theoretical predictions, we performed potentiometric titrations and zeta-potential measurements of all studied polyzwitterions. By comparing these experiments with theoretical predictions, we could show that molecular simulations can predict and explain the origin of the differences between the effective and bare pK a values of individual titratable groups. Furthermore, we have shown that it is not possible to obtain these effective pK a values directly from the equivalence point recognition criterion (ERC), commonly used in potentiometric titrations. However, the effective pK a values can be reliably obtained by calculating the net charge per monomer from the potentiometric titration curves and validating these results against theoretical predictions. The approach we propose works reliably for polyzwitterions in which the ionization response is dominated by electrostatic interactions, such as PDAGA or PDha; however, it fails if other specific interactions contribute significantly, such as in the case of PImAA.

Poly(dehydroalanine)‐Based Hydrogels as Efficient Soft Matter Matrices for Light‐Driven Catalysis

“…Similarly, the pK a values of PDha are shifted compared to the pK a values of small molecule l-alanine containing the same functional groups. [61,62] The presence of a charge, either positive or negative, contributes to swelling in hydrogels due to electrostatic repulsion. [63] The swelling degree for PDha PEG2 was 27 ± 2 at pH 11 indicating that repulsive forces have a major influence on swelling.…”

Asymmetric Block Extension of Star‐Shaped [PEG‐SH]4 – toward Poly(dehydroalanine)‐Functionalized PEG Hydrogels for Catch and Release of Charged Guest Molecules

“…Recently, it was found in theoretical calculations that the equivalence point at 5.5 (or 5.8 in the case of the homopolymer) cannot be assigned to the protonation of the carboxylic acid but rather is related to an intramolecular equilibrium. [ 35 ] Subsequently, the carboxylic groups of the copolymer are protonated which results in a transition from the polyzwitterion toward a polycation with an equivalence point at a pH of 3.2 (pK a = 3.9) which is in accordance with the titration of the homopolymer. In conclusion, we expect the copolymer to be a polyanion at a pH value above 10 (pK a = 11.7), while in the pH range of 10 – 2, it is polyzwitterionic with a slight excess positive or negative charge – depending on the pH value, and below pH 2 the copolymer behaves like a polycation.…”

Polyelectrolyte Brush Interacting with Ampholytic Nanoparticles as Coarse-Grained Models of Globular Proteins: Poisson–Boltzmann Theory

“…According to eqs and , ionization of acidic and basic ionogenic groups is controlled by local electrostatic potential ψ­( z ) in the brush, while the Coulomb interactions between ionized groups on NP surface are disregarded. These interactions could shift the ionization constants with respect to “bare” constants K i + and K i – (see refs and ). Within the applied here approximation, { N i ± } and { K i ± } are considered as independent sets of variables.…”