Local pH and Effective p<i>K</i> of a Polyelectrolyte Chain: Two Names for One Quantity?

Murmiliuk, Anastasiia; Košovan, Peter; Janata, Miroslav; Procházka, Karel; Uhlı́k, Filip; Štěpánek, Miroslav

doi:10.1021/acsmacrolett.8b00484

Cited by 36 publications

(39 citation statements)

References 20 publications

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“…Various weak polyelectrolyte systems have been simulated using the RxMC method 24,4448 or cpH method 25,4957 . In RxMC 40 , we simulate chemical reactions by inserting and deleting particles, or by changing their chemical identity, as prescribed by the stoichiometry of the simulated reaction.…”

Section: Introductionmentioning

confidence: 99%

Grand-reaction method for simulations of ionization equilibria coupled to ion partitioning

Landsgesell¹,

Rud²,

Hebbeker³

et al. 2020

Preprint

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We developed a new method for coarse-grained simulations of acid-base equilibria in a system coupled to a reservoir at a given pH and concentration of added salt, that we term the Grand-reaction method. More generally, it can be used for simulations of any reactive system coupled to a reservoir of a known composition. Conceptually, it can be regarded as an extension of the reaction ensemble, combining explicit simulations of reactions within the system and Grand-canonical exchange of particles with the reservoir. To demonstrate its strength, we applied our method to a solution of weak polyelectrolytes in equilibrium with a reservoir. Our results show that the ionization and swelling of a weak polyelectrolyte are aected by the Donnan eect due to the partitioning of ions and by the polyelectrolyte eect due to electrostatic repulsion along the chain. Both eects lead to a similar shift in ionization and swelling as a function of pH; albeit for dierent physical reasons. By comparison with published results, 1 we showed that neglecting one or the other eect may lead to erroneous predictions or misinterpretations of results. In contrast, the Grand-reaction method accounts for both eects on the results and allows us to quantify them. Finally, we outline possible extensions and generalizations of the method and provide a set of guidelines for its safe application by a broad community of users.

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Section: Introductionmentioning

confidence: 99%

Grand-reaction method for simulations of ionization equilibria coupled to ion partitioning

Landsgesell¹,

Rud²,

Hebbeker³

et al. 2020

Preprint

Self Cite

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show abstract

“…As well as their role in underwater adhesives and encapsulation [21,23,24]. Extensive studies on the effects of counterions in determining the assembly and stability of polyelectrolyte complexes have been performed by several groups [25,26,27,28,29,30,31,32,33], though these have largely ignored the role of solution acidity in determining the charge on these compounds, which is crucial for dense polyelectrolyte assemblies [28,34,35,36,37,38]. Importantly, it was recently shown that the pH could significantly alter the charging equilibrium, and indeed the underlying thermodynamics of the process, when acidity and salinity are explicitly accounted for [33].…”

Section: Introductionmentioning

confidence: 99%

Explicit Ion Effects on the Charge and Conformation of Weak Polyelectrolytes

et al. 2019

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The titration behavior of weak polyelectrolytes is of high importance, due to their uses in new technologies including nanofiltration and drug delivery applications. A comprehensive picture of polyelectrolyte titration under relevant conditions is currently lacking, due to the complexity of systems involved in the process. One must contend with the inherent structural and solvation properties of the polymer, the presence of counterions, and local chemical equilibria enforced by background salt concentration and solution acidity. Moreover, for these cases, the systems of interest have locally high concentrations of monomers, induced by polymer connectivity or confinement, and thus deviate from ideal titration behavior. This work furthers knowledge in this limit utilizing hybrid Monte Carlo–Molecular Dynamics simulations to investigate the influence of salt concentration, pK a , pH, and counterion valence in determining the coil-to-globule transition of poorly solvated weak polyelectrolytes. We characterize this transition at a range of experimentally relevant salt concentrations and explicitly examine the role multivalent salts play in determining polyelectrolyte ionization behavior and conformations. These simulations serve as an essential starting point in understanding the complexation between weak polyelectrolytes and ion rejection of self-assembled copolymer membranes.

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“…This non-monotonic trend in pK a cannot be explained by the polymer composition alone and is a complex function of monomer distribution and polymer conformation. [46][47][48] Compared to the low pK a value of the cationic homopolymer (P9 had a pK a =5.9), the copolymers incorporating HEMA exhibited pK a values that were up to 1.4 pH units higher, highlighting the critical, but frequently overlooked impact of polymer composition on polycation protonation. In summary, parallelized approaches to synthesis and characterization generated synthetic vector libraries that encompass a wide range of chemical compositions, interfacial properties, and protonation equilibria.…”

Section: Parallel Synthesis and Characterization Of A Combinatoriallymentioning

confidence: 98%

Efficient Polymer-Mediated Delivery of Ribonucleoprotein Payloads Through Combinatorial Design & Parallelized Experimentation

Kumar

Le²,

Tan³

et al. 2020

Preprint

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Genome editing is almost completely reliant on viral delivery to achieve therapeutic goals, hindering widespread clinical adoption. Chemically defined delivery vehicles such as cationic polymers are versatile alternatives to engineered viruses, but their clinical translation hinges on rapidly exploring vast chemical design spaces and deriving structure-function relationships governing delivery performance. Here, we discovered a polymer for efficient ribonucleoprotein (RNP) delivery through combinatorial polymer design and parallelized experimental workflows. A chemically diverse library of 43 statistical copolymers was synthesized via combinatorial RAFT polymerization, realizing systematic variations in physicochemical properties. We selected cationic monomers that varied in their pK<sub>a</sub> values (8.1 to 9.2) as well as in the steric bulk and lipophilicity of their alkyl substituents. We also incorporated co-monomers of varying hydrophilicity and elucidated the roles of protonation equilibria and hydrophobic-hydrophilic balance. We screened our multiparametric vector library through image cytometry and rapidly uncovered a hit polymer (P38), which outperforms state-of-the-art commercial transfection reagents, achieving nearly 60\% editing efficiency via non-homologous end-joining. Structure-function correlations underlying editing efficiency, cellular toxicity, and RNP uptake were probed through unbiased statistical learning approaches to uncover the physicochemical basis of P38's performance. Although cellular toxicity and RNP uptake were solely determined by polyplex size distribution and protonation degree respectively, these two polyplex design parameters were found to be inconsequential during RNP delivery. Instead, polymer hydrophobicity and the Hill coefficient, a parameter describing cooperativity-enhanced polymer deprotonation, were identified as the critical determinants of RNP delivery. Our unconventional approach not only discovered a novel polymeric vehicle that may have remained inaccessible to chemical intuition, but also yielded statistically derived design rules to guide the synthesis of future polymer libraries.

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Local pH and Effective pK of a Polyelectrolyte Chain: Two Names for One Quantity?

Cited by 36 publications

References 20 publications

Grand-reaction method for simulations of ionization equilibria coupled to ion partitioning

Grand-reaction method for simulations of ionization equilibria coupled to ion partitioning

Explicit Ion Effects on the Charge and Conformation of Weak Polyelectrolytes

Efficient Polymer-Mediated Delivery of Ribonucleoprotein Payloads Through Combinatorial Design & Parallelized Experimentation

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Local pH and Effective pK of a Polyelectrolyte Chain: Two Names for One Quantity?

Cited by 36 publications

References 20 publications

Grand-reaction method for simulations of ionization equilibria coupled to ion partitioning

Grand-reaction method for simulations of ionization equilibria coupled to ion partitioning

Explicit Ion Effects on the Charge and Conformation of Weak Polyelectrolytes

Efficient Polymer-Mediated Delivery of Ribonucleoprotein Payloads Through Combinatorial Design &amp; Parallelized Experimentation

Contact Info

Product

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Efficient Polymer-Mediated Delivery of Ribonucleoprotein Payloads Through Combinatorial Design & Parallelized Experimentation